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Arguments against Arguments againste
Arguments for Arguments for
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Clinical Practice Clinical Practice
Transferable Evidence Transferable Evidence
Procedure Specific Evidence Procedure Specific Evidence

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Abdominal Hysterectomy 2006

   

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Summary Recommendations

The recommendations of the PROSPECT Working Group are graded A–D, based on the level of evidence from the studies, which is in accordance with the Oxford Centre for Evidence-Based Medicine (CEBM website accessed Dec 2003, Sackett 2000). In the context of PROSPECT, recommendations based on procedure-specific evidence are grade A (randomised clinical trials), those based on transferable evidence are grade B (randomised clinical trials) or grade C (retrospective studies or case series) and those based on clinical practice are grade D. (Click here for further information on levels of evidence and grades of recommendation) PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted. The following pre-, intra- and postoperative interventions have been evaluated for the management of postoperative pain following abdominal hysterectomy:

Pre-operative

Recommended:
  • Single-dose spinal local anaesthetic plus strong opioid, for anaesthetic (grade D) and postoperative analgesic purposes (grade A), but the benefits must be weighed against the risks of the invasive nature of the procedure
  • Cognitive intervention (grade A)
Not recommended:
  • Systemic analgesics (e.g. IV COX-2 inhibitors, conventional NSAIDs, strong opioids), except to secure sufficient analgesia when the patient wakes up (e.g. oral COX-2 inhibitors) (grade A)
  • Clonidine, NMDA-receptor antagonists and benzodiazepines (grade A)
  • Epidural single dose for postoperative analgesia (grade A)
  • Local anaesthetic skin infiltration at the proposed site of incision (grade A) (but intra-operative wound infiltration is recommended, see below)
  • Homeopathic arnica and self-relaxation techniques (grade A)

Intra-operative

Recommended:
  • General anaesthesia, or single dose spinal anaesthesia with or without light general anaesthesia in low-risk patients (grade D)
  • Epidural anaesthesia combined with light general anaesthesia or combined spinal-epidural anaesthesia, in high-risk patients (grade A)
  • Strong opioids administered in enough time to secure sufficient analgesia when the patient wakes (grade A)
  • Wound infiltration before closure (grade A)
  • LAVH or VH rather than abdominal hysterectomy, only if allowed by the surgical requirements (based on technical feasibility, patient indication for hysterectomy and risk factors) (grade A)
  • Pfannenstiel incision, only if allowed by the surgical requirements (based on technical feasibility, patient indication for hysterectomy and risk factors) (grade B)
  • Diathermy incision (grade B)
  • Active patient warming in high-risk patients (grade A)
  • Intra-operative music (grade A)
Not recommended:
  • Epidural single dose for postoperative analgesia (grade A)
  • Adenosine, NMDA-receptor antagonists, benzodiazepines or tryptophan (all grade A)
  • Intraperitoneal analgesia (grade A)
  • Unsutured peritoneum, wet film dressing (both grade A) or surgical drains (grade D)
  • Therapeutic suggestions or electroacupuncture (both grade A)

Postoperative

Recommended:
  • COX-2 selective inhibitors or conventional NSAIDs, in combination with strong opioids for high-intensity pain (VAS=50) or with weak opioids for moderate- (VAS<50>30) or low-intensity pain (VAS=30) (grade A)
  • Strong opioids by IV PCA or by fixed IV dosing titrated to pain intensity (grade A)
  • Paracetamol for moderate- (VAS>30<50) or low-intensity (VAS=30) pain, in combination with COX-2 inhibitors or conventional NSAIDs (grade A)
  • Epidural analgesia in high-risk patients (grade A and D)
Not recommended:
  • Epidural analgesia for routine use in low-risk patients (grade D)
  • Repeat spinal boluses of analgesic (grade D)
  • Concomitant administration of COX-2 selective inhibitors or conventional NSAIDs with epidural analgesia (grade B)
  • Continuous infusion of strong opioid during PCA bolus dosing (grade D)
  • IM administration of strong opioids (grade D)
  • Intra-nasal, slow-release oral and transdermal patch administration of strong opioids (grade D)
  • Paracetamol for high-intensity pain (VAS=50 mm) (grade B)
  • NMDA-receptor antagonists and benzodiazepines (both grade A)
  • Clonidine, pentazocine, clomipramine, delta-9-tetrahydrocannabinol and naloxone (all grade A)
  • Continuous wound infiltration of local anaesthetics after closure (grade A) (although pre-closure wound infiltration is recommended, see above)
  • Music in PACU, homeopathic arnica or self-relaxation techniques (all grade A)
See Overall PROSPECT Recommendations  for the overall strategy for managing pain after abdominal hysterectomy  

Overall PROSPECT Recommendations

Click here for Algorithm for the management of postoperative pain

This algorithm for managing postoperative pain is based on the PROSPECT recommendations and illustrates the different treatment pathways for low-  ¢ and high-  ¢ risk patients, as well as describing the steps of the peri-operative pathway/therapies that apply to all patients ¢. Therapies that are not recommend are also indicated. a Low-risk patients are otherwise healthy patients who are not considered to be at a higher risk than is typically associated with anaesthetic or analgesic agents b High-risk patients are those considered to be at a high risk of adverse effects from inhalation anaesthetics and high-dose opioids, e.g. those at risk of organ dysfunction or undergoing extensive surgery for malignancy.  

Description of studies 

Literature search

Explanation for the focus on abdominal over vaginal hysterectomy

  • The significant majority of studies found in the literature search were in abdominal hysterectomy, with the exception of: 
  • The studies showed that LAVH is associated with significantly lower postoperative pain scores than abdominal hysterectomy: meta-analyses showed a reduction of up to 29 mm at 48 h on a 100-mm VAS (p<0.00001) (see Operative Techniques section)
  • In light of the different pain profiles for LAVH and abdominal hysterectomy, and the absence of studies in LAVH, these procedures will be assessed separately, and an analysis of analgesia for controlling postoperative pain in LAVH conducted when more studies are available  

Transferable evidence
As for all of the procedures in PROSPECT, abdominal hysterectomy-specific evidence was supplemented with transferable evidence, the majority of which was from other major gynaecological and abdominal procedures.  

PROSPECT Recommendations

  • A recommendation of anaesthetic choice based on postoperative analgesic effect cannot be made for abdominal hysterectomy, because there is no evidence for the comparative benefits of different anaesthetic techniques in reducing postoperative pain. Moreover, anaesthetic choice should be based on factors other than the management of postoperative pain, including individual patient risk factors and local practice (Grade D)
  • General anaesthesia or single shot spinal anaesthesia with or without sedation is recommended for routine use in abdominal hysterectomy, but the continuous epidural catheter technique is not recommended for routine use, based on the relative risks and benefits of these techniques in this patient population (grade D)
  • Continuous epidural with or without a light general anaesthetic or combined epidural-spinal anaesthesia is recommended over general anaesthesia alone in high-risk patients, e.g. those at risk of organ dysfunction and some patients undergoing extensive surgery for malignancy. In these high-risk patients, the benefits of neuraxial anaesthesia (e.g. reduction in inhalation anaesthetics and opioid use as well as reduced paralytic ileus and improved pulmonary function) outweigh the risks. In these pa

Clinical Practice

  • The continuous epidural technique produces a less profound block than spinal anaesthesia and takes a longer time to perform as well as conveying a higher risk of rare complications such as epidural haematoma

Transferable Evidence from Other Procedures

  • Inhaled anaesthesia was similar to combined nitrous oxide/propofol anaesthesia for postoperative pain scores, supplementary analgesic consumption and time to recovery from anaesthetic in patients undergoing laparoscopic hysterectomy Nelskyla et al 1997 Click here for more information
  • Epidural and spinal anaesthesia are not significantly different for: the need for postoperative pain relief, anaesthetic failure rate, need for additional intra-operative analgesia, need for conversion to general anaesthesia, maternal satisfaction and the need for neonatal intervention as determined in a systematic review of caesarean section Ng et al 2004
  • Combined spinal-epidural anaesthesia has a higher postoperative analgesic efficacy than epidural anaesthesia alone Lew et al 2004 Click here for more information

Abdominal Hysterectomy-Specific Evidence - Study information

  • Combined general-epidural anaesthetic was superior to general anaesthetic alone for reducing postoperative pain scores in two studies, and one study showed greater postoperative benefits with an additional epidural bolus at closure Jorgensen et al 2001 Click here for more information
  • Combined general-epidural anaesthetic plus epidural at closure was superior to general anaesthetic alone and to combined general-epidural anaesthesia alone for reducing supplementary analgesic consumption Jorgensen et al 2001 Click here for more information
  • General plus epidural anaesthesia was superior to spinal plus epidural anaesthesia for reducing postoperative pain scores at rest (p=0.026) and on movement (p<0.001; n=40) within 0–72 h Callesen et al 1999
  • General plus epidural anaesthesia was superior to spinal plus epidural anaesthesia for reducing postoperative supplementary opioid consumption from PACU-72 h (p<0.05; n=40) Callesen et al 1999
  • Spinal plus epidural was associated with a significantly lower incidence of nausea (p<0.0001) and vomiting (p<0.002) than general plus epidural anaesthesia within 0–72 h (n=40) Callesen et al 1999

PROSPECT Recommendations

  • Intra-operative strong opioids are recommended for the treatment of postoperative pain in hysterectomy based on their analgesic efficacy in the early postoperative period (grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

PROSPECT Recommendations

  • Intra-operative adenosine is not recommended based on limited evidence of its analgesic efficacy (grade A) and a lack of clinical experience with this agent (grade D)
  • Intra-operative NMDA-receptor antagonists are not recommended based on inconsistent evidence of their analgesic efficacy and effect on reducing PONV (grade A), as well as a lack of clinical understanding of these agents
  • Intra-operative benzodiazepines are not recommended based on limited evidence for their analgesic efficacy (grade A)
  • Intra-operative tryptophan is not recommended based on a lack of analgesic efficacy (grade A)

Clinical Practice

  • Adenosine and tryptophan are not used routinely because of a lack of clinical experience with these agents
  • NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship; in addition, they are associated with adverse side-effects, e.g. ketamine is known for its toxicity and for causing dysphoria

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence

PROSPECT Recommendations

  • Intra-operative administration of single dose epidural analgesia, in addition to anaesthesia, is not recommended for the treatment of postoperative pain based on evidence of a limited duration of effect in reducing postoperative pain and a lack of benefit in reducing supplementary analgesic consumption (grade A)
  • A recommendation cannot be made for epidural anaesthesia based on its postoperative analgesic effects because there is no evidence for its relative postoperative analgesic benefits compared with other methods of anaesthesia. Moreover, the choice of anaesthetic regimen should be based on anaesthetic requirement and the relative risks and benefits of the anaesthetic related to the patient and the surgical procedure (grade D) (See Anaesthetic techniques section)

Clinical Practice

  • Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications
  • Epidural clonidine is not used routinely because it is associated with an increased risk of hypotension, sedation and bradycardia

Transferable Evidence from Other Procedures

  • Epidural and spinal anaesthesia were not significantly different for: the need for postoperative pain relief, anaesthetic failure rate, need for additional intra-operative analgesia, need for conversion to general anaesthesia, and maternal satisfaction in a systematic review of caesarean section Ng et al 2004

Abdominal Hysterectomy-Specific Evidence - Study information

  • Intra-operative epidural morphine, with or without postoperative epidural boluses, provided a significant benefit over epidural saline placebo in reducing postoperative pain scores at 6 h, but the results at 12 and 24 h were not significant Jorgensen et al 1982 Click here for more information
  • Intra-operative epidural morphine extended the time to first analgesic request in one study (p<0.05; n=14) Jorgensen et al 1982
  • Intra-operative epidural clonidine provided a significant benefit over placebo in reducing postoperative pain scores on cough and mobilisation at 4–12 h (p<0.05 for all times; n=22) Mogensen et al 1992a
  • Intra-operative epidural ketamine conferred a significant benefit over placebo for reducing the supplementary analgesic consumption within 0–4 (p<0.05), 0–8, 0–12 and 0–24 h (p<0.001), but at 0–1 and 0–2 h the results were not significant (n=40) Abdel-Ghaffar et al 1998
  • Intra-operative ketamine conferred a significant benefit over placebo for extending the time to first analgesic request (p<0.01; n=40) Abdel-Ghaffar et al 1998
  • Combined general-epidural anaesthetic plus epidural at closure was superior to general anaesthetic alone and to combined general-epidural anaesthetic alone for reducing postoperative pain Jorgensen et al 2001 Click here for more information
  • Combined general-epidural anaesthetic plus epidural at closure was superior to general anaesthetic alone and to combined general-epidural anaesthetic alone for reducing supplementary analgesic consumption Jorgensen et al 2001 Click here for more information
  • Intra-operative epidural morphine plus postoperative IV morphine was associated with a similar incidence of PONV as placebo plus IV morphine in one study (n=14) Jorgensen et al 1982
  • Intra-operative epidural morphine provided no significant benefit over placebo for reducing supplementary analgesic consumption within 0–24 h Jorgensen et al 1982 Click here for more information
  • Intra-operative epidural bupivacaine plus fentanyl conferred no significant benefit over placebo for reducing postoperative pain scores within 0–48 h in one study (n=50) Richards et al 1998
  • Intra-operative epidural bupivacaine plus fentanyl conferred no significant benefit over placebo for reducing supplementary analgesic consumption within 0–48 h in one study (n=50) Richards et al 1998
  • Intra-operative epidural clonidine provided no significant benefit over placebo in reducing postoperative pain scores at rest (n=22; n=40) Mogensen et al 1992a
  • Intra-operative epidural clonidine was associated with a significant decrease in arterial blood pressure compared with placebo in two studies (p<0.05 for both; n=40; n=22) Mogensen et al 1992a
  • Intra-operative epidural ketamine conferred no significant benefit over placebo for reducing postoperative pain scores within 0–24 h (n=40) Abdel-Ghaffar et al 1998
  • Intra-operative epidural neostigmine conferred no significant benefit for reducing postoperative pain scores or supplementary analgesic consumption within 0–24 h (n=45) Nakayama et al 2001a

PROSPECT Recommendations

  • Intra-operative wound infiltration is recommended based on specific evidence that it reduces pain following hysterectomy at 8 h (grade A). Although this outcome did not reach clinical significance, this method of analgesia is convenient and has a favourable safety profile Gallagher et al 2001 Click here for more information

Clinical Practice

  • Intra-operative wound infiltration is a well-established method of analgesia with a favourable safety profile

Transferable Evidence from Other Procedures

  • Intra-operative wound infiltration with local anaesthetic was superior to pre-incisional administration, which in turn was superior to placebo for reducing pain scores (mean VAS = 51, 59 and 76 mm, respectively) and the proportion of patients requiring postoperative analgesics (28, 50 and 76%, respectively), in patients undergoing laparoscopic cholecystectomy (n=70) Sarac et al 1996
  • Intra-operative wound infiltration plus intraperitoneal administration of bupivacaine reduced postoperative overall pain for 0–2 h and incisional pain for 0–3 h (p<0.01, for both comparisons), as well as 3-h morphine consumption (p<0.05) and nausea (p<0.05) in patients undergoing laparoscopic cholecystectomy (n=58) Bisgaard et al 1999

Abdominal Hysterectomy-Specific Evidence - Study information

  • There is mixed evidence for a benefit of intra-operative wound infiltration for reducing postoperative pain scores, and the benefits are of marginal clinical significance Cobby et al 1997 Click here for more information
  • Intra-operative wound infiltration provides no significant benefit over placebo for reducing supplementary analgesic consumption Cobby et al 1997 Click here for more information
  • Wound infiltration with ketorolac provided no significant benefit over placebo for reducing postoperative pain scores or supplementary analgesic consumption in one study (n=20) Richman et al 1994
  • Wound infiltration with local anaesthetic provided no significant benefit over placebo for extending the time to first analgesic request in one study (n=41) Hannibal et al 1996
  • Wound infiltration with local anaesthetic was not significantly different from placebo for the incidence of PONV in the three studies reporting this parameter (all groups received postoperative strong opioids) Klein et al 2000

PROSPECT Recommendations

  • Intraperitoneal analgesia is not recommended based on its lack of benefit in reducing pain scores and supplementary analgesic consumption following abdominal hysterectomy (grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Intraperitoneal analgesia is an effective method for controlling postoperative pain in gynaecological laparoscopy Narchi 1995
  • Intraperitoneal wound infiltration with local anaesthetic produced a clinically significant decrease in VAS score of 13 mm on a 100-mm scale at 1–4 h in patients undergoing laparoscopic cholecystectomy, from a meta-analysis of 13 studies (p<0.05) Møiniche et al 2000
  • Intraperitoneal plus wound infiltration with bupivacaine reduced postoperative overall pain for 0–2 h and incisional pain for 0–3 h (p<0.01, for both comparisons), as well as 3-h morphine consumption (p<0.05) and nausea (p<0.05) in patients undergoing laparoscopic cholecystectomy (n=58) Bisgaard et al 1999

Abdominal Hysterectomy-Specific Evidence - Study information

PROSPECT Recommendations

  • The type of surgical technique for hysterectomy should be based on factors other than the management of postoperative pain, such as the technical feasibility of the operation, the indication for hysterectomy and operative risk-factors of the patient (grade D)
  • If the surgical requirements (based on technical feasibility, patient indication for hysterectomy and risk factors) allow, LAVH or VH is recommended over open hysterectomy because it is associated with significantly lower postoperative pain, reduced supplementary analgesic consumption and a shorter recovery time compared with abdominal hysterectomy (grade A)

Clinical Practice

  • Abdominal rather than transvaginal hysterectomy is indicated in patients who have never been pregnant, who suffer from cancer of the uterus or patients having a uterus size that precludes the transvaginal approach

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

  • LAVH provided a significant benefit over abdominal hysterectomy for reducing postoperative pain scores over the first week following surgery, providing a reduction in 100-mm VAS scores of 16 mm at 24 h, 24 mm at 48 h and 18 mm at 1 week Hwang et al 2002 Click here for more information
  • LAVH was superior to abdominal hysterectomy for reducing total supplementary analgesic consumption Falcone et al 1999 Click here for more information
  • There is some evidence that LAVH may be associated with a lower incidence of nausea at 34 h, in one study (p<0.05; n=40) Ellstrom et al 1998
  • LAVH was associated with a significantly shorter hospital stay/convalescence time than abdominal hysterectomy Howard et al 1993
  • LAVH and total vaginal hysterectomy were similar for postoperative pain scores (n=60) Hwang et al 2002
  • LAVH was associated with a lower total number of complications (e.g. febrile morbidity, infections and major organ or vessel injury) than total vaginal hysterectomy (p<0.05; n=60) Hwang et al 2002
  • Vaginal hysterectomy was superior to abdominal hysterectomy for reducing postoperative pain scores at 24 h (p<0.001; n=60) Hwang et al 2002
  • Vaginal hysterectomy was associated with a lower total number of complications than abdominal hysterectomy (p<0.05; n=60) Hwang et al 2002
  • Vaginal hysterectomy was associated with a shorter hospital stay and faster return to work than abdominal hysterectomy (p<0.05; n=60) Hwang et al 2002
  • One study reported no significant difference between vaginal and laparoscopic hysterectomy for the complication rate (n=473) Garry et al 2004
  • Vaginal hysterectomy and laparoscopic hysterectomy produced no significant difference in postoperative pain scores over 24 h in one study (n=473) Garry et al 2004
  • LAVH was associated with significantly longer operating times than abdominal hysterectomy Ellstrom et al 1998
  • LAVH was associated with longer operative times and greater blood loss than total vaginal hysterectomy (p=0.01 for both comparisons; n=60) Hwang et al 2002
  • One study reported a significantly longer operative time for laparoscopic compared with vaginal hysterectomy (p<0.05; n=45) Richardson et al 1995

PROSPECT Recommendations

  • Active patient warming is recommended in high-risk patients because there is evidence that it reduces intra-operative bleeding (grade A) and improves outcome in high-risk patients (grade D); however, it has no analgesic benefit (grade A)
  • Leaving the peritoneum open is not recommended over the conventional technique of peritoneal closure because there is evidence that it has no significant analgesic benefit (grade A)
  • Routine use of drains is not recommended, despite some evidence for an analgesic benefit in laparoscopic hysterectomy, because there is a lack of specific evidence, and a risk of infection and patient dissatisfaction (grade D)
  • Wet dressings are not recommended over conventional dressings because there is not yet sufficient evidence to support their benefit in reducing postoperative pain (grade A)
  • It is recommended that the choice of surgical incision for hysterectomy is based on surgical requirements (dependent on the technical feasibility of the operation, the indication for hysterectomy and operative risk-factors of the patient) rather than postoperative pain outcome. If allowed by the surgical requirements, a transverse incision is recommended over a vertical incision because it is associated with lower postoperative pain and less pulmonary dysfunction, while it is has a similar morbi
  • Diathermy is recommended over the scalpel for hysterectomy incisions based on lower postoperative pain and opioid use as well as greater speed of incision and less blood loss, as shown in patients undergoing elective midline laparotomy (grade B)

Clinical Practice

  • A transverse incision is the preferred method for hysterectomy for safety and cosmetic reasons. However, a vertical incision may be required where large fibroids need to be removed or where the upper abdomen must be explored. Pulmonary complications are also less likely with transverse incisions
  • Wound drains are invasive and can increase the risk of infection and, in addition, their extraction is associated with significant patient anxiety

Transferable Evidence from Other Procedures

  • Drains were superior to no drains for reducing postoperative shoulder-tip pain at 24 h (p=0.01) and 48 h (p=0.018) (non-significant at 3 h), and for reducing abdominal pain at 48 h (p=0.007) (non-significant at 3 and 24 h); but the results were not significant for back pain at any time, in LAVH Shen et al 2003 Click here for more information
  • Drains were superior to no drains for reducing postoperative paracetamol consumption, in LAVH (p<0.001; n=164) Shen et al 2003
  • The Pfannenstiel incision decreased the operating time and hospital stay without affecting morbidity and mortality compared with the vertical incision - as shown in two retrospective studies of surgery for uterine cancer, which did not assess postoperative pain (n=332; n=113) Horowitz et al 2003
  • Laparotomy incisions using diathermy were significantly faster (p<0.04) and were associated with significantly less blood loss (p=0.002), lower 48-h postoperative pain scores (p<0.05) and lower 5-day morphine consumption compared with scalpel incisions (p<0.04), in patients undergoing elective midline laparotomy (n=100) Kearns et al 2001
  • Active patient warming and prevention of intra-operative hypothermia decreases the risk of wound infection, hospitalisation time and the incidence of morbid cardiac events in high-risk patients, in a review Leslie et al 2003

Abdominal Hysterectomy-Specific Evidence - Study information

  • Operative time was significantly shorter for the unsutured compared with the conventional sutured peritoneum (n=66; n=144) Behtash et al 2001
  • Active intra-operative warming was associated with significantly less intra-operative bleeding than placebo (p<0.05; n=41) Persson et al 2001
  • Wet film dressing showed a marginally significant benefit over conventional dressing at day 3 for reducing postoperative pain scores (p=0.046; n=30), but this result was non-significant at all other times Briggs 1996
  • Unsutured and sutured peritoneum techniques were not significantly different for postoperative pain scores at rest or for supplementary analgesic consumption, for up to 5 days following the operation (n=66; n=144) Behtash et al 2001
  • There was no significant benefit of active intra-operative warming over placebo for reducing postoperative pain scores or supplementary analgesic consumption for the 48-h study period (n=41) Persson et al 2001
  • Wet film dressing was not significantly different from conventional dressing for supplementary analgesic consumption (n=30) Briggs 1996

PROSPECT Recommendations

  • Intra-operative music played to the patient during general anaesthesia is recommended based on its effects in reducing postoperative pain scores, supplementary analgesic consumption and rehabilitation time (grade A)
  • Therapeutic suggestions and electroacupuncture are not recommended based on their lack of analgesic efficacy (grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

  • Intra-operative music was superior to placebo for reducing postoperative pain scores on the first postoperative day (p<0.001) (non-significant on the second and third day) (n=58) Nilsson et al 2001
  • Intra-operative music was superior to placebo for reducing supplementary analgesic consumption on the day of surgery (p=0.028), and there was a trend towards significance on the first postoperative day (p=0.057; n=89) Nilsson et al 2001
  • Intra-operative music was superior to placebo for time to sitting (p=0.008; n=89) Nilsson et al 2001
  • Of six studies, all showed no significant benefit of intra-operative therapeutic suggestions over placebo for reducing postoperative pain scores for up to 5 days Block et al 1991
  • Five out of six studies showed no significant benefit of intra-operative therapeutic suggestions over placebo for reducing supplementary analgesic consumption McLintock et al 1990 Click here for more information
  • Electroacupuncture provided no significant benefit over placebo for reducing postoperative pain scores at rest and on coughing, or for reducing supplementary analgesic consumption (n=50) Christensen et al 1993

PROSPECT Recommendations

  •  Pre-operative local anaesthetic infiltration at the proposed site of incision is not recommended for abdominal hysterectomy because of its lower benefit compared with post-incisional infiltration for reducing postoperative pain in hysterectomy (grade A). Post-incisional wound infiltration is recommended (see Intra-operative Wound Infiltration)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Pre-incisional wound infiltration of local anaesthetic had a lower analgesic efficacy than post-incisional infiltration: mean 100-mm VAS score was 59 mm and 51 mm, respectively; and the proportion of patients requiring postoperative analgesics was 50 and 28%, respectively, in patients undergoing laparoscopic cholecystectomy (n=45) Sarac et al 1996

Abdominal Hysterectomy-Specific Evidence - Study information

  • Pre-incisional wound infiltration provided a significant benefit over placebo for reducing supplementary analgesic consumption, in two of three studies Eriksson-Mjoberg et al 1997a Click here for more information
  • Pre-incisional wound infiltration and placebo were associated with a similar incidence of PONV in five of the studies reporting this parameter Hannibal et al 1996
  • Pre-incisional wound infiltration provided no significant benefit over placebo for reducing postoperative pain scores in three studies (n=19, n=41, n=40) Eriksson-Mjoberg et al 1997a
  • Pre-incisional wound infiltration provided no significant benefit over placebo for extending the time to first analgesic request in one study (n=41) Hannibal et al 1996
  • Pre-incisional wound infiltration was not significantly different from post-incisional administration for reducing postoperative pain scores within 0–96 h in two studies Click here for more information
  • Pre-incisional wound infiltration was not significantly different from post-incisional administration for reducing supplementary analgesic consumption within 0–96 h in two studies Click here for more information

PROSPECT Recommendations

  • Pre-operative cognitive intervention for patients undergoing hysterectomy is recommended based on its effect on reducing postoperative pain, analgesic consumption and anxiety as well as increasing patient satisfaction (grade A)
  • Homeopathic arnica and self-relaxation techniques are not recommended based on their lack of analgesic efficacy (grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

  • Cognitive intervention reduced postoperative pain scores and the duration of pain compared with no cognitive intervention Cheung et al 2003 Click here for more information
  • Cognitive intervention was superior to placebo for reducing supplementary analgesics Ridgeway et al 1982 Click here for more information
  • One study reported that state and trait anxiety scores were significantly lower for patients receiving pre-operative cognitive therapy than those not receiving cognitive intervention (p<0.05; n=96) Cheung et al 2003
  • One study reported that patient satisfaction was significantly higher in patients receiving pre-operative cognitive therapy than those not receiving cognitive intervention (p<0.05; n=96) Cheung et al 2003
  • Homeopathic arnica had no significant benefit compared with placebo for VAS pain scores or supplementary analgesia (n=73) Hart et al 1997
  • Self-relaxation provided no significant benefit over placebo for reducing postoperative pain scores or supplementary analgesic consumption (n=28) Mogan et al 1985

Pre-operative analgesia

Data are available from studies that assessed pre-operative analgesia versus pre-operative placebo, as well as those that examine the concept of pre-emptive – or preventive – analgesia, assessed pre-operative analgesia versus the same analgesia given postoperatively. However, a previous systematic review of pre-emptive analgesia for acute or chronic postoperative pain relief in a variety of surgical procedures – such as orthopaedic, dental, gynaecological and abdominal – has concluded that there is no benefit of pre-emptive over postoperative administration (Møiniche 2002). Nevertheless, it is considered that analgesic medication needs to be initiated in time to ensure an adequate analgesic effect in the immediate postoperative period. This may necessitate administration prior to the postoperative period. 

PROSPECT Recommendations

  • Pre- and postoperative gabapentin is recommended (Grade A) for its procedure-specific effects in reducing postoperative opioid use and postoperative nausea
  • Further studies are required before it is possible to recommend a specific dose or regimen for administration (single or repeated doses)
  • Procedure-specific and transferable evidence suggests that gabapentin may be associated with sedation, and it is recommended (Grade B) that this side effect should be considered when determining the dose that will be administered

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Two systematic reviews and a meta-analysis evaluated the use of gabapentin for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls Dahl et al 2004
  • One systematic review Ho et al 2006
  • One systematic review Ho et al 2006

Abdominal Hysterectomy-Specific Evidence – Study information

  • Three out of five studies demonstrated that pre- and postoperative oral gabapentin was superior compared with placebo for reducing pain scores Gilron et al 2005 Click here for more information
  • Two studies out of two showed a significant reduction in pain scores following pre- and postoperative oral gabapentin + rofecoxib administration compared with placebo following abdominal hysterectomy Gilron et al 2005 Click here for more information
  • Four out of five studies demonstrated a decrease in supplementary postoperative analgesic use following pre- and postoperative oral gabapentin administration compared with placebo Dierking et al 2004 Click here for more information
  • Two out of two studies demonstrated a decrease in supplementary postoperative analgesic use following pre- and postoperative oral gabapentin + rofecoxib administration compared with placebo Gilron et al 2005 Click here for more information
  • Qualitative analysis demonstrated that in three out of four studies there was no significant difference in the incidence of adverse effects following pre- and postoperative oral gabapentin administration compared with placebo Dierking et al 2004
  • Quantitative analysis showed that there was a significantly lower incidence of nausea in gabapentin group compared with the placebo group Click here for more information
  • The incidence of side effects following pre- and postoperative oral gabapentin + rofecoxib was significantly lower in two studies out of two when compared with placebo Gilron et al 2005 Click here for more information
  • Patient satisfaction with postoperative pain management was significantly higher at 24 h following pre- and postoperative oral gabapentin compared with placebo (p<0.001) Turan et al 2006
  • Patient satisfaction with postoperative pain management was significantly higher in the pre- and postoperative oral gabapentin + rofecoxib group compared with placebo at 24 (p<0.01), 48 (p<0.01) and 72 h (p value not stated) postoperatively Turan et al 2006
  • There was a significant inverse association between plasma levels of gabapentin at 2 h postoperatively, and morphine usage from 0–4 h postoperatively (R2=0.30, p=0.003, and R2=0.24, p=0.008, respectively), compared with placebo Dierking et al 2004
  • Peak expiratory flow was higher in the pre- and postoperative oral gabapentin group compared with the placebo group throughout postoperative days 1 and 2 (p=0.002-0.0032) Gilron et al 2005
  • Peak expiratory flow was higher in the pre- and postoperative oral gabapentin + rofecoxib group compared with the placebo group throughout postoperative days 1 and 2 (p<0.001) Gilron et al 2005

PROSPECT Recommendations

  • Pre-operative COX-2-selective inhibitors for hysterectomy are recommended because they have an analgesic effect postoperatively (grade A). However, there is no procedure-specific evidence that pre-operative administration of COX-2-selective inhibitors is more effective than postoperative administration
  • The use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (cardiovascular morbidity, actual or recent gastroduodenal ulcer history, renal function and hepatic function [grade B] or aspirin-sensitive asthma [grade D])

Clinical Practice

  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Transferable Evidence from Other Procedures

  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation Greenberg et al 2000
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) (in press, Anesthesiology)
  • Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003

Abdominal Hysterectomy-Specific Evidence - Study information

  • A pre-operative single bolus of IV parecoxib was superior to placebo for postoperative pain scores on sitting up over 24 h (p=0.02), providing a mean drop of 14 mm in VAS scores on a 100-mm scale (n=36) Ng et al 2003
  • A pre-operative single bolus of IV parecoxib or oral rofecoxib reduced morphine consumption over 24 h compared with placebo Ng et al 2003 Click here for more information
  • Pre-operative oral rofecoxib was associated with a lower incidence of PONV compared with placebo in one study (p<0.05; n=40) Celik et al 2003
  • Pre-operative oral COX-2-selective inhibitors were as effective as oral conventional NSAIDs for reducing postoperative pain scores in two studies (n=25; n=40) Celik et al 2003
  • COX-2-selective inhibitors are similarly effective compared with conventional NSAIDs for reducing postoperative opioid consumption Celik et al 2003 Click here for more information
  • Compared with the conventional NSAID diclofenac, pre-operative rofecoxib was associated with significantly less intra-operative blood loss (p=0.01) and a lower decrease in haemoglobin (p=0.01) in a group of patients undergoing abdominal or vaginal hysterectomy (n=25) Hegi et al 2004
  • A pre-operative single bolus of rofecoxib or parecoxib did not significantly reduce postoperative pain scores at rest compared with placebo within 0–24 h in two studies (n=40; n=36) Celik et al 2003

PROSPECT Recommendations

  • Pre-operative conventional NSAIDs are not recommended because there is evidence that pre-operative administration of conventional NSAIDs is no more effective than postoperative administration (grade A). Moreover, pre-operative administration of these agents can increase the risk of intra- and postoperative bleeding (grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004

Abdominal Hysterectomy-Specific Evidence - Study information

  • Pre-operative conventional NSAIDs significantly reduced postoperative pain scores compared with placebo, but a significant clinical benefit was only evident for up to 4 h Scott et al 1994 Click here for more information
  • The combination of paracetamol with a conventional NSAID was superior to a higher dose of paracetamol alone, administered as a single pre-operative rectal dose for VAS pain scores at rest at 4 h (p<0.05), but there was no significant difference at 2 h and 6–24 h (n=46) Beck et al 2000b
  • Conventional NSAIDs were equally as effective as COX-2-selective inhibitors for reducing postoperative pain scores in two studies Celik et al 2003
  • Pre-operative conventional NSAIDs showed no significant or clinically meaningful benefit over placebo in reducing supplementary analgesic consumption Beck et al 2000b Click here for more information
  • Pre-operative conventional NSAIDs provided no significant benefit over placebo for extending the time to first analgesic request in two out of the three studies that reported this parameter Scott et al 1994 Click here for more information
  • Pre-operative conventional NSAIDs and placebo were not significantly different for the incidence of PONV (all studies used postoperative PCA strong opioids) Beck et al 2000a Click here for more information
  • Conventional NSAIDs and COX-2-selective inhibitors similarly reduce the use of supplementary analgesics Celik et al 2003 Click here for more information
  • Compared with diclofenac, pre-operative rofecoxib caused significantly less intra-operative blood loss (p=0.01) and a lower decrease in haemoglobin (p=0.01) following abdominal hysterectomy (n=25) Hegi et al 2004
  • There was no significant benefit of pre-incisional conventional NSAIDs over post-incisional conventional NSAIDs in two of three studies for reducing postoperative pain scores Nakayama et al 2001b Click here for more information
  • Of three studies, all showed no significant difference between pre-incisional and post-incisional conventional NSAIDs for supplementary analgesic consumption (n=65; n=77; n=30) Gabbott et al 1997
  • Pre-incisional administration of flurbiprofen was associated with a shorter time to first analgesic request compared with post-incisional administration of a conventional NSAID, in one study (p<0.05; n=30) Nakayama et al 2001b
  • Pre-incisional administration of conventional NSAIDs conferred no significant benefit over post-incisional administration for the incidence of PONV in two studies (n=65, n=30) Gabbott et al 1997

PROSPECT Recommendations

  • Pre-incisional administration of strong opioids is not recommended because of the lack of effect in reducing postoperative pain and supplementary analgesic consumption compared with placebo, and the lack of benefit over post-incisional administration of strong opioids (grade A). Moreover, post-incisional strong opioids are significantly more effective for reducing postoperative pain compared with a similar dose of pre-incisional strong opioids (grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

PROSPECT Recommendations

  • Pre-operative clonidine is not recommended based on its limited analgesic efficacy (grade A) and risk of side effects (grade D)
  • NMDA-receptor antagonists are not recommended based on inconsistent evidence of their analgesic efficacy (grade A), lack of clinical understanding of these agents, and the risk of side effects (grade D)
  • Benzodiazepines are not recommended based on their lack of analgesic efficacy (grade A)

Clinical Practice

  • Clonidine is not used routinely for postoperative analgesia, despite its analgesic efficacy, because of the risk of hypotension, sedation and bradycardia
  •  NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship; in addition, they are associated with adverse side-effects, e.g. ketamine is known for its toxicity and for causing dysphoria

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence

  • Pre-operative clonidine provided no consistent significant benefit over placebo for reducing postoperative pain scores; and other postoperative pain outcomes were mixed Dimou et al 2003 Click here for more information
  • Pre-operative benzodiazepines provided no significant benefit in reducing postoperative pain scores, and there is evidence that they have a limited effect on reducing supplementary analgesic consumption Caumo et al 2002 Click here for more information
  • NMDA-receptor antagonists provided no significant benefit over placebo in reducing postoperative pain scores, supplementary analgesic consumption or PONV in the majority of studies, but the results were mixed and were independent of the specific type of agent and timing of administration Burstal et al 2001 Click here for more information

PROSPECT Recommendations

  • Pre-operative administration of single dose epidural analgesia, in addition to that required for anaesthetic purposes, is not recommended for the treatment of postoperative pain following hysterectomy, based on specific evidence that pre-operative epidural analgesia is not as effective as postoperative epidural analgesia (grade A)
  • A recommendation cannot be made for epidural anaesthesia based on its postoperative analgesic effect because there is no evidence for its relative postoperative analgesic benefits compared with other methods of anaesthesia. Moreover, the choice of anaesthetic regimen should be based on anaesthetic requirement and the relative risks and benefits of the anaesthetic related to the patient and the surgical procedure (grade D) (See Anaesthetic techniques section)
  • Despite the analgesic benefits of pre-operative epidural clonidine, it is not recommended for treating postoperative pain following abdominal hysterectomy because of the incidence of hypotension, sedation and bradycardia (grade D)

Clinical Practice

  • Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications
  • Epidural clonidine is not used routinely because it is associated with an increased risk of hypotension, sedation and bradycardia

Transferable Evidence from Other Procedures

  • Epidural and spinal anaesthesia are not significantly different for: the need for postoperative pain relief, anaesthetic failure rate, need for additional intra-operative analgesia, need for conversion to general anaesthesia, and maternal satisfaction as determined in a systematic review of caesarean section Ng et al 2004

Abdominal Hysterectomy-Specific Evidence - Study information

  • Pre-operative epidural morphine bolus was superior to epidural saline placebo for reducing postoperative pain scores at rest and on movement at 1 and 6 h (p<0.05 for all comparisons; n=36) Goyagi et al 1999
  • Pre-operative epidural morphine bolus was superior to epidural saline placebo for reducing postoperative supplementary analgesic consumption at 6 and 12 h (p<0.05 for both times; n=36) Goyagi et al 1999
  • Pre-operative epidural morphine was superior to placebo for extending the time to first analgesic request (p<0.05; n=36) Goyagi et al 1999
  • Pre-operative plus postoperative treatment with epidural bupivacaine plus fentanyl was superior to postoperative treatment alone for reducing postoperative pain scores at rest and on coughing within 0–72 h (no p-values; n=41) Beilin et al 2003
  • Pre-operative epidural clonidine was superior to placebo for reducing postoperative pain scores in the PACU (p<0.003; n=40) Murga et al 1994
  • Pre-operative epidural clonidine was superior to placebo for reducing intra-operative anaesthetic requirement (p<0.0001; n=40) Murga et al 1994
  • There was no difference between epidural morphine and placebo (with rescue PCA morphine) for the incidence of postoperative nausea (n=36) Goyagi et al 1999
  • Pre-operative epidural ketamine conferred no significant benefit over placebo for reducing postoperative pain scores within 0–24 h (n=40) Murga et al 1994
  • Pre-operative epidural ketamine conferred no significant benefit over placebo for reducing supplementary analgesic consumption within 0–24 h (n=41) Abdel-Ghaffar et al 1998
  • Pre-incisional epidural analgesia provided no significant benefit over post-incisional administration for reducing postoperative pain scores in four out of four studies Garcia et al 2002 Click here for more information
  • Three of four studies showed no significant benefit of pre-incisional epidural analgesia compared with post-incisional administration for reducing supplementary analgesic consumption Espinet et al 1996 Click here for more information

PROSPECT Recommendations

  • Pre-operative single-shot spinal analgesia with local anaesthetic and strong opioid reduces postoperative pain scores and opioid consumption for up to 24 h (grade A). However, these benefits should be weighed against the risks associated with the invasive nature of this technique
  • Pre-operative single-shot spinal local anaesthetic plus strong opioid can be used, with or without sedation, as an alternative to general anaesthesia (Grade A). However, the choice of anaesthetic regimen should be based on anaesthetic requirement and the relative risks and benefits of the anaesthetic related to the patient and the surgical procedure (Grade D) (see Anaesthetic techniques section)
  • Spinal neostigmine is not recommended based on limited evidence for its analgesic efficacy, evidence of an associated increase in PONV (grade A) and a lack of clinical experience with this agent (grade D)

Clinical Practice

  • There is limited clinical experience of spinal neostigmine

Transferable Evidence from Other Procedures

  • Spinal and epidural anaesthesia are not significantly different for: the need for postoperative pain relief, anaesthetic failure rate, need for additional intra-operative analgesia, need for conversion to general anaesthesia, and maternal satisfaction as determined in a systematic review of caesarean section Ng et al 2004

Abdominal Hysterectomy-Specific Evidence - Study information

  • Pre-operative spinal analgesia (local anaesthetic, strong opioid or both) was superior to placebo for reducing postoperative pain scores within 0–24 h Vaida et al 2000 Click here for more information
  • Pre-operative spinal local anaesthetic or strong opioid provided a significant benefit over placebo for reducing supplementary analgesic consumption within 0–24 h (p<0.05; n=20) Lauretti et al 1998b
  • There was no significant difference between spinal strong opioid and placebo for the incidence of PONV in two studies (all groups received postoperative diclofenac) (n=20, n=30) Lauretti et al 1998b
  • Pre-operative spinal neostigmine (25, 50 or 75 µg) was superior to placebo for reducing postoperative pain scores at the following times: 30 and 60 min (p<0.05; n=92) Lauretti et al 1998a
  • Pre-operative spinal neostigmine (25, 50 or 75 µg) was superior to placebo for reducing supplementary analgesic consumption within 0–24 h (p<0.05; n=92, n=20) Lauretti et al 1998a
  • There is evidence from one of two studies showing a significant benefit of pre-operative spinal neostigmine over placebo for extending the time to first analgesic request (p<0.05; n=92) Lauretti et al 1998a
  • Spinal morphine was superior to IV analgesia for reducing postoperative pain scores Yokota et al 2000 Click here for more information
  • Pre-operative bolus dose of spinal morphine was superior to IV buprenorphine for extending the time to first analgesic request (p<0.01) in one study (n=29) Beltrutti et al 2002
  • Pre-operative spinal neostigmine was associated with a higher incidence of postoperative nausea than placebo Lauretti et al 1998a Click here for more information
  • Pre-operative spinal adenosine provided no significant benefit over placebo for reducing postoperative pain scores or supplementary analgesic consumption within 0–24 h (n=40) Rane et al 2000
  • Pre-induction spinal local anaesthetic was not significantly different to local anaesthetic given at extubation for postoperative pain scores within 0–12 h (n=38) Dakin et al 1996
  • Pre-induction spinal local anaesthetic was not significantly different to local anaesthetic given at extubation for postoperative pain scores within 0–12 h (n=38) Dakin et al 1996

PROSPECT Recommendations

  • The choice of anaesthetic regimen should be based on anaesthetic requirement and the relative risks and benefits of the anaesthetic related to the patient and the surgical procedure, rather than on the management of postoperative pain (grade D)
  • Combined spinal-epidural anaesthesia is a recommended alternative to epidural plus light general anaesthesia for hysterectomy in high-risk patients (grade D), and may have a greater analgesic efficacy compared with epidural alone as shown in caesarean section (grade B)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

Abdominal Hysterectomy-Specific Evidence

  • [No data found within the parameters of this review]

PROSPECT Recommendations

  • Pre- and postoperative gabapentin is recommended (Grade A) for its procedure-specific effects in reducing postoperative opioid use and postoperative nausea
  • Further studies are required before it is possible to recommend a specific dose or regimen for administration (single or repeated doses)
  • Procedure-specific and transferable evidence suggests that gabapentin may be associated with sedation, and it is recommended (Grade B) that this side effect should be considered when determining the dose that will be administered

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Two systematic reviews and a meta-analysis evaluated the use of gabapentin for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls Dahl et al 2004
  • One systematic review Ho et al 2006
  • One systematic review Ho et al 2006

Abdominal Hysterectomy-Specific Evidence - Study information

  • Three out of five studies demonstrated that pre- and postoperative oral gabapentin was superior compared with placebo for reducing pain scores Gilron et al 2005 Click here for more information
  • Two studies out of two showed a significant reduction in pain scores following pre- and postoperative oral gabapentin + rofecoxib administration compared with placebo following abdominal hysterectomy Gilron et al 2005 Click here for more information
  • Four out of five studies demonstrated a decrease in supplementary postoperative analgesic use following pre- and postoperative oral gabapentin administration compared with placebo Dierking et al 2004 Click here for more information
  • Two out of two studies demonstrated a decrease in supplementary postoperative analgesic use following pre- and postoperative oral gabapentin + rofecoxib administration compared with placebo Gilron et al 2005 Click here for more information
  • Qualitative analysis of three out of four studies demonstrated that there was no significant difference in the incidence of adverse effects following pre- and postoperative oral gabapentin administration compared with placebo Dierking et al 2004
  • Quantitative analysis showed that there was a significantly lower incidence of nausea in gabapentin group compared with the placebo group Click here for more information
  • The incidence of side effects following pre- and postoperative oral gabapentin + rofecoxib was significantly lower in two studies out of two when compared with placebo Gilron et al 2005 Click here for more information
  • Patient satisfaction with postoperative pain management was significantly higher at 24 h following pre- and postoperative oral gabapentin compared with placebo (p<0.001) Turan et al 2006
  • Patient satisfaction with postoperative pain management was significantly higher in the pre- and postoperative oral gabapentin + rofecoxib group compared with placebo at 24 (p<0.01), 48 (p<0.01) and 72 h (p value not stated) postoperatively Turan et al 2006
  • There was a significant inverse association between plasma levels of gabapentin at 2 h postoperatively, and morphine usage from 0–4 h postoperatively (R2 =0.30, p=0.003, and R2 =0.24, p=0.008, respectively), compared with placebo Dierking et al 2004
  • Peak expiratory flow was higher in the pre- and postoperative oral gabapentin group compared with the placebo group throughout postoperative days 1 and 2 (p=0.002-0.0032) Gilron et al 2005
  • Peak expiratory flow was higher in the pre- and postoperative oral gabapentin + rofecoxib group compared with the placebo group throughout postoperative days 1 and 2 (p<0.001) Gilron et al 2005

PROSPECT Recommendations

  • COX-2-selective inhibitors are recommended for their effect in reducing supplementary analgesic use (grade B). They should be given in combination with strong opioids for high-intensity pain, or with weak opioids for moderate- or low-intensity pain (grade D)
  • In patients receiving postoperative epidural analgesia, it is recommended that COX-2-selective inhibitors are used only if analgesia is inadequate (grade B) (see Postoperative, Conventional NSAIDs section)
  • COX-2-selective inhibitors may be preferred to conventional NSAIDs in the peri-operative setting, in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (grade B)
  • The use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (cardiovascular morbidity, actual or recent gastroduodenal ulcer history, renal function and hepatic function [grade B] or aspirin-sensitive asthma [grade D])

Clinical Practice

  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Transferable Evidence from Other Procedures

  • Parecoxib 20 or 40 mg IV every 12 h reduced supplementary analgesic consumption compared with placebo in patients undergoing major gynaecological surgery (n=60) (p<0.05) Tang et al 2002
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation Greenberg et al 2000
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) (in press, Anesthesiology)
  • Parecoxib 20 or 40 mg IV every 12 h did not significantly reduce postoperative pain scores compared with placebo in patients undergoing major gynaecological surgery (n=60) (p<0.05) Tang et al 2002
  • Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003

Abdominal Hysterectomy-Specific Evidence

  • [No data found within the parameters of this review]

PROSPECT Recommendations

  • Conventional NSAIDs are recommended for their analgesic and opioid-sparing effects (grade A). They should be given in combination with strong opioids for high-intensity pain, or with weak opioids for moderate- or low-intensity pain (grade D)
  • In patients receiving epidural analgesia, it is recommended that conventional NSAIDs are used only if analgesia is inadequate (grade B)
  • Conventional NSAIDs are not recommended in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (grade B)
  • The use of conventional NSAIDs should depend upon assessment of individual patient risks (bleeding complications including epidural haematoma, cardiovascular morbidity, actual or recent gastroduodenal ulcer history, aspirin-sensitive asthma, renal function and hepatic function) (grade B)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987
  • Piroxicam plus thoracic epidural analgesia using bupivacaine and morphine provided no significant benefit over epidural analgesia alone for reducing postoperative pain scores and supplementary analgesic consumption, in major upper abdominal surgery (n=44) Mogensen et al 1992b
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004

Abdominal Hysterectomy-Specific Evidence - Study information

  • Six out of eight studies showed a significant benefit of postoperative conventional NSAIDs compared with placebo for postoperative pain scores Ng et al 2002a Click here for more information
  • Conventional NSAIDs conferred a significant benefit over placebo for reducing supplementary analgesia requirements over 24 h or more Blackburn et al 1995 Click here for more information
  • One study showed a marginal but significant benefit of rectal diclofenac over rectal paracetamol for reducing mean pain scores over 24 h (p=0.008; n=44): mean reduction in VAS of 0 mm at 8 h, 8 mm at 16 h and 21 mm for 0–24 h on a 100-mm scale Cobby et al 1999
  • Ketorolac combined with morphine was not significantly different from a higher dose of morphine alone for reducing postoperative pain scores in one study (n=22) Kim et al 2001
  • Ketorolac combined with morphine was superior to a higher dose of morphine alone for significantly reducing postoperative morphine consumption at 4 h (p=0.037) and 24 h (p=0.015) in one study (n=22) Kim et al 2001
  • There was no significant difference between postoperative ketorolac and morphine each given by IM PCA for reducing postoperative pain scores at the doses studied (both study groups were allowed rescue morphine) (n=29) Black et al 1990
  • Four studies and two arms of a fifth study showed no significant difference between conventional NSAIDs and weak opioids for VAS pain scores at rest over 24 h Rodriguez et al 1993 Click here for more information
  • There was no significant difference between conventional NSAIDs and weak opioids for time to first analgesic request in one study reporting this parameter (n=58) Ilias et al 1996
  • There is evidence that diclofenac is superior to paracetamol for reducing mean 24-h postoperative pain scores Cobby et al 1999 Click here for more information
  • Results were mixed for conventional NSAIDs compared with placebo for the time to first analgesic request Ilias et al 1996 Click here for more information
  • Conventional NSAIDs and placebo were not significantly different for the incidence of PONV (all groups received background strong opioid) Blackburn et al 1995 Click here for more information
  • There is evidence that weak opioids are superior to conventional NSAIDs for reducing supplementary analgesic consumption Rodriguez et al 1993 Click here for more information
  • There was no significant difference between conventional NSAIDs and paracetamol for the requirement of postoperative supplementary analgesics Cobby et al 1999 Click here for more information
  • Conventional NSAIDs and paracetamol were not significantly different for the incidence of vomiting Cobby et al 1999 Click here for more information
  • There is limited evidence of a reduction in the incidence of PONV with a conventional NSAID compared with a weak opioid Torres et al 2001 Click here for more information

PROSPECT Recommendations

  • Strong opioids are recommended based on their analgesic efficacy in reducing high-intensity pain (VAS=50) in the early postoperative period (grade A)
  • At clinical doses, different strong opioids are equally effective (grade A)
  • IV PCA administration of strong opioids is recommended based on its greater analgesic efficacy, lower opioid load and greater patient satisfaction compared with regular (fixed-interval) or on-request dosing in hysterectomy and other procedures (grade A); however, fixed-interval IV administration titrated to pain intensity is also recognised as an effective mode of administration (grade D)
  • Continuous infusion of strong opioid during PCA bolus dosing is not recommended, despite its analgesic efficacy over PCA bolus doses alone (grade A), because of potential opioid accumulation (grade D)
  • IM administration of strong opioids is not recommended based on the pain associated with these injections (grade D)
  • To minimise the dose of strong opioids, and associated side-effects, it is recommended that strong opioids are combined with COX-2-selective inhibitors or conventional NSAIDs, plus paracetamol (grade B) (see respective sections)
  • There are not currently enough data to make a recommendation for other modes of administration of strong opioids, such as intra-nasal or slow-release tablets
  • Transdermal patches are not recommended: they are not approved for routine use due to the risk of opioid accumulation (grade D)

Clinical Practice

  • Strong opioids are considered to be an effective analgesic for postoperative pain following abdominal hysterectomy, but, because of their adverse effects, they are generally used in combination with non-opioid analgesics to minimise the opioid
  • Regular administration, titrated for pain intensity, is generally accepted as an effective method of administering strong opioids
  • IM administration of strong opioids is considered to be more painful than IV administration. However, the dose and rapidity of IV administration should be assessed to minimise the risk of respiratory depression
  • Transdermal patches are not approved for routine use because of the risk of opioid accumulation
  • Continuous infusions of strong opioids by PCA, on top of PCA bolus doses, are being used less frequently as a precaution against opioid accumulation

Transferable Evidence from Other Procedures

  • Opioids administered by PCA decreased the risk of pulmonary complications and patients preferred them compared with regular IM, IV or subcutaneous opioid treatment, although there was no significant difference for pain scores, as determined in a quantitative systematic review of randomised trials in various surgical procedures Walder et al 2001

Abdominal Hysterectomy-Specific Evidence - Study information

  • Three studies showed that strong opioids administered pre-, intra- and postoperatively were superior to placebo for reducing supplementary analgesic consumption Broome et al 1995 Click here for more information
  • Different strong opioids were not significantly different from each other, for reducing postoperative pain scores, supplementary analgesia and PONV, in the majority of studies assessing different strong opioid regimens Chui et al 1992 Click here for more information
  • Morphine gave a numerically longer time to first analgesic request than tramadol in one study reporting this parameter, although the result did not reach statistical significance Coetzee et al 1998
  • Strong opioids gave numerically lower postoperative pain scores than weak opioids in three studies Coetzee et al 1998
  • Oral slow-release and IM morphine were similar for postoperative pain scores, supplementary analgesic consumption and the incidence of PONV in two studies (n=38; n=30) Fell et al 1982
  • IV pethidine was superior to intranasal pethidine for reducing postoperative pain scores at 5–80 min (p<0.05) and for reducing the total amount of pethidine consumed (p<0.05), in one study (n=60) Striebel et al 1993
  • Bolus plus infusion IV PCA morphine conferred a significant benefit over bolus IV PCA morphine alone for reducing postoperative pain scores with no significant difference in overall analgesic consumption El-Falaki et al 2000 Click here for more information
  • The incidence of PONV was not significantly different between PCA and IM morphine, in two studies reporting this parameter (n=126, n=22) Choiniere et al 1998
  • There is mixed evidence for the benefit of PCA compared with regular/on-request IM administration of strong opioids for reducing overall opioid consumption, although one study suggests that they produced different patterns of dosing Thomas et al 1995 Click here for more information
  • Three out of five studies showed a significant benefit of IV PCA over IM regular/on-request administration of strong opioids for reducing postoperative pain scores D'Haese et al 1998 Click here for more information
  • Sufentanil provided a significant benefit over morphine for reducing the supplementary analgesic consumption from 0–24 h (p<0.05), in one study reporting this parameter (n=40) Ginsberg et al 2000
  • Sufentanil provided a significant benefit over morphine for reducing postoperative pain scores at rest and on movement for the first 2 h following initiation of PCA, but there was no significant difference for the remaining 24 h Ginsberg et al 2000 Click here for more information
  • The incidence of PONV was not significantly different between strong opioid and placebo plus rescue strong opioid in four out of five studies reporting this parameter Broome et al 1995 Click here for more information
  • Strong opioid administered as a single postoperative bolus provided a significant benefit over placebo for reducing postoperative pain scores at 24 h Collis et al 1995 Click here for more information
  • Strong opioids administered pre-, intra- and postoperatively were superior to placebo for reducing postoperative pain scores Broome et al 1995 Click here for more information
  • Bolus IV PCA plus background infusion of morphine was associated with a consistently greater consumption of morphine than IV PCA alone but the results did not reach statistical significance, in two studies (n=20, n=20) El-Falaki et al 2000
  • Three studies showed no significant benefit of a postoperative bolus of strong opioid over placebo for reducing supplementary analgesic consumption Collis et al 1995
  • Strong opioids provided no significant benefit over NMDA-receptor antagonists for postoperative pain scores or supplementary analgesic consumption in two studies Knoche et al 1983 Click here for more information

PROSPECT Recommendations

  • Weak opioids are recommended based on evidence for their analgesic efficacy in gynaecological and abdominal surgery, as well as in other procedures (grade B). Weak opioids should be combined with COX-2-selective inhibitors or conventional NSAIDs and paracetamol, for controlling moderate- (VAS<50>30) or low-intensity (VAS £30) pain later in the postoperative period (grade D)

Clinical Practice

  • It is considered that maximum doses of weak opioids have a plateau of effect on controlling high-intensity pain (VAS³ 50) following abdominal hysterectomy and that strong opioids should be used instead; weak opioids are considered to be effective for lower intensity pain later in the postoperative period

Transferable Evidence from Other Procedures

  • Tramadol 20 mg was superior to placebo for reducing postoperative pain scores measured after an initial bolus dose (p=0.002) in patients undergoing gynaecological or abdominal surgery (n=120) Stamer et al 1997
  • Tramadol plus paracetamol is superior to either drug administered alone for reducing postoperative pain in a meta-analysis of gynaecological, dental and orthopaedic patients McQuay H et al 2003

Abdominal Hysterectomy-Specific Evidence - Study information

  • Four studies and two arms of a fifth study showed that weak opioids and conventional NSAIDs had a similar effect of reducing VAS pain scores at rest over 24 h Rodriguez et al 1993 Click here for more information
  • Weak opioids and conventional NSAIDs had a similar effect of reducing supplementary analgesic consumption in one study reporting this parameter (n=130) Torres et al 2001
  • Conventional NSAIDs and weak opioids have a similar effect for prolonging the time to first analgesic request in one study reporting this parameter (n=58) Ilias et al 1996
  • Tramadol 50 mg IV administered postoperatively on request gave numerically lower postoperative pain scores than placebo, but this was not statistically significant, in one study (n=40) Ilias et al 1996
  • Tramadol 50 mg IV administered postoperatively on request gave a numerically longer time to first analgesic request than placebo but this was not statistically significant in one study (n=80) Ilias et al 1996
  • Strong opioids gave numerically lower postoperative pain scores than weak opioids in three studies Coetzee et al 1998
  • Morphine gave a numerically longer time to first analgesic request than tramadol in one study reporting this parameter, although the result did not reach statistical significance Coetzee et al 1998

PROSPECT Recommendations

  • Paracetamol is recommended for moderate- (VAS<50>30 mm) or low-intensity (VAS £30 mm) pain, in combination with COX-2-inhibitors or conventional NSAIDs, based on its mild analgesic and opioid-sparing effect following hysterectomy (grade A)
  • However, paracetamol is not recommended for high-intensity pain (VAS³ 50 mm) because it has no additional analgesic benefit over that conferred by NSAIDs following abdominal gynaecological procedures (grade B)

Clinical Practice

  • Paracetamol is a well-established analgesic for mild-to-moderate pain (VAS <50 mm) and has a favourable safety profile

Transferable Evidence from Other Procedures

  • Paracetamol 1 g plus diclofenac 100 mg was superior to diclofenac 100 mg alone given once postoperatively, for reducing postoperative pain in dental surgery (p<0.05; n=46) Breivik et al 1999
  • There was no benefit of paracetamol with NSAID compared with NSAID alone for reducing pain scores in a meta-analysis of results from a variety of surgical procedures including dental, orthopaedic and gynaecological operations Rømsing et al 2002
  • Paracetamol 1.5 g plus diclofenac 100 mg was not significantly different from diclofenac 100 mg alone given once pre-operatively, for reducing postoperative pain in abdominal gynaecological surgery (n=39) Montgomery et al 1996

Abdominal Hysterectomy-Specific Evidence - Study information

  • Paracetamol was superior to placebo for reducing postoperative pain scores, producing reductions in VAS scores of £13 mm Cobby et al 1999 Click here for more information
  • Paracetamol was superior to placebo for reducing supplementary analgesic consumption within 0–24 h Cobby et al 1999 Click here for more information
  • One study showed that IV paracetamol was as effective as IV ketorolac for reducing postoperative pain scores (n=176) Varrassi et al 1999
  • One study showed a marginal but significant benefit of rectal diclofenac compared with rectal paracetamol for reducing mean pain scores over 24 h, giving a mean difference in VAS of 0 mm at 8 h, 8 mm at 16 h and 21 mm for 0–24 h, on a 100-mm scale (p=0.008; n=44) Cobby et al 1999

PROSPECT Recommendations

  • NMDA-receptor antagonists are not recommended based on inconsistent evidence of their analgesic efficacy (grade A), lack of clinical understanding of these agents, and the risk of side-effects (grade D)
  • Benzodiazepines are not recommended based on their lack of analgesic efficacy (grade A)
  • Other agents, such as pentazocine, clomipramine, delta-9-tetrahydrocannabinol and naloxone cannot be recommended for postoperative analgesia based on limited evidence for their analgesic efficacy (grade A) and a lack of clinical experience with these agents (grade D)

Clinical Practice

  • NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship. In addition, they are associated with adverse side-effects, e.g. ketamine is known for its toxicity and for causing dysphoria
  • There is limited clinical experience of using pentazocine, clomipramine, delta-9-tetrahydrocannabinol and naloxone for analgesic purposes

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence

  • A regimen of ketamine plus midazolam was superior to pethidine for reducing postoperative pain scores, and was associated with a lower incidence of PONV compared with pethidine Jahangir et al 1993 Click here for more information
  • Piritramide was superior to pentazocine, which was superior to ketamine for reducing postoperative pain scores Knoche et al 1983 Click here for more information
  • Buprenorphine 0.4 mg SL on request was superior to papaveretum 20 IM on request for reducing postoperative pain scores (p<0.01) and supplementary analgesic consumption (p<0.001; n=60) Fry 1979
  • NMDA-receptor antagonists provided no significant benefit over placebo in reducing postoperative pain scores, supplementary analgesic consumption or PONV in the majority of studies, but the results were mixed and were independent of the timing of administration Burstal et al 2001 Click here for more information
  • Postoperative midazolam provided no significant benefit in reducing postoperative pain scores or supplementary analgesic consumption for 0–24 h in one study Egan et al 1992 Click here for more information
  • Clomipramine 50 mg IM and pentazocine 30 mg IM, each administered 30 min postoperatively, were similar for postoperative pain scores within 0–7 h (n=40) Tiengo et al 1987
  • Delta-9-tetrahydrocannabinol 5 mg, administered as a single dose orally 24 h after surgery, did not provide a significant benefit over placebo for reducing postoperative pain scores at 0–6 h after administration (n=40) Buggy et al 2003
  • Naloxone 0.25 µg/kg/h or 1 µg/kg/h conferred no benefit over placebo for reducing postoperative pain scores within 0–24 h and high-dose naloxone increased analgesic consumption over 0–24 h (p<0.05) (although low-dose naloxone decreased analgesic consumption, p<0.05) (n=60) Gan et al 1997

PROSPECT Recommendations

  • Continuous postoperative epidural infusion is not recommended for routine use in hysterectomy patients because its analgesic benefits compared with systemic analgesia are short-lasting and are of marginal clinical significance (up to 4 h) (grade A). Therefore, the risks of the epidural technique outweigh the analgesic benefits in low-risk patients (grade D)
  • Continuous postoperative epidural analgesia with local anaesthetic plus strong opioid is recommended in high-risk patients (e.g. those at risk of organ dysfunction and some patients undergoing extensive surgery for malignancy) – and in these patients it is recommended that the epidural is also used for anaesthesia – because the benefits of the epidural technique, e.g. reduction in inhaled anaesthetics and systemic opioids as well as reduced paralytic ileus and improved pulmonary function (grade
  • Despite the analgesic benefits of epidural clonidine, it is not recommended to control postoperative pain following abdominal hysterectomy because of the incidence of hypotension (grade A), sedation and bradycardia (grade D)

Clinical Practice

  • Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications

Transferable Evidence from Other Procedures

  • Epidural analgesia using local anaesthetic was superior to systemic strong opioid for reducing postoperative pain scores in six studies identified in a systematic review of abdominal surgery Jorgensen et al 2000b
  • Epidural analgesia using a combination of local anaesthetic and strong opioid was superior to local anaesthetic alone for reducing postoperative pain – 15 mm reduction in VAS score on a 100-mm scale – in a meta-analysis of five studies in abdominal surgery Jorgensen et al 2000b
  • Epidural analgesia using local anaesthetics was superior to epidural opioids or systemic opioids for reducing the incidence of postoperative gastrointestinal paralysis, in a systematic review in abdominal surgery Jorgensen et al 2000b

Abdominal Hysterectomy-Specific Evidence - Study information

  • Postoperative epidural ropivacaine was superior to placebo for reducing postoperative pain scores at rest and on coughing within 0–2, 0–4 and 4–12 h, but results at 2–22 h were non-significant (n=104) Chinachoti et al 2002
  • Combined epidural strong opioid and local anaesthetic was superior to epidural strong opioid alone for reducing postoperative pain scores within 12–24 h (p<0.05; n=40) Madej et al 1992
  • Combined epidural strong opioid and local anaesthetic was associated with a lower incidence of PONV than epidural strong opioid alone (p<0.05; n=40) Madej et al 1992
  • Addition of sufentanil to morphine, as an epidural bolus dose, gave lower postoperative pain scores than morphine alone for 0–6 h (n=30; n=120) Sinatra et al 1991
  • Epidural bolus morphine alone was superior to sufentanil alone and to morphine plus sufentanil, at 240 min after administration (n=45) Sinatra et al 1991
  • Bupivacaine was superior to morphine for reducing pain scores and for reducing times to recovery of bowel motility Thoren et al 1989 Click here for more information
  • Postoperative epidural high-dose naloxone (0.167 µg/kg/hr) was superior to placebo for reducing postoperative pain scores at 8, 16 and 32 h (p<0.05), but results at 2, 4 and 48 h were non-significant Choi et al 2000 Click here for more information
  • Clonidine or clonidine plus sumatriptan conferred a significant benefit over sumatriptan alone for reducing postoperative pain scores within 0–4 h (p<0.01) in one study Liu at al 1997b Click here for more information
  • Epidural bupivacaine was superior to ropivacaine for reducing supplementary ketorolac consumption and gave a larger spread of sensory block than ropivacaine, while recovery outcomes were not significantly different Jorgensen et al 2000a Click here for more information
  • Diamorphine was superior to ketamine for reducing postoperative pain scores and for extending the time to first analgesic request Peat et al 1989 Click here for more information
  • Epidural analgesia had a statistically significant, and marginally clinically significant, benefit over systemic analgesia for reducing postoperative pain scores at 4 h Hindsholm et al 1993 Click here for more information
  • Epidural analgesia provided a significant benefit over IV administration for reducing analgesic consumption over 24 h Eriksson-Mjoberg et al 1997b Click here for more information
  • Epidural analgesia was associated with a significantly lower incidence of PONV compared with systemic analgesia Camu et al 1991 Click here for more information
  • There is evidence for a limited benefit of epidural clonidine over epidural morphine for reducing postoperative pain scores, but two of two studies showed that clonidine causes hypotension Lund et al 1989 Click here for more information

PROSPECT Recommendations

  • Repeated peri-operative doses by the spinal route are not recommended because they are not considered to be safe or practical (grade D)
  • Spinal local anaesthetic plus strong opioid should be administered only as a single pre-operative bolus dose for postoperative analgesia (grade A) or anaesthetic (grade D) purposes (see Pre-operative Spinal analgesia and Intra-operative Anaesthetic techniques sections)

Clinical Practice

  • Spinal anaesthetics are generally administered as a single pre-operative bolus, and repeated peri-operative doses are not considered to be safe or practical

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

PROSPECT Recommendations

  • Postoperative wound infiltration administered by PCA may have a benefit in controlling postoperative pain, but there is not currently enough evidence to recommend it. However, intra-operative wound infiltration is recommended (grade A) (see Intra-operative Wound Infiltration)

Clinical Practice

  • Intra-operative wound infiltration is a well-established method of analgesia with a favourable safety profile. However, methods of postoperative wound infiltration are not well established

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

  • Postoperative wound infiltration administered by PCA with a 1-h lockout showed a significant benefit of reducing postoperative pain scores on coughing and when raising leg at 4 h (p=0.006 and p=0.009 respectively); however, these comparisons at 1–3 and 5–24 h were non-significant, and results at rest showed no significant benefit at all times (n=36) Zohar et al 2001
  • Postoperative wound infiltration administered by PCA with a 1-h lockout showed a significant benefit in reducing supplementary analgesic consumption within 0–24 h (p<0.001; n=36) Zohar et al 2001
  • Postoperative wound infiltration administered as regular 4-hourly doses provided no significant benefit over placebo for reducing postoperative pain scores at any time (n=41) Kristensen et al 1999
  • Postoperative wound infiltration administered as regular 4-hourly doses provided no significant benefit over placebo for reducing supplementary analgesic consumption (n=41) Kristensen et al 1999

PROSPECT Recommendations

  • Postoperative music is not recommended based on its lack of analgesic efficacy (grade A). However intra-operative music is recommended (See Intra-operative section)
  • Homeopathic arnica and self-relaxation techniques are not recommended based on their lack of analgesic efficacy (grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

  • Homeopathic arnica had no significant benefit compared with placebo for VAS pain scores or supplementary analgesic consumption (n=73) Hart et al 1997
  • Postoperative music conferred no significant benefit over placebo for reducing postoperative pain scores or supplementary analgesic consumption (n=40) Taylor et al 1998
  • Self-relaxation provided no significant benefit over placebo for reducing postoperative pain scores or supplementary analgesic consumption (n=28) Mogan et al 1985

A systematic search of the literature between January 2004 and June 2006 identified additional studies of interventions in abdominal hysterectomy, as listed in this folder, together with brief summaries of the study outcomes and a comment from the PROSPECT Working Group regarding the impact of the recent evidence on the recommendations. Additional details of the studies will be included in the main review text at the next full update of the evidence and recommendations.

  • Four out of four studies found that conventional NSAID was superior to placebo or no treatment. In two studies pre-operative conventional NSAID significantly reduced postoperative VAS pain scores at 2 h (at rest and on coughing; Akarsu 2004) and 2, 4, 6 and 12 h (Karaman 2006), compared with placebo. In one study, pre- and intra-operative conventional NSAID significantly reduced postoperative VAS pain scores at 6 h compared with control (no treatment) (Yan 2004). In one study postoperative conventional NSAID significantly increased pain intensity difference (VAS) scores compared with placebo (at 30 min–24 h) and compared with morphine (at 30 min and 1–12 h) groups (Bikhazi 2004)
  • In one study, time to first request for rescue analgesia was significantly longer, and total analgesic consumed was less, following pre-operative conventional NSAID administration, compared with placebo (Akarsu 2004); in another study, PCA morphine consumption was significantly reduced in the group receiving pre-operative conventional NSAID at 2, 4, 6, 12 and 24 h compared with the saline control group (Karaman 2006)
  • In one study there was a significantly higher incidence of nausea and vomiting in the placebo group compared with the pre-operative conventional NSAID group (Akarsu 2004). In two studies there were no significant differences between the incidence of adverse events in the conventional NSAID and placebo groups (Bikhazi 2004; Karaman 2006)

No change to recommendations

  • Three studies out of three showed COX-2-selective inhibitor superior to control for reducing pain scores:
    • In one study, the pre-operative COX-2-selective inhibitor significantly reduced postoperative VAS pain scores at 1, 2, 4, 6, 8 and 12 h compared with placebo (Karamanlioglu 2004)
    • In one study peri-operative COX-2-selective inhibitor, alone and in combination with gabapentin, significantly reduced postoperative VAS pain scores at rest at 20, 24, 28, 32, 44, 48, 52 and 56 h compared with placebo; VAS pain scores at sitting were significantly reduced in the COX-2-selective inhibitor plus gabapentin group at 20h, and following the COX-2-selective inhibitor both alone and in combination with gabapentin at 24, 28, 32, 44, 48, 52, and 56 h compared with placebo; VAS pain scores at peak expiration were significantly reduced following administration of the COX-2-selective inhibitor alone and in combination with gabapentin at 20, 24, 28, 32, 44, 48, 52, and 56 h compared with placebo; VAS pain scores during coughing were significantly reduced in the COX-2-selective inhibitor plus gabapentin group at 20, 24, 28, 32 h, and following administration of the COX-2-selective inhibitor both alone and in combination with gabapentin at 44, 48, 52 and 56 h, compared with placebo (Gilron 2005)
    • In one study, peri-operative COX-2-selective inhibitor, alone and in combination with gabapentin, significantly reduced VRS postoperative pain scores at rest at 4, 8, 16 and 20 h, compared with placebo; COX-2-selective inhibitor in combination with gabapentin significantly reduced VRS pain scores at rest at 12 and 24 h compared with placebo; COX-2-selective inhibitor alone, and in combination with gabapentin, significantly reduced VRS postoperative pain scores during movement at 8 h, and the COX-2 inhibitor alone also showed a significant reduction at 20 h, compared with placebo (Turan 2006)
  • Three out of three studies showed COX-2-selective inhibitor superior to placebo for reducing supplementary analgesic consumption
    • Total and incremental supplementary analgesic consumptions were significantly less in the pre-operative COX-2-selective inhibitor group compared with placebo at 1, 2, 4, 6, 8, and 12 h postoperatively (Karamanlioglu 2004)
    • Cumulative morphine consumption was significantly less in the COX-2-selective inhibitor plus gabapentin group compared with placebo at 2, 3, 4, 8, 20, 24, 28 and 32 h postoperatively, and interval morphine consumption was significantly less in the COX-2-selective inhibitor group at 4–8, 8–20, 20–32, 32–44 and 44–56 h and in the COX-2-selective inhibitor plus gabapentin group at all time points recorded after surgery, compared with placebo (Gilron 2005)
    • PCA morphine requirement was significantly less following administration of the COX-2-selective inhibitor, alone and in combination with gabapentin at 1, 8, 12, 16, 24, and 30 h postoperatively, and at 20 h following the COX-2-selective inhibitor plus gabapentin, compared with placebo (Turan 2006)
  • Three out of three studies showed that COX-2-selective inhibitors are not superior to placebo for reducing the incidence of adverse effects
    • In two studies there was no significant difference in the incidence of adverse events between the COX-2-selective inhibitor group and control (Gilron 2005; Karamanlioglu 2004)
    • In one study there was no significant difference between COX-2 inhibitor alone or gabapentin alone compared with placebo, but there was a significantly lower incidence of nausea in the combination of COX-2-selective inhibitor and gabapentin group compared with the placebo group (Turan 2006)

No change to recommendations

  • One study showed that pre-operative oral clonidine did not significantly reduce pain scores both at rest and during movement compared with placebo at all time points assessed (Oofuvong 2005); one study showed that pre- and postoperative oral clonidine significantly reduced pain scores compared with placebo at all time points assessed (Hidalgo 2005) 
  • One study showed that intra-operative dexmedetomidine had no effect on pain scores at rest and during movement compared with placebo, both in the PACU and 0–48 h after surgery (Gurbet 2006)
  • Morphine consumption was not significantly different between clonidine and placebo groups at all time points assessed (Hidalgo 2005; Oofuvong 2005)
  • Patients in the intra-operative dexmedetomidine group consumed significantly less postoperative morphine compared with the placebo group, both in the PACU and 0–48 h after surgery (Gurbet 2006)

Systemic clonidine: no change to recommendation
Dexmedetomidine: limited data, so not recommended at the current time

  • One study showed that pre-operative morphine did not significantly reduce subjective pain scores (0–10) compared with saline control (Goldstein 2005)
  • One study showed that postoperative IV morphine significantly reduced VRS pain scores compared with placebo 2 min after administration, but not at any other time point assessed (5, 10 and 15 min) (Larijani 2004)
  • One study showed that intraoperative pethidine significantly reduced VAS pain scores at rest at 0–120 min after surgery compared with postoperative pethidine (Mavioglu 2005)
  • One study showed a significant reduction in supplemental analgesic demands between 15 and 30 min postoperatively, cumulative PCA demands, cumulative pethidine consumption after the first 24 h, and additional pethidine consumption during the first 2 h, in the intraoperative pethidine group compared with the postoperative pethidine group (Mavioglu 2005)

No change to recommendations

  • One study showed that postoperative tramadol significantly reduced VAS pain scores compared with saline control at all time points assessed (0–24 h) (Kocabas 2005)
  • One study demonstrated a significant reduction in PCA morphine requirements at 1, 2, 3, 4, 8, 12, 16, 20 and 24 h after surgery in the postoperative tramadol group compared with the saline control group (Kocabas 2005)

No change to recommendation

  • One study showed that pre-operative spinal morphine significantly reduced VAS pain scores at rest and during coughing at all time points assessed (up to 20 h post-surgery) compared with control (no treatment) (Karaman 2006)
  • One study showed that intra-operative spinal morphine significantly reduced VAS pain scores at 0, 1, 2, 4, and 8 h after surgery compared with IV morphine (Togal 2004)
  • One study showed that pre-operative spinal morphine significantly reduced postoperative morphine consumption in 20 h compared with control (no treatment) (Karaman 2006)
  • One study showed that postoperative total morphine consumption and PCA demands were significantly lower in the group receiving intra-operative spinal morphine compared with the IV morphine group during postoperative 24 h (Togal 2004)

No change to recommendations

  • One study showed that postoperative IV PCA droperidol (50 µg droperidol premixed with 1 mg/ml morphine compared with morphine alone) significantly reduced VRS pain scores at rest (at 72 h) and on coughing/movement (at 48 and 72 h) compared with control (no droperidol). Morphine consumption was significantly lower in the postoperative IV droperidol group at all time points assessed, when compared with control (no droperidol) (Lo 2005)

Not recommended for pain relief due to limited procedure-specific evidence (although droperidol has proven effects on nausea and vomiting)

  • One study showed that pre-operative antihistamine, combined with either a 1.2:1 or a 4.8:1 ratio of antihistamine-morphine mixture for postoperative PCA, did not significantly reduce VAS pain scores at rest or supplemental analgesic requirements at any time point assessed (0–24 h) compared with saline control (Lin 2005)
  • One study showed that neither pre-operative antihistamine alone nor postoperative antihistamine alone significantly reduced VAS pain scores at rest or during movement compared with saline control (Chia 2004)
  • One study showed that patients in the pre-operative antihistamine alone group consumed significantly less morphine at 3, 6, 12, and 24 h postoperatively compared with patients in the postoperative antihistamine alone and saline control groups (Chia 2004)

Not recommended due to limited evidence of analgesic efficacy

  • One study showed that pre- and intra-operative beta-blockers had no effect on VAS pain scores at rest and during movement at all time points assessed compared with saline control (Chia 2004)
  • Patients receiving beta-blockers consumed significantly less PCA morphine at all time points assessed, and the mean total morphine consumption was significantly less, compared with saline control (Chia 2004)

Not recommended because of limited evidence of analgesic efficacy

Single bolus wound instillation

  • One study showed that intra-operative single bolus wound instillation (topically on to peritoneum for 10 min) significantly reduced NRS pain scores at 60 min after surgery compared with placebo (pain assessed every 15 min from 0–120 min after surgery; all other time points not significantly different) (Heid 2005)
  • There were no differences in cumulative morphine consumption or adverse effects observed between the wound instillation and placebo groups (Heid 2005)

Not recommended currently due to limited procedure-specific evidence

 

Continuous wound infusion

  • One study showed that postoperative continuous wound infusion significantly reduced VAS pain scores compared with no wound infusion at rest at 4, 5, 6, and 12h, on coughing at 0–24 h, and on leg raising at 3, 4, 5, 6, and 12 h after surgery (Gupta 2005)
  • Significantly less rescue analgesia was consumed in the continuous wound infusion group compared with the no wound infusion group (pentazocine administered 0–6 h, diclofenac administered 6–24 h) (Gupta 2005)

Not recommended currently due to limited procedure-specific evidence

 

PCA wound infusion

  • One study (published January 2004–June 2006) showed that there were no significant differences in analgesic outcomes between two doses of ropivacaine delivered via PCA wound infusion (Zohar 2004)

Not recommended currently due to limited procedure-specific evidence  

  • One study showed that IP LA + IP conventional NSAID + IP weak opioid significantly reduced VAS pain scores compared with IP LA + IP conventional NSAID (at 1 and 2 h) and IP LA + IP weak opioid (at 2 h) (Pirbudak 2004)
  • Time to first analgesic request was significantly longer, and total supplementary analgesic consumption was significantly lower, in the IP LA + IP conventional NSAID + IP weak opioid group compared with the IP LA + IP conventional NSAID group and the IP LA + IP weak opioid group (Pirbudak 2004)

No change to recommendations

  • One study showed that there were no significant differences in analgesic efficacy between pre-operative and postoperative epidural analgesia (LA + ketamine) (DeCastro 2005)
  • One study showed that there were no significant differences in VAS pain scores at rest and during coughing (at 4, 8, and 21 h), or total morphine consumption, between the postoperative epidural 0.1% ropivacaine + fentanyl group and the postoperative epidural 0.2% ropivacaine group (Thienthong 2004)

No change to recommendations

Two studies showed that abdominal laparoscopic hysterectomy significantly reduced pain scores compared with abdominal hysterectomy (Garry 2004; Garry 2004). One study showed that laparoscopic hysterectomy significantly reduced pain scores compared with abdominal hysterectomy (Learman 2004). One study showed that vaginal hysterectomy significantly reduced pain compared with abdominal hysterectomy (Silva 2006)

 Vaginal hysterectomy studies:

  • Two studies showed that there were no significant differences in pain scores between vaginal hysterectomy and vaginal laparoscopic hysterectomy (Garry 2004; Garry 2004)
  • One study showed that electrosurgical bipolar vessel sealing significantly reduced pain compared with traditional suturing in vaginal hysterectomy (Cronjé 2005)

Further data are required before any changes can be made to the recommendations

C-Section 2014

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Notes on PROSPECT recommendations

PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted.Grades of recommendation (GoR) are assigned according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence.  

Grades of recommendation (GoR) based on source and level of evidence (LoE): Summary table

An explanation of how study quality assessments are performed to determine the LoE and GoR can be found at the following link: C-Section: levels of evidence and grades of recommendation. The AGREE II instrument (Brouwers 2010) is used internationally to assess the methodological rigour and transparency of practice guidelines. As far as possible, the methodology of the PROSPECT C-Section review meets the requirements of ‘Domain 3: Rigour of development’ of the AGREE II instrument:
  • Systematic methods were used to search for evidence.
  • The criteria for selecting the evidence are clearly described.
  • The strengths and limitations of the body of evidence are clearly described.
  • The methods for formulating the recommendations are clearly described.
  • The health benefits, side effects, and risks have been considered in formulating the recommendations.
  • There is an explicit link between the recommendations and the supporting evidence.
  • The guideline has been externally reviewed by experts prior to its publication. [The evidence and recommendations will be submitted for peer-review after publication on the PROSPECT website]
  • A procedure for updating the guideline is provided. [Methodology is provided so that the systematic review can be updated as required]
 

Summary recommendations

Pre-operative interventions that are recommended for C-Section

Note: Unless otherwise stated, ‘pre-operative’ refers to interventions applied before surgical incision

Note: Analgesics should be administered at the appropriate time
(pre- or intra-operatively) to provide sufficient analgesia in the early recovery period

Oral gabapentin

·        A single dose of pre-operative oral gabapentin is recommended (GoR A) for improving postoperative pain relief (LoE 1)

Anaesthetic techniques and co-administered analgesics

Anaesthetic techniques: Combined spinal-epidural anaesthesia or spinal anaesthesia

·        Combined spinal-epidural anaesthesia or spinal anaesthesia are recommended (GoR A) based on procedure-specific evidence (LoE 1)

·        There is no evidence of analgesic benefit to recommend general anaesthesia over neuraxial anaesthesia (i.e., epidural anaesthesia, spinal anaesthesia, and combined spinal epidural anaesthesia), due to lack of direct comparative studies focusing on postoperative analgesia (GoR D).

·        However, neuraxial anaesthesia techniques are recommended for safety reasons (e.g., neuraxial anaesthesia obviates the need for airway manipulation and avoids the postoperative sedative effects of general anaesthetics) (GoR D)

Intrathecal opioid analgesia

·        Intrathecal morphine below 200 µg is recommended if the patient has received spinal anaesthesia (GoR A) based on procedure-specific evidence for improved postoperative analgesia (LoE 1)

·        However, due to opioid-related side effects, including delayed respiratory depression, alternative analgesic techniques should be considered

Epidural opioid analgesia

·        Epidural opioids are recommended if the patient has received epidural anaesthesia (GoR A) based on procedure-specific evidence for improved postoperative analgesia (LoE 1)

·        However, due to opioid related side effects, including delayed respiratory depression, alternative analgesic techniques should be considered

Surgical techniques that are recommended for C-Section

Surgical techniques: Transverse abdominal incision and non-closure of the peritoneum

·        Transverse abdominal incision is recommended over vertical incision (GoR A, LoE 1). Amongst transverse incisions the Joel-Cohen incision and similar modifications are superior to the Pfannenstiel incision for outcomes related to postoperative pain (GoR A, LoE 1)

·        Non-closure of the peritoneum is recommended (GoR A) based on procedure-specific evidence for postoperative analgesia (LoE 1)

Intraoperative interventions that are recommended for C-Section

Note: Unless otherwise stated, ‘intra-operative’ refers to interventions applied after incision and before wound closure. In C-Section, ‘post-delivery’ refers to administration after the umbilical cord is clamped and the baby is delivered.

Note: Analgesics should be administered at the appropriate time
(pre- or intra-operatively) to provide sufficient analgesia in the early recovery period

Post-delivery
IV NSAIDs

·        Post-delivery NSAIDs are recommended (GoR A) based on procedure-specific evidence (LoE 1), even in breastfeeding women (LoE 3)

Post-delivery
IV paracetamol

·        Post-delivery paracetamol is recommended (GoR A) based on procedure-specific evidence (LoE 1)

Post-delivery iliohypogastric and ilioinguinal blocks

·        Bilateral iliohypogastric and ilioinguinal blocks are recommended (GoR A) based on procedure-specific evidence for postoperative analgesia (LoE 1)

Post-delivery bilateral TAP blocks

·        Bilateral TAP blocks are recommended (GoR A) based on procedure-specific evidence for postoperative analgesia (LoE 1)

Post-delivery wound infiltration with local anaesthetics

·        Wound infiltration with local anaesthetics is recommended (GoR A) based on procedure-specific evidence (LoE 1)

Postoperative interventions that are recommended for C-Section

Note: ‘Postoperative’ refers to interventions applied at or after wound closure

Note: Analgesics should be administered at the appropriate time
(pre- or intra-operatively) to provide sufficient analgesia in the early recovery period

Oral NSAIDs

·        Postoperative NSAIDs are recommended (GoR A) based on procedure-specific evidence (LoE 1), even in breastfeeding women (LoE 3)

Oral paracetamol

·        Postoperative paracetamol is recommended (GoR A) based on procedure-specific evidence (LoE 1)

Systemic opioids as rescue analgesia

·        Systemic opioids provide effective analgesia (GoR A, LoE 1), but are only recommended as rescue analgesics due to side effects (GoR D)

Continuous wound infusion with local anaesthetics

·        Continuous wound infusion with local anaesthetics is recommended (GoR A) based on procedure-specific evidence (LoE 1)

Overall Recommendations: Pain Management for Elective Caesarean Section Surgery

Pre-operative 

Oral gabapentin

Pre-/intra-operative anaesthetic technique

CSEA or SpA*

Intra-operative, post-delivery

IV paracetamol + IV NSAID #

Wound infiltration with LA or TAP blocks or iliohypogastric/ilioinguinal blocks

Surgical technique

Transverse incision†

Non-closure of peritoneum

Postoperative

Oral paracetamol + oral NSAID + systemic opioid as rescue

Continuous wound infusion with LA

* IT morphine/epidural opioids are recommended, but alternative analgesic techniques such as wound infiltration with LA, TAP block, iliohypogastric and ilioinguinal blocks should be considered to avoid the potential opioid-related side effects of neuraxial opioids

# IV paracetamol and IV NSAID may not be necessary if neuraxial opioids are used

† Amongst transverse incisions, the Joel-Cohen incision and similar modifications are superior to the Pfannenstiel incision for outcomes related to postoperative pain

Not recommended for C-Section

Dexamethasone

Pre-operative dexamethasone cannot be recommended at this time (GoR D) based on limited procedure-specific evidence

Neuraxial clonidine

Neuraxial clonidine is not recommended (GoR D), although procedure-specific evidence suggests it provides superior analgesia, because of side effects (e.g. hypotension)

Ketamine

Ketamine cannot be recommended at this time (GoR D) based on inconsistent procedure-specific evidence

TENS

TENS is not recommended (GoR D) based on limited procedure-specific evidence

Wound infiltration with NSAIDs

Wound infiltration with NSAIDs is not recommended at this time (GoR D) due to limited comparative data with systemic administration

Continuous wound infusion with NSAIDs

Continuous wound infusion with NSAIDs is not recommended (GoR D) based on limited procedure-specific evidence

Overall Recommendations: Pain Management for Elective Caesarean Section Surgery

Pre-operative 

Oral gabapentin

Pre-/intra-operative anaesthetic technique

CSEA or SpA*

Intra-operative, post-delivery

IV paracetamol + IV NSAID #

Wound infiltration with LA or TAP blocks or iliohypogastric/ilioinguinal blocks

Surgical technique

Transverse incision†

Non-closure of peritoneum

Postoperative

Oral paracetamol + oral NSAID + systemic opioid as rescue

Continuous wound infusion with LA

* IT morphine/epidural opioids are recommended, but alternative analgesic techniques such as wound infiltration with LA, TAP block, iliohypogastric and ilioinguinal blocks should be considered to avoid the potential opioid-related side effects of neuraxial opioids

# IV paracetamol and IV NSAID may not be necessary if neuraxial opioids are used

† Amongst transverse incisions, the Joel-Cohen incision and similar modifications are superior to the Pfannenstiel incision for outcomes related to postoperative pain

PROSPECT C-Section Subgroup and Working Group process

For each review, a Subgroup of the PROSPECT Working Group performs an initial evaluation of the evidence and also drafts clinical practice statements and recommendations, which are then discussed by the whole Working Group before a final consensus is reached. For the C-Section review, the Subgroup members were:
  • Professor Marc Van De Velde (PROSPECT Working Group member)
  • Professor Girish Joshi (PROSPECT Working Group member)
  • Professor Narinder Rawal (PROSPECT Working Group member)
Dr Thomas Jaschinski (IFOM - Institut für Forschung in der Operativen Medizin, Universität Witten/Herdecke, Köln, Germany) provided support in conducting the literature search, preparing the evidence summary and coordinating the Subgroup and Working Group reviews of the evidence to prepare the final recommendations. The recommendations for postoperative pain management in C-Section were voted on by nine Working Group members to show the strength of consensus. The results of each vote are indicated within the PROSPECT recommendations sub-folders.

Literature search

  • Systematic review of the literature from 1966–April 2014 using MEDLINE and EmBASE, following the protocol of the Cochrane Collaboration
  • Inclusion of randomised/controlled studies assessing analgesic, anaesthetic or operative techniques in C-Section and reporting pain assessment, required analgesia or adverse events (C-Section: Inclusion criteria, C-Section: Search strategy)
  • 137 studies included (C-Section: Included studies)
  • 139 studies excluded after full-text screening (C-Section: Excluded studies)
  • The most common reason for exclusion was that the study did not investigate an intervention affecting postoperative pain (63 studies)

C-Section: Sources and levels of evidence (LoE) determine the grades of recommendation (GoR)

GoR are assigned according to the overall LoE, which is determined by the quality of studies cited, the consistency of evidence and the source of evidence:
C-Section: levels of evidence and grades of recommendation

Sources of evidence in PROSPECT
The evidence for prospect is derived from three separate sources, and this evidence is taken into consideration by the prospect Working Group to determine the prospect recommendations:
  • Procedure-specific evidence derived from the systematic reviews of the literature
  • Transferable evidence from comparable procedures, or from other relevant sources, identified by the members of the prospect Working Group
  • Current practice – A commentary on the interventions from the members of the prospect Working Group
  • Practical prospect recommendations are based on all the information
Study quality assessment
For the C-Section review, the quality of procedure-specific evidence has been assessed according to NICE methodology, to determine the possibility of selection bias, performance bias, attrition bias and detection bias (http://www.nice.org.uk/article/pmg6b).

Quality indicators used to determine the LoE of individual studies:
  • Allocation concealment: indicates whether there was adequate prevention of foreknowledge of treatment assignment by those involved in recruitment (in the table below, A=adequate, B=unclear, C=inadequate, D=not used). Empirical research has shown that trials with inadequate or unclear allocation concealment report significantly greater estimates of treatment effect than those trials in which concealment was adequate (Chalmers 1983, Schulz 1995, Moher 1998). Allocation concealment was found to be more important for preventing bias than other aspects of study quality, such as generation of the allocation sequence and double-blinding (Chalmers 1983, Schulz 1995, Moher 1998, HigginsandGreen 2005, http://handbook.cochrane.org/)
  • Statistical analyses and patient follow-up: indicates whether statistical analyses were reported, and whether patient follow-up was greater or less than 80%.
  • Numerical scores (total 1–5) for study quality: assigned using the method proposed by Jadad 1996, to indicate whether a study reports appropriate randomisation, double-blinding and statements of possible withdrawals. Empirical research found that low-quality trials were associated with an increased estimate of treatment benefit compared with high-quality trials (Moher 1998)
Study quality assessments for the C-Section review are summarised:
For systematic reviews, a critical appraisal was performed to determine the LoE:


Quantitative analyses

No meta-analyses were performed due to a limited number of studies of homogeneous design that reported similar outcome measures. Therefore, the procedure-specific evidence was only assessed qualitatively.

Transferable evidence

Transferable evidence has not been included in the C-Section review as there was sufficient procedure-specific evidence on which to base the recommendations for the most common analgesic interventions.

Topics for future research
  • Transcutaneous (Electrical) Nerve Stimulation (TNS or TENS)
  • Transversus abdominis plane blocks (TAP block)
  • Other abdominal wall local anaesthetic nerve blocks
  • Postoperative non-steroidal anti-inflammatory drug (NSAID) wound infiltration
  • Preoperative dexamethasone

List of abbreviations

CG

control group

CS

caesarean section

CSEA

combined spinal-epidural anaesthesia

EA

epidural anaesthesia

EVE

epidural volume extension

GA

general anaesthesia

h

hours

IG

intervention group

IHII

iliohypogastric-ilioinguinal

IM

intramuscular

iPCA

intravenous patient controlled analgesia

IQR

interquartile range

IT

intrathecal

IV

intravenous

LoE

level of evidence

MD

mean difference

n. r.

not reported

PACU

post-anaesthesia care unit

PO

peroral

rg.

range

SEM

standard error of mean

SpA

spinal anaesthesia

TENS

transcutaneous electrical nerve stimulation

mEq

milliequivalent

PCA

patient controlled analgesia

PCEA

patient-controlled epidural analgesia

POD

postoperative day

PONV

postoperative nausea and vomiting

POW

postoperative week

SMD

standardised mean difference

VAS

visual analogue scale

wk.

weeks

yr.

years

PROSPECT Recommendations

  • A single dose of pre-operative oral gabapentin is recommended (GoR A) for improving postoperative pain relief (LoE 1)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • The administration of oral gabapentin 300 mg 2 h before surgery during spinal anaesthesia (without fentanyl) was superior to placebo capsule combined with fentanyl 10 µg during spinal anaesthesia for pain relief and time to first analgesic request Najafi Anaraki and Mirzaei 2014
  • A single pre-operative dose of oral gabapentin 600 mg compared to placebo reduced post-caesarean pain and increased maternal satisfaction Moore et al 2011
  • A single pre-operative dose of either 300 mg or 600 mg oral gabapentin did not improve post-caesarean pain management and maternal satisfaction (Study was underpowered) Short et al 2012
  • Gabapentin study details Click here for more information

PROSPECT Recommendations

  • Pre-operative dexamethasone cannot be recommended at this time (GoR D) based on limited procedure-specific evidence
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • Dexamethasone 10 mg given intravenously before surgery decreased postoperative pain with movement at 1 h, 6 h, 12 h and 24 h, but not at 2 h and 3 h, compared with placebo. Although the cumulative incidence of PONV was significantly lower in women receiving dexamethasone, there were no significant differences in PONV at specific assessment time points Cardoso et al 2013
  • Intravenous dexamethasone 8 mg administered before skin incision was superior to placebo in pain scores at rest and on movement between 6 and 24 h, but not before. However, there was no significant difference in the consumption of supplemental analgesia Wu et al 2007
  • Dexamethasone study details Click here for more information

PROSPECT Recommendations

  • Combined spinal-epidural anaesthesia or spinal anaesthesia are recommended (GoR A) based on procedure-specific evidence (LoE 1)
  • Consensus agreement 100% (9/9)
  • There is no evidence of analgesic benefit to recommend general anaesthesia over neuraxial anaesthesia (i.e., epidural anaesthesia, spinal anaesthesia, and combined spinal epidural anaesthesia), due to lack of direct comparative studies focusing on postoperative analgesia (GoR D). However, neuraxial anaesthesia techniques are recommended for safety reasons (e.g., neuraxial anaesthesia obviates the need for airway manipulation and avoids the postoperative sedative effects of general anaesthetics)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • Three studies comparing CSEA with EA showed a significant reduction in pain scores with CSEA during or after surgery but the results related to the time to first analgesic request were inconsistent Davies et al 1997 Click here for more information
  • A systematic review comparing the efficacy and side effects of SpA and EA showed no differences in unplanned interventions for pain relief postoperatively. However, there was an increased need for treatment for hypotension in women undergoing SpA Ng et al 2004
  • A systematic review comparing the effects of regional anaesthesia with those of GA showed (based upon one RCT) that the time to first request for analgesia was longer with EA compared with GA. There were no significant differences in the Apgar scores at 1, 5 and 10 min Afolabi and Lesi 2012
  • CSEA with epidural volume extension (EVE) was not superior to SpA in reducing intraoperative pain scores and the time to first analgesic request Lew et al 2004
  • One study showed a significant reduction in the time to first analgesic request for the SpA group compared with the CSEA group. However, there was no significant difference in supplemental analgesic use Thorén et al 1994
  • Two studies comparing EA with SpA showed inconsistent results related to pain scores and the need for supplemental analgesic use Paraskeva et al 2012 Click here for more information
  • Combined spinal-epidural anaesthesia (CSEA) vs epidural anaesthesia (EA) or spinal anaesthesia (SpA) study details Click here for more information
  • EA vs SpA study details Click here for more information
  • EA or SpA versus general anaesthesia (GA) study details Click here for more information
  • CSEA vs EA or SpA
  • EA vs SpA
  • EA or SpA vs GA

PROSPECT Recommendations

  • Intrathecal morphine below 200 µg is recommended if the patient has received spinal anaesthesia (GoR A) based on procedure-specific evidence for improved postoperative analgesia (LoE 1)
  • However, due to opioid-related side effects, including delayed respiratory depression, alternative analgesic techniques should be considered
  • Consensus agreement 100% (9/9)
  • Epidural opioids are recommended if the patient has received epidural anaesthesia (GoR A) based on procedure-specific evidence for improved postoperative analgesia (LoE 1)
  • However, due to opioid related side effects, including delayed respiratory depression, alternative analgesic techniques should be considered
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence: Epidural or IT Analgesia With Anaesthesia

  • IT ketamine 0.1 mg/kg added to spinal bupivacaine compared with bupivacaine alone prolonged intraoperative anaesthesia, increased the time to the first analgesic request and decreased the total analgesic consumption in the first 24 postoperative hours Khezri et al 2013
  • IT morphine 0.1 mg was superior in postoperative pain relief, supplemental need for analgesia and time to first analgesic request compared with IT fentanyl 25 µg, when combined with IT hyperbaric bupivacaine Siti Salmah and Choy 2009
  • In combination with SpA with 0.5% hyperbaric bupivacaine 10 mg, morphine 0.2 mg was associated with longer duration of analgesia and less requirement for supplementary analgesia compared with nalbuphine 0.2 mg, 0.8 mg or 1.6 mg Culebras et al 2000 Click here for more information
  • The combination of neostigmine 12.5 µg and morphine 50 µg administered with SpA with 0.5% hyperbaric bupivacaine 12 mg had a prolonged analgesic effect compared with either neostigmine or morphine alone Chung et al 1998 Click here for more information
  • For patients receiving IT morphine, the addition of diclofenac IM every 8 h compared to diclofenac IM only on request significantly reduced pain scores at 24 h, independent of the doses of IT morphine (0.1 mg, 0.05 mg, 0.025 mg) Cardoso et al 1998
  • A randomised controlled study comparing IT morphine 100 µg, IT morphine 200 µg and epidural morphine 3 mg showed no significant differences in postoperative pain scores and the time to first request for rescue analgesia Sarvela et al 2002
  • CSEA with hyperbaric bupivacaine plus sufentanil 5 µg and epidural lidocaine combined with either epidural morphine or IT morphine produced similar postoperative pain relief and similar time to first analgesic demand. However, women receiving epidural morphine had a decreased 24 h morphine consumption Dualé et al 2003
  • Similar pain relief was achieved with the administration of PCEA pethidine compared with IT morphine during surgery plus IV pethidine via PCA or IT morphine during surgery plus postoperative oral paracetamol and codeine. Patients receiving epidural pethidine had a trend for higher pain scores but also lower nausea and pruritus scores Paech et al 2000
  • Time to first analgesic request was significantly shorter following epidural diamorphine 3 mg (2 boluses) administration compared with IT morphine 0.2 mg. However, IT morphine was associated with higher incidence of PONV Caranza et al 1999
  • Women undergoing caesarean delivery with CSEA benefited from the additional administration of IT morphine (0.1 and 0.2 mg) to 15 mg of spinal levobupivacaine. It prolonged the time to the first analgesic request compared with saline; however, there were no significant differences in postoperative pain scores Unlugenc et al 2012
  • The coadministration of IT sufentanil 5 µg and IT morphine 100 µg was superior to IT sufentanil 5 µg plus a single injection of s.c. morphine 10 mg for postoperative pain relief and consumption of supplemental analgesia Draisci et al 2009
  • The administration of IT morphine 0.25 mg or 0.1 mg during SpA was superior to saline for postoperative pain relief. However, the higher dose of IT morphine was associated with significantly increased occurrence of pruritus Abboud et al 1988
  • The addition of IT morphine 0.2 mg to hyperbaric bupivacaine 0.5% for SpA compared with hyperbaric bupivacaine alone reduced postoperative pain scores, the need for additional analgesia and prolonged the time to first analgesic request Terajima et al 2003
  • Postoperative pain was significantly lower in a group receiving IT morphine added to SpA with bupivacaine than in a group receiving saline plus SpA. Morphine consumption was significantly lower in the IT morphine group Swart et al 1997
  • IT morphine 50 µg or 100 µg reduced pain scores, rescue analgesia requirements and increased the time to first request for rescue analgesics compared with no IT morphine Mikuni et al 2010 Click here for more information
  • The time to first PCA demand was longer in each of four groups receiving IT morphine (0.1, 0.2, 0.3, 0.4 mg) in combination with SpA bupivacaine than in the control group (0 mg morphine). The IT morphine groups showed a significantly lower total PCA morphine demand in the first 24 hours than the control group. There were no significant differences between mean VAS scores Girgin et al 2008
  • The combination of IT morphine 0.2 mg with spinal bupivacaine compared with spinal bupivacaine alone prolonged the time to first analgesic request. However, women receiving IT morphine reported nausea and pruritus significantly more often Abouleish et al 1988
  • Fewer patients receiving IT morphine 100 µg during surgery requested supplemental analgesia compared with patients receiving postoperative oral oxycodone, but there was no significant difference in pain scores or consumption of supplemental analgesia and IT morphine was associated with a higher incidence of pruritus McDonnell et al 2010 Click here for more information
  • The addition of dextromethorphan to different doses of IT morphine was not superior to placebo combined with the same doses of IT morphine for pain relief. Higher doses of morphine were associated with a significantly increased incidence of PONV and pruritus Choi et al 2003
  • Spinal morphine 0.1 mg combined with IV ketorolac was not superior to different doses of spinal morphine (0.1 mg or 0.2 mg) or IV ketorolac alone in terms of pain relief and time to first analgesic request Cohen et al 1996
  • The administration of IT fentanyl 25 µg was superior to IT ketamine 0.05 mg/kg, both added to plain bupivacaine for spinal analgesia, for providing postoperative pain relief and prolonging the time to first analgesic request Unlugenc et al 2006
  • The addition of IT fentanyl 0, 5, 10 or 25 µg to SpA with IT morphine showed no difference in postoperative morphine consumption via PCA. However, pain scores were higher in women receiving fentanyl 5, 10 and 25 µg compared with 0 µg Carvalho et al 2012
  • IT ketamine study details Click here for more information
  • IT or epidural opioids study details
  • Other regimens
  • Comparisons of different IT opioid regimens
  • IT opioid vs epidural opioid
  • IT opioid vs placebo/control or systemic opioid
  • IT ketamine with spinal LA
  • There were no significant differences between groups receiving either morphine 0.1 mg or 0.2 mg combined with IT 0.5% bupivacaine 2.5 mL in VAS pain scores and time to first analgesic request Milner et al 1996
  • The comparison of either IT morphine 0.1 mg or diamorphine 0.25 mg in combination with SpA using hyperbaric bupivacaine and fentanyl 12.5 µg showed no differences in postoperative pain relief, time of first PCA use or cumulative morphine requirement postoperatively Barkshire et al 2001

C-Section-Specific Evidence: Epidural Analgesia Continued After Anaesthesia

  • The administration of epidural fentanyl via PCA was superior to IV morphine via PCA in pain scores at rest 4 and 8 h, but not at recovery, 12 and 21 h as well as in lower pain scores on coughing at 4, 8 and 21 h, but not at remaining assessment times. The incidence of PONV and drowsiness was significantly lower in patients receiving epidural fentanyl via PCA Cooper et al 1999
  • The duration of analgesia was significantly longer in patients receiving epidural buprenorphine plus bupivacaine in comparison to patients receiving epidural bupivacaine plus clonidine and it was the lowest in patients receiving epidural bupivacaine alone Agarwal et al 2010
  • Ropivacaine plus fentanyl administered by PCEA was superior to ropivacaine alone for pain scores and supplemental analgesics. But patients receiving ropivacaine plus fentanyl reported pruritus significantly more frequently Buggy et al 2000
  • PCEA meperidine was significantly superior to IM meperidine for pain relief. The incidence of nausea and pruritus was similar between the two groups Yarnell et al 1992
  • The combination of epidural morphine 2 mg plus diclofenac sodium 75 mg IM was superior to epidural morphine 2 mg plus saline solution IM and to epidural saline plus diclofenac 75 mg IM for pain relief. However, patients receiving epidural morphine experienced PONV and pruritus significantly more often Sun et al 1992
  • The administration of epidural diamorphine was superior to IV diamorphine via PCA for pain scores at 1 and 2 h, but not between 4 and 48 h. The incidence of pruritus and PONV was similar between the two groups Stoddart et al 1993
  • The duration of analgesia was significantly longer in patients receiving epidural diamorphine 3 mg compared with IM morphine 10 mg. However, only the pain score at 5 hours was lower in the diamorphine group Stevens et al 1991
  • There was no significant difference between the incidence of PONV, sedation and dizziness in the epidural pethidine group and IM pethidine group. However, patients receiving epidural pethidine had lower pain scores during the first 2 h Perriss et al 1990
  • The administration of epidural meperidine via PCA was superior to IV meperidine via PCA for pain, sedation and satisfaction scores Paech et al 1994
  • PCEA administration reduced drug consumption within 24 h compared with IV PCA administration for both pethidine and fentanyl. The number of PCA demands was lower with pethidine than fentanyl. Patients preferred PCEA to IV PCA administration for pethidine but not fentanyl Ngan Kee et al 1997
  • The administration of sufentanil PCEA was superior to morphine iPCA in reducing pain at rest at 30 min and 2 h, but not between 6 h and POD 2 and in reducing pain on movement at POD 2, but not on POD 1. The incidence of PONV was similar between the two groups, but patients receiving epidural sufentanil experienced pruritus significantly more frequently Grass et al 1994
  • Epidural morphine was superior to IM morphine in pain relief and the need for morphine consumption. The two groups were similar in the occurrence of PONV and pruritus Daley et al 1990
  • Fentanyl (20 µg, 10 min lockout) administered via PCEA compared with the same dose via IV PCA resulted in lower pain scores at rest at 8, 12, 24 h, but not at 0.5 and 4 h and in lower pain scores on coughing at 8 and 12 h, but not at remaining points in time. There was no significant difference in PONV between the two groups, but patients receiving fentanyl via PCEA experienced pruritus significantly more frequently Cooper et al 1995
  • Epidural fentanyl was associated with lower postoperative pain scores and a lower incidence of PONV than IV fentanyl Cohen et al 2002
  • Epidural morphine 5 mg compared with IV morphine 5 mg was superior for reducing the need for supplemental analgesics and prolonging the time to first analgesic request. However, significantly more patients receiving epidural morphine experienced pruritus Cohen and Woods 1983
  • There were no significant differences in pain scores, morphine consumption and time to first analgesic request between butorphanol 2 mg IV (with epidural saline) and epidural butorphanol 2 mg (plus saline IV), but both regimens provided superior analgesia to saline placebo in the first 2 h postoperatively Camann et al 1992
  • A systematic review of RCTs comparing epidural morphine with parenteral opioids showed that a single bolus of epidural morphine provides better pain relief than parenteral opioids but with an effect limited to the POD 1 and with an increase in morphine side effects Bonnet et al 2010
  • Epidural morphine was superior to placebo for pain relief, duration of pain relief and reduction of additional analgesics. However, patients in the morphine group reported pruritus significantly more frequently Binsted 1983
  • Epidural fentanyl plus bupivacaine was associated with reduced fentanyl consumption in 48 h compared with epidural fentanyl alone Cohen et al 2002
  • The administration of fentanyl or bupivacaine plus fentanyl administered via PCEA was superior to bupivacaine alone via PCEA in pain scores at rest at 12 h, but not at 0.5, 4, 8 and 24 h. There were no significant differences between the three groups in pain scores on coughing at any assessment time. However, the incidence of pruritus was significantly lower in patients receiving only bupivacaine compared with the two other groups Cooper et al 1996
  • Epidural morphine 2 mg twice per day for 3 days was not superior to 0.1% ropivacaine administered by PCEA (5 mg bolus, 15 min lockout, with 3 mg/h background infusion, <60 mg/4 h) for 3 days in pain relief and supplemental analgesic request. Moreover, epidural morphine was associated with significantly higher incidence of nausea, vomiting and pruritus Chen et al 2011
  • The duration of analgesia was significantly longer in patients receiving epidural buprenorphine plus bupivacaine in comparison to patients receiving epidural bupivacaine plus clonidine and it was the lowest in patients receiving epidural bupivacaine alone Agarwal et al 2010
  • No significant additive or synergistic interactions were observed between the administration of epidural fentanyl, epidural clonidine and combined epidural fentanyl plus clonidine with regards to morphine given via iPCA Eisenach et al 1994
  • Epidural opioid vs IT opioid study details Click here for more information
  • Epidural opioids vs systemic opioids/placebo study details
    Click here for more information
  • Epidural clonidine study details Click here for more information
  • Comparative studies of different epidural opioids study details Click here for more information
  • Epidural opioid +/- LA vs epidural opioid or LA study details Click here for more information
  • Epidural opioid vs IT opioid
  • Epidural opioids vs systemic opioids/placebo
  • Comparative studies of different opioids
  • Epidural clonidine
  • Epidural opioid +/- LA vs epidural opioid or LA
  • Epidural morphine was superior to epidural fentanyl for duration of analgesia. However patients that received fentanyl had significantly lower pain scores during the first two hours, but not afterwards Blanco et al 1987
  • The comparison of patients receiving epidural fentanyl intraoperatively and epidural fentanyl via PCEA after surgery with patients receiving epidural morphine during surgery and saline via PCEA afterwards showed no significant difference for pain relief Yu and Gambling 1993
  • Epidural sufentanil delivered by PCA with a concomitant infusion of either sufentanil or saline produced similar pain scores overall, with significantly less pain at 6 h in the sufentanil infusion group, but not at 0,12, 18 and 24h. The incidence of PONV did not differ between the groups Vercauteren et al 1995
  • The epidural administration of morphine bolus (5 mg) and subsequent saline infusion for 24 h compared with morphine bolus (2.6 mg) and subsequent morphine infusion (0.1 mL/h, 5 mg/24 h) produced similar pain scores and occurrence of side effects Sharar et al 1991
  • Epidural meperidine 30 mg (10 mg/mL) followed by epidural meperidine via PCA for 24 h (group 1) produced higher pain scores between 8 and 16 h compared with epidural morphine 3 mg (1 mg/mL) followed by saline via PCA for 24 h (group 2) or epidural morphine 3 mg (1 mg/mL) without saline PCEA (group 3). However, women receiving epidural morphine (groups 2 and 3) experienced nausea and pruritus more frequently Rosaeg et al 1994
  • PCEA administration reduced drug consumption within 24 h compared with IV PCA administration for both pethidine and fentanyl. The number of PCA demands was lower with pethidine than fentanyl. Patients preferred PCEA to IV PCA administration for pethidine but not fentanyl Ngan Kee et al 1997
  • The epidural administration of morphine 4 mg and combination of morphine 2 mg plus sufentanil 25 µg was superior compared to sufentanil 50 µg in pain relief between 2 and 12 h, but not before. Patients receiving sufentanil 50 µg required more frequent supplementary analgesia. The incidence of pruritus and PONV did not differ between the three groups; however, dizziness was only observed in patients receiving sufentanil alone or in combination with morphine Dottrens et al 1992
  • Epidural butorphanol produced a longer duration of analgesia with less pruritus than epidural sufentanil, but pain scores of patients receiving sufentanil were significantly lower Bansal et al 2009
  • The duration of analgesia was significantly longer in patients receiving epidural morphine compared with epidural fentanyl, buprenorphine or butorphanol. However, the incidence of pruritus was significantly higher in the morphine and fentanyl groups Ackerman et al 1989
  • Epidural butorphanol (1 mg, or 2 mg, or 4 mg) provided significantly faster pain relief compared with 5 mg epidural morphine, but the duration of pain relief and the time before remedication was significantly longer in patients receiving morphine instead of butorphanol Abboud et al 1987
  • The administration of PCEA pethidine compared with IT morphine during surgery plus IV pethidine via PCA or IT morphine during surgery plus postoperative oral paracetamol and codeine produced similar pain relief at most time points. Patients receiving epidural pethidine had a trend towards higher pain scores but also lower nausea and pruritus scores Paech et al 2000

C-Section-Specific Evidence: IT Analgesia Continued After Anaesthesia

  • IT morphine was superior to wound infiltration with ropivacaine or placebo for reducing the consumption of supplemental analgesics Kainu et al 2012 Click here for more information
  • IT opioid versus LA wound infiltration or placebo study details Click here for more information
  • IT opioid vs epidural opioid study details Click here for more information
  • IT opioid vs LA wound infiltration or placebo
  • IT opioid vs epidural opioid
  • The administration of PCEA pethidine compared with IT morphine during surgery plus IV pethidine via PCA or IT morphine during surgery plus postoperative oral paracetamol and codeine produced similar pain relief at most time points. Patients receiving epidural pethidine had a trend towards higher pain scores but also lower nausea and pruritus scores Paech et al 2000

PROSPECT Recommendations

  • Neuraxial clonidine is not recommended (GoR D), although procedure-specific evidence suggests it provides superior analgesia, because of side effects (e.g. hypotension)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • The comparison of three doses of IT clonidine (150 µg, 300 µg and 450 µg) demonstrated a dose-dependent effect. A higher dose was significantly associated with lower pain scores and a delayed request for supplemental analgesics Filos et al 1994
  • Epidural infusion of clonidine (400 µg bolus plus 10 µg/h) and (800 µg bolus plus 20 µg/h) compared with placebo prolonged the time to first analgesic request. Only the high-dose clonidine group needed less morphine via iPCA compared with the placebo group Mendez et al 1990
  • Analgesia with bupivacaine (0.06 mg/cm body height) plus clonidine (75 µg) or plus clonidine and fentanyl (12.5 µg) was superior to bupivacaine alone. Time to first analgesic request was significantly prolonged following anaesthesia with bupivacaine, clonidine and fentanyl compared with the other groups. Intraoperative nausea-vomiting was more frequent in the group given bupivacaine alone Benhamou et al 1998
  • The administration of IT clonidine 150 µg was superior to placebo in terms of postoperative pain relief and time to first analgesic request. However, the side effects sedation, hypotension and dryness of mouth were more frequent in the clonidine group Filos et al 1992
  • Spinal bupivacaine combined with sufentanil 2 µg and 75 µg clonidine was superior to sufentanil 2 µg alone and 150 µg clonidine alone in the time to first analgesic request. However, there was no significant difference among the three groups in postoperative pain scores and in the need for supplemental analgesia Lavand'homme et al 2008
  • Spinal anaesthesia with a combination of subarachnoid morphine100 µg and clonidine at different doses compared with subarachnoid morphine100 µg alone or clonidine 150 µg alone significantly improves postoperative pain relief, but increases intraoperative sedation Paech et al 2004
  • Spinal bupivacaine plus clonidine 75 µg was superior in terms of duration of postoperative analgesia compared with spinal bupivacaine plus fentanyl 25 µg without any increase in maternal side effects Singh et al 2013
  • Spinal anaesthesia with bupivacaine 0.5% (2.2 mL) plus clonidine 75 µg was superior to bupivacaine 0.5% (2.2 mL) alone in time to first analgesic request and pain score at 1h, but not on 24h, without significant maternal and neonatal side-effects van Tuijl et al 2006
  • Neuraxial clonidine study details Click here for more information

PROSPECT Recommendations

  • Transverse abdominal incision is recommended over vertical incision (GoR A, LoE 1). Amongst transverse incisions the Joel-Cohen incision and similar modifications are superior to the Pfannenstiel incision for outcomes related to postoperative pain (GoR A, LoE 1)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • Joel-Cohen-based compared with Pfannenstiel caesarean section techniques were associated with lower duration of postoperative pain and with less use of analgesia Hofmeyr et al 2008
  • The Joel-Cohen incision was significantly superior to the Pfannenstiel incision for operative time, postoperative pain, postoperative need for supplemental analgesia, time to get out from bed and time to walk straight without support Abuelghar et al 2013
  • A systematic review of RCTs comparing different abdominal incisions showed that the Joel-Cohen incision was superior to the Pfannenstiel approach in reducing postoperative analgesic requirements, total dose of analgesia in the first 24 h and in increasing the time to first analgesic request Mathai et al 2013
  • A systematic review showed that there is little information available to inform the choice of the most appropriate surgical technique for uterine incision and uterine closure to adopt Dodd et al 2008
  • Surgical techniques study details Click here for more information

PROSPECT Recommendations

  • Non-closure of the peritoneum is recommended (GoR A) based on procedure-specific evidence for postoperative analgesia (LoE 1)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • A systematic review evaluating the effects of non-closure as an alternative to closure of the peritoneum showed that the number of postoperative analgesic doses was reduced in the peritoneal non-closure group Bamigboye and Hofmeyr 2003
  • Non-closure of both the visceral and the parietal peritoneum produced a significant reduction in pain scores and need for supplemental analgesia compared with closure Tabasi et al 2013
  • Non-closure and closure of the parietal peritoneum showed no differences in duration of surgery and postoperative pain scores. However, the non-closure group had a significantly reduced requirement for supplemental analgesia as well as shorter time to mobilisation and oral intake Altinbas et al 2013
  • Parietal peritoneal non-closure was associated with significantly lower pain scores and morphine consumption compared with closure Shahin et al 2009
  • Non-closure versus closure study details Click here for more information

PROSPECT Recommendations

  • No recommendation can be made with respect to skin closure techniques, as there is no effect on postoperative analgesia (GoR A, LoE 1)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • A systematic review assessing different effects of skin closure techniques and materials showed no conclusive evidence about how the skin should be closed after caesarean section Mackeen et al 2012
  • Techniques and materials for skin closure study details Click here for more information

PROSPECT Recommendations

  • Post-delivery NSAIDs are recommended (GoR A) based on procedure-specific evidence (LoE 1), even in breastfeeding women (LoE 3)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • Rectal naproxen followed by oral naproxen compared with placebo reduced postoperative pain scores, especially on the first day after surgery, reduced the need for additional analgesics and prolonged the time to first analgesic request Angle et al 2002
  • There were no significant differences in postoperative pain scores and supplemental analgesic use between the intravenous paracetamol group versus oral ibuprofen group Alhashemi et al 2006
  • Postoperative ketorolac 30 mg IM and postoperative pethidine 75 mg IM showed similar analgesic efficacy and time to first analgesic request, although more side-effects were noted in the pethidine group Gin et al 1993
  • The administration of diclofenac 75 mg IM every 12 h for 2 doses compared to no intervention reduced the need for rescue analgesia and produced significantly lower pain scores Surakarn and Tannirandorn 2009
  • The combination of epidural morphine 2 mg plus diclofenac sodium 75 mg IM was superior to epidural morphine 2 mg plus saline solution IM and to epidural saline plus diclofenac 75 mg IM for pain relief. However, patients receiving epidural morphine experienced PONV and pruritus significantly more often Sun et al 1992
  • Diclofenac suppository 100 mg after surgery followed by 3 additional doses at 8 h intervals was superior to pethidine 1 mg/kg IM after surgery followed by three additional doses at 8 h intervals for pain relief at 10 h, 18 h and 26 h, but not at 2 h. The incidence of PONV was similar between the two groups, but patients receiving pethidine reported dizziness significantly more frequently Soroori et al 2006
  • Diclofenac rectally plus propacetamol IV or diclofenac rectally provided more effective analgesia compared with placebo or propacetamol IV alone Siddik et al 2001 Click here for more information
  • The administration of intravenous ketorolac (</=120 mg/day) compared with placebo reduced the consumption of meperidine for 24 h, but not afterwards. The pain relief was similar between the two groups Pavy et al 2001
  • Rectal indomethacin significantly reduced pain scores and prolonged the time to first analgesic request compared with placebo Pavy et al 1995
  • Administration of rectal diclofenac (3x 50 mg) was superior to placebo for reducing the need for supplemental analgesia. Postoperative pain was lower in patients receiving diclofenac during the first 3 h, but not afterwards Olofsson et al 2000
  • The postoperative administration of paracetamol and diclofenac was not superior to diclofenac alone and to paracetamol alone in pain scores at rest and on movement. However, patients receiving the combination of paracetamol and diclofenac needed significantly less morphine given via iPCA compared with paracetamol alone, but not compared with diclofenac. The groups did not differ in time to first independent ambulation Munishankar et al 2008
  • The use of diclofenac suppository 100 mg compared to no suppository reduced the need for ropivacaine and fentanyl given via PCEA from 6 to 18 h, but not from 0 to 6 h and not from 18 to 24 h. There was no significant difference between the two group in pain scores on movement Lim et al 2001
  • Rectal diclofenac 100 mg every 12 h led to less morphine consumption compared with placebo. However, pain scores were similar between the two groups Dahl et al 2002
  • For patients receiving IT morphine, the addition of diclofenac IM every 8 h compared to diclofenac IM only on request significantly reduced pain scores at 24 h, independent of the doses of IT morphine (0.1 mg, 0.05 mg, 0.025 mg) Cardoso et al 1998
  • The administration of oral valdecoxib 20 mg every 12 h for 72 h compared with placebo was not superior in pain relief, need for supplemental analgesics and time to first analgesic request Carvalho et al 2006
  • Spinal morphine 0.1 mg combined with IV ketorolac was not superior to different doses of spinal morphine (0.1 mg or 0.2 mg) or IV ketorolac alone in terms of pain relief and time to first analgesic request Cohen et al 1996
  • The administration of subcutaneous pethidine 1 mg/kg followed by subcutaneous pethidine 1 mg/kg with metoclopramide 10 mg IM every 8 h for three days was superior to oral diclofenac sodium 75 mg twice daily in terms of the need for rescue analgesia. However, both groups were not different in pain scores and incidence of PONV Marzida 2009
  • NSAIDs study details Click here for more information

PROSPECT Recommendations

  • Ketamine cannot be recommended at this time (GoR D) based on inconsistent procedure-specific evidence
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • The administration of IV low-dose ketamine as an adjuvant to bupivacaine for spinal anaesthesia was associated with longer postoperative analgesia and a reduced need for analgesia consumption than bupivacaine alone Menkiti et al 2012
  • IV low-dose ketamine combined with IT bupivacaine provided better pain relief and lower postoperative analgesic consumption than bupivacaine alone Sen et al 2005
  • The administration of IV ketamine 0.2 mg/kg before the induction of anaesthesia decreased postoperative pain scores, the need for supplemental analgesia and prolonged the time to first analgesic request Ghazi-Saidi and Hajipour 2002
  • Women receiving IM S-ketamine 0.5 mg/kg followed by a 2 µg/kg/min IV continuous infusion over 12 h had a prolonged time to first analgesic request and a reduced cumulative morphine consumption compared with placebo. However, ketamine was associated with a significantly increased incidence of drowsiness, diplopia, nystagmus, dizziness, light-headness, positive dysphoria and vomiting Suppa et al 2012
  • The addition of IV ketamine compared to placebo for postoperative analgesia showed no benefit in time to first analgesic request, incidence of breakthrough pain and supplemental analgesics Bauchat et al 2011
  • The IV use of different doses of ketamine (0.25 mg/kg, 0.5 mg/kg, 1 mg/kg) compared with placebo produced similar postoperative pain scores and need for supplemental analgesia Bilgen et al 2012
  • Intraoperative IV ketamine (0.5 mg/kg) compared with placebo had no effect on pain relief and morphine consumption between 2 and 24 h Reza et al 2010
  • The administration of IV ketamine 0.5 mg/kg before the skin incision and infused continually at 0.25 mg/kg/h until the end of surgery was not superior to placebo in postoperative pain relief and supplemental fentanyl consumption Han et al 2013
  • Ketamine study details Click here for more information

PROSPECT Recommendations

  • Systemic opioids provide effective analgesia (GoR A, LoE 1), but are only recommended as rescue analgesics due to side effects (GoR D)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • Oral opioid vs IT opioid Click here for more information
  • The administration of subcutaneous pethidine 1 mg/kg followed by subcutaneous pethidine 1 mg/kg with metoclopramide 10 mg IM every 8 h for three days was superior to oral diclofenac sodium 75 mg twice daily for the need for rescue analgesia. However, both groups were not different in pain scores and incidence of PONV Marzida 2009
  • Oral oxycodone and IT morphine were similar for postoperative pain scores, but fewer patients receiving IT morphine requested supplemental analgesia McDonnell et al 2010 Click here for more information
  • Postoperative ketorolac 30 mg IM and postoperative pethidine 75 mg IM showed similar analgesic efficacy and time to first analgesic request, although more side-effects were noted in the pethidine group Gin et al 1993
  • Diclofenac suppository 100 mg after surgery followed by another three doses at 8 h intervals was superior to pethidine 1 mg/kg IM after surgery followed by another three doses at 8 h intervals for pain relief at 10 h, 18 h and 26 h, but not at 2 h. The incidence of PONV was similar between the two groups, but patients receiving pethidine experienced dizziness significantly more frequently Soroori et al 2006
  • Oral opioid versus IT opioid study details Click here for more information
  • Systemic opioid versus conventional NSAID study details Click here for more information
  • Systemic opioid: route of administration study details Click here for more information
  • Systemic opioid vs NSAID
  • Systemic opioid: route of administration
  • Transnasal butorphanol was superior to butorphanol IV in terms of quality and duration of analgesia Abboud et al 1991 Click here for more information
  • Pain relief was significantly greater in the group receiving oral oxycodone-paracetamol compared with the group receiving morphine via iPCA for 12 h and oral oxycodone-paracetamol after 12 h Davis et al 2006
  • The administration of piritramide via iPCA versus oral oxycodone was similar in terms of pain scores, need for supplemental anagesics and in the incidence of PONV Dieterich et al 2012
  • Subcutaneous and IM morphine produced a similar incidence of side effects and pain scores at rest, but pain scores on movement were reduced in the subcutaneous morphine group at 12, 16 and 20 h Safavi and Honarmand 2007

PROSPECT Recommendations

  • Post-delivery paracetamol is recommended (GoR A) based on procedure-specific evidence (LoE 1)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • There were no significant differences in postoperative pain scores and supplemental analgesic use between the IV paracetamol group and the oral ibuprofen group
  • The administration of IV paracetamol at the end of surgery and every 6 h for 24 h was superior to placebo for pain scores at 6, 12 and 24 h and for consumption of rescue analgesia Omar and Issa 2011
  • The postoperative administration of paracetamol and diclofenac was not superior to diclofenac alone and to paracetamol alone in pain scores at rest and on movement. However, patients receiving the combination of paracetamol and diclofenac needed significantly less morphine given via iPCA compared with paracetamol alone, but not compared with diclofenac. The groups did not differ in time to first independent ambulation Munishankar et al 2008
  • Paracetamol study details Click here for more information

PROSPECT Recommendations

  • Bilateral iliohypogastric and ilioinguinal blocks are recommended (GoR A) based on procedure-specific evidence for postoperative analgesia (LoE 1)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • In a systematic review, abdominal nerve blocks were found to reduce pain scores and postoperative opioid requirements vs placebo/no block Bamigboye and Hofmeyr 2009
  • An iliohypogastric-ilioinguinal peripheral nerve block using 0.5% bupivacaine 24 mL compared to saline decreased pain scores and delayed the first request for analgesia Wolfson et al 2012
  • Ilioinguinal and iliohypogastric nerve block with 0.5% ropivacaine was superior to nerve block with saline for pain scores at rest at 6, 8, 12, and 24 h and with movement at 6 and 8 h and led to a decreased supplemental analgesia need without increasing side effects Sakalli et al 2010
  • Ilioinguinal nerve block with 0.5% bupivacaine was superior to no nerve block for pain scores at 0, 4, 8 and 24 h while consumption of supplemental analgesia was decreased Bunting and McConachie 1988
  • Ilioinguinal and iliohypogastric nerve block under ultrasound guidance compared with placebo did not improve postoperative analgesia or decrease postoperative analgesic requirements Vallejo et al 2012
  • Iliohypogastric and ilioinguinal blocks study details Click here for more information

PROSPECT Recommendations

  • Bilateral TAP blocks are recommended (GoR A) based on procedure-specific evidence for postoperative analgesia (LoE 1)
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • US-guided TAP block compared with no block significantly reduced postoperative morphine consumption. There were no differences between the groups in pain scores at rest and on moving, sedation level and PONV Tan et al 2012
  • TAP block compared with no block significantly reduced postoperative tramadol consumption, postoperative pain scores at rest and on coughing Eslamian et al 2012
  • A systematic review comparing TAP block with placebo showed inconsistent results concerning time to first analgesic request, postoperative opioid consumption and postoperative pain scores Fusco et al 2014
  • Spinal morphine 100 µg, but not TAP block, improved postoperative pain relief. The additional use of bilateral TAP block with bupivacaine 2 mg/kg combined with spinal morphine did not further improve postoperative pain relief McMorrow et al 2011
  • TAP block study details Click here for more information

PROSPECT Recommendations

  • TENS is not recommended (GoR D) based on limited procedure-specific evidence
  • Consensus agreement 78% (7/9)

C-Section-Specific Evidence

  • IV morphine-PCA combined with Hi-TENS significantly reduced the consumption of morphine compared with IV morphine-PCA alone. However, there were no significant differences in pain scores between the two groups Binder et al 2011
  • TENS versus placebo-TENS was superior for pain relief at rest and on movement. There was no difference in the request for additional analgesics Smith et al 1986
  • TENS was superior to placebo-TENS for pain relief at 8 h after delivery and associated with a reduced need for supplemental analgesia Kayman-Kose et al 2014
  • TENS study details Click here for more information

PROSPECT Recommendations

  • Wound infiltration with local anaesthetics is recommended (GoR A) based on procedure-specific evidence (LoE 1)
  • Consensus agreement 100% (9/9)
  • Wound infiltration with NSAIDs is not recommended at this time (GoR D) due to limited comparative data with systemic administration
  • Consensus agreement 89% (8/9)
  • Continuous wound infusion with local anaesthetics is recommended (GoR A) based on procedure-specific evidence (LoE 1)
  • Consensus agreement 100% (9/9)
  • Continuous wound infusion with NSAIDs is not recommended (GoR D) based on limited procedure-specific evidence
  • Consensus agreement 100% (9/9)

C-Section-Specific Evidence

  • In a systematic review, wound infiltration with LA reduced opioid use compared with control Bamigboye and Hofmeyr 2009
  • Combined pre- plus post-incisional local wound infiltration with lidocaine was superior to either pre-incisional or post-incisional local wound infiltration alone in postoperative pain scores Fouladi et al 2013
  • The addition of ketorolac to subcutaneous wound instillation of bupivacaine compared with bupivacaine resulted in lower pain scores on movement, but not at rest. However, the addition of hydromorphone to LA wound instillation did not significantly decrease postoperative pain scores at all. The use of supplemental analgesics was significantly lower in the group with additional ketorolac compared to the only bupivacaine group Carvalho et al 2013
  • Ropivacaine wound instillation via an elastometric pump was superior to sterile water in the reduction of postoperative morphine consumption. Pain scores at rest did not differ between the groups during the first 6 h. However, patients receiving ropivacaine had lower pain scores during coughing and leg raising between 3 and 6 h, but not before Fredman et al 2000
  • Continuous wound infusion with ropivacaine for 48 h was superior to epidural morphine for postoperative pain at rest and on movement. Patients receiving epidural morphine experienced significantly more PONV, pruritus and urinary retention O'Neill et al 2012
  • Wound infiltration with tramadol or levobupivacaine was superior to saline for the consumption of supplemental analgesia and for pain relief at 15 min, but not between 2 and 24 h Demiraran et al 2013
  • Continuous wound infusion for 48 h with 0.5% ropivacaine and ketoprofen through a multiholed wound catheter inserted below the fascia resulted in a reduced need for supplemental morphine compared with administration above the fascia. The groups did not differ in pain scores at movement. However, patients receiving administration below the fascia reported lower pain scores at 3, 6, 12, 24 and 36 h, but not at 48 h Rackelboom et al 2010
  • Subcutaneous surgical wound infiltration with bupivacaine 5 mg/mL compared with saline at 2 mL/h for 24 h resulted in similar postoperative pain scores and need for supplemental and rescue analgesia Carvalho et al 2010
  • IT morphine was superior to wound infiltration with ropivacaine or placebo for reducing the consumption of supplemental analgesics Kainu et al 2012 Click here for more information
  • Epidural levobupivacaine was superior to levobupivacaine administered via subfascial catheter in reducing pain scores at rest during the first 4 hours, but not afterwards. However, pain scores at walking and consumption for opioids were similar between the groups Ranta et al 2006
  • The IV system with morphine 10 mg and ketorolac 120 mg was more effective than continuous infusion of 0.2% levobupivacaine in reducing the need for supplemental analgesic and in reducing pain scores Magnani et al 2006
  • Wound infiltration or infusion study details Click here for more information

Colonic Resection 2009

PROSPECT Colonic Resection Subgroup

For each review, a Subgroup of the prospect Working Group performs an initial evaluation of the evidence and also drafts clinical practice statements and recommendations, which are then discussed by the whole Working Group before a final consensus is reached. The Subgroup may sometimes include a non-Working Group member, to provide additional expertise in the procedure being reviewed.

For the colonic resection surgery review (update 2009), the Subgroup members were:

  • Professor Francis Bonnet (PROSPECT Working Group member)
  • Professor Frederic Camu (PROSPECT Working Group member)

Grades of Recommendation

Recommendations are graded according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence: Levels of evidence and grades of recommendation in PROSPECT reviews (from 2006)

PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted.

Summary Recommendations

Pre-, intra- and postoperative interventions have been evaluated for the management of postoperative pain following colonic resection. Unless otherwise stated, ‘pre-operative’ refers to interventions applied before surgical incision, ‘intra-operative’ refers to interventions applied after incision and before wound closure, ‘postoperative’ refers to interventions applied at or after wound closure. The following pre-, intra- and postoperative interventions have been evaluated, for the management of postoperative pain following open colonic resection:

Pre-operative

Recommended:

Systemic analgesia

  • COX-2-selective inhibitors (Grade B) (only for patients who do not receive epidural analgesia)
  • Continuous administration of pre-/intra-operative IV lidocaine if continued during the immediate postoperative period (Grade B), when epidural analgesia is not feasible or contra-indicated

Epidural analgesia

  • Continuous thoracic epidural anaesthesia and analgesia, at a level appropriate to the site of incision are recommended for routine use (Grade A)
  • A combination of strong opioid and local anaesthetic is recommended (Grade A) because of the increased analgesic efficacy of the combination compared with strong opioids alone

Not recommended:

Systemic analgesia 

  • IV clonidine (Grade D) because it is associated with an increased risk of hypotension and bradycardia
  • Conventional NSAIDs (Grade B) because pre-operative administration of these agents can increase the risk of intra- and postoperative bleeding
  • Corticosteroids for analgesia (Grade A) because of procedure-specific evidence showing no significant benefit in reducing pain scores and concerns that they could affect anastomotic and wound integrity (but they may be used for reduction of PONV)
  • Gabapentin/pregabalin (Grade D) due to a lack of procedure-specific evidence
  • Continuous administration of IV lidocaine limited to the pre-/intra-operative period (Grade D) because of inconsistent and insufficient procedure-specific evidence
  • NMDA receptor antagonists (Grade D) because of limited procedure-specifc evidence
  • Strong opioids (Grade B) as they are significantly less effective than postoperative strong opioids for reducing postoperative pain
  • Weak opioids (Grade B) based on procedure-specific evidence that they provide limited postoperative analgesic benefit compared with postoperative administration
  • Calcium channel antagonists (Grade B) based on limited procedure-specific evidence showing a lack of postoperative analgesic effect

Spinal anaesthesia

  • Spinal morphine (Grade D) because of the risk of side effects
  • Spinal clonidine (Grade B) based on procedure-specific evidence showing limited analgesic effect and the risk of side effects

Non-pharmacological therapy

  • Pre-operative use of guided imagery (Grade D) because of limited procedure-specific evidence
  • Laxatives for analgesia (Grade B) because limited procedure-specific evidence shows no analgesic benefit (but they may be used for reasons other than pain relief
  • Pentoxifylline (Grade D) due to limited procedure-specific evidence of its analgesic effect

LA for analgesia

  • Bilateral TAP block (Grade D) because of limited procedure-specific evidence

Intra-operative

Recommended:

Systemic analgesia

  • COX-2-selective inhibitors (Grade B) (only for patients who do not receive epidural anaesthesia)
  • Strong opioids (Grade B) (only for patients who do not receive epidural anaesthesia) 
  • Continuous administration of pre-/intra-operative IV lidocaine if continued during the immediate postoperative period, when epidural analgesia is not feasible or contra-indicated (Grade B)

Epidural analgesia

  • Continuous thoracic epidural anaesthesia and analgesia, at a level appropriate to the site of incision are recommended for routine use (Grade A)
  • Combination of strong opioid and local anaesthetic is recommended (Grade A) based on procedure-specific evidence of their combined efficacy, in reducing postoperative pain and opioid use, compared with LA alone

Operative techniques

  • The decision concerning the type of operative technique or incision to use for colonic resection should be primarily based on factors other than the management of postoperative pain, e.g. malignancy versus benign disease operative risk factors of the patient, risk of wound infection, and availability of surgical expertise (Grade D)
  • Laparoscopic colonic resection is recommended over open colon surgery for reducing postoperative pain, if the conditions outlined above allow (Grade A)
  • Horizontal/curved (transverse) incision is recommended over a vertical incision for analgesic and other benefits if the operative conditions allow (Grade B). In addition, the horizontal/curved incision is preferred for its cosmetic benefits (Grade D)
  • Diathermy is recommended over the scalpel (Grade C)
  • Maintenance of normothermia is recommended for improved clinical outcomes, but it is not helpful for reducing postoperative pain (Grade A)

Not recommended:

Systemic analgesia

  • IV clonidine (Grade D) because it associated with an increased risk of hypotension, sedation and bradycardia
  • Calcium channel antagonists (Grade B), based on limited procedure-specific evidence showing a lack of postoperative analgesic effect
  • Gabapentin/pregabalin (Grade D) due to a lack of procedure-specific evidence
  • Continuous administration of IV lidocaine limited to the pre-/intra-operative period (Grade D) because of inconsistent and insufficient procedure-specific evidence
  • NMDA receptor antagonists (Grade D) because of limited procedure-specific evidence of analgesic efficacy
  • Strong opioids (Grade D), in patients receiving epidural analgesia
  • Weak opioids (Grade D), as placebo-controlled evidence for their benefit in reducing postoperative pain is limited. In patients not receiving epidural analgesia, strong opioids, not weak opioids, are recommended

Epidural analgesia

  • Addition of clonidine to the combination of epidural LA + opioid (Grade D) because of side effects

Spinal analgesia

  • Spinal analgesia in combination with epidural anaesthesia (Grade B) based on a lack of benefit in reducing postoperative pain in colonic resection

Postoperative

Recommended:

Systemic analgesia

  • COX-2-selective inhibitors (Grade B) (only for patients who do not receive epidural analgesia or with the cessation of epidural analgesia)
  • Conventional NSAIDs (Grade A) (only for patients who do not receive epidural analgesia or with cessation of epidural analgesia)
  • IV lidocaine (Grade B) (when epidural is not feasible or contra-indicated)
  • Strong opioids (Grade B) (for high-intensity pain)
  • Weak opioids (Grade B) in association with other non-opioid analgesics (for moderate- or low-intensity pain), or if non-opioid analgesia is insufficient or contra-indicated
  • Paracetamol (Grade B) for moderate- or low-intensity pain (only for patients that do not receive epidural analgesia, or after cessation of epidural analgesia)

Epidural analgesia

  • Continuous thoracic epidural anaesthesia and analgesia at a level appropriate to the site of incision (Grade A)
  • A combination of strong opioid and local anaesthetic is recommended for epidural analgesia (Grade A)

Wound infiltration or infusion

  • Continuous pre-peritoneal infusion of LA, as an alternative when epidural analgesia is not feasible or contra-indicated (Grade B)

Multi-modal rehabilitation protocols

  • Care protocols (which include controlled rehabilitation with early ambulation and diet, or multi-modal optimisation programmes) (Grade A)

Not recommended:

Systemic analgesia

  • Gabapentin/pregabalin (Grade D) due to a lack of procedure-specific evidence
  • NMDA receptor antagonists (Grade D) because of limited procedure-specific evidence of analgesic efficacy
  • IM strong opioids (Grade D)
  • Weak opioids (for controlling high-intensity pain) (Grade B)

Wound infiltration or infusion

  • Continuous postoperative wound infusion with LA (Grade D) as procedure-specific evidence is limited and inconsistent
  • Pre-closure wound infiltration with local anaesthetic (Grade D) due to lack of procedure-specific evidence and inconclusive transferable evidence from other large abdominal surgeries

Multi-modal rehabilitation protocols

  • Mechanical massage with aspiration of abdominal wall (Grade D) as further supportive data are needed
  • Nasogastric tubes (Grade A) because they are associated with discomfort and inconvenience and do not decrease the duration of postoperative ileus

Laparoscopic colonic resection:

Recommended:

Systemic analgesia

  • Conventional NSAIDs (Grade B) based on limited procedure-specific evidence

Epidural analgesia

  • Epidural analgesia is recommended in high-risk pulmonary patients (Grade D)

Wound infiltration/infusion

  • Pre-closure wound infiltration with LA (Grade B)

Operative techniques

  • The decision concerning the type of operative technique or incision to use for colonic resection should be primarily based on factors other than the management of postoperative pain, e.g. malignancy versus benign disease; operative risk factors of the patient; risk of wound infection; and availability of surgical expertise (Grade D)
  • Laparoscopic colonic resection is recommended over open colon surgery for reducing postoperative pain, if the conditions outlined above allow (Grade A)

Not recommended:

Systemic analgesia

  • Continuous intra-/postoperative IV lidocaine (Grade D) because of limited procedure-specific data, despite some postive transferable evidence

Spinal analgesia

  • Combination of spinal analgesia and general anaesthesia (Grade D) as the risk: benefit balance is not positive, and because of limited procedure-specific evidence

Epidural analgesia

  • Epidural LA + strong opioid (Grade D) due to poor risk:benefit ratio

Gasless laparoscopic colectomy

  • Gasless laparoscopy (Grade B) based on procedure-specific evidence showing lack of analgesic effect

Laxatives

  • Laxatives for analgesia (Grade B) because limited procedure-specific evidence shows no analgesic benefit (but they may be used for reasons other than pain relief)

Multi-modal rehabilitation protocols

  • Postoperative restriction of IV fluids (Grade B) due to procedure-specific evidence showing limited analgesic efficacy

See Overall PROSPECT Recommendations for the overall strategy for managing pain after colonic resection

Overall PROSPECT Recommendations for open and laparoscopic colonic resection

Algorithm for the management of postoperative pain

Not recommended for open and laparoscopic colonic resection

This algorithm for treating postoperative pain is based on the PROSPECT Recommendations and illustrates the different treatment pathways for patients with no contra-indications to epidurals, patients with contra-indications to epidurals, patients undergoing laparoscopic colonic resection, as well as describing the steps of the peri-operative pathway and therapies that apply to all patients. Therapies that are not recommended are also indicated.

 

Literature search

 • Systematic review of the literature from 1966–March 2009 using MEDLINE and EmBASE, following the protocol of the Cochrane Collaboration

 • Inclusion of randomised studies assessing analgesic interventions in colonic resection and reporting pain on a linear analogue scale (Colonic Resection Search terms March 2009)

 • Identification of studies of peri-operative interventions for postoperative pain following colonic resection

• 80 studies included (Click here for further information)

• 73 studies excluded (Click here for further information)

• The most common reasons for exclusion were the lack of VAS postoperative pain scores (32 studies), and the lack of a defined subgroup of patients undergoing colonic resection (16 studies)

This website provides recommendations for open and laparoscopic colonic resection. Results from the open and laparoscopic colonic resection studies are dealt with separately, because of the different pain profiles associated with these approaches.

• A majority of the studies assessed the effect of analgesic interventions in open colonic resection with the exception of:

• In five of seven studies, laparoscopic colonic resection was superior to open colonic resection for reducing postoperative pain scores: at rest, during coughing and mobilisation at 6 h (all p<0.05; n=29) (Stage 1997; LoE 2); at rest at 48 h (p<0.01) and during coughing 24–72 h, (p<0.01; n=44) (Danelli 2002; LoE 2); at rest and on coughing within the first week (p<0.02; n=60) (Schwenk 1998; LoE 2) and on Day 1 in two studies (p=0.003; n=403; p<0.05, n=39) (Leung 2004; LoE 1, Liang 2002; LoE 2). One study reported that open colonic resection was superior to laparoscopic colonic resection for the reduction of VAS pain scores at rest and activity at day 1 (p<0.05; n=60), but not from days 2–30 (Basse 2005; LoE 1). Another study showed no significant difference between laparoscopic-assisted colectomy and open colectomy for pain distress scores from baseline to 2 days, 2 weeks and 2 months postoperatively (Weeks 2002; LoE 1)

• In two of three studies, hand-assisted laparoscopic colonic surgery was superior to open colonic surgery for reduction of postoperative pain scores: during the first postoperative week (p<0.001; n=81) (Chung 2007; LoE 1), and on Day 1 (p=0.03), Day 3 and Day 14 (p<0.001; n=60) (Kang 2004; LoE 2); the third study reported no significant difference in postoperative VAS pain scores at rest and during movement on Days 1, 2, 3 and 7, and at Week 4 (n=55) (Maartense 2004; LoE 1)

• In addition, a meta-analysis of randomized clinical trials (comprising of 2512 procedures from 12 trials) comparing the short-term outcomes of laparoscopic with those of open resection for colorectal cancer demonstrated that laparoscopic colonic resection is associated with lower morbidity, reduced pain and/or analgesic consumption, a faster recovery and a shorter hospital stay than open resection, without compromising oncological clearance (Abraham 2004; LoE 1)

Study quality assessments, levels of evidence and grades of recommendation

Recommendations are graded according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence: Levels of evidence and grades of recommendations in PROSPECT reviews (from 2006).

Click here for quality scores and levels of evidence for included procedure-specific studies: Colonic Resection September 2009 Quality Scoring + Levels of Evidence. 

Transferable evidence

Transferable evidence of analgesic efficacy from comparable procedures, or evidence of other outcomes such as adverse effects, has been included to support the procedure-specific evidence where this is insufficient to formulate the recommendations.

Most of the transferable evidence for colonic resection was supplemented from major abdominal surgery and gynaecological procedures.

Quantitative analyses

Overall, few meta-analyses could be performed that used data from more than two studies. This is because there are a limited number of studies of homogeneous design that report similar outcome measures. Therefore, the majority of the procedure-specific evidence was assessed only qualitatively.

Topics for future research

In certain circumstances, recommendations for a type of treatment cannot be made due to limited or conflicting evidence. Areas which have been identified as requiring further investigation in the future are as follows:

  • TAP blocks
  • Alpha-2-delta ligands
  • NMDA receptor antagonists
  • Postoperative continuous LA wound infusion

Abbreviations

AUC

area under curve

GA

general anaesthetic

IM

intramuscular

Intra-op

intra-operatively

IV

intravenous

LA

local anaesthetic

NRS  

numerical rating scale

PACU

post-anaesthesia care unit

PCA   

patient-controlled analgesia

PCEA

patient-controlled epidural analgesia

POD

postoperative day

PONV

postoperative nausea and vomiting

Postop

postoperatively

Pre-op

pre-operatively

VAS   

visual analogue scale

VRS   

verbal rating scale

VNS

verbal numerical scale

In this section, data are available from studies that assessed pre-operative analgesia versus pre-operative placebo, as well as those that examine the concept of pre-emptive – or preventive – analgesia, assessed pre-operative analgesia versus the same analgesia given postoperatively.

A previous systematic review of pre-emptive analgesia for postoperative pain relief in a variety of surgical procedures – such as orthopaedic, dental, gynaecological and abdominal – concluded that there is no benefit of pre-emptive over postoperative administration (Møiniche 2002). More recently, a meta-analysis of studies comparing pre-operative interventions with similar postoperative interventions in various procedures, found that pre-operative epidural analgesia was effective in reducing postoperative pain scores, but that pre-operative NSAIDs, local anaesthetic wound infiltration, NMDA antagonists and opioids did not improve postoperative analgesia (Ong 2005b).

 Despite these findings, it is considered that analgesic medication needs to be initiated in time to ensure an adequate analgesic effect in the immediate postoperative period. This may necessitate administration prior to the postoperative period.

PROSPECT Recommendations

  • Clonidine is not recommended (Grade D), despite limited procedure-specific evidence for analgesic efficacy, because it is associated with an increased risk of hypotension and bradycardia (LoE 4)

Clinical Practice

  • The risk:benefit ratio for clonidine is unclear. Recognised side-effects include hypotension, sedation, dizziness and bradycardia
  • There is no consensus among clinicians on the optimum dose of clonidine that should be used

Transferable Evidence from Other Procedures

Open Colonic Resection-Specific Evidence - Study information

PROSPECT Recommendations

  • Pre-operative COX-2-selective inhibitors are recommended (Grade B) for colonic resection based on procedure-specific evidence that they have an analgesic effect postoperatively (LoE 2), only for patients who do not receive epidural analgesia (LoE 4)
  • It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B): cardiovascular morbidity (transferable evidence, LoE 1), renal function and hepatic function (transferable evidence, LoE 3), or actual or recent gastroduodenal ulcer history (LoE 4). In addition, the potential risk of anastomotic leakage needs to be considered (transferable evidence, LoE 3). Further observations are required regarding the potential risk of N

Clinical Practice

  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries
  • There is no procedure-specific evidence that pre-operative administration of COX-2-selective inhibitors is more effective than postoperative administration

Transferable Evidence from Other Procedures - Study information

  • A pre-operative single bolus of parecoxib was superior to placebo for postoperative pain scores on sitting-up over 24 h (p=0.02), providing a mean decrease of 14 mm in VAS scores on a 100 mm scale in patients undergoing abdominal hysterectomy (n=36)
  • A retrospective cohort study showed that the COX-2-selective inhibitors rofecoxib and celecoxib were associated with a lower risk of acute kidney infection than less-selective NSAIDs
  • A meta-analysis that included data from 17 parecoxib and 15 valdecoxib placebo-controlled trials in non-cardiac surgery showed that there was no significant association between short-term treatment with parecoxib and/or valdecoxib and an increase in cardiovascular thromboembolic adverse events, compared with placebo (n=8511 overall)
  • A review concluded that COX-2-selective inhibitors were as effective as conventional NSAIDs for treatment of postoperative pain in various surgical models, and offer a number of other advantages including: reduced incidence of gastrointestinal ulceration, no inhibitory effect on platelet function (and thereby a reduced risk of blood loss) and no induction of bronchospasm in patients with aspirin-sensitive asthma
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062)
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function
  • A randomised clinical trial showed that the COX-2-selective inhibitor rofecoxib was associated with significantly less intra-operative blood loss than the conventional NSAID diclofenac in patients undergoing abdominal or vaginal hysterectomy or breast surgery
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use
  • Pre-operative oral rofecoxib compared with placebo had significantly lower pain scores at rest and after spirometry at 12 h postoperatively in patients undergoing abdominal surgery (rofecoxib 25 mg and 50 mg versus placebo p<0.05; n=48)
  • COX-2-selective inhibitors are similarly effective compared with conventional NSAIDs for reducing postoperative opioid consumption in patients undergoing abdominal hysterectomy Celik et al 2003 Click here for more information
  • Pre-operative oral COX-2-selective inhibitors were as effective as oral conventional NSAIDs for reducing postoperative pain scores in two studies of patients undergoing abdominal hysterectomy (n=25; n=40)
  • Pre-operative oral rofecoxib was associated with a lower incidence of PONV compared with placebo in one study (p<0.05; n=40)
  • One study found that pre-operative oral etoricoxib was superior to placebo for reducing mean postoperative morphine consumption after 24 h (120 and 180 mg etoricoxib versus placebo, p=0.012) (n=49)
  • A pre-operative single bolus of IV parecoxib or oral rofecoxib reduced morphine consumption over 24 h compared with placebo in patients undergoing abdominal hysterectomy Ng et al 2003 Click here for more information
  • Pre-operative oral etoricoxib was superior to placebo for reducing pain scores at rest and on coughing at a minority of timepoints Chau-in et al 2008 Click here for more information
  • COX-2-selective inhibitors provide similar postoperative analgesia to conventional NSAIDs
  • Pre-operative oral rofecoxib reduced morphine consumption at 24 h postoperatively compared with placebo in patients undergoing abdominal surgery (rofecoxib 25 mg versus placebo p<0.01; n=48)
  • One study in patients undergoing fast-track colonic surgery found that postoperative analgesia with the COX-2-selective inhibitor celecoxib was associated with a higher risk of anastomotic leakage, compared with when celecoxib was not used
  • Although there is some concern COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting (
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents
  • Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo
  • Two meta-analyses comparing pre-incisional and post-incisional NSAIDs/COX-2-selective inhibitors have found no significant benefit of pre-incisional administration for reducing pain scores
  • A pre-operative single bolus of COX-2-selective inhibitor did not significantly reduce postoperative pain scores at rest compared with placebo within 0–24 h in two studies of patients undergoing abdominal hysterectomy (n=40; n=36)

Open Colonic Resection-Specific Evidence – Study information

  • Pre-operative + postoperative oral valdecoxib was superior to placebo for reducing postoperative pain scores Sim et al 2007 Click here for more information
  • Pre-operative parecoxib was superior to placebo for reducing postoperative morphine consumption at a minority of timepoints Lee et al 2008 Click here for more information
  • Pre-operative + postoperative oral valdecoxib was superior to placebo for reducing postoperative morphine consumption Sim et al 2007 Click here for more information
  • The time until first flatus and first bowel movement was significantly shorter with pre-operative + postoperative oral valdecoxib, compared with placebo (p=0.003 and p=0.041, respectively; n=79)
  • The time taken to tolerate a solid diet was significantly shorter with pre-operative + postoperative oral valdecoxib versus placebo (p=0.029; n=79)
  • The length of hospital stay was significantly shorter for patients in the pre-operative + postoperative oral valdecoxib group, compared with the placebo group (p=0.009; n=79)
  • Pre-operative + postoperative administration of oral valdecoxib was associated with superior patient-assessed global evaluation scores (p=0.001; n=79), compared with placebo, but not with surgeon-assessed global evaluation scores
  • Pre-operative IV parecoxib did not confer any significant benefit over intra-operative IV parecoxib or placebo for the reduction of postoperative pain scores Lee et al 2008 Click here for more information
  • There was no significant difference in postoperative morphine consumption between the pre-operative IV parecoxib and intra-operative IV parecoxib groups from 0–48 h postoperatively (n=40)
  • The incidence of postoperative nausea and vomiting, dizziness and pruritus was similar between the pre-operative IV parecoxib, intra-operative IV parecoxib and placebo groups (n=60)
  • The incidence of postoperative sedation and nausea was similar with pre-operative + postoperative oral valdecoxib, and placebo (n=79)
  • Pre-operative + postoperative oral valdecoxib had no significant effect on the time taken to tolerate intake of liquids compared with placebo (n=79)
  • The hospital re-admission rate was similar in both the pre-operative + postoperative oral valdecoxib, and placebo groups (n=79)
  • The incidence of postoperative nausea and vomiting, dizziness and pruritus was similar in the pre-operative IV parecoxib and intra-operative IV parecoxib groups

PROSPECT Recommendations

  • Pre-operative conventional NSAIDs are not recommended (Grade B) despite their analgesic efficacy, because pre-operative administration of these agents can increase the risk of intra- and postoperative bleeding (transferable evidence, LoE 1)
  • In addition, pre-operative conventional NSAIDs are not recommended, because there is evidence from other procedures that pre-operative administration of conventional NSAIDs is no more effective than postincisional administration for reducing pain scores (Grade B) (transferable evidence, LoE 1). In addition, the potential risk of anastomotic leakage needs to be considered (transferable evidence, LoE 3)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures - Study information

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures
  • A meta-analysis of randomised controlled trials performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs, demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression
  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo
  • Pre-operative naproxen was equally as effective as the COX-2-selective inhibitor rofecoxib for reducing postoperative pain scores at rest over 24 h, in patients undergoing abdominal hysterectomy (n=40)
  • A restrospective, case-control study showed that postoperative analgesia with the conventional NSAID diclofenac (150 mg daily) was associated with a significantly higher number of anastomotic leakages than postoperative opioid analgesia in patients undergoing laparoscopic colorectal surgery
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease
  • A randomised clinical trial showed that the conventional NSAID diclofenac was associated with significantly greater intra-operative blood loss than the COX-2-selective inhibitor rofecoxib in patients undergoing abdominal or vaginal hysterectomy or breast surgery
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use
  • Pre-incisional administration of conventional NSAIDs conferred no significant benefit over post-incisional administration for reducing the incidence of PONV in two studies of patients undergoing abdominal hysterectomy (n=65, n=30)
  • Post-incisional NSAID was superior to pre-incisional NSAID for extending the time to first analgesic request in one study (n=30)
  • Of three studies in abdominal hysterectomy, all showed no significant difference between pre-incisional and post-incisional conventional NSAIDs for supplementary analgesic consumption (n=65; n=30; n=77)
  • Two of three studies showed no significant difference between single bolus conventional NSAIDs administered before or after incision for postoperative pain scores in patients undergoing abdominal hysterectomy Nakayama et al 2001a Click here for more information
  • Two meta-analyses comparing pre-incisional and post-incisional NSAIDs/COX-2-selective inhibitors have found no significant benefit of pre-incisional administration for reducing pain scores
  • Pre-operative rofecoxib was superior to naproxen for reducing the use of postoperative supplementary analgesics within 12–18 h (p<0.05), but there was no significant difference within 0–24 h in patients undergoing abdominal hysterectomy

Open Colonic Resection-Specific Evidence

  • Pre-operative + postoperative IV flurbiprofen was superior to placebo for reducing postoperative pain scores Xu et al 2008 Click here for more information
  • Pre-operative + postoperative IV flurbiprofen axetil was superior to placebo for reducing the time to first pass of flatus and first bowel movement (both p=0.01; n=40)
  • The incidence of postoperative nausea and vomiting was similar in the pre-operative + postoperative flurbiprofen axetil and placebo groups (n=40)

PROSPECT Recommendations

  • Pre-operative corticosteroids are not recommended for analgesia (Grade A) because of procedure-specific evidence showing no significant benefit in reducing VAS pain scores (LoE 1) and concerns that they could affect anastomotic and wound integrity (LoE 4). However, they may be used for reduction of PONV (transferable evidence, LoE 1)

Clinical Practice

  • Nausea and vomiting are frequent in abdominal surgeries, and corticosteroids may be used for their anti-emetic effects in patients at risk
  • A single pre-operative high-dose bolus of corticosteroid may be considered in high-risk pulmonary patients
  • Corticosteroids are not used in routine clinical practice because of the concerns that they could affect anastomotic and wound integrity

Transferable Evidence from Other Procedures - Study information

  • A single prophylactic dose of corticosteroid is effective for preventing PONV in surgery associated with high emetic effects
  • A review of major abdominal surgery, a randomised study of patients at high-risk of nausea and vomiting undergoing surgery, and a systematic review of drugs that prevent PONV, all showed that corticosteroids decrease PONV
  • IV methylprednisolone significantly improved postoperative recovery outcomes compared with placebo in abdominal surgery Krantz et al 1990 Click here for more information
  • A meta-analysis showed that a single pre-operative dose of IV methylprednisolone (15–30 mg/kg) was associated with significantly fewer pulmonary complications compared with placebo or no treatment, but data on postoperative pain could not be meta-analysed Sauerland et al 2000 Click here for more information
  • IV methylprednisolone (30 mg/kg) significantly decreased pulmonary complications compared with placebo in one study identified in a review of major abdominal surgery
  • Corticosteroids did not significantly decrease pain compared with placebo in two studies identified in a review of major abdominal surgery

Open Colonic Resection-Specific Evidence - Study information

  • IV methylprednisolone sodium succinate (30 mg/kg) given 90 min before induction of anaesthesia significantly improved mobilisation and recovery compared with IV placebo (p<0.05) Schulze et al 1997 Click here for more information
  • IV methylprednisolone sodium succinate (30 mg/kg) given 90 min before induction of anaesthesia significantly improved pulmonary function (as measured by peak flow, forced vital capacity, and forced expiratory volume) compared with IV placebo 6 hours postoperatively (p<0.05; n=24)
  • IV methylprednisolone sodium succinate (30 mg/kg) given 90 min before induction of anaesthesia and epidural analgesia did not confer a significant benefit over IV placebo for cumulative VAS pain scores Schulze et al 1997 Click here for more information
  • Pre-operative IV dexamethasone did not confer a significant benefit over placebo for reduction of VAS pain scores at rest at any time point assessed (4 and 8 h, Days 1, 2 and 3) (n=27)
  • Pre-operative IV dexamethasone had no signficant effect on postoperative IM morphine (10 mg) requirements, compared with placebo (n=27)
  • Incidence of postoperative nausea and vomiting was similar in the pre-operative IV dexamethasone and placebo groups (n=27)
  • There were no significant differences in the time to first flatus, first bowel sound or first bowel movement with pre-operative IV dexamethasone versus placebo (n=27)
  • The length of hospital stay was similar for patients in the pre-operative IV dexamethasone and placebo groups (n=27)

PROSPECT Recommendations

  • Gabapentin/pregabalin cannot be recommended at this time (Grade D, LoE 4) due to a lack of procedure-specific evidence, although analgesic data from other procedures are promising

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Four systematic reviews and a meta-analysis evaluated the use of gabapentinoids for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls
  • Two systematic reviews
  • Two systematic reviews

Open Colonic Resection-Specific Evidence

  • [No data found within the parameters of the systematic review]

PROSPECT Recommendations

  • Continuous administration of IV lidocaine limited to the pre-/intra-operative period is not recommended (Grade D, LoE 4) because of inconsistent and insufficient procedure-specific evidence (LoE 1)
  • Continuous administration of pre/intra-operative IV lidocaine is recommended if continued during the immediate postoperative period, when epidural analgesia is not feasible or contra-indicated (Grade B), based on transferable evidence (LoE 1) and limited procedure-specific evidence (LoE 2) for recovery benefits, compared with control (see Intra-operative and Postoperative IV lidocaine sections)

Clinical Practice

  • IV lidocaine can be considered as an alternative when there are contra-indications to epidural analgesia techniques
  • Further evidence is needed to precisely define the role of IV lidocaine in this setting, including direct comparisons with epidural analgesia
  • IV lidocaine may induce hypotension
  • If IV lidocaine is used it is recommended that safety data are taken into account

Transferable Evidence from Other Procedures

  • [None cited]

Open Colonic Resection-Specific Evidence - Study information

  • Pre-/intra-operative IV lidocaine reduced postoperative pain scores at rest and on coughing at a minority of time points compared with control Kuo et al 2006 Click here for more information
  • Pre-/intra-operative IV lidocaine significantly reduced postoperative morphine requirement compared with control Kuo et al 2006 Click here for more information
  • Pre-/intra-operative IV lidocaine significantly reduced intra-operative fentanyl requirement compared with control Kuo et al 2006 Click here for more information
  • Pre-/intra-operative IV lidocaine was associated with a lower incidence of morphine-related nausea or vomiting compared with control (p<0.01; n=40)
  • Pre-/intra-operative IV lidocaine significantly reduced the time to first flatus, compared with the control group (p<0.01; n=40)
  • Peri-operative IV lidocaine significantly reduced the time to first flatus, compared with the control group (p<0.05; n=60)
  • The time to first bowel movement was significantly shorter with peri-operative IV lidocaine, compared with the control (p<0.05; n=60)
  • Peri-operative IV lidocaine significantly reduced the time taken to solid food intake compared with the control (p<0.001; n=60)
  • Peri-operative IV lidocaine significantly reduced the duration of hospital stay compared with the control (p=0.004; n=60)
  • Pre-/intra-operative IV lidocaine conferred no significant benefit over control for reducing the length of hospital stay (n=40)
  • Peri-operative IV lidocaine conferred no significant benefit over the control for the reduction of VAS pain scores at rest or during movement at any of the time points assessed (n=60)
  • Peri-operative IV lidocaine conferred no significant benefit over control for reducing the consumption of PCA IV piritramide (2 mg dose with a lockout period of 10 minutes) (n= 60)

PROSPECT Recommendations

  • Pre-operative NMDA receptor antagonists are not recommended (Grade D, LoE 4) because of limited procedure-specific evidence of analgesic efficacy

Clinical Practice

  • There is a lack of clinical experience with NMDA receptor antagonists. Moreover, NMDA receptor antagonists are associated with adverse events, e.g. ketamine is known for its increased risk of CNS side effects

Transferable Evidence from Other Procedures

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine
  • In patients undergoing laparoscopic cholecystectomy, dextromethorphan (pre- incisional and post gallbladder removal) was superior to control for reducing VAS scores, reducing the use of supplementary analgesics, and increasing the time to first analgesic request
  • Low-dose ketamine was associated with few and mild adverse effects, especially when administered in conjunction with general anaesthesia
  • A systematic review found that dextromethorphan did not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases
  • Two meta-analyses comparing pre-incisional and postincisional treatments found no significant analgesic benefit of pre-incisional administration of NMDA receptor antagonists
  • Two systematic reviews of randomised controlled trials comparing magnesium with placebo demonstrated inconclusive results overall with regards to pain scores and supplemental analgesic use

Open Colonic Resection-Specific Evidence - Study information

  • IM dextromethorphan was superior to control for reducing postoperative pain scores during coughing at 1, 2, 4, 8 and 24 h (p<0.001; n=60), although there were no significant differences in resting pain scores between the groups at any time point assessed
  • IM dextromethorphan was more effective than control for reducing postoperative opioid requirements Yeh et al 2005 Click here for more information
  • IM dextromethorphan significantly reduced the time to passage of first flatus, compared with the control (p<0.0001; n=60)
  • IV magnesium provided no significant benefit over placebo for reducing the following postoperative outcomes: pain scores at rest or during movement; morphine requirements for 0–24 h; sedation scores 0–48 h; incidence of nausea and vomiting; time to first bowel movement; and time to first flatus (n=47)
  • The incidence of morphine-related side-effects (drowsiness, dizziness, nausea, vomiting and pruritus) was similar in both the IM dextromethorphan and control groups (n=60)
  • Dextromethorphan conferred no significant benefit over control for reducing the length of hospital stay (n=60)

PROSPECT Recommendations

  • Pre-operative administration of strong opioids is not recommended (Grade B) for colonic resection as they are significantly less effective than postoperative strong opioids for reducing postoperative pain (transferable evidence, LoE 1)

Clinical Practice

  • [None Cited]

Transferable Evidence from Other Procedures - Study information

  • Pre-incisional strong opioids showed no significant benefit over post-incisional strong opioids for reducing postoperative pain scores (LoE 1) Fassoulaki et al 1995 Click here for more information
  • Pre-incisional strong opioids did not confer a significant benefit over post-incisional strong opioids for reducing supplementary analgesic consumption in patients undergoing abdominal hysterectomy (LoE 1) Kilickan et al 2001 Click here for more information
  • Pre-incisional strong opioids provided no significant benefit over post-incisional strong opioids for increasing the time to first analgesic request in three studies of patients undergoing abdominal hysterectomy reporting this parameter (n=34, n=85, n=39)
  • A meta-analysis of studies comparing pre-operative interventions with similar postoperative interventions in various procedures found that pre-operative NSAIDs and local anaesthetic wound infiltration improved analgesic consumption and time to first rescue analgesic request, but not pain scores. Evidence did not support an improvement in postoperative analgesia following administration of pre-operative NMDA antagonists and opioids
  • Pre-incisional strong opioids were associated with a similar incidence of PONV to post-incisional strong opioids in patients undergoing abdominal hysterectomy (n=34, n=40, n=60)

Open Colonic Resection-Specific Evidence

  • [No data found within the parameters of the systematic review]

PROSPECT Recommendations

  • Pre-operative administration of weak opioids is not recommended (Grade B) based on procedure-specific evidence that it has limited postoperative analgesic benefit compared with postoperative administration (LoE 2)

Clinical Practice

  • Tramadol 300 mg is considered to be a clinically effective dose, and therefore the 100 mg dose used in the study by Wordliczek et al. is probably too low to provide sufficient pain relief

Transferable Evidence from Other Procedures

  • A systematic review of pre-emptive analgesia for postoperative pain relief in a variety of surgical procedures – such as orthopaedic, dental, gynaecological and abdominal – has concluded that there is no benefit of pre-emptive over postoperative administration
  • A meta-analysis of studies comparing pre-operative interventions with similar postoperative interventions in various procedures found that pre-operative NSAIDs and local anaesthetic wound infiltration improved analgesic consumption and time to first rescue analgesic request, but not pain scores. Evidence did not support an improvement in postoperative analgesia following administration of pre-operative NMDA antagonists and opioids

Open Colonic Resection-Specific Evidence - Study information

  • Pre-operative administration of IV tramadol was superior to administration immediately after peritoneal closure or postoperatively for reducing total tramadol consumption (p<0.05; n=90)
  • Pre-, or intra-operative IV tramadol 100 mg did not confer any benefit for reducing postoperative pain scores compared with postoperative IV tramadol 100 mg Wordliczek et al 2002 Click here for more information
  • Pre-operative administration of IV tramadol resulted in a significantly shorter time to first analgesic request compared with administration immediately after peritoneal closure, or immediately following surgery (p<0.01; n=90)
  • Tramadol 100 mg administered pre- or intra-operatively, did not confer any benefit for reducing the incidence of PONV compared with postoperative IV tramadol 100 mg (n=90)

PROSPECT Recommendations

  • Continuous thoracic epidural anaesthesia and analgesia at a level appropriate to the site of incision are recommended for routine use (Grade A), based on superior postoperative analgesic and safety benefits compared with systemic techniques (procedure-specific evidence, LoE 1, also see Intra-operative and Postoperative Epidural Analgesia sections), except in a minority of patients with a contra-indication to epidural administration
  • Pre-operative administration of a single-shot epidural analgesia produces a similar postoperative analgesic efficacy to postoperative administration
  • Where epidural techniques are used, it is recommended that a combination of strong opioid and local anaesthetic is used (Grade A) because of the increased analgesic efficacy of the combination compared with strong opioids alone and to reduce the dose of strong opioid and its associated side-effects (procedure-specific evidence, LoE 1, see Intra-operative and Postoperative Epidural Analgesia sections)
  • Where epidural techniques are used, it is recommended that the epidural catheter is inserted pre-operatively because this is the most practical timing for insertion (Grade D, LoE 4)

Clinical Practice

  • In colonic surgery, the analgesic and recovery benefits of an epidural outweigh the risks of rare major complications and warrant the use of this more labour-intensive treatment
  • Where epidural techniques are used, the most practical timing for insertion of the epidural catheter is pre-operatively
  • 1 mg epidural morphine is considered inadequate to block visceral pain; however, larger doses are likely to cause bladder dysfunction. Therefore, pre-operative epidural administration of local anaesthetic with opioids is preferred to opioids alone

Transferable Evidence from Other Procedures - Study information

  • Pre-operative epidural morphine bolus was superior to epidural saline placebo for reducing postoperative pain scores at rest and on movement at 1 and 6 h (p<0.05 for all comparisons; n=36) in patients undergoing abdominal hysterectomy
  • Pre-operative epidural morphine bolus was superior to epidural saline placebo for reducing postoperative supplementary analgesic consumption at 6 and 12 h (p<0.05 for both times; n=36) in patients undergoing abdominal hysterectomy
  • Pre-operative epidural morphine bolus was superior to epidural saline placebo for extending the time to first analgesic request (p<0.05; n=36) in patients undergoing abdominal hysterectomy
  • Pre-operative epidural morphine and placebo were not different for the incidence of postoperative nausea in patients undergoing abdominal hysterectomy (n=36)
  • Pre- plus intra-operative epidural ropivacaine was superior to placebo for reducing intra-operative sufentanil in major abdominal tumour surgery (p<0.001; n=30)
  • Pre- plus intra-operative epidural ropivacaine provided no significant benefit over placebo for reducing postoperative pain scores for 0–96 h following major abdominal tumour surgery (both groups received postoperative epidural) (n=30)
  • Pre- plus intra-operative epidural ropivacaine provided no significant benefit over placebo for reducing supplementary analgesic consumption for 0–96 h following major abdominal tumour surgery (both groups received postoperative epidural) (n=30)
  • Pre- plus intra-operative epidural ropivacaine provided no significant benefit over placebo for reducing side-effects for 0–96 h following major abdominal tumour surgery (both groups received postoperative epidural) (n=30)
  • Pre-incisional epidural analgesia provided no significant benefit for reducing postoperative pain scores compared with post-incisional administration in a variety of abdominal procedures (LoE 1) Abdel-Ghaffar et al 1998 Click here for more information
  • Evidence for the benefit of pre-incisional compared with post-incisional epidural analgesia for reducing supplementary analgesic consumption in abdominal procedures is inconsistent (LoE 4) Espinet et al 1996 Click here for more information

Open Colonic Resection-Specific Evidence - Study information

  • Pre-operative bolus epidural morphine 1 mg plus postoperative parenteral analgesia was superior to postoperative parenteral analgesia alone on the day of surgery for VAS scores Simpson et al 1993 Click here for more information
  • Adding pre-operative bolus epidural morphine reduced parenteral opioid consumption on the first and second postoperative day compared with parenteral analgesia alone (p=0.002 and p=0.07, respectively; n=13)
  • Adding pre-operative bolus epidural morphine increased the time to first request of analgesia compared with parenteral analgesia alone (p=0.03; n=13)
  • Pre-operative + postoperative epidural clonidine was superior to control for the reduction of postoperative pain scores Wu et al 2004 Click here for more information
  • Pre-operative + postoperative epidural clonidine was superior to control for reducing postoperative analgesic requirement Wu et al 2004 Click here for more information
  • Pre-operative + postoperative epidural clonidine significantly reduced the time to return of normal bowel function, compared with control (p<0.001; n=40)
  • The incidence of morphine-associated nausea, vomiting, and itching was significantly lower with pre-operative + postoperative epidural clonidine, compared with control (p<0.001; n=40)
  • Epidural LA plus morphine 40 min before surgical incision conferred no significant benefit over administration at wound closure for reducing postoperative VAS pain scores Dahl et al 1992 Click here for more information
  • Epidural LA plus morphine given 40 min before surgical incision was similar to that given at closure for level of sensory block to pinprick for 0–72 h (n=32)
  • The length of hospital stay was similar for patients in the pre-operative + postoperative epidural clonidine and control groups (n=40)

PROSPECT Recommendations

  • Spinal morphine is not recommended (Grade D) because of the risk of side-effects (LoE 4)
  • Spinal clonidine is not recommended (Grade B) because of limited analgesic effect (procedure-specific evidence LoE 2) and the risk of side-effects (LoE 4)

Clinical Practice

  • Spinal morphine may produce some postoperative pain relief but also produces risk of PONV and prolongation of postoperative ileus, and limited duration of analgesic effect

Transferable Evidence from Other Procedures

  • [None Cited]

Open Colonic Resection-Specific Evidence - Study information

  • The incidence of postoperative nausea or vomiting was similar with pre-operative spinal morphine + IV PCA morphine, compared with PCA morphine alone (n=52)
  • Spinal bupivacaine was superior to placebo for reducing postoperative PCA morphine consumption Click here for more information
  • Spinal bupivacaine significantly reduced the area of hyperalgesia around the incision site, compared with placebo, at 24, 48, and 72 h postoperatively (p<0.05; n=40)
  • Pre-operative spinal bupivacaine significantly reduced the incidence of postoperative residual pain, compared with placebo, at 2 weeks, and after 1 month (p<0.05; n=40)
  • Spinal clonidine was superior to placebo for reducing postoperative morphine requirements Click here for more information
  • Spinal clonidine was superior to placebo for reducing postoperative pain at a minority of time points Click here for more information
  • Pre-operative spinal morphine + IV PCA morphine was superior to IV PCA morphine alone for reducing postoperative pain scores Click here for more information
  • Intra-operative IV sufentanil requirements were similar in the spinal morphine and spinal morphine + sufentanil groups (n=77)
  • There was no significant difference in patient satisfaction (VAS scale 1–100) with pre-operative spinal morphine versus spinal morphine + sufentanil (n=77)
  • Incidence of postoperative nausea and vomiting was similar between the pre-operative spinal morphine group and the pre-operative spinal morphine + sufentanil group (n=77)
  • There was no significant difference in postoperative PCA morphine consumption with spinal morphine versus spinal morphine + sufentanil in the PACU, or at 24 or 48 h postoperatively (n=77)
  • There were no significant differences between the spinal morphine and spinal morphine + sufentanil groups for VAS pain scores at rest and coughing during the first 48 h postoperatively (n=77)
  • Spinal bupivacaine conferred no significant benefit over placebo for reducing VAS pain scores at rest, mobilisation or during coughing at any of the time points assessed (2, 6 and 12 h, Days 1, 2 and 3) (n=40)
  • Spinal clonidine conferred no significant benefit over spinal bupivacaine for reducing VAS pain scores at rest, mobilisation or during coughing at any of the time points assessed (2, 6 and 12 h, Days 1, 2 and 3) (n=40)
  • The incidence of intra-operative adverse haemodynamic events was significantly greater with pre-operative spinal clonidine compared with pre-operative spinal bupivacaine or placebo (p<0.05) (n=20/group)
  • Spinal clonidine versus placebo
  • Spinal bupivacaine versus placebo
  • Spinal morphine versus spinal morphine + sufentanil
  • Pre-operative spinal morphine + IV PCA morphine versus IV PCA morphine alone
  • Spinal clonidine versus spinal bupivacaine

PROSPECT Recommendations

  • Bilateral TAP block is not recommended at the current time (Grade D, LoE 4) because of limited procedure-specific evidence, despite some positive transferable evidence (LoE 1)

Clinical Practice

  • The single-shot TAP block technique may provide effective postoperative analgesia but the duration is limited. Despite this, further study evidence is expected which may support the use of this technique

Transferable Evidence from Other Procedures

  • Unilateral TAP block significantly reduced postoperative VAS pain scores and postoperative morphine consumption compared with control, in patients undergoing open appendicectomy (n=52)
  • Bilateral TAP block with ropivacaine significantly reduced postoperative VAS pain scores, postoperative morphine consumption and the incidence of postoperative sedation, compared with placebo, in patients undergoing abdominal hysterectomy (n=50)

Open Colonic Resection-Specific Evidence - Study information

  • Pre-operative bilateral TAP block was superior to control for reducing postoperative pain scores Click here for more information
  • Pre-operative bilateral TAP block was superior to control for reducing postoperative morphine requirements Click here for more information
  • Pre-operative bilateral TAP block significantly reduced postoperative sedation scores, compared with control, at 4 and 6 h postoperatively (p=0.01), although there was no significant difference between the groups at 2 and 24 h, or in the PACU
  • Pre-operative bilateral TAP block was associated with a significantly higher incidence of PONV, compared with control (p<0.05)

PROSPECT Recommendations

  • Pre-operative use of guided imagery is not recommended (Grade D, LoE 4) because of limited procedure-specific evidence, despite some evidence of analgesic effect (LoE 1)

Clinical Practice

  • [None Cited]

Transferable Evidence from Other Procedures

  • Pre-operative use of guided imagery was significantly more effective for reducing postoperative pain intensity (p<0.05), distress from pain (p<0.01) and the ability to cope with pain (p<0.01) compared with routine postoperative care, in patients undergoing abdominal surgery (n=51)
  • Pre-operative use of guided imagery resulted in significantly lower supplementary analgesic consumption over 0–48 h compared with routine postoperative care (p<0.05; n=51)

Open Colonic Resection-Specific Evidence - Study information

  • One of two studies showed that care by guided imagery was more effective than standard care for reducing postoperative pain scores Click here for more information
  • One of two studies found that care by guided imagery was more effective than routine postoperative care for reducing postoperative analgesic requirements Click here for more information
  • One of two studies showed that care by guided imagery was more effective than routine postoperative care for reducing time to first bowel movement Click here for more information
  • Guided imagery tapes provided no significant benefit over relaxation tapes for reducing VAS pain scores at rest or coughing during postoperative Days 1–4 (n=38)
  • Relaxation tapes provided no significant benefit over routine postoperative care for the reduction of VAS pain scores at rest or coughing during postoperative Days 1–4 (n=40)
  • There was no significant difference in the total analgesic consumption or the number of analgesic requests between patients in the relaxation and guided imagery groups (n=42)
  • Time to first flatus and first bowel movement was similar for patients in the guided imagery and relaxation groups (n=42)
  • Time to first flatus and first bowel movement was similar for patients in the relaxation and routine care groups (n=42)
  • One study found that care by guided imagery provided no benefit over routine postoperative care for reducing the median length of hospital stay, postoperative ileus or the incidence of nausea or vomiting (n=130)

PROSPECT Recommendations

  • Laxatives are not recommended for analgesia (Grade B) because limited procedure-specifc evidence shows no analgesic benefit (LoE 2), but they may be used for reasons other than pain relief (LoE 4)

Clinical Practice

  • [None Cited]

Transferable Evidence from Other Procedures

  • Time until first defecation and GI recovery were significantly shorter with biscodyl versus placebo (p=0.001 and p=0.007, respectively; n=169)
  • Pre-operative + postoperative administration of biscodyl provided no significant benefit over placebo for the reduction of VAS pain scores (n=169)
  • There was no significant difference in the level of opioid consumption between patients who received bisacodyl or placebo during the first 8 postoperative days (n=169)
  • The incidence of postoperative cramping and nausea was similar in the biscodyl and placebo groups (n=169)
  • Biscodyl conferred no significant benefit over placebo for reducing the length of hospital stay (n=169)

Open Colonic Resection-Specific Evidence - Study information

  • [None Cited]

PROSPECT Recommendations

  • Pre-operative pentoxifylline is not recommended (Grade D, LoE 4) due to limited procedure-specific evidence of its analgesic effect

Clinical Practice

  • Further studies are needed to recommend the use of pentoxifylline in clinical practice

Transferable Evidence from Other Procedures

  • [None Cited]

Open Colonic Resection-Specific Evidence - Study information

  • Pre-operative IV pentoxifylline was superior to placebo for the reduction of VAS pain scores during coughing after 1, 2, and 4 h, and on Days 1 and 2 (p<0.05; n=40), however, there was no siginificant difference between the groups for resting pain scores at each of the time points assessed (1, 2, 4 h and Days 1, 2 and 3)
  • Pre-operative IV pentoxifylline was superior to placebo for reducing morphine consumption during Days 1–3 (p<0.0001; n=40)
  • Pre-operative IV pentoxifylline was superior to placebo for extending the time until first PCA morphine trigger (p<0.0001; n=40)
  • Pre-operative IV pentoxifylline was superior to placebo for reducing the time until first flatus
  • Pre-operative IV pentoxifylline was superior to placebo for reducing inflammatory cytokines related to postoperative pain
  • The incidence of morphine-related adverse effects (drowsiness, dizziness, nausea, and vomiting) was similar in both the pre-operative IV pentoxifylline and placebo groups

PROSPECT Recommendations

  • Intra-operative COX-2-selective inhibitors are recommended (Grade B) for colonic resection based on procedure-specific evidence that they have an analgesic effect postoperatively (LoE 2), only for patients who do not receive epidural analgesia (LoE 4)
  • It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B) (cardiovascular morbidity [transferable evidence, LoE 1], renal function and hepatic function [transferable evidence, LoE 3], or actual or recent gastroduodenal ulcer history [LoE 4]). In addition, the potential risk of anastomotic leakage needs to be considered (transferable evidence, LoE 3). Further observations are required regarding the potential risk of NSAIDs and

Clinical Practice

  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries
  • There is no procedure-specific evidence that intra-operative administration of COX-2-selective inhibitors is more effective than postoperative administration

Transferable Evidence from Other Procedures - Study information

  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use
  • A retrospective cohort study showed that the COX-2-selective inhibitors rofecoxib and celecoxib were associated with a lower risk of acute kidney infection than less-selective NSAIDs
  • A meta-analysis that included data from 17 parecoxib and 15 valdecoxib placebo-controlled trials in non-cardiac surgery showed that there was no significant association between short-term treatment with parecoxib and/or valdecoxib and an increase in cardiovascular thromboembolic adverse events, compared with placebo (n=8511 overall)
  • A review concluded that COX-2-selective inhibitors were as effective as conventional NSAIDs for treatment of postoperative pain in various surgical models, and offer a number of other advantages including: reduced incidence of gastrointestinal ulceration, no inhibitory effect on platelet function (and thereby a reduced risk of blood loss) and no induction of bronchospasm in patients with aspirin-sensitive asthma
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062)
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function
  • A randomised clinical trial showed that the COX-2-selective inhibitor rofecoxib was associated with significantly less intra-operative blood loss than the conventional NSAID diclofenac in patients undergoing abdominal or vaginal hysterectomy or breast surgery
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation
  • COX-2-selective inhibitors provide similar postoperative analgesia to conventional NSAIDs
  • A pre-operative single bolus of COX-2-selective inhibitor did not significantly reduce postoperative pain scores at rest compared with placebo within 0–24 h in two studies of patients undergoing abdominal hysterectomy (n=40; n=36)
  • Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication
  • Although there is some concern COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting
  • One study in patients undergoing fast-track colonic surgery found that postoperative analgesia with the COX-2-selective inhibitor celecoxib was associated with a higher risk of anastomotic leakage, compared with when celecoxib was not used

Open Colonic Resection-Specific Evidence - Study information

  • Intra-operative parecoxib was superior to placebo for the reduction of postoperative morphine consumption Click here for more information
  • Intra-operative IV parecoxib (40 mg) conferred some benefit over placebo for the reduction of postoperative resting pain scores Click here for more information
  • There were no significant differences between the intra-operative IV parecoxib and pre-operative IV parecoxib groups for NRS pain scores at rest, or during coughing, during the first 48 h postoperatively
  • Intra-operative IV parecoxib conferred no significant benefit over placebo for reducing PCA morphine consumption in the recovery room
  • There was no significant difference in postoperative morphine consumption between the intra-operative IV parecoxib group and the pre-operative IV parecoxib group within 0–48 h after surgery
  • The incidence of postoperative nausea and vomiting, dizziness and pruritus was similar between the intra-operative IV parecoxib, pre-operative IV parecoxib, and placebo groups

PROSPECT Recommendations

  • Clonidine is not recommended (Grade D), despite limited procedure-specific evidence for analgesic efficacy, because it is associated with an increased risk of hypotension, sedation and bradycardia (LoE 4)

Clinical Practice

  • The risk/benefit ratio for clonidine is unclear. Recognised side effects include hypotension, sedation, dizziness and bradycardia
  • There is no consensus among clinicians on the optimum dose of clonidine that should be used

Transferable Evidence from Other Procedures

Open Colonic Resection-Specific Evidence - Study information

  • IV clonidine given before skin incision, or before peritoneal incision, was superior to fentanyl given before skin incision for postoperative analgesic outcomes Click here for more information

PROSPECT Recommendations

  • Pre- or intra-operative calcium channel antagonists are not recommended (Grade B), based on limited procedure-specific evidence showing a lack of postoperative analgesic effect (LoE 2)

Clinical Practice

  • Clinical experience with calcium channel antagonists is lacking

Transferable Evidence from Other Procedures

  • [None Cited]

Open Colonic Resection-Specific Evidence - Study information

  • IV nimodipine conferred no significant benefit over placebo for postoperative pain scores at rest or movement 0–120 h postoperatively, except at 72 h when a reduction in movement pain reached significance (n=47)
  • Oral nifedipine was significantly inferior to placebo for postoperative pain scores at rest at 16 and 24 h (p<0.05; n=46)
  • Nimodipine or nifedipine provided no significant benefit over placebo for reducing the following postoperative outcomes: morphine requirements for 0–24 h; sedation scores for 0–48 h; the incidence of nausea and vomiting; time to first bowel movement and time to first flatus (n=69)

PROSPECT Recommendations

  • Gabapentin/pregabalin cannot be recommended at this time (Grade D, LoE 4) due to a lack of procedure-specific evidence, although analgesic data from other procedures are promising

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Four systematic reviews and a meta-analysis evaluated the use of gabapentinoids for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls
  • Two systematic reviews
  • Two systematic reviews

Open Colonic Resection-Specific Evidence

  • [No data found within the parameters of the systematic review]

PROSPECT Recommendations

  • Continuous administration of IV lidocaine limited to the pre/intra-operative period is not recommended (Grade D) because of inconsistent and insufficient procedure-specific evidence
  • Continuous administration of pre/intra-operative IV lidocaine continuous administration is recommended if continued during the immediate postoperative period when epidural analgesia is not feasible or contra-indicated (Grade B), based on transferable evidence (LoE 1) and limited procedure-specific evidence (LoE 2) for recovery benefits compared with control

Clinical Practice

  • IV lidocaine can be considered as an alternative when there are contra-indications to epidural analgesia techniques
  • Further evidence is needed to precisely define the role of IV lidocaine in this setting, including direct comparisons with epidural analgesia
  • IV lidocaine may induce hypotension
  • If IV lidocaine is used it is recommended that safety data are taken into account

Transferable Evidence from Other Procedures - Study information

  • A meta-analysis of randomised clinical trials performed to evaluate the effect of continuous IV lidocaine infusion during and after abdominal surgery reported that lidocaine significantly reduced postoperative VAS pain scores, duration of postoperative ileus, incidence of PONV, and length of hospital stay, compared with the controls

Open Colonic Resection-Specific Evidence - Study information

  • Pre-/intra-operative IV lidocaine reduced postoperative pain scores compared with control Click here for more information
  • Pre-/intra-operative IV lidocaine significantly reduced postoperative morphine requirement compared with control Click here for more information
  • Pre-/intra-operative IV lidocaine significantly reduced intra-operative fentanyl requirement compared with control Click here for more information
  • Pre-/intra-operative IV lidocaine was associated with a lower incidence of morphine-related nausea or vomiting compared with control (p<0.01; n=40)
  • Pre-/intra-operative IV lidocaine significantly reduced the time to first flatus compared with the control group (p<0.01; n=40)
  • Peri-operative IV lidocaine significantly reduced the time to first flatus compared with the control group (p<0.05; n=60)
  • The time to first bowel movement was significantly shorter with peri-operative IV lidocaine compared with the control (p<0.05; n=60)
  • Peri-operative IV lidocaine significantly reduced the time taken to solid food intake, compared with the control (p<0.001; n=60)
  • Peri-operative IV lidocaine significantly reduced the duration of hospital stay, compared with the control (p=0.004; n=60)
  • Pre-/intra-operative IV lidocaine conferred no significant benefit over control for reducing the length of hospital stay (n=40)
  • Peri-operative IV lidocaine conferred no significant benefit over the control for the reduction of VAS pain scores at rest or during movement at any of the time points assessed (n=60)
  • Peri-operative IV lidocaine conferred no significant benefit over control for reducing the consumption of PCA IV piritramide (2 mg dose with a lockout period of 10 minutes) (n= 60)

PROSPECT Recommendations

  • Intra-operative NMDA receptor antagonists are not recommended (Grade D, LoE 4) because of limited procedure-specific evidence of analgesic efficacy

Clinical Practice

  • There is a lack of clinical experience with NMDA receptor antagonists. Moreover, NMDA receptor antagonists are associated with adverse events, e.g. ketamine is known for its increased risk of CNS side effects

Transferable Evidence from Other Procedures

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine
  • In patients undergoing laparoscopic cholecystectomy, dextromethorphan (pre- incisional and post gallbladder removal) was superior to control for reducing VAS scores, reducing the use of supplementary analgesics, and increasing the time to first analgesic request
  • Low-dose ketamine was associated with few and mild adverse effects, especially when administered in conjunction with general anaesthesia
  • A systematic review found that dextromethorphan did not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases
  • Two meta-analyses comparing pre-incisional and postincisional treatments found no significant analgesic benefit of pre-incisional administration of NMDA receptor antagonists
  • Two systematic reviews of randomised controlled trials comparing magnesium with placebo demonstrated inconclusive results overall with regards to pain scores and supplemental analgesic use (

Open Colonic Resection-Specific Evidence - Study information

  • Intra-operative ketamine was superior to placebo for reducing postoperative pain scores in the first 15 min (p<0.05), decreasing morphine use for 0–24 h compared with placebo (p<0.01), and extending the time to first analgesic request (p<0.001) compared with placebo (n=50)
  • IV magnesium provided no significant benefit over placebo for reducing the following postoperative outcomes: pain scores at rest or during movement; morphine requirements for 0–24 h; sedation scores 0–48 h; incidence of nausea and vomiting; time to first bowel movement; and time to first flatus (n=47)

PROSPECT Recommendations

  • In patients undergoing colonic resection and receiving epidural anaesthesia, intra-operative administration of systemic, long-acting strong opioids to provide postoperative analgesia is not recommended (Grade D, LoE 4)
  • However, in patients not indicated for epidural anaesthesia, systemic intra-operative strong opioids are recommended to provide early postoperative pain relief (Grade B), based on transferable evidence (LoE 1) of analgesic efficacy

Clinical Practice

  • [None Cited]

Transferable Evidence from Other Procedures - Study information

  • Intra-operative strong opioid provided a benefit over placebo up to 4 h for reducing postoperative pain scores at rest (one of three studies) and reducing the supplementary analgesic consumption (three studies), but showed no significant difference for the time to first analgesic request (one study), in patients undergoing hysterectomy Click here for more information

Open Colonic Resection-Specific Evidence - Study information

  • Low-dose remifentanil infusion plus titrated desflurane conferred a benefit for reducing postoperative pain scores at 3 and 4 h compared with a high-dose remifentanil infusion plus fixed-dose desflurane (both times p<0.05; n=49)
  • Low-dose remifentanil infusion plus titrated desflurane was superior for reducing cumulative supplementary analgesic consumption compared with a high-dose remifentanil infusion plus fixed-dose desflurane (p<0.01; n=49)
  • Low-dose remifentanil infusion plus titrated desflurane increased the number of patients classified as 'calm' compared with a high-dose remifentanil infusion plus fixed-dose desflurane Click here for more information
  • Low-dose remifentanil infusion plus titrated desflurane had a similar time to first request of supplementary analgesia and a similar incidence of PONV compared with a high-dose remifentanil infusion plus fixed-dose desflurane (n=49)
  • Sufentanil anaesthesia was superior to remifentanil anaesthesia plus intra-operative bolus IV morphine for reducing postoperative pain scores at 2 h, but the scores were similar from 2–12 h (p<0.01; n=30)
  • Sufentanil anaesthesia was superior to remifentanil anaesthesia plus intra-operative bolus IV morphine for the reduction of supplementary analgesic consumption in the PACU and at 4, 12 and 24 h (p<0.05; n=30)
  • Sufentanil anaesthesia was superior to remifentanil anaesthesia plus intra-operative bolus IV morphine for extending the time to first analgesic request (p<0.05; n=30)
  • Sufentanil anaesthesia was similar to remifentanil anaesthesia plus intra-operative bolus IV morphine for the incidence of PONV and sedation scores (n=30)
  • Remifentanil infusion at a low-dose compared with remifentanil infusion at a high-dose was associated with a similar percentage of sedated patients Click here for more information

PROSPECT Recommendations

  • Intra-operative systemic weak opioids are not recommended (Grade D, LoE 4), as placebo-controlled evidence for their benefit in reducing postoperative pain is limited. Moreover, epidural LA + strong opioid is the regimen recommended for routine use in patients undergoing colonic resection
  • In patients not receiving epidural anaesthesia, intra-operative strong opioids, not weak opioids, are recommended to provide early postoperative pain relief (Grade B, see Intra-operative Strong Opioid section)

Clinical Practice

  • Tramadol 300 mg is considered to be a clinically effective dose, and therefore the 100 mg dose used in the study by Wordliczek et al. is likely to be too low to provide sufficient pain relief

Transferable Evidence from Other Procedures - Study information

  • Intra-operative IV tramadol was superior to placebo for reducing tramadol use and postoperative pain scores in the PACU following abdominal surgery (p<0.05 for all comparisons; n=60)
  • Intra-operative IV tramadol was superior to placebo for reducing the incidence (p<0.05) and severity (p<0.05) of PONV following abdominal surgery (n=60)
  • For patients undergoing laparoscopic cholecystectomy, intra-operative tramadol IV at wound closure was superior to control for reducing VAS scores, reducing the use of supplementary analgesics and increasing the time to first analgesic request
  • Intra-operative IV tramadol was similar to placebo for the number of postoperative PCA boluses delivered and total tramadol consumption (n=60)

Open Colonic Resection-Specific Evidence - Study information

  • Administration of IV tramadol immediately after peritoneal closure, or immediately following surgery extended the time to first analgesic request compared with pre-operative administration (p<0.01; n=90)
  • Pre-, or intra-operative IV tramadol 100 mg did not confer any benefit for reducing postoperative pain scores compared with postoperative IV tramadol 100 mg Click here for more information
  • Tramadol 100 mg administered pre- or intra-operatively, did not confer any benefit for reducing the incidence of PONV compared with postoperative IV tramadol 100 mg (n=90)
  • Pre-operative administration of IV tramadol was superior to administration immediately after peritoneal closure or postoperatively for reducing total tramadol consumption (p<0.05; n=90)

PROSPECT Recommendations

  • Continuous thoracic epidural anaesthesia and analgesia is recommended (Grade A) for routine use in colonic resection based on its benefit in reducing postoperative pain, systemic opioid use and bowel recovery time (procedure-specific evidence, LoE 1)
  • A combination of epidural local anaesthetic (LA) and strong opioid is recommended for epidural analgesia (Grade A), based on procedure-specific evidence of their combined efficacy in reducing postoperative pain and systemic opioid use, compared with LA alone (LoE 1). However, the addition of opioid to epidural LA results in an increase in time to first bowel movement (LoE 1)
  • Addition of clonidine to the combination of epidural LA + opioid is not recommended (Grade D) because of side effects, despite favourable effects on pain scores

Clinical Practice

  • Thoracic epidural is considered to be more appropriate than lumbar epidural for anaesthesia and analgesia in colonic resection
  • Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications
  • A minority of patients may need to receive general anaesthesia plus systemic analgesia due to a contra-indication to the epidural technique

Transferable Evidence from Other Procedures

  • [None Cited]

Open Colonic Resection-Specific Evidence - Study information

  • Epidural LA and strong opioid produced a significant reduction in the use of supplementary analgesia compared with GA plus systemic analgesia in two studies (p<0.05, n=64; p<0.001, n=20)
  • Cumulative number of satisfied analgesic requests was significantly lower with intra-/postoperative epidural bupivacaine-sufentanil-clonidine + intra-operative IV ketamine, compared with intra-operative IV lidocaine-sufentanil-clonidine + intra-operative IV ketamine + postoperative IV lidocaine-morphine-clonidine, from 24–72 h after surgery (p<0.05; n=40), but not at 12 h
  • Intra-/postoperative epidural bupivacaine-sufentanil-clonidine was superior to intra-operative IV lidocaine-sufentanil-clonidine + postoperative IV lidocaine-morphine-clonidine for reducing postoperative pain Click here for more information
  • The addition of opioid to epidural LA conferred a benefit over epidural LA alone in reducing postoperative pain scores in two studies Click here for more information
  • Epidural lidocaine was associated with a lower incidence of morphine-related nausea or vomiting, compared with control (p<0.01; n=40)
  • Epidural lidocaine was superior to control for reducing the time until first flatus (p<0.01; n=40)
  • The proportion of patients receiving intra-operative epidural lidocaine that required an intra-operative fentanyl supplement, was significantly lower compared with the control group (n=40)
  • Epidural lidocaine was superior to the control for reducing postoperative opioid requirement Click here for more information
  • Epidural lidocaine was more effective than the control for the reduction of postoperative pain scores Click here for more information
  • GA + intra-operative epidural lidocaine + postoperative PCEA significantly reduced the time to first flatus compared with GA alone + postoperative PCEA (p<0.0001; n=60)
  • GA + intra-operative epidural lidocaine + postoperative PCEA was more effective than GA alone + postoperative PCEA for reducing postoperative opioid requirements Click here for more information
  • GA + intra-operative epidural lidocaine + postop PCEA was superior to GA alone + postop PCEA for reducing VAS pain scores on coughing at a minority of time points Click here for more information
  • A meta-analysis of randomised studies performed to compare the effect of local anaesthetic epidural analgesia with parenteral opioid analgesia in patients undergoing colorectal surgery, reported that epidural analgesia significantly reduced postoperative VAS pain scores at 24 h (11 studies analysed, n=630) and 48 h postoperatively (6 studies analysed, n=281) (p<0.001 for both comparisons)
  • Epidural LA and opioid showed a significant benefit for reducing postoperative pain scores compared with GA plus systemic analgesia in six studies Click here for more information
  • Epidural LA and strong opioid was superior to GA plus systemic analgesia for increasing the time to first request of supplementary analgesia in one study (p<0.005; n=20)
  • Epidural LA plus opioid was associated with a similar length of hospital stay compared with GA plus systemic analgesia in two studies (n=42, n=20)
  • Epidural LA plus opioid produced a significantly quicker time for first flatus and time for first bowel movement compared with GA plus systemic analgesia in two studies (all p<0.05; n=64, n=42)
  • Epidural bupivacaine plus morphine was associated with recovery of gastrointestinal function and fulfilled discharge criteria approximately 1.5 days earlier compared with GA and IV plus postoperative PCA morphine (p<0.005; n=26)
  • Epidural bupivacaine plus morphine had a similar incidence of orthostatic hypotension compared with GA and IV plus postoperative PCA morphine (n=26)
  • Two studies demonstrated that epidural bupivacaine conferred a benefit over general anaesthesia and systemic analgesia for reducing postoperative pain scores at rest for 1–72 h in one study (all p<0.05; n=116)
  • Epidural bupivacaine administration resulted in significantly fewer patients requiring supplementary analgesia compared with GA plus systemic analgesia for 1–48 h postoperatively (p<0.05; n=116)
  • Epidural bupivacaine administration resulted in significantly more patients having a bowel movement by Day 4 compared with GA plus systemic analgesia (p<0.05; n=116)
  • Epidural bupivacaine was associated with recovery of gastrointestinal function and fulfilled discharge criteria approximately 1.5 days earlier compared with GA and IV bolus plus postoperative PCA morphine (p<0.005; n=26)
  • A meta-analysis of 11 randomised studies showed that the duration of gastrointestinal dysfunction was significantly shorter with epidural analgesia, compared with parenteral opioid analgesia (n=510, p<0.001)
  • Epidural infusion of opioid was similar to GA and IV plus postoperative PCA morphine for postoperative pain scores
  • Epidural morphine was associated with a similar incidence of nausea and orthostatic hypotension compared with GA and IV plus postoperative PCA morphine (n=24)
  • Epidural bupivacaine was associated with an increased incidence of orthostatic hypotension compared with GA and IV plus postoperative PCA morphine (p<0.05) (n=26)
  • Epidural bupivacaine had a similar incidence of nausea compared with GA and IV plus postoperative PCA morphine (n=26)
  • A meta-analysis of randomised studies performed to compare the effect of local anaesthetic epidural analgesia with parenteral opioid analgesia in patients undergoing colorectal surgery, found no significant difference in the incidence of PONV (5 studies analysed; n=189), anastomotic leakage (7 studies analysed; n=459), or length of hospital stay (n=716)
  • Epidural lidocaine + GA conferred no significant benefit over GA alone for reducing the length of hospital stay (n=60)
  • There was no significant difference in the incidence of morphine-related side-effects (drowsiness, dizziness, nausea, vomiting and pruritus) with epidural lidocaine + GA versus GA alone (n=60)
  • Epidural lidocaine conferred no significant benefit over the control for reducing the length of hospital stay (n=40)
  • Epidural LA plus strong opioid showed no difference in the incidence of nausea and vomiting compared with GA plus systemic analgesia in four studies Click here for more information
  • Intra-/postoperative epidural bupivacaine-sufentanil-clonidine + intra-operative IV ketamine was associated with a higher incidence of orthostatic hypotension at first mobilisation, compared with intra-operative IV lidocaine-sufentanil-clonidine + intra-operative IV ketamine + postoperative IV lidocaine-morphine-clonidine (p=0.05; n=40)

PROSPECT Recommendations

  • Spinal analgesia is not recommended in combination with epidural anaesthesia (Grade B), based on a lack of benefit in reducing postoperative pain in colonic resection (LoE 2). Moreover, it introduces a greater level of complexity (LoE 4)

Clinical Practice

  • [None Cited]

Transferable Evidence from Other Procedures

  • [None Cited]

Open Colonic Resection-Specific Evidence - Study information

  • Combined spinal/thoracic epidural anaesthesia conferred no additional benefit over peri-operative thoracic epidural infusion alone for postoperative pain scores at rest and on coughing from 4–24 h (n=20)
  • Combined spinal/thoracic epidural anaesthesia compared with continuous epidural infusion alone were similar for supplementary analgesic consumption (n=20)

PROSPECT Recommendations

  • No recommendation can be made about general anaesthetic techniques for open colonic resection because of limited procedure-specific evidence

Clinical Practice

  • For laparoscopic procedures, the use of nitrous oxide may result in increased bowel distension

Transferable Evidence from Other Procedures

  • One randomised study investigating the efficacy of prophylactic antimetic interventions in patients undergoing surgery with general anaesthesia concluded that the risk of PONV was 12% greater with N2O compared with nitrogen
  • One randomised study comparing nitrous oxide-based anaesthesia with nitrous oxide-free anaesthesia in patients undergoing major surgery, found that the avoidance of nitrous oxide decreased the incidence of postoperative complications, but did significantly reduce the length of hospital stay (Myles 2007)

Open Colonic Resection-Specific Evidence - Study information

  • Two studies reported that postoperative VAS pain scores were significantly lower with nitrogen compared with nitrous oxide after 2 h (p=0.02; n=344 and p=0.014; n=408)
  • Two studies reported that VAS nausea scores were significantly lower with nitrogen compared with nitrous oxide (p=0.04; n=344 and p=0.007; n=408)
  • One study reported that moderate-to-severe bowel distension was significantly less common in patients following GA with nitrogen, compared with nitrous oxide (p<0.001; n=344)
  • Nitrous oxide was superior to intra-operative IV remifentanil for the reduction of VAS pain scores on arrival in the PACU (p<0.05; n=60), but not after 5, 10 or 15 min
  • Two studies reported no significant difference in the level of PCA opioid consumption (piritramide) between patients receiving GA with nitrogen or nitrous oxide (n=344; n=408)
  • Two studies showed that the incidence of postoperative nausea and vomiting was similar with nitrous oxide and nitrogen (n=344; n=408)
  • There was no significant difference in the time to first flatus, first bowel movement, or first intake of solid food between patients in the groups receiving GA with nitrogen or nitrous oxide (n=408)
  • The length of hospital stay was similar for patients in the groups that received general anaesthesia with nitrogen and general anaesthesia with nitrous oxide (n=408)
  • There were no significant differences between the nitrous oxide and intra-operative IV remifentanil groups in VAS pain scores at rest or movement from 0–24 h postoperatively (n=60)
  • There was no significant difference between the nitrous oxide and intra-operative IV remifentanil groups for postoperative morphine consumption in the PACU, or during the first postoperative day (n=60)
  • There was a similar incidence of postoperative nausea and vomiting between patients receiving nitrous oxide and IV remifentanil (n=60)

PROSPECT Recommendations

  • The decision concerning the type of operative technique or incision to use for colonic resection should be primarily based on factors other than the management of postoperative pain, e.g. malignancy versus benign disease; operative risk factors of the patient; risk of wound infection; and availability of surgical expertise (Grade D, LoE 4)
  • Laparoscopic colonic resection is recommended over open colon surgery for reducing postoperative pain (Grade A), if the conditions outlined above allow, based on procedure-specific evidence (LoE 1).
  • See laparoscopic section for recommendations on pain management for laparoscopic colonic resection
  • A horizontal/curved (transverse) incision is recommended over a vertical incision for analgesic and other benefits, if the operative conditions allow (Grade B) based on limited procedure-specific evidence (LoE 2) and transferable evidence. In addition, the horizontal/curved incision is preferred for its cosmetic benefits (Grade D, LoE 4)
  • Diathermy is recommended over the scalpel (Grade B), based on analgesic benefits as well as greater speed of incision and less blood loss (transferable evidence, LoE 2)

Clinical Practice

  • The decision to employ a laparoscopic versus open approach for colonic surgery is based on multiple factors such as the indication for surgery (e.g. benign or malignant disease) and surgical expertise, as well as the desired outcomes
  • If the surgical indication allows, a transverse incision is preferred for abdominal procedures such as colonic resection

Transferable Evidence from Other Procedures

  • The transverse incision was similar to the vertical incision for access to intra-abdominal structures and resulted in significantly less postoperative pain and a lower incidence of pulmonary complications; however, vertical laparotomy is associated with a shorter operating time and better possibilities for extension of the incision, as found in a systematic review in abdominal surgery
  • Laparotomy incisions using diathermy had significantly lower VAS scores at 48 h (p<0.05), morphine consumption over the first 5 days (p<0.04), less blood loss (p=0.002), and were associated with a faster speed of incision (p<0.04) compared with scalpel incisions in patients undergoing elective midline laparotomy (n=100)
  • Laparoscopic surgery resulted in an increased operating time, but reduced postoperative pain, hospital stay and return to normal activity compared with open surgery, as demonstrated in a number of reviews of the literature of patients undergoing resection for colonic cancer, cholecystectomy, appendectomy (systematic) and groin hernia (systematic)

Open Colonic Resection-Specific Evidence - Study information

  • A transverse incision was similar to a midline vertical incision for the time to resume normal diet, time to first bowel movement and duration of hospital stay (n=40)
  • One study showed that hand-assisted laparoscopic colectomy was superior to open colectomy for reducing the time until first oral food intake (p<0.05, n=60)
  • Two studies showed that hand-assisted laparoscopic colectomy was superior to open colectomy for reducing the length of hospital stay (p=0.004, n=81; p<0.001, n=60)
  • Hand-assisted laparoscopic colectomy was superior to open colectomy for reducing the time to first flatus and first bowel movement Click here for more information
  • Hand-assisted laparoscopic colectomy was superior to open colectomy for reducing supplementary analgesic consumption Click here for more information
  • Hand-assisted laparoscopic colectomy was superior to open colectomy for the reduction of postoperative pain scores Click here for more information
  • A systematic review comparing laparoscopic versus open total mesorectal excision for rectal cancer reported that one of two randomised controlled studies showed laparoscopic surgery was superior for reducing postoperative pain scores
  • A systematic review comparing laparoscopic with open surgery for colorectal cancer, concluded that laparoscopic surgery was associated with less blood loss, less postoperative pain, less postoperative analgesic consumption, faster return to normal bowel function, and a shorter hospital stay
  • A systematic review of laparoscopic resection of colon cancer, combined with expert opinion, concluded that pain is less severe and that less analgesia is required after laparoscopic resection than open resection
  • Meta-analysis of twelve studies showed that laparoscopic resection reduced morbidity, wound infection, time to recovery and hospital stay compared with open resection
  • A meta-analysis of seven studies reporting analgesic outcomes showed a significant benefit of laparoscopic resection over open colonic resection for reduced pain at rest and on coughing, and reduced analgesic requirement for up to 3 days (not all studies recorded pain scores)
  • One study reported that there was no significant difference in the incidence of PONV between the laparoscopic colonic resection and open colonic resection techniques (n=60)
  • Laparoscopic resection was superior to open colonic resection for reducing length of hospital stay in four of five studies Click here for more information
  • Laparoscopic resection was superior to open colonic resection for reducing time to first flatus and bowel movement in three studies Click here for more information
  • Laparoscopic resection was superior to open colonic resection for reducing supplementary analgesic consumption Click here for more information
  • Laparoscopic resection was superior to open colonic resection for reducing postoperative pain scores Click here for more information
  • A transverse incision conferred significant benefit over a midline vertical incision for reducing postoperative pain on movement on Days 1 and 3, and reducing supplementary analgesic consumption (all p<0.05); however, both incision techniques were similar for postoperative pain scores at rest (n=40)
  • A systematic review comparing laparoscopic versus open total mesorectal excision for rectal cancer reported that two of three randomised studies found no significant difference between laparoscopic and open techniques for reducing postoperative analgesic consumption. However, there was a trend for less analgesia in the laparoscopic group
  • Hand-assisted laparoscopic proctocolectomy conferred no significant benefit over open proctocolectomy for reducing VAS pain scores at rest and during movement on Days 1, 2, 3 and 7, and at Week 4 (n=55)
  • There was no significant difference in the postoperative morphine requirement between patients who received hand-assisted laparoscopic proctocolectomy versus open proctolectomy at 24, 48 or 72 h (n=55)
  • Hand-assisted laparoscopic proctocolectomy conferred no significant benefit over open proctolectomy for reducing the time taken for patients to return to normal fluid or food consumption (n=55)

PROSPECT Recommendations

  • Maintenance of normothermia is recommended (Grade A) for improved clinical outcomes (procedure-specific evidence, LoE 1) but it is not helpful for reducing postoperative pain (LoE 1)

Clinical Practice

  • Although there are no benefits for pain reduction, keeping patients normothermic has benefits for reducing oxygen consumption and decreasing myocardial work, which is important for elderly patients and those at risk of cardiac events

Transferable Evidence from Other Procedures - Study information

  • One study showed that aggressive warming was superior to conventional warming in total hip arthroplasty for reducing intra-operative and total blood loss (p=0.002), but no difference in postoperative blood loss was observed (n=150)
  • A randomized controlled trial in high-risk patients showed that maintenance of normothermia reduced the incidence of morbid cardiac events in the peri-operative period compared with routine thermal care (p=0.02, n=300)
  • Maintenance of normothermia decreased the post-anaesthetic recovery time compared with routine thermal management (p<0.001, n=150) in patients undergoing abdominal surgery
  • Maintenance of normothermia may prevent adverse effects of mild hypothermia, which reduces resistance to wound infection, is associated with increased protein wasting and decreased collagen synthesis, reduces platelet function and impairs coagulation, increases the incidence of morbid cardiac events, decreases drug metabolism, increases anaesthetic recovery time, and induces shivering
  • Patients kept normothermic showed no significant difference in postoperative pain scores compared with patients kept hypothermic during elective major abdominal surgery (n=150)

Open Colonic Resection-Specific Evidence - Study information

  • Patients kept normothermic required significantly less bupivacaine to maintain adequate epidural blockade than patients kept hypothermic in one study (p=0.006; n=30)
  • Maintenance of normothermia was associated with higher comfort scores and a similar heart rate and blood pressure than maintenance of hypothermia in one study (n=74)
  • Maintenance of normothermia was associated with lower incidence of wound infections, fewer transfusions and quicker suture removal and hospital discharge compared with maintenance of hypothermia (p=0.01 for all outcomes) (n=200)
  • Patients kept normothermic were similar to patients kept hypothermic for postoperative pain scores in three studies (n=74, n=200, n=30)

PROSPECT Recommendations

  • COX-2-selective inhibitors are recommended (Grade B) based on limited procedure-specific evidence (LoE 2) and transferable evidence (LoE 1). They should be given in combination with strong opioids for high-intensity pain, or with weak opioids for moderate- or low-intensity pain (Grade D, LoE 4), only for patients who do not receive epidural analgesia or with cessation of epidural analgesia (Grade D, LoE 4)
  • COX-2-selective inhibitors may be preferred to conventional NSAIDs in the peri-operative setting, in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (Grade B, transferable evidence, LoE1) or who have NSAID-induced asthma (transferable, LoE 1)
  • The use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B), cardiovascular morbidity (transferable evidence, LoE 1), actual or recent gastroduodenal ulcer history (LoE 4), renal function and hepatic function (transferable evidence, LoE 3). In addition, the potential risk of anastomotic leakage should be considered (transferable evidence, LoE 3). Further observations are required regarding the potential risk of NSAIDs and COX-2-selective inhibitors o

Clinical Practice

  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Transferable Evidence from Other Procedures

  • COX-2-selective inhibitors provide similar postoperative analgesia to conventional NSAIDs
  • Parecoxib 20 or 40 mg IV every 12 h reduced supplementary analgesic consumption compared with placebo in patients undergoing major gynaecological surgery (p<0.05; n=60)
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062)
  • A meta-analysis that included data from 17 parecoxib and 15 parecoxib placebo-controlled trials in non-cardiac surgery, showed that there was no significant association between short-term treatment with parecoxib and/or valdecoxib and an increase in cardiovascular thromboembolic adverse events, compared with placebo (n=8511 overall)
  • A retrospective cohort study showed that the COX-2-selective inhibitors rofecoxib and celecoxib were associated with a lower risk of acute kidney infection than less-selective NSAIDs
  • Parecoxib 20 or 40 mg IV every 12 h did not significantly reduce postoperative pain scores compared with placebo in patients undergoing major gynaecological surgery (p<0.05; n=60)
  • Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting
  • One study in patients undergoing fast-track colonic surgery found that postoperative analgesia with the COX-2-selective inhibitor celecoxib was associated with a higher risk of anastomotic leakage, compared with when celecoxib was not used

Open Colonic Resection-Specific Evidence

  • Pre-operative + postoperative oral valdecoxib was superior to placebo for reducing postoperative pain scores Click here for more information
  • Pre-operative + postoperative oral valdecoxib was superior to placebo for reducing postoperative morphine requirement Click here for more information
  • Pre-/postoperative oral valdecoxib was associated with superior patient-assessed global evaluation scores (p=0.001; n=79), compared with placebo, but not with surgeon-assessed global evaluation scores
  • The time until first flatus and first bowel movement was significantly shorter with pre-/postoperative oral valdecoxib, compared with placebo (p=0.003 and p=0.041, respectively)
  • The time taken to tolerate solids was significantly shorter with pre-operative + postoperative oral valdecoxib versus placebo (p=0.029)
  • The length of hospital stay was significantly shorter for patients in the pre-/ postoperative oral valdecoxib group, compared with the placebo group (p=0.009)
  • The incidence of postoperative sedation or nausea was similar with pre-/ postoperative oral valdecoxib, and placebo (n=79)
  • Pre-operative + postoperative oral valdecoxib had no significant effect on the time taken to tolerate intake of liquids compared with placebo
  • The hospital re-admission rate was similar for patients in the pre-/ postoperative oral valdecoxib and placebo groups

PROSPECT Recommendations

  • Conventional NSAIDs are recommended (Grade A), for their analgesic and opioid-sparing effect (procedure-specific evidence, LoE 1). They should be given in combination with strong opioids for high-intensity pain, or with weak opioids for moderate- or low-intensity pain (Grade D, LoE 4), only for patients who do not receive epidural analgesia or with cessation of epidural analgesia (Grade D, LoE 4)
  • Conventional NSAIDs are not recommended in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (Grade B, transferable evidence, LoE 1)
  • The use of conventional NSAIDs should depend upon assessment of individual patient risks (Grade B), including bleeding complications, actual or recent gastroduodenal ulcer history (transferable evidence, LoE 1), cardiovascular morbidity (LoE 4), aspirin-sensitive asthma, renal function and hepatic function (transferable evidence, LoE 3)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures - Study information

  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression
  • Six out of eight studies showed a significant benefit of postoperative conventional NSAIDs compared with placebo for reducing postoperative pain scores in patients undergoing hysterectomy Click here for more information
  • Conventional NSAIDs conferred a significant benefit over placebo for reducing supplementary analgesia requirements over 24 h or more in patients undergoing abdominal hysterectomy Click here for more information
  • Conventional NSAIDs were superior to placebo for reducing morphine consumption in abdominal surgery but did not consistently reduce pain scores in two studies in abdominal surgery Click here for more information
  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo
  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures
  • A restrospective, case-control study showed that postoperative analgesia with the conventional NSAID diclofenac (150 mg daily) was associated with a significantly higher number of anastomotic leakages than postoperative opioid analgesia in patients undergoing laparoscopic colorectal surgery
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease. Aspirin-induced asthma occurs in approximately 4–10% of the adult asthmatic population
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use
  • Diclofenac 50 mg IM bolus pre-operatively then postoperatively at 4 and 10 h, plus epidural analgesia using bupivacaine 0.5% continually infused at 8 mL/h did not confer a benefit for extending the time to first analgesic request compared with epidural analgesia alone in patients undergoing abdominal hysterectomy (n=26)
  • Conventional NSAIDs and placebo were not significantly different for the incidence of PONV (all groups received background strong opioid) in patients undergoing abdominal surgery Click here for more information
  • Results were inconsistent for conventional NSAIDs compared with placebo for the time to first analgesic request following abdominal hysterectomy Click here for more information
  • Two of three studies showed no significant analgesic benefit of conventional NSAIDs plus epidural analgesia compared with epidural analgesia alone Click here for more information

Open Colonic Resection-Specific Evidence - Study information

  • Pre-operative + postoperative IV flurbiprofen was superior to placebo for reducing postoperative pain scores Click here for more information
  • Pre-operative + postoperative IV flurbiprofen axetil was superior to placebo for reducing the time to first pass of flatus and first bowel movement (both p=0.01; n=40)
  • Regular IM ketorolac was superior to regular IV morphine for reducing supplementary PCA morphine use 0–24 h and total morphine consumption 0–72 h (p=0.001; n=30)
  • IM ketorolac (PRN) was superior to IM morphine (PCA or PRN) alone for reducing postoperative pain scores at 3–6 h and 18–110 h (dosing regimens not clear) (all p<0.05; n=90)
  • IM ketorolac (PRN) was superior to IM morphine (PCA or PRN) for reducing the time to first flatus (p<0.05) and length of hospital stay (dosing regimens not clear) (p<0.01; n=90)
  • IM ketorolac was superior to IM ketorolac plus IM or IV morphine on demand for reducing the length of time taken to recover from postoperative ileus (2.3 ± 0.5 days versus 4.2 ± 0.6 days; p<0.05; n=14)
  • IV PCA morphine + ketorolac was superior to IV PCA morphine alone for reducing total morphine consumption (p<0.05; n=74); however there was no significant difference between the groups for the duration of IV PCA morphine use
  • IV PCA morphine + ketorolac significantly reduced the time to first mobilisation, compared with IV PCA morphine alone (p<0.05; n=74)
  • IV PCA morphine + ketorolac significantly reduced the time to first bowel movement, compared with IV PCA morphine alone (P<0.05; n=74)
  • The incidence of postoperative nausea and vomiting was similar in the pre-operative + postoperative flurbiprofen axetil and placebo groups (n=40)
  • IM ketorolac plus PCA morphine conferred no significant benefit over PCA morphine alone for reducing postoperative pain scores, time to first flatus, time to first bowel movement and tolerance to liquids and regular diet (n=30)
  • There were no significant differences between the groups receiving IV PCA morphine or IV PCA morphine + ketorolac for VAS pain scores at rest or movement during postoperative Days 1–3 (n=74)
  • IV PCA morphine + ketorolac conferred no significant benefit over IV PCA morphine alone for reducing the time to first flatus (n=74)
  • The incidence of morphine-related side-effects (pruritus, nausea and vomiting and dizziness) was similar in the groups receiving IV PCA morphine + ketorolac or IV PCA morphine alone (n=74)
  • IV PCA morphine + ketorolac and IV PCA morphine alone were associated with a similar length of hospital stay (n=74)

PROSPECT Recommendations

  • Gabapentin/pregabalin cannot be recommended at this time (Grade D, LoE 4) due to a lack of procedure-specific evidence, although analgesic data from other procedures are promising

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Four systematic reviews and a meta-analysis evaluated the use of gabapentinoids for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls
  • Two systematic reviews
  • Two systematic reviews

Open Colonic Resection-Specific Evidence

  • [No data found within the parameters of the systematic review]

PROSPECT Recommendations

  • Postoperative IV lidocaine is recommended (Grade D, LoE 4) for open colonic resection when epidural analgesia is not feasible or contra-indicated (Grade B) based on transferable evidence (LoE 1) and limited procedure-specific evidence (LoE 2) for recovery benefits compared with control

Clinical Practice

  • IV lidocaine can be considered as an alternative when there are contra-indications to epidural analgesia techniques
  • If IV lidocaine is used it is recommended that safety data be taken into account
  • IV lidocaine may induce hypotension
  • Further evidence is needed to precisely define the role of IV lidocaine in this setting, including direct comparisons with epidural analgesia

Transferable Evidence from Other Procedures

  • A meta-analysis of randomised clinical trials performed to evaluate the effect of continuous IV lidocaine infusion during and after abdominal surgery reported that lidocaine significantly reduced postoperative VAS pain scores, duration of postoperative ileus, incidence of PONV, and length of hospital stay, compared with the controls

Open Colonic Resection-Specific Evidence - Study information

  • Peri-operative IV lidocaine significantly reduced the time to first flatus compared with the control group (p<0.05; n=60)
  • The time to first bowel movement was significantly shorter with peri-operative IV lidocaine compared with the control (p<0.05; n=60)
  • Peri-operative IV lidocaine significantly reduced the time taken to solid food intake compared with the control (p<0.001; n=60)
  • Peri-operative IV lidocaine significantly reduced the duration of hospital stay compared with control (p=0.004; n=60)
  • Peri-operative IV lidocaine conferred no significant benefit over the control for the reduction of VAS pain scores at rest or during movement at any of the time points assessed (n=60)
  • Peri-operative IV lidocaine conferred no significant benefit over control for reducing the consumption of PCA IV piritramide (2 mg dose with a lockout period of 10 min) (n= 60)

PROSPECT Recommendations

  • Postoperative NMDA receptor antagonists are not recommended (Grade D, LoE 4) because of limited procedure-specific evidence of analgesic efficacy

Clinical Practice

  • The maximum dose of ketamine that should be given to avoid side effects is 0.5 mg/kg
  • Clinical experience with NMDA receptor antagonists is lacking. Moreover, NMDA receptor antagonists are associated with adverse events, e.g. ketamine is known for its increased risk of CNS side effects

Transferable Evidence from Other Procedures

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine
  • In patients undergoing laparoscopic cholecystectomy, dextromethorphan (pre- incisional and post gallbladder removal) was superior to control for reducing VAS scores, reducing the use of supplementary analgesics, and increasing the time to first analgesic request
  • Low-dose ketamine was associated with few and mild adverse effects, especially when administered in conjunction with general anaesthesia
  • A systematic review found that dextromethorphan did not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases
  • Two systematic reviews of randomised controlled trials comparing magnesium with placebo demonstrated inconclusive results overall with regards to pain scores and supplemental analgesic use

Open Colonic Resection-Specific Evidence - Study information

  • IV magnesium provided no significant benefit over placebo for reducing the following postoperative outcomes: pain scores at rest or during movement; morphine requirements for 0–24 h; sedation scores 0–48 h; incidence of nausea and vomiting; time to first bowel movement; and time to first flatus (n=47)

PROSPECT Recommendations

  • Systemic strong opioids are recommended (Grade B) following colonic resection, based on transferable evidence for their efficacy in reducing high-intensity postoperative pain (VAS =50 mm) (LoE 1), with the following considerations:
  • In patients receiving epidural anaesthesia, epidural strong opioids are recommended 2–3 days postoperatively; after the catheter has been removed, systemic strong opioids can be administered for analgesia (Grade D, LoE 4)
  • Systemic strong opioids should only be used in combination with conventional NSAIDs or COX-2-selective inhibitors and paracetamol to reduce opioid use and its associated side-effects (Grade D, LoE 4)
  • Even though IV PCA strong opioids showed no analgesic benefit over IM PRN opioids in procedure-specific evidence (LoE 1), they are recommended (Grade B) based on greater patient satisfaction compared with regular (fixed-interval) or PRN dosing (transferable evidence, LoE 1); however, fixed-interval IV administration titrated to pain intensity is also recognised as an effective mode of administration (LoE 4)
  • IM strong opioids are not recommended because of the pain associated with these injections (Grade D, LoE 4)

Clinical Practice

  • Regular administration, titrated for pain intensity, is generally accepted as an effective method of administering strong opioids
  • Strong opioids are not associated with a ceiling effect, and thus can provide effective analgesia for most types of surgical procedures
  • Strong opioids may be used in a variety of preparations and routes of administration, enabling choice for onset, duration of action, and mode of delivery
  • The opioid antagonist alvimopan has been demonstrated to reduce the incidence of postoperative ileus and accelerate GI function without compromising opioid analgesia in patients undergoing bowel resection (Ludwig 2008)
  • Most clinical trials showing benefits of intramuscular strong opioids use nurse-administered regimens. In regular clinical practice, full adherence to nurse-administered regimens is not usually achievable, and the full analgesic benefits of intramuscular strong opioids are also not achieved
  • Intramuscular administration of strong opioids is considered to be more painful than intravenous administration; however, the dose and rapidity of intravenous administration should be assessed to minimise the risk of respiratory depression

Transferable Evidence from Other Procedures - Study information

  • Three out of five studies showed a significant benefit of IV PCA over IM regular/PRN administration of strong opioids for reducing postoperative pain scores in patients undergoing abdominal hysterectomy Click here for more information
  • Evidence for a benefit of PCA compared with regular/PRN IM administration of strong opioids for reducing overall opioid consumption is inconsistent, although one study suggests that they produced different patterns of dosing in patients undergoing abdominal hysterectomy Click here for more information
  • The incidence of PONV was not significantly different between PCA and IM morphine Click here for more information
  • Opioids administered by PCA improved analgesia, decreased the risk of pulmonary complications and patients preferred them compared with regular IM, IV or SC opioid treatment, as determined in a quantitative systematic review of randomised trials in various surgical procedures
  • Strong opioids are effective for reducing high- and moderate-intensity postoperative pain
  • Strong opioids are associated with adverse effects, including nausea, vomiting, sedation, confusion, paralytic ileus and urinary retention

Open Colonic Resection-Specific Evidence - Study information

  • IM regular or PRN morphine was superior to IV PCA morphine for reducing daily opioid use (both p<0.05) and the total amount of opioid used in two studies (no statistics provided, n=41; p<0.05, n=62)
  • IM morphine was similar to PCA morphine for the frequency of PONV in one study reporting this parameter (n=41)
  • IM morphine was similar to PCA morphine for the level of postoperative pain and activity (measured by patient questionnaire), frequency of PONV, level of sedation and the duration of ileus and of hospital stay. However, this study did not record pain on a linear scale (n=62)
  • PCA morphine had a similar effect to PRN or regular IM morphine for reducing postoperative pain scores in two studies Click here for more information
  • PCA morphine and IM morphine use were associated with similar length of hospital stay in two studies (n=41, n=62)
  • IM or IV morphine plus IM ketorolac prolonged the length of time taken to recover from postoperative ileus compared with IM ketorolac alone (2.3 ± 0.5 days versus 4.2 ± 0.6 days; p<0.05; n=14)

PROSPECT Recommendations

  • Weak opioids are not recommended for controlling high-intensity pain (Grade D, LoE 4)
  • Weak opioids are recommended to be used for moderate- or low-intensity pain if non-opioid analgesia is insufficient or is contra-indicated (Grade B, transferable evidence, LoE 1)
  • Weak opioids are recommended to be used in combination with non-opioid analgesics (Grade B, transferable evidence, LoE 1)

Clinical Practice

  • Tramadol 300 mg is considered to be a clinically effective dose, and therefore the 100 mg dose used in the study by Wordliczek et al. is probably too low to provide sufficient pain relief

Transferable Evidence from Other Procedures

  • Tramadol was more effective than placebo for pain relief in a meta-analysis of post-surgical patients
  • The combination of tramadol and paracetamol enhances analgesic efficacy compared with either agent alone
  • A systematic review found that the combination of dextropropoxyphene 65 mg with paracetamol 650 mg showed similar efficacy to tramadol 100 mg but with a lower incidence of adverse effects
  • A systematic review found that the combination of codeine with paracetamol provided additional pain relief compared with paracetamol alone
  • Two studies found that codeine 30mg + paracetamol 300 mg was associated with a higher incidence of constipation and vomiting than tramadol 37.5 mg + paracetamol 325 mg following arthroscopy
  • Adverse effects associated with tramadol include headache, nausea, vomiting, dizziness, somnolence. A meta-analysis of individual patient data from randomised controlled trials found a dose-response of adverse effects with tramadol; postsurgical patients had fewer side-effects than dental patients
  • A systematic review found that the combination of codeine with paracetamol was associated with an increase in drowsiness and dizziness compared with paracetamol alone
  • A systematic review found an increased incidence of central nervous system adverse effects with paracetamol plus dextropropoxyphene compared with placebo

Open Colonic Resection-Specific Evidence - Study information

  • Administration of IV tramadol immediately after peritoneal closure, or immediately following surgery extended the time to first analgesic request compared with pre-operative administration (p<0.01; n=90)
  • Pre-, intra- or postoperative IV tramadol 100 mg were similar for postoperative pain scores Click here for more information
  • Pre-, intra- or postoperative administration of tramadol 100 mg were similar for the incidence of PONV (n=90)
  • Pre-operative administration of IV tramadol was superior to administration immediately after peritoneal closure or postoperatively for reducing total tramadol consumption (p<0.05; n=90)

PROSPECT Recommendations

  • Paracetamol is recommended for pain of moderate- (>30 VAS <50) or low- (VAS =30) intensity, in combination with COX-2-selective inhibitors or conventional NSAIDs (Grade B), based on its mild analgesic and opioid-sparing effect in transferable evidence (LoE 1), only for patients who do not receive epidural analgesia or with cessation of epidural analgesia (Grade D, LoE 4)
  • However, paracetamol is not recommended for high-intensity pain (VAS =50 mm) (Grade B) because it has no additional analgesic benefit over that conferred by conventional NSAIDs in transferable evidence (LoE 1)

Clinical Practice

  • Paracetamol is a well-established analgesic for low- (VAS=30) or moderate- (VAS>30<50) intensity pain and has a favourable safety profile
  • If paracetamol is used as part of a multi-modal regimen, the anti-pyretic effect can mask complications such as anastomotic leakage

Transferable Evidence from Other Procedures - Study information

  • Paracetamol was superior to placebo for reducing postoperative pain scores, but produced reductions in VAS scores of <13 mm Click here for more information
  • Paracetamol was superior to placebo for reducing supplementary analgesic consumption within 0–24 h in patients undergoing abdominal hysterectomy Click here for more information
  • One study showed that IV paracetamol was equally as effective as IV ketorolac for reducing postoperative pain scores in patients undergoing abdominal hysterectomy (n=176)
  • Paracetamol combined with weak opioids (codeine, tramadol) is superior to weak opioids alone in a review of dental, gynaecological and orthopaedic surgery
  • A meta-analysis of randomised controlled trials showed that paracetamol combined with PCA morphine induced a significant morphine-sparing effect but did not change the incidence of morphine-related adverse effects in the postoperative period
  • There is evidence that concurrent use of paracetamol and conventional NSAIDs improves pain relief compared with paracetamol alone, but there is no evidence for a superior analgesic effect of the combination compared with conventional NSAIDs alone
  • One study showed a marginal but significant benefit of rectal diclofenac over rectal paracetamol for reducing average pain scores over 24 h, (p=0.008; n=44) in patients undergoing abdominal hysterectomy
  • In a systematic review of a variety of surgical procedures, paracetamol plus NSAID conferred no significant benefit over NSAID alone for reducing pain scores in orthopaedic and gynaecological operations. However, a significant benefit was seen in the lower-intensity pain associated with dental operations
  • Paracetamol 1.5 g plus diclofenac 100 mg was not significantly different from diclofenac 100 mg alone given once pre-operatively, for reducing postoperative pain in abdominal gynaecological surgery

Open Colonic Resection-Specific Evidence

  • [No data found within the parameters of the systematic review]

PROSPECT Recommendations

  • Continuous epidural anaesthesia and postoperative analgesia is recommended for routine use in colonic resection (Grade A), based on its benefits for reducing postoperative pain, systemic opioid use and improving bowel recovery time (procedure-specific evidence, LoE 1)
  • A combination of epidural local anaesthetic (LA) and strong opioid is recommended for epidural analgesia (Grade A), based on procedure-specific evidence of their combined efficacy, in reducing postoperative pain and systemic opioid use, compared with LA alone (LoE 1). However, the addition of opioid to epidural LA results in an increase in time to first bowel movement (LoE 1)

Clinical Practice

  • Thoracic epidural is considered to be more appropriate than lumbar epidural for anaesthesia and analgesia in open colon surgery
  • Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications
  • Clonidine is not used routinely because it is associated with an increased risk of hypotension, sedation and bradycardia

Transferable Evidence from Other Procedures - Study information

  • Epidural analgesia using LA was superior to systemic strong opioid for reducing postoperative pain scores in six studies identified in a systematic review of abdominal surgery
  • Epidural analgesia using a combination of LA and strong opioid was superior to epidural LA alone for reducing postoperative pain – 15 mm reduction in VAS score on a 100-mm scale – in a meta-analysis of five studies in abdominal surgery
  • Epidural analgesia using LA was superior to epidural opioids or systemic opioids for reducing the incidence of postoperative gastrointestinal paralysis, in a systematic review in abdominal surgery
  • Epidural LA was superior to epidural LA plus opioid for reducing the time to first passage of stool Click here for more information
  • Epidural LA was suggested to be the most effective method of reducing ileus and improving postoperative catabolism in patients undergoing abdominal surgery Click here for more information
  • Results for the incidence of postoperative nausea were inconsistent for comparison of epidural LA with epidural LA plus opioid, and no significant difference for the incidence of vomiting was seen Click here for more information
  • Epidural clonidine is associated with an increased risk of hypotension, sedation and bradycardia Click here for more information

Open Colonic Resection-Specific Evidence - Study information

  • Epidural LA plus opioid produced a significant reduction in the use of supplementary analgesia compared with GA plus systemic analgesia in two studies (p<0.05, n=64; p<0.001, n=20)
  • A significantly higher proportion of patients in the PCEA group were 'very satisfied' with the treatment compared with the continuous epidural infusion group at 72 h postoperatively and at discharge (both p<0.0001; n=205)
  • PCEA was superior to continuous epidural infusion for reducing postoperative analgesic consumption Click here for more information
  • Mean summary area under the curve (AUC) of VRS pain scores at rest for 0–72 h postoperatively was significantly lower with PCEA, compared with continuous epidural analgesia (p<0.001; n=205), and median summary VRS pain scores on movement for 24–72 h postoperatively were significantly lower in the PCEA group compared with the continuous epidural group (p<0.001; n=205)
  • Cumulative number of satisfied analgesic requests was significantly lower with intra-/postoperative epidural bupivacaine-sufentanil-clonidine + intra-operative IV ketamine, compared with intra-operative IV lidocaine-sufentanil-clonidine + intra-operative IV ketamine + postoperative IV lidocaine-morphine-clonidine, from 24–72 h after surgery
  • Intra-/postoperative epidural bupivacaine-sufentanil-clonidine + intra-operative IV ketamine was superior to intra-operative IV lidocaine-sufentanil-clonidine + intra-operative IV ketamine + postoperative IV lidocaine-morphine-clonidine for reducing postoperative pain Click here for more information
  • The incidence of morphine-associated nausea, vomiting, and itching was significantly lower with pre-/postoperative epidural clonidine, compared with control (p<0.001; n=40)
  • Pre-/postoperative epidural clonidine significantly reduced the time to return of normal bowel function compared with control (p<0.001; n=40)
  • Pre-/postoperative epidural clonidine was superior to the control for reducing postoperative analgesic requirement Click here for more information
  • Pre-/postoperative epidural clonidine was superior to control for the reduction of postoperative pain scores Click here for more information
  • Epidural clonidine was superior to control for reducing the amount of fentanyl administered postoperatively for 12–24 and 24–36 h (all p<0.05; n=25)
  • Continuous epidural bupivacaine was superior to epidural morphine (bolus or continuous) in reducing the time to first bowel movement (p<0.05; n=45)
  • Continuous epidural bupivacaine was associated with similar supplementary analgesic consumption compared with epidural morphine (bolus or continuous) (n=45)
  • Continuous epidural bupivacaine was similar to continuous epidural morphine for reducing postoperative pain scores (n=45) Click here for more information
  • The addition of opioid to epidural LA conferred a benefit over epidural LA alone in reducing postoperative pain scores in two studies Click here for more information
  • Daily bolus epidural morphine was superior to IM oxycodone for reducing supplementary analgesic consumption (p<0.01; n=30)
  • Continuous epidural morphine was superior to control for reducing supplementary analgesic consumption in one study (p<0.01; n=30)
  • Daily bolus epidural morphine was superior to IM oxycodone for reducing postoperative pain scores at 3 h (n=30) Click here for more information
  • Epidural LA and opioid showed a significant benefit for reducing postoperative pain scores compared Click here for more information
  • Epidural LA plus opioid was superior to GA plus systemic analgesia for increasing the time to first request of supplementary analgesia in one study (p<0.005; n=20)
  • Epidural LA plus opioid was associated with a similar length of hospital stay compared with GA plus systemic analgesia in two studies (n=42, n=20)
  • Epidural LA plus opioid produced a significantly quicker time for first flatus and time for first bowel movement compared with GA plus systemic analgesia in two studies (all p<0.05; n=64, n=42)
  • Epidural bupivacaine plus morphine was associated with recovery of gastrointestinal function and fulfilled discharge criteria approximately 1.5 days earlier compared with GA and IV plus postoperative PCA morphine (p<0.005; n=26)
  • Epidural bupivacaine plus morphine had a similar incidence of orthostatic hypotension compared with GA and IV plus postoperative PCA morphine (n=26)
  • Postoperative thoracic epidural analgesia was superior to postoperative PCA for reduction of VAS pain scores at Day 2 (p=0.01; n=59), but there was no significant difference between the groups at discharge, or on Days 1, 10 and 30
  • Two studies demonstrated that epidural bupivacaine conferred a benefit over general anaesthesia and systemic analgesia for reducing postoperative pain scores at rest for 1–72 h in one study (all p<0.05; n=116)
  • Epidural bupivacaine administration resulted in significantly fewer patients requiring supplementary analgesia compared with GA plus systemic analgesia for 1–48 h postoperatively (p<0.05; n=116)
  • Epidural bupivacaine administration resulted in significantly more patients having a bowel movement by Day 4 compared with GA plus systemic analgesia (p<0.05; n=116)
  • Epidural bupivacaine was associated with recovery of gastrointestinal function and fulfilled discharge criteria approximately 1.5 days earlier compared with GA and IV bolus plus postoperative PCA morphine (p<0.005; n=26)
  • A meta-analysis of randomised studies performed to compare the effect of local anaesthetic epidural analgesia with parenteral opioid analgesia in patients undergoing colorectal surgery, reported that epidural analgesia significantly reduced postoperative VAS pain scores at 24 h (11 studies analysed, n=630) and 48 h postoperatively (6 studies analysed, n=281) (p<0.001 for both comparisons)
  • Continuous epidural infusion of opioids was superior to systemic regimens for reducing postoperative pain scores in two out of three studies Click here for more information
  • Intra-/postoperative epidural bupivacaine-sufentanil-clonidine + intra-operative IV ketamine was associated with a higher incidence of orthostatic hypotension at first mobilisation, compared with intra-operative IV lidocaine-sufentanil-clonidine + intra-operative IV ketamine + postoperative IV lidocaine-morphine-clonidine (p=0.05; n=40)
  • Pre-/postoperative epidural clonidine provided no significant benefit for reducing the length of hospital stay compared with control (n=40)
  • Epidural clonidine provided no significant benefit for sedation scores compared with control at 12–24 h and 24–36 h postoperatively (p<0.05; n=25)
  • Epidural clonidine provided no significant benefit for postoperative pain scores 0–72 h (n=25)
  • High dose continuous epidural infusion of bupivacaine plus fentanyl provided no significant benefit over a lower dose regimen for improving various postoperative outcomes (n=100) Click here for more information
  • Continuous epidural morphine was similar to systemic analgesia for the length of postoperative hospital stay in two studies (n=21, n=24)
  • Epidural bupivacaine had a similar incidence of nausea compared with GA and IV plus postoperative PCA morphine (n=26)
  • Epidural bupivacaine was associated with an increased incidence of orthostatic hypotension compared with GA and IV plus postoperative PCA morphine (p<0.05) (n=26)
  • Epidural morphine was associated with a similar incidence of nausea and orthostatic hypotension compared with GA and IV plus postoperative PCA morphine (n=24)
  • Epidural morphine (bolus or continuous) was similar to IM baralgine or IM oxycodone for the time to first bowel movement in two studies (n=21, n=30)
  • Postoperative thoracic epidural analgesia conferred no significant benefit over postoperative PCA for reducing the length of hospital stay (n=59)
  • There was no significant difference between the postoperative thoracic epidural analgesia group and postoperative PCA group for a return to normal levels of activities at discharge, 10 days and 30 days postoperatively ((n=59)
  • There was no significant difference in patient quality of life or satisfaction with hospital stay scores between the groups receiving postoperative thoracic epidural analgesia and postoperative PCA (n=59)
  • Postoperative thoracic epidural analgesia conferred no significant benefit over postoperative PCA for reducing the time to first bowel movement (n=34 analysed)
  • A meta-analysis of randomised studies performed to compare the effect of local anaesthetic epidural analgesia with parenteral opioid analgesia in patients undergoing colorectal surgery, found no significant difference in the incidence of PONV (5 studies analysed; n=189), anastomotic leakage (7 studies analysed; n=459), or length of hospital stay (n=716)
  • Epidural LA plus strong opioid showed no difference in the incidence of nausea and vomiting compared with GA plus systemic analgesia in four studies Click here for more information

PROSPECT Recommendations

  • Continuous postoperative wound infusion with LA is not recommended (Grade D, LoE 4) as procedure-specific evidence is limited and inconsistent
  • Pre-closure wound infiltration with local anaesthetic is not recommended for open colonic resection (Grade D, LoE 4), due to lack of procedure-specific evidence and inconclusive transferable evidence from other large abdominal surgeries

Clinical Practice

  • Continuous pre-peritoneal infusion of LA may be considered as an alternative when epidural analgesia is not feasible or contraindicated based on limited procedure-specific evidence for analgesic benefit (LoE 2)
  • Intra-operative wound infiltration is a well-established method of analgesia with a favourable safety profile. However, methods of postoperative wound infusion are not well established

Transferable Evidence from Other Procedures - Study information

  • A qualitative and quantitative systematic review compared continuous postoperative wound infusion with LA versus control in multiple surgical procedures (cardiothoracic, general, gynaecology-urology, orthopaedics). Meta-analysis of 44 randomised studies showed that continuous wound infusion with LA was superior to control for reduction of postoperative pain scores and postoperative morphine consumption (n=1814)
  • Five of eight studies showed no significant benefit of intra-operative wound infiltration over placebo for reducing postoperative pain scores following abdominal hysterectomy Click here for more information
  • Postoperative PCA wound infiltration with LA following hysterectomy provided limited benefit over placebo for reducing postoperative pain scores, but significantly reduced postoperative analgesic consumption Click here for more information
  • A systematic review of incisional local anaesthesia showed that evidence of analgesic efficacy in hysterectomy (4 studies), open cholecystectomy (8 studies) and a variety of other surgical procedures (9 studies) was inconclusive Click here for more information
  • Three randomised trials in patients undergoing abdominal hysterectomy showed that single-shot postoperative LA wound infiltration conferred no significant benefit over placebo/no treatment for reducing postoperative pain scores

Open Colonic Resection-Specific Evidence - Study information

  • Continuous wound infusion with Lidocaine and bupivacaine was similar to an intermittent IV morphine infusion for postoperative pain scores Click here for more information
  • Continuous wound infusion with Lidocaine and bupivacaine was superior to IV morphine infusion for the total amount of morphine used (p<0.001; n=70)
  • Continous wound infusion with ropivacaine was superior to placebo for reducing postoperative pain scores during movement at a minority of timepoints Click here for more information
  • Continuous pre-peritoneal infusion with ropivacaine was superior to placebo for reducing postoperative pain scores Click here for more information
  • Continuous pre-peritoneal infusion with 0.2% ropivacaine significantly reduced postoperative consumption of PCA morphine compared with placebo during the first 3 postoperative days (p=0.0004) (n=42)
  • Continuous pre-peritoneal infusion with ropivacaine was superior to placebo for reducing the time to hospital discharge (p=0.02) (n=42)
  • Continuous wound infusion with lidocaine and bupivacaine conferred no benefit over intermittent IV morphine infusion for reducing time to first bowel movement, time to first flatus and timing of postoperative mobilisation (n=70)
  • Continuous wound infusion with lidocaine and bupivacaine was associated with a similar incidence of vomiting compared with intermittent IV PCA morphine infusion (n=70)
  • Continuous wound infusion with 0.54% ropivacaine conferred no significant benefit over placebo for reducing PCA morphine use on postoperative Days 1, 2 and 3 (n=310 analysed)
  • Continuous wound infusion with ropivacaine conferred no significant benefit over placebo for reducing the length of hospital stay (n=310)
  • Continuous wound infusion with ropivacaine had no significant effect on the incidence of postoperative nausea and vomiting, compared with placebo (n=42)
  • Pre-peritoneal continuous infusion with ropivacaine had no significant effect on the incidence of postoperative nausea and vomiting, compared with placebo (n=310)
  • Continuous wound infusion with 0.54% ropivacaine conferred no significant benefit over placebo for the reduction of VAS mobility scores on postoperative Days 1,2, and 3 (n=310)

PROSPECT Recommendations

  • Care protocols (which include controlled rehabilitation with early ambulation and diet, or multi-modal optimisation programmes) following colonic resection are recommended (Grade A) based on factors other than the management of postoperative pain (e.g. postoperative ileus (procedure specific LoE 1) and length of hospital stay (procedure specifc LoE 1)), as postoperative pain benefits are inconsistent (LoE 4). Controlled studies are necessary to define the influence of the various components
  • The 'anti-inflammatory regimen' (GA combined with spinal, epidural, IV corticosteroid and NSAID) is not recommended over GA + IV opioid analgesia (Grade D, LoE 4) because of limited evidence in colonic resection. Moreover, it introduces an increased level of complexity

Clinical Practice

  • Epidural anaesthesia combined with general anaesthesia is used routinely for colonic resection, except in patients with contra-indications to epidurals, where general anaesthesia alone is used.
  • Nasogastric tubes should be removed as early as possible to avoid gastroparesis.

Transferable Evidence from Other Procedures - Study information

  • Multimodal rehabilitation protocols (the fast-track methodology, enhanced recovery programmes, etc.) have been assessed in large prospective cohort studies, randomised trials and systematic reviews. These concluded that integration of optimised pain relief together with early oral nutrition, anti-ileus treatment, mobilisation, appropriate fluid therapy and revision of perioperative care principles hasten recovery, thereby decreasing duration of postoperative hospitalisation as well as reducing m
  • Studies integrating continuous epidural LA with enforced early nutrition and mobilisation uniformly suggest an improved recovery, and decreased hospital stay and convalescence Click here for more information
  • A meta-analysis showed that omitting nasogastric tubes conferred a significant benefit over their use for reducing the time to first oral intake, pulmonary complications, fever, atelectasis and pneumonia
  • A meta-analysis showed that patients managed without nasogastric tubes had significantly greater abdominal distension and vomiting

Open Colonic Resection-Specific Evidence - Study information

  • Care by CREAD was superior to TRAD care for reducing the time to discharge and length of hospital stay (5.4 versus 7.1 days, p=0.02; n=64)
  • The 'anti-inflammatory' regimen (GA, spinal, epidural, IV corticosteroid and NSAID) significantly enhanced ambulatory function (i.e. washing and mobility) compared with GA and IV opioid analgesia (p<0.05; n=20) Schulze et al 1992
  • The 'anti-inflammatory' regimen (GA, spinal, epidural, IV corticosteroid and NSAID) significantly reduced fatigue compared with GA and IV opioid analgesia (p<0.05; n=20) Schulze et al 1992
  • The 'anti-inflammatory' regimen (GA, spinal, epidural, IV corticosteroid and NSAID) reduced VAS pain scores at rest and during coughing for 0–8 days postoperatively compared with GA and IV opioid analgesia (p<0.001; n=20)
  • Mechanical massage with aspiration of abdominal wall was superior to mechanical massage without aspiration for reducing the time to first flatus (p<0.01; n=50)
  • Mechanical massage with aspiration of abdominal wall was superior to mechanical massage without aspiration for reducing supplementary analgesic consumption Days 1–3 (p<0.05; n=50)
  • Mechanical massage with aspiration of abdominal wall was superior to mechanical massage without aspiration for reducing mean postoperative pain scores from Days 2–5 (p<0.001; n=50)
  • Gastrostomy tubes were superior to nasogastric tubes for reducing patient discomfort levels (p<0.01; n=107)
  • A multi-modal optimisation programme conferred a significant benefit over traditional care for tolerating a regular hospital diet earlier (48 versus 76 h; p<0.001), and reduced the median length of hospital stay (3 versus 7 days; p<0.002; n=25)
  • A multi-modal optimisation programme conferred a significant benefit over traditional care for reducing postoperative fatigue scores on Day 7 (p=0.008; n=25)
  • A multi-modal optimisation programme conferred a significant benefit over traditional care for reducing postoperative pain scores Click here for more information
  • Care by CREAD numerically but not statistically reduced the number of patients with postoperative ileus or small-bowel obstruction compared with patients undergoing TRAD care (3 versus 4 patients; n=64)
  • Care by CREAD numerically, but not statistically, lowered morphine consumption compared with patients undergoing TRAD care (137 ± 109 versus 187 ± 125 mg; p=0.08; n=64)
  • Patients receiving gastrostomy tubes reported significantly less tube-related inconvenience than patients receiving nasogastric tubes on postoperative Day 2, at discharge and at 4 weeks postoperatively (all p<0.02; n=107)
  • Peri-operative IV glucose + amino acids conferred no signficant benefit over peri-operative IV glucose alone, for the reduction of VAS pain scores at rest or during movement at 12, 24, 36 or 48 h postoperatively (n=16)
  • Postoperative restriction of IV fluids conferred no significant benefit over the standard postoperative fluid regimen for reducing the time to medical discharge or hospital discharge (n=80)
  • Time to passage of first flatus was similar for patients allocated to the restricted postoperative IV fluid and standard postoperative IV fluid regimens (n=80)
  • Postoperative restriction of IV fluids did not confer any benefit over the standard IV fluid regimen for reducing the incidence of postoperative nausea and vomiting (n=80)
  • Postoperative restriction of IV fluids did not confer any benefit over the standard IV fluid regimen for reducing the consumption of postoperative supplementary analgesics (n=80) Click here for more information
  • Postoperative restriction of IV fluids did not confer any benefit over the standard IV fluid regimen for reducing VAS pain scores at rest or during movement during the hospital stay (n=80)
  • Gastrostomy and nasogastric tubes were associated with similar postoperative pain scores (n=107)
  • Mechanical massage with aspiration of abdominal wall and mechanical massage without aspiration groups had a similar time to discharge from hospital (n=50)
  • Mechanical massage with aspiration of abdominal wall and mechanical massage without aspiration groups both demonstrated similar Hamilton anxiety scores at the end of the study (n=50)
  • Care by CREAD showed that pain scores evaluated by the McGill pain questionnaire were higher at discharge but were equal on postoperative Day 10 compared with care by TRAD (p<0.02; n=64)
  • Care by CREAD did not confer a benefit over TRAD care for reducing postoperative pain scores on Days 2, 10 or 30 (n=64)

PROSPECT Recommendations

  • Conventional NSAIDs are recommended (Grade B) based on limited procedure-specific evidence (LoE 2) and transferable evidence (LoE1) showing analgesic benefit

Clinical Practice

  • Conventional NSAIDs are used in preference to strong opioids in laparoscopic procedures

Transferable Evidence from Other Procedures

  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression
  • Six out of eight studies showed a significant benefit of postoperative conventional NSAIDs compared with placebo for reducing postoperative pain scores in patients undergoing hysterectomy Click here for more information
  • Conventional NSAIDs conferred a significant benefit over placebo for reducing supplementary analgesia requirements over 24 h or more in patients undergoing abdominal hysterectomy Click here for more information
  • Conventional NSAIDs were superior to placebo for reducing morphine consumption in abdominal surgery but did not consistently reduce pain scores in two studies in abdominal surgery Click here for more information
  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo
  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures
  • A case-control study in patients undergoing laparoscopic colonic resection with primary anastomosis found that patients given postoperative oral diclofenac (150 mg daily) were at higher risk of anastomotic leakage, compared with patients receiving postoperative opioid analgesics
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use
  • Diclofenac 50 mg IM bolus pre-operatively then postoperatively at 4 and 10 h, plus epidural analgesia using bupivacaine 0.5% continually infused at 8 mL/h did not confer a benefit for extending the time to first analgesic request compared with epidural analgesia alone in patients undergoing abdominal hysterectomy (n=26)
  • Conventional NSAIDs and placebo were not significantly different for the incidence of PONV (all groups received background strong opioid) in patients undergoing abdominal surgery Click here for more information
  • Results were inconsistent for conventional NSAIDs compared with placebo for the time to first analgesic request following abdominal hysterectomy Click here for more information
  • Two of three studies showed no significant analgesic benefit of conventional NSAIDs plus epidural analgesia compared with epidural analgesia alone Click here for more information

Laparoscopic Colonic Resection-Specific Evidence

  • Postoperative IV ketorolac was superior to placebo for reduction of VAS pain scores during walking on Days 1 (p<0.001), 2 (p<0.05) and 3 (p<0.001), but not on Day 4
  • Postoperative IV ketorolac significantly reduced postoperative PCA morphine requirement, compared with placebo (p=0.011; n=44)
  • Postoperative IV ketorolac was superior to placebo for reducing the time to first flatus (p=0.005; n=44)
  • Postoperative IV ketorolac significantly reduced the time to return to full diet, compared with placebo (p=0.033; n=44)
  • VAS pain scores on coughing were significantly greater with IV ketorolac, compared with placebo at Day 4 (p<0.001), but there was no significant difference between the groups on Days 1, 2, and 3 (n=44)
  • There was no significant difference between the IV ketorolac and placebo groups for VAS pain scores at rest on Days 1–4
  • There was no significant difference in the length of hospital stay between the postoperative IV ketorolac and placebo groups (n=44)
  • There was no significant difference in the incidence of anastomotic leaks in the IV ketorolac and placebo groups (n=44)

PROSPECT Recommendations

  • Continuous intra-/postoperative IV lidocaine is not recommended currently (Grade D, LoE 4) because of limited procedure-specific data, despite some positive transferable evidence

Clinical Practice

  • Further evidence is needed to precisely define the role of IV lidocaine in this setting, including direct comparisons with epidural analgesia
  • IV lidocaine may induce hypotension
  • If IV lidocaine is used, it is recommended that safety data are taken into account

Transferable Evidence from Other Procedures

  • A meta-analysis of randomised clinical trials performed to evaluate the effect of continuous IV lidocaine infusion during and after abdominal surgery, reported that lidocaine significantly reduced postoperative VAS pain scores, duration of postoperative ileus, incidence of PONV and length of hospital stay, compared with the controls

Laparoscopic Colonic Resection-Specific Evidence

  • Continuous intra-/postoperative IV lidocaine was superior to placebo for reducing postoperative pain scores during mobilization and on coughing Click here for more information
  • Continuous intra-/postoperative IV lidocaine was superior to placebo for reducing postoperative opioid consumption Click here for more information
  • Continuous intra-/postoperative IV lidocaine significantly reduced the dose of IV sufentanil administered during surgery, compared with placebo (p< 0.001; n=40)
  • Continuous intra-/postoperative IV lidocaine was superior to placebo for reducing the time to first flatus and first bowel movement (both p=0.001; n=40)
  • Continuous intra-/postoperative IV lidocaine significantly reduced the length of hospital stay compared with placebo (p=0.001; n=40)
  • Incidence of postoperative nausea or vomiting was similar in both the continuous intra-/postoperative lidocaine and placebo groups (n=40)

PROSPECT Recommendations

  • Epidural LA + strong opioid reduces postoperative pain (procedure-specific evidence, LoE 1), but is not recommended (Grade D), due to poor risk:benefit ratio (LoE 4)
  • Epidural analgesia is recommended in high-risk pulmonary patients (Grade D; LoE 4)

Clinical Practice

  • The risk of side-effects associated with epidural analgesia may outweigh the benefits of analgesia in laparoscopic colonic resection

Transferable Evidence from Other Procedures

  • None cited

Laparoscopic Colonic Resection-Specific Evidence

  • One study showed that thoracic epidural LA + opioid was associated with significantly lower VAS fatigue scores on postoperative Day 3 (p=0.025), compared with IV PCA morphine, although there was no significant difference between the groups on Days 1, 2 and 4
  • One study found that thoracic epidural LA + opioid was superior to IV PCA opioid for reducing postoperative vomiting on Days 1 and 2 (p=0.033 and p=0.005; n=50), but not on Days 3 or 4
  • One study showed that time to first flatus and first bowel movement was significantly shorter with thoracic epidural LA + opioid, compared with IV PCA morphine (p=0.0061 and p=0.0027, respectively; n=50)
  • One study reported that time taken to return to fluid diet and full diet was significantly shorter for patients in the thoracic epidural LA + opioid group, compared with the IV PCA group (p=0.0442 and p=0.0436, respectively; n=50)
  • Two of two studies showed that epidural LA plus opioid was superior to IV PCA morphine for reducing postoperative pain scores Click here for more information
  • GA + thoracic epidural analgesia was associated with a significantly shorter time to recovery of GI function (GI-3) and time to first bowel movement (p=0.025 and p=0.038, respectively; n=75), compared with GA alone, but there was no significant difference for time to first flatus or time to solid food tolerance
  • GA + thoracic epidural analgesia was superior to GA alone for reducing postoperative analgesic consumption Click here for more information
  • VAS pain scores during Days 1–8 were significantly lower in the group receiving GA + thoracic epidural analgesia, compared with the group receiving GA alone (p=0.004; n=75 overall)
  • Thoracic epidural ropivacaine + IV PCA morphine was superior to IV PCA opioid alone, for reducing the amount of supplementary IV PCA morphine administered between surgery to Day 2 (p=0.04). However, there was no significant difference between the groups from Day 2–4, or from surgery to Day 4 overall (n=20)
  • The incidence of postoperative nausea and vomiting, frequency of naso-gastric tube reinsertion and length of hospital stay was similar between the groups receiving GA + thoracic epidural analgesia or GA alone (n=75 overall)
  • Thoracic epidural ropivacaine + IV PCA morphine did not confer any significant benefit for reducing VAS pain scores at rest, or during coughing, from surgery to Day 4, or the time to first bowel movement, compared with IV PCA morphine alone (n=20)
  • Two studies of two reported no significant difference in the length of hospital stay between the groups receiving thoracic epidural LA + opioid or PCA IV morphine (n=38)
  • One study reported that the incidence of nausea requiring antiemetics, urinary retention, hypotension, and respiratory depression was similar in the groups receiving thoracic epidural LA + opioid and IV PCA morphine (n=38)
  • One study reported that the incidence of postoperative nausea was similar in patients receiving thoracic epidural LA + opioid and IV PCA opioid (n=50)
  • One study reported that thoracic epidural LA + opioid conferred no significant benefit over IV PCA morphine for reducing postoperative analgesic requirements (n=50)
  • Continuous epidural LA + IV PCA opioid versus control (IV PCA opioid alone) Click here for more information
  • GA plus thoracic epidural analgesia (TEA) versus GA alone Click here for more information

PROSPECT Recommendations

  • The combination of spinal analgesia and general anaesthesia is not recommended (Grade D) as the risk:benefit balance is not positive (LoE 4), and because of limited procedure-specific evidence

Clinical Practice

  • Spinal analgesia (LA + opioid) has a limited duration of action
  • Spinal morphine may produce some postoperative pain relief but also produces risk of PONV and prolongation of postoperative ileus, and limited duration of analgesic effect

Transferable Evidence from Other Procedures

  • One study showed that spinal analgesia with fentanyl + LA was superior to spinal analgesia with LA alone for reducing postoperative pain scores during from 0–8 h, but not between 8–24 h, following abdominal hysterectomy (n=20 overall)
  • The same study found spinal fentanyl + LA was superior to spinal LA alone for reducing the time to first analgesia request; the incidence of patients with PONV was similar between the two groups (n=20)

Laparoscopic Colonic Resection-Specific Evidence – Study information

  • Single bolus spinal hyperbaric bupivacaine with morphine was superior to hyperbaric bupivacaine alone for reducing cumulative VAS pain scores at rest or during coughing from 0?48 h (p=0.035 and p=0.01, respectively; n=35)
  • Single bolus spinal hyperbaric bupivacaine with morphine was superior to hyperbaric bupivacaine alone for reducing supplementary morphine consumption over 48 h (p=0.003; n=35)
  • Single bolus spinal hyperbaric bupivacaine with morphine was associated with a similar incidence of nausea/vomiting to hyperbaric bupivacaine alone. However, numerically more metoclopramide tablets were required by patients receiving spinal hyperbaric bupivacaine plus morphine (22 tablets), compared with hyperbaric bupivacaine alone (12 tablets) (n=35)

PROSPECT Recommendations

  • Gasless laparoscopy is not recommended (Grade B) based on procedure-specific evidence showing lack of analgesic effect (LoE 2)

Clinical Practice

  • None cited

Transferable Evidence from Other Procedures

  • None cited

Laparoscopic Colonic Resection-Specific Evidence

  • Gasless pneumoperitoneum was associated with increased cumulative VAS pain scores during mobilization and coughing (p=0.008 and p=0.006, respectively), but not at rest, up to 30 days after surgery, compared with conventional carbon dioxide pneumoperitoneum (n=17 overall)

PROSPECT Recommendations

  • The decision concerning the type of operative technique or incision to use for colonic resection should be primarily based on factors other than the management of postoperative pain, e.g. malignancy versus benign disease; operative risk factors of the patient; risk of wound infection; and availability of surgical expertise (Grade D, LoE 4)
  • Laparoscopic colonic resection is recommended over open colon surgery for reducing postoperative pain (Grade A), if the conditions outlined above allow, based on procedure-specific evidence (LoE 1)

Clinical Practice

  • The decision to employ a laparoscopic versus open approach for colonic surgery is based on multiple factors such as the indication for surgery (e.g. benign or malignant disease) and surgical expertise, as well as the desired outcomes

Transferable Evidence from Other Procedures

  • None cited

Laparoscopic Colonic Resection-Specific Evidence

  • Laparoscopic resection was superior to open colonic resection for reducing postoperative pain scores Click here for more information
  • Laparoscopic resection was superior to open colonic resection for reducing supplementary analgesic consumption in four studies of four Click here for more information
  • Laparoscopic resection was superior to open colonic resection for reducing time to first flatus and bowel movement in three of four studies Click here for more information
  • Laparoscopic resection was superior to open colonic resection for reducing length of hospital stay in four of five studies Click here for more information
  • A meta-analysis of seven studies reporting analgesic outcomes showed a significant benefit of laparoscopic resection over open colonic resection for reduced pain at rest and on coughing, and reduced analgesic requirement for up to 3 days (not all studies recorded pain scores)
  • A meta-analysis of twelve studies showed that laparoscopic resection reduced morbidity, wound infection, time to recovery and hospital stay compared with open resection
  • A systematic review of laparoscopic resection of colon cancer, combined with expert opinion, concluded that pain is less severe and that less analgesia is required after laparoscopic resection than open resection
  • Hand-assisted laparoscopic colectomy was superior to open colectomy for the reduction of postoperative pain scores Click here for more information
  • Hand-assisted laparoscopic colectomy was superior to open colectomy for reducing supplementary analgesic consumption Click here for more information
  • Hand-assisted laparoscopic colectomy was superior to open colectomy for reducing the time to first flatus and first bowel movement Click here for more information
  • Two studies showed that hand-assisted laparoscopic colectomy was superior to open colectomy for reducing the length of hospital stay (p=0.004, n=81; p<0.001, n=60)
  • One study showed that hand-assisted laparoscopic colectomy was superior to open colectomy for reducing the time until first oral food intake (p<0.05, n=60)
  • One study reported that there was no significant difference in the incidence of postoperative nausea and vomiting between the laparoscopic colonic resection and open colonic resection techniques (n=60)
  • Hand-assisted laparoscopic proctocolectomy conferred no significant benefit over open proctocolectomy for reducing VAS pain scores at rest and during movement on Days 1, 2, 3 and 7, and at week 4 (n=55)
  • There was no significant difference in the postoperative morphine requirement between patients who received hand-assisted laparoscopic proctocolectomy versus open proctocolectomy at 24, 48 or 72 h (n=55)
  • Hand-assisted laparoscopic proctocolectomy conferred no significant benefit over open proctocolectomy for reducing the time taken for patients to return to normal fluid or food consumption (n=55)

PROSPECT Recommendations

  • The decision concerning the type of laparoscopic technique to use for colonic resection should be primarily based on factors other than the management of postoperative pain, e.g. malignancy versus benign disease; operative risk factors of the patient; risk of wound infection; and availability of surgical expertise (Grade D, LoE 4)

Clinical Practice

  • None cited

Transferable Evidence from Other Procedures

  • None cited

Laparoscopic Colonic Resection-Specific Evidence

  • Operative time was significantly shorter with hand-assisted laparoscopic colectomy versus standard laparoscopic colectomy for both sigmoid/left colectomy (p=0.021; n=66) and total colectomy (p=0.015; n=29)
  • Two studies of two reported no significant difference between hand-assisted laparoscopic and conventional laparoscopic techniques for reducing postoperative pain scores Click here for more information
  • Two studies of two reported no significant difference between hand-assisted laparoscopic and conventional laparoscopic techniques for reducing postoperative analgesic requirement Click here for more information
  • One study reported that time to passage of first flatus and return of first bowel movement, was similar with the hand-assisted laparoscopic and standard laparoscopic techniques for both sigmoid/left colectomy (n=66) and total colectomy (n=29)
  • One study found that time to first tolerance of liquids or solids was similar with hand-assisted laparoscopic and standard laparoscopic techniques for both sigmoid/left colectomy (n=66) and total colectomy (n=29)
  • One study reported that the duration of hospital stay was similar with hand-assisted laparoscopic, compared conventional laparoscopic colectomy (n=54)

PROSPECT Recommendations

  • Pre-closure wound infiltration with LA can be recommended (Grade B) for laparoscopic colonic resection based on transferable evidence from other laparoscopic abdominal surgical procedures (LoE 1)

Clinical Practice

  • None cited

Transferable Evidence from Other Procedures

  • Nine out of 11 studies showed a significant benefit of LA wound infiltration over placebo or no treatment for reducing VAS pain scores in laparoscopic cholecystectomy Click here for more information
  • Six studies out of 11 reported that LA wound infiltration reduced analgesic consumption compared with placebo or no treatment; each of those studies also showed significantly reduced VAS pain scores with LA wound infiltration Click here for more information

Laparoscopic Colonic Resection-Specific Evidence

  • None cited

PROSPECT Recommendations

  • Care protocols (which include controlled rehabilitation with early ambulation and diet, or multi-modal optimisation programmes) following colonic resection are recommended (Grade A) based on factors other than the management of postoperative pain (e.g. postoperative ileus (procedure specific LoE 1) and length of hospital stay (procedure specifc LoE 1)), as postoperative pain benefits are inconsistent (LoE 4). Controlled studies are necessary to define the influence of the various components of s
  • Postoperative restriction of IV fluids is not recommended for analgesia (Grade B) due to limited procedure-specific evidence showing lack of analgesic efficacy (LoE 2)

Clinical Practice

  • None cited

Transferable Evidence from Other Procedures

  • Multimodal rehabilitation protocols (the fast-track methodology, enhanced recovery programmes, etc.) have been assessed in large prospective cohort studies, randomised trials and systematic reviews. These concluded that integration of optimised pain relief together with early oral nutrition, anti-ileus treatment, mobilisation, appropriate fluid therapy and revision of perioperative care principles hasten recovery, thereby decreasing duration of postoperative hospitalisation as well as reducing m

Laparoscopic Colonic Resection-Specific Evidence

  • Postoperative restriction of IV fluids did not confer any benefit over the standard IV fluid regimen for reducing VAS pain scores at rest or during movement during the hospital stay (n=80)
  • Postoperative restriction of IV fluids did not confer any benefit over the standard IV fluid regimen for reducing the consumption of postoperative supplementary analgesics (n=80) Click here for more information
  • Postoperative restriction of IV fluids did not confer any benefit over the standard IV fluid regimen for reducing the incidence of postoperative nausea and vomiting (n=80)
  • Time to passage of first flatus was similar for patients allocated to the restricted postoperative IV fluid and standard postoperative IV fluid regimens (n=80)
  • Postoperative restriction of IV fluids conferred no significant benefit over the standard postoperative fluid regimen for reducing the time to medical discharge or hospital discharge (n=80)

PROSPECT Recommendations

  • Laxatives are not recommended for analgesia (Grade D, LoE 4), but may be used for reasons other than pain relief (LoE 4)

Clinical Practice

  • None cited

Transferable Evidence from Other Procedures

  • Time until first defecation and GI recovery were significantly shorter with bisacodyl versus placebo (p=0.001 and p=0.007, respectively; n=169)
  • Pre-operative + postoperative administration of bisacodyl provided no significant benefit over placebo for the reduction of VAS pain scores (n=169)
  • There was no significant difference in the level of opioid consumption between patients who received bisacodyl or placebo during the first 8 postoperative days (n=169)
  • The incidence of postoperative cramping and nausea was similar in the bisacodyl and placebo groups (n=169)
  • Bisacodyl conferred no significant benefit over placebo for reducing the length of hospital stay (n=169)

Laparoscopic Colonic Resection-Specific Evidence

  • None cited

Haemorrhoid Surgery 2006

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PROSPECT Haemorrhoid Surgery Subgroup

For each review, a Subgroup of the prospect Working Group performs an initial evaluation of the evidence and also drafts clinical practice statements and recommendations, which are then discussed by the whole Working Group before a final consensus is reached. The Subgroup may sometimes include a non-Working Group member, to provide additional expertise in the procedure being reviewed. For the haemorrhoid surgery review, the Subgroup members were:
  • Professor Girish Joshi (PROSPECT Working Group member)
  • Professor Edmund Neugebauer (PROSPECT Working Group member)

Grades of Recommendation

Recommendations are graded according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence: Levels of evidence and grades of recommendation in PROSPECT reviews (from 2006) PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted.

Summary Recommendations

Pre-, intra- and postoperative interventions have been evaluated for the management of postoperative pain following haemorrhoid surgery. Unless otherwise stated, ‘pre-operative’ refers to interventions applied before surgical incision, ‘intra-operative’ refers to interventions applied after incision and before wound closure, ‘postoperative’ refers to interventions applied at or after wound closure. After haemorrhoid surgery, pain is not only related to the early postoperative period, but is also a problem after 2–3 days, around the time of first defecation. The following peri-operative interventions for haemorrhoid surgery have been reviewed: See Overall PROSPECT recommendations for the overall strategy for managing pain after haemorrhoid surgery.

PROSPECT overall recommendations for postoperative pain management following haemorrhoid surgery:

Recommended for postoperative analgesia:

Overall PROSPECT Recommendations for Haemorrhoid Surgery

Not recommended for postoperative analgesia:

Not recommended for Haemorrhoid Surgery

Description of studies

Literature search

  • Systematic review of the literature from 1966–June 2006 using MEDLINE and EmBASE, following the protocol of the Cochrane Collaboration Haemorrhoid Surgery June 2006 Search Terms
  • Inclusion of randomised studies in English, assessing analgesic interventions in haemorrhoid surgery in adults, and reporting pain on a linear analogue, verbal or numerical rating scale
    • Primary outcome measure: postoperative pain scores
    • Secondary outcome measures: supplemental analgesic requirements, other recovery outcomes (adverse effects, functional recovery)
  • Identification of 207 studies of peri-operative interventions for postoperative pain following haemorrhoid surgery
  • 106 studies included Haemorrhoid Surgery June 2006 Included References
  • 101 studies excluded Haemorrhoid Surgery June 2006 Excluded References
  • The most common reasons for exclusion were that the method of haemorrhoid removal was not surgical (35 studies), or pain scores were not reported (24 studies), or the study was not a randomised controlled trial (29 studies; see Table 1 below) Haemorrhoid Surgery June 2006 Reasons for Exclusion

Study quality assessments, levels of evidence and grades of recommendation

Recommendations are graded according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence: Levels of evidence and grades of recommendation in PROSPECT reviews (from 2006)

Click here for quality scores and levels of evidence for included procedure-specific studies: Haemorrhoid Surgery June 2006 Quality Scoring + Levels of Evidence

Quantitative analyses

No meta-analyses were performed due to a limited number of studies of homogeneous design that reported similar outcome measures. Therefore, the procedure-specific evidence was only assessed qualitatively.

Transferable evidence

Transferable evidence of analgesic efficacy from comparable procedures (e.g. anorectal surgery) or evidence of other outcomes, such as adverse effects, has been included to support the procedure-specific evidence where this is insufficient to formulate the recommendations. Several studies that were identified in the literature search reported data pooled from patients undergoing mixed surgical procedures including haemorrhoid surgery. Such studies are excluded from the procedure-specific systematic review, but have been used as additional transferable evidence in cases where the Working Group considered it appropriate.

Descriptions of haemorrhoid surgery

Operative techniques

  • Open (Milligan-Morgan technique): dissection of the haemorrhoid and ligation of the vascular pedicle, wounds are left open to heal naturally
  • Closed
    • Conventional closed (Ferguson’s technique): the wound is closed with a continuous suture to promote healing
    • Stapled: reduces the prolapse of haemorrhoidal tissue by excising a band of the prolapsed anal mucosa membrane above the dentate line, using a specific circular stapling device. This interrupts the blood supply to the haemorrhoids and reduces the potential for available rectal mucosa to prolapse. May also be referred to as stapled haemorrhoidopexy or stapled anopexy
    • Submucosal (Park’s technique): removes the vascular pedicle corresponding to every haemorrhoidal nodule and preserves the overlying mucosa, which is then accurately reconstructed

Dissection techniques

  • Conventional scissors
  • Diathermy: uses high current bipolar electrocautery for cutting and haemostasis
    • Ligasure™ vessel sealing system: complete haemostasis is achieved by reforming the collagen and elastin in vessel walls to form an autologous seal
  • Harmonic Scalpel: ultrasonically-activated scalpel, associated with decreased thermal damage to tissue and facilitated dissection within tissue planes
  • Radiofrequency bistoury: cuts and coagulates tissues in an atraumatic manner, using radio waves (maximum temperature 80 °C). Eliminates diffuse bleeding because all vessels of 1.5–2 mm diameter are coagulated on the sectioning line, thus haemostasis is controlled
  • Laser: concentrates the energy from electromagnetic radiation into a narrow beam that can be used for cutting, and causes very little damage to the surrounding tissue. It has a coagulative haemostatic effect that allows a dry operative field and obviates the need for ligation or diathermy

Adjuncts to surgery

  • Sphincterotomy: part of the internal sphincter muscle is cut, which relieves the tension of the muscle
  • Anal dilator: widens the anal canal if it has become narrowed because of tightness or spasm in the muscles (anal sphincters) that control the opening and closing of the anus

Topics for future research

In certain circumstances, recommendations for a type of treatment cannot be made due to limited or conflicting evidence. Areas which have been identified as requiring further investigation in the future are listed:

  • Gabapentinoids
  • Ketamine
  • Flavonoids
  • Botulinum toxin injection
  • Topical therapies, including glyceryl trinitrate (GTN) and calcium channel blockers, and haemostatic dressings, including calcium alginate dressing

Abbreviations

CPM

chlorpheniramine maleate

EMLA  

Eutectic Mixture of Local Anaesthetic

GA

general anaesthetic

GTN

glyceryl trinitrate

IM

intramuscular

Intra-op

intra-operatively

IV

intravenous

LA

local anaesthetic

LIS

lateral internal sphincterotomy

MFF

micronized flavonoid fraction

MPFF  

micronized purified flavonoid fraction

NRS    

numerical rating scale

PACU

post-anaesthesia care unit

PCA    

patient-controlled analgesia

POD

postoperative day

PONV  

postoperative nausea and vomiting

Postop

postoperatively

Pre-op

pre-operatively

VAS    

visual analogue scale

VIS      

visual intensity scale

VRS    

verbal rating scale

Pre-operative studies

To ensure an adequate analgesic effect in the immediate postoperative period, it may be necessary to administer analgesic medication prior to the postoperative period.

Data in this section are available from studies that assessed pre-operative analgesia versus pre-operative placebo, as well as those that assessed pre-operative analgesia versus the same analgesia given postoperatively (to examine the concept of pre-emptive – or preventive – analgesia).

A meta-analysis of studies comparing pre-operative interventions with similar postoperative interventions in various procedures found that pre-operative NSAIDs and local anaesthetic wound infiltration improved analgesic consumption and time to first rescue analgesic request, but not pain scores. Evidence did not support an improvement in postoperative analgesia following administration of pre-operative NMDA antagonists and opioids (Ong 2005b). A previous systematic review of pre-emptive analgesia for acute or chronic postoperative pain relief in a variety of surgical procedures — such as orthopaedic, dental, gynaecological and abdominal — has concluded that there is no benefit of pre-emptive over postoperative administration (Møiniche 2002).

PROSPECT recommendations

  • Pre-operative gabapentinoids cannot be recommended (Grade D, LoE 4) because there is no procedure-specific evidence and because the benefit:risk ratio is not sufficiently favourable for this ambulatory procedure, despite analgesic efficacy in other procedures (transferable evidence, LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • Three systematic reviews and a meta-analysis evaluated the use of gabapentinoids for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls (
  • Two systematic reviews (
  • Two systematic reviews (

Haemorrhoid surgery-specific evidence

  • None cited

PROSPECT Recommendations

  • Based on transferable evidence showing analgesic efficacy (LoE 1), it is recommended (Grade B) that systemic conventional NSAIDs should be administered at the appropriate time to provide sufficient analgesia in the early recovery period
  • There is not enough evidence at this time to recommend the use of one NSAID over another
  • The use of conventional NSAIDs should depend upon assessment of individual patient risks (Grade B), including bleeding complications, actual or recent gastroduodenal ulcer history (transferable evidence, LoE 1), cardiovascular morbidity (LoE 4), aspirin-sensitive asthma, renal function and hepatic function (transferable evidence, LoE 3)

Clinical practice

  • The risk of bleeding complications from haemorrhoid surgery with pre-operative conventional NSAIDs is not a concern, as haemorrhoid surgery is a short, ambulatory procedure, and bleeding complications are minimal
  • Conventional NSAIDs should be administered at the appropriate time to provide sufficient analgesia when the patient wakes

Transferable evidence

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures (
  • In a randomized controlled trial of patients undergoing anorectal surgery, patients experienced less pain and required fewer rescue analgesics when treated with pre-operative ketorolac (either IV or as an infusion with a local anaesthetic solution) than when treated with placebo
  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression (
  • One randomised trial in patients undergoing vaginal hysterectomy or breast surgery showed that diclofenac was as effective as rofecoxib in terms of postoperative analgesia, but was associated with greater use of anti-emetics and more blood loss 
  • Two meta-analyses comparing pre-incisional and post-incisional NSAIDs/COX-2-selective inhibitors have found no significant benefit of pre-incisional administration for reducing pain scores (
  • Randomised endoscopic trials in healthy elderly volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use (
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo (
  • Meta-analyses of randomised controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls (
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease (
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported (with lumiracoxib; (
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients (
  • Chronic administration of conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication (

Haemorrhoid surgery-specific evidence

  • There were no significant differences between groups receiving IV or caudal ketorolac in VAS pain scores when sitting or supine at any time-point assessed (i.e. at 1, 1.5, 2, 2.5, 3, 4, 5, 6, 10 and 24 h) (
  • There were no significant differences between groups receiving IV or caudal ketorolac in the proportion of patients requiring IV pethidine injection, the number of pethidine doses requested, or the time to first request for rescue analgesia (
  • The incidence of bleeding disorders was significantly lower with caudal ketorolac compared with IV ketorolac (p=0.0098) (
  • The incidence of gastric upsets was significantly lower with caudal ketorolac versus IV ketorolac (p=0.0444) (
  • Study details Yosry 2004 Click here for more information

PROSPECT Recommendation

  • Based on transferable evidence showing analgesic efficacy (LoE 1), it is recommended (Grade B) that COX-2-selective inhibitors should be administered at the appropriate time to provide sufficient analgesia in the early recovery period
  • It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B) (cardiovascular morbidity (transferable evidence, LoE 1), renal function and hepatic function (transferable evidence, LoE 3) or actual or recent gastroduodenal ulcer history (LoE 4)

Clinical practice

  • COX-2-selective inhibitors should be administered at the appropriate time to provide sufficient analgesia when the patient wakes
  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Transferable evidence

  • One randomised trial in patients undergoing vaginal hysterectomy or breast surgery showed that rofecoxib was as effective as diclofenac in terms of postoperative analgesia, but was associated with less use of anti-emetics
  • Rofecoxib 50 mg and parecoxib 40 mg have an equipotent analgesic efficacy relative to traditional NSAIDs in postoperative pain after minor and major surgical procedures (
  • A systematic review to quantify the efficacy of single-dose oral valdecoxib and IV parecoxib demonstrated that both are effective treatments for acute postoperative pain, and show similar incidences of adverse effects
  • Randomised endoscopic trials in healthy elderly volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use (
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation or bleeding time compared with placebo Greenberg et al 2000 Click here for more information
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function (
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following non-cardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) (
  • Two meta-analyses comparing pre-incisional and post-incisional conventional NSAIDs/COX-2-selective inhibitors have found no significant benefit of pre-incisional administration for reducing pain scores (
  • Two clinical trials showed that in patients who had undergone CABG surgery, COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo (
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents (
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported (with lumiracoxib; (
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients (
  • Chronic administration of COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication (

Haemorrhoid surgery-specific evidence

  • None cited

PROSPECT Recommendations

  • Pre-operative parenteral glucocorticoids are recommended (Grade B), based on limited procedure-specific (LoE 1 and 2) and transferable evidence (LoE 1) for analgesic efficacy

Clinical practice

  • None cited

Transferable evidence

  • Dexamethasone significantly reduced pain scores compared with placebo following laparoscopic cholecystectomy (
  • Dexamethasone was shown to prevent postoperative nausea and vomiting after surgery in a systematic review
  • A single prophylactic dose of dexamethasone (4–8 mg) is effective for preventing PONV in surgery associated with high emetic effects (
  • Meta-analyses of randomised controlled trials showed that peri-operative methylprednisolone was not associated with a significant increase in adverse effects after cardiac, non-cardiac and trauma surgery
  • A randomised controlled trial in patients undergoing anorectal surgery demonstrated that pre-operative IV dexamethasone did not increase the incidence of adverse events or the rate of wound infection compared with placebo
  • A randomised controlled trial in patients undergoing anorectal surgery reported comparable pain scores with pre-operative IV dexamethasone versus placebo

Haemorrhoid surgery-specific evidence

  • VAS pain scores were significantly lower with betamethasone versus placebo at 2 h (p<0.04), but not at 0, 1, 3, and 4 h. Verbal pain scores when sitting were significantly lower with betamethasone compared with placebo at 5–24 h (p<0.04), but verbal pain scores at rest were not significantly different at any time point (i.e. at 0, 1, 2, 3, 4 or 5–24 h) (
  • Pain scores (assessed using a verbal categorical scale, where 0=no pain, 1=mild pain, 2=moderate pain, and 3=severe pain) were lower with betamethasone compared with diclofenac, but no statistics were reported (
  • Significantly fewer patients required rescue analgesia (parenteral pethidine 50 mg) in a betamethasone group versus a diclofenac group (p<0.05) (
  • The incidence of postoperative nausea and vomiting was lower with betamethasone compared with placebo, although no statistics were reported (
  • A greater proportion of patients receiving betamethasone (75%) were discharged from hospital on the day of surgery compared with patients receiving diclofenac (0%), although no statistics were reported (
  • Time to eligibility for discharge and time to actual discharge from hospital were not significantly different between groups receiving either betamethasone or placebo (
  • Study details Aasboe 1998 Click here for more information

PROSPECT Recommendation

  • Ketamine cannot be recommended (Grade D, LoE 4) because there is no procedure-specific evidence and because the benefit:risk ratio is not sufficiently favourable for this ambulatory procedure, despite analgesic efficacy in other procedures (transferable evidence, LoE 1)
  • Dextromethorphan is not recommended (Grade D, LoE 4) based on inconclusive procedure-specific evidence and transferable evidence

Clinical practice

  • Administration of IM dextromethorphan is not widely used in clinical practice

Transferable evidence

  • Studies of ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain or opioid use when used as an adjunct to morphine (
  • Low-dose ketamine was associated with few and mild adverse effects, especially when administered in conjunction with general anaesthesia (
  • A systematic review found that dextromethorphan did not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases (
  • Two meta-analyses comparing pre-incisional and postincisional treatments found no significant analgesic benefit of pre-incisional administration of NMDA receptor antagonists (
  • Two systematic reviews of randomised controlled trials comparing magnesium with placebo demonstrated inconclusive results overall with regards to pain scores and supplemental analgesic use

Haemorrhoid surgery-specific evidence

  • Highest VAS pain scores were significantly lower with oral dextromethorphan 240 mg compared with placebo (p<0.001); there were no significant differences between oral dextromethorphan 120 mg and placebo groups (
  • Worst pain scores were significantly lower with IM dextromethorphan + CPM compared with CPM alone (p<0.001) (
  • In a group receiving IM dextromethorphan + CPM, the total pethidine consumption was significantly lower, compared with a group receiving CPM alone (p<0.001). The proportion of patients who required pethidine injection was significantly fewer with dextromethorphan + CPM versus CPM alone (p<0.005) (
  • Total pethidine consumption was significantly lower with oral dextromethorphan 240 mg compared with placebo (p<0.001); there were no significant differences between oral dextromethorphan 120 mg and placebo groups, and no significant differences in the proportion of patients who required pethidine injections between any of the three groups were observed (
  • The time to first pethidine injection was significantly longer with IM dextromethorphan + CPM compared with CPM alone (p=0.006) (
  • Patients receiving oral dextromethorphan 240 mg had a significantly longer time to first pethidine injection compared with patients receiving placebo (p<0.001); there were no significant differences between oral dextromethorphan 120 mg and placebo groups (
  • The incidence of pethidine-related side-effects (nausea, vomiting, dizziness and headache) was significantly lower with oral dextromethorphan 240 mg compared with placebo (p<0.05); the incidence was similar with oral dextromethorphan 120 mg and placebo (
  • The incidence of pethidine-related side-effects (such as nausea, vomiting, dizziness and headache) was similar with IM dextromethorphan + CPM and CPM alone (
  • The incidence of urinary retention was comparable between patients receiving IM dextromethorphan + CPM and those receiving CPM alone (
  • There was no significant difference in the incidence of postoperative bleeding in patients receiving IM dextromethorphan + CPM and those receiving CPM alone (
  • Study details Liu 2000 Click here for more information

PROSPECT Recommendations

  • Pre-incisional administration of strong opioids, including transdermal fentanyl, is not recommended (Grade D, LoE 4) due to lack of procedure-specific and transferable evidence

Clinical practice

  • The use of a transdermal patch is not feasible, as haemorrhoid surgery is an outpatient procedure and it is not practical to administer the patch 6 h prior to surgery
  • The use of transdermal fentanyl patches is contraindicated in settings of acute and postoperative pain, in particular in opioid-naiive patients, due to the risk of severe respiratory depression; fatal outcomes have been reported
  • Strong opioids cause constipation, which may hinder recovery
  • Non-opioid analgesics should be used instead of opioids to avoid the risk of constipation

Transferable evidence

  • Strong opioids are effective for reducing high- and moderate-intensity postoperative pain (
  • Pethidine induced significantly higher sedation and respiratory depression compared with tramadol (both 100 mg intravenously) in patients undergoing orthopaedic surgery (n=48) (
  • Strong opioids are associated with adverse effects, including nausea, vomiting, sedation, confusion, paralytic ileus and urinary retention (

Haemorrhoid surgery-specific evidence

  • VAS pain scores were significantly lower with the fentanyl patch compared with the placebo patch at 12, 16 and 24 h (all p<0.05), but not at 6, 30, 36, 48 and 72 h (
  • Consumption of rescue analgesia was significantly lower with the fentanyl patch compared with the placebo patch (IM pethidine, and propoxyphene tablets from 24–72 h; both p<0.05) (
  •  No patients reported pruritus with the fentanyl patch and only one patient reported pruritus with the placebo patch (
  • The incidence of postoperative nausea and vomiting was similar with the fentanyl patch and the placebo patch (
  • The number of patients with urinary retention was similar with the fentanyl patch and the placebo patch (
  • Study details Kilbride 1994 Click here for more information

PROSPECT Recommendations

  • It is recommended (Grade B) that paracetamol should be administered at the appropriate time to provide sufficient analgesia in the early recovery period, based on transferable evidence showing efficacy for treating pain of moderate intensity (LoE 1)

Clinical practice

  • It is considered that paracetamol is ineffective as a single therapy for treatment of high-intensity pain (VAS >/=50 mm)

Transferable evidence

  • Paracetamol is an effective analgesic for the treatment of postoperative pain of moderate intensity (
  • There is evidence that concurrent use of paracetamol and conventional NSAIDs improves pain relief compared with paracetamol alone, but there is no evidence for a superior analgesic effect of the combination compared with conventional NSAIDs alone (

Haemorrhoid surgery-specific evidence

  • None cited

PROSPECT Recommendations

  • Laxatives are recommended (Grade A) in the days prior to surgery, as an adjunct to analgesic therapy, based on procedure-specific evidence (LoE 1 and 2)

Clinical Practice

  • Stool softeners are an alternative to laxatives in clinical practice

Transferable Evidence

  • None cited

Haemorrhoid surgery-specific evidence

  • Two studies out of two demonstrated that laxatives caused a significant reduction in pain scores on defecation compared with placebo/control London 1987 Click here for more information
  • There was a significant reduction in VAS pain scores on day 10 with Plantago ovata compared with control (p<0.01), but not on day 20 (
  • In one study, oral paracetamol requirements after defecation were significantly lower with lactulose compared with placebo (p<0.01), although IM papaveretum consumption was not significantly different between groups, and analgesic requirements before defecation (papaveretum and paracetamol) were similar (
  • Two studies out of two demonstrated a shorter length of hospital stay with laxatives compared with placebo/control (
  • The tenesmus rate in patients in a Plantago ovata group was significantly lower than in patients in a control group (p<0.01) (
  • The time to first bowel action was significantly shorter in patients receiving lactulose compared with patients receiving placebo (p=0.01), although the number of bowel actions in the first week was not significantly different between groups (p=0.05) (
  • There were no significant differences between groups treated with lactulose and placebo in VAS or VRS pain scores in the 24 h preceding defecation on POD 1–3 (
  • Study details London 1987 Click here for more information

PROSPECT Recommendations

  • Topical EMLA is not recommended (Grade B) based on limited procedure-specific evidence (LoE 1) showing a lack of analgesic benefit

Clinical Practice

  • None cited

Tranferable Evidence

  • None cited

Haemorrhoid surgery-specific evidence

  • Pain scores were not significantly different between groups receiving EMLA or placebo cream (
  • Patient satisfaction scores with the procedure as a whole were similar with EMLA cream and placebo cream (
  • Study details Roxas 2003 Click here for more information

PROSPECT Recommendations

  • When used as an adjunct to anaesthesia, perianal LA infiltration is recommended for intra- and postoperative analgesia (Grade A), based on procedure-specific evidence for analgesic efficacy (LoE 1)

Clinical Practice

  • Haemorrhoid surgery is a short procedure, and therefore the effects of LA infiltration may be most beneficial when administered pre-operatively
  • Long-acting local anaesthetics are preferred to short-acting local anaesthetics for analgesia by local injection
  • Epinephrine is commonly used for LA infiltration, as it is often combined in a preparation with lidocaine and some other LAs

Transferable Evidence

  • There is evidence from a variety of surgical procedures that the efficacy of local anaesthetics for postoperative analgesia is similar following pre-operative or post-incisional administration
  • A systematic review of local anaesthesia infiltration showed inconclusive evidence of analgesic efficacy in hysterectomy, open cholecystectomy and a variety of other surgical procedures, but consistent and clinically relevant pain relief in herniorraphy (Moiniche 1998). Also see the Herniorraphy review at www.postoppain.org: Pre-operative or Intra-operative section, Local Anaesthetic Techniques, Inguinal nerve block/field block/infiltration and instillation

Haemorrhoid surgery-specific evidence

  • Two studies out of two demonstrated lower VAS pain scores at rest with LA infiltration compared with placebo Morisaki 1996 Click here for more information
  • One study out of one reported significantly lower VAS pain scores during coughing with LA infiltration compared with placebo on POD3 (p<0.05), but not on POD1–2 (
  • One study out of two demonstrated lower VAS pain scores on first bowel movement with LA (lidocaine) infiltration compared with placebo (p<0.05;
  • In two studies out of two, rescue analgesic requirements were lower with LA infiltration compared with placebo Morisaki 1996 Click here for more information
  • In one study out of one, the time to first analgesic request was significantly longer with LA infiltration compared with placebo (p=0.02;
  • In one study out of one, the time to first passage of faeces was similar with LA infiltration and placebo (
  • In one study out of one, micturition difficulties occurred with a similar frequency in patients receiving LA infiltration or placebo, and there was no reported incidence of nausea or vomiting in either group (
  • Study details Morisaki 1996 Click here for more information

PROSPECT Recommendations

  • Nerve blocks (perineal, pudendal, ischiorectal fossa blocks), as adjuncts to anaesthesia, are recommended for intra- and postoperative analgesia (Grade A) based on procedure-specific evidence for analgesic efficacy (LoE 1)
  • No recommendation can be made regarding the choice of nerve block at this time due to a lack of procedure-specific evidence directly comparing different blocks
  • Perianal LA infiltration may be preferable to nerve blocks because of the simplicity of administration (Grade D, LoE 4) but there is a lack of procedure-specific evidence comparing these techniques

Clinical Practice

  • Perineal and pudendal nerve blocks require clinical experience, and their risks and benefits have not yet been evaluated in comparison with perianal LA infiltration

Transferable Evidence

  • A randomised study reported similar pain scores, satisfaction scores and incidences of urinary retention and bleeding with local perianal nerve block and with regional anaesthesia (spinal or caudal), in patients undergoing a variety of anorectal procedures (including haemorrhoidectomy, fistulectomy, lateral sphincterotomy, excision of anal polyps, and drainage of abscesses)

Haemorrhoid surgery-specific evidence

  • VAS pain scores were significantly lower with posterior perineal block compared with no injection at 1, 2, 4, 8 and 24 h (all p=0.001), but not at 12 h (
  • Consumption of IV morphine in the PACU and 24 h morphine consumption were significantly lower with posterior perineal block compared with no injection (both p<0.001) (
  • Patients receiving posterior perineal block had a shorter duration of PACU stay compared with patients receiving no injection (p<0.001), although duration of hospital stay was not significantly different between groups (
  • Patient satisfaction scores were significantly higher with posterior perineal block compared with no injection (p<0.05) (
  • VAS pain scores were significantly lower with ischiorectal fossa block compared with no block at 30 min (p=0.0313), 4 h (p=0.0144) and 24 h (p=0.0015), but not at 2 h (
  • Two studies out of two demonstrated that patient satisfaction was significantly higher with GA plus pudendal nerve block compared with GA plus placebo nerve blocks and/or GA alone (
  • Two out of two studies showed that patients receiving GA plus pudendal nerve block resumed normal activities in a significantly shorter period of time compared with GA plus placebo nerve blocks and/or GA alone (
  • Two out of two studies demonstrated significantly lower VAS pain scores with GA plus pudendal nerve block compared with GA plus placebo nerve blocks or GA alone Naja 2005 Click here for more information
  • Two out of two studies demonstrated that patients receiving GA plus pudendal nerve block had significantly fewer days of pain during walking (p=0.001) and while sitting (p=0.0001) compared with patients receiving GA plus placebo nerve blocks or GA alone (
  • Two out of two studies showed that significantly fewer patients required opioid-containing analgesics during the first 6 days after surgery with GA plus pudendal nerve block compared with GA plus placebo nerve blocks and/or GA alone (IM pethidine 1 mg/kg if VAS >/=40, oral dextropropoxifen 30 mg + paracetamol 400 mg if VAS<40) (
  • One study out of two showed that the incidence of urinary retention was significantly lower with GA plus pudendal nerve block compared with GA alone (p=0.004), although the incidence of urinary incontinence was similar between groups ( Naja 2005 Click here for more information
  • Two studies out of two reported that the length of hospital stay was significantly shorter with GA plus pudendal nerve block compared with GA plus placebo nerve blocks and/or GA alone (
  • The length of hospital stay was similar with ischiorectal fossa block and no block (
  • There were no significant differences in parenteral fentanyl, oral oxycodone, or 'simple analgesia' (dextropropoxyphene + paracetamol, or paracetamol alone) requirements, in patients treated with either ischiorectal fossa block or no block
  • Two studies out of two reported that the incidences of nausea and vomiting were similar with GA plus pudendal nerve block compared with GA plus placebo nerve blocks and/or GA alone (
  • There were no incidences of nausea or vomiting, fecaloma or urinary retention in patients receiving either posterior perineal block or no injection (
  • Patients treated with either posterior perineal block or no injection had a similar time to first bowel action (
  • Study details Naja 2005 Click here for more information
  • Pudendal nerve block versus placebo nerve block/no treatment (GA in all groups)
  • Ischiorectal fossa block versus no block (perianal infiltration and GA in both groups)
  • Study details Luck 2000 Click here for more information
  • Study details Brunat 2003 Click here for more information
  • Posterior perineal injection versus no treatment (GA in both groups)

PROSPECT Recommendations

  • Caudal LA or opioid reduces postoperative pain (procedure-specific evidence, LoE 1 and 2), but is not recommended (Grade D, LoE 4), due to an insufficient risk:benefit ratio

Clinical Practice

  • The risk of side-effects associated with caudal analgesia may outweigh the analgesic benefits in routine haemorrhoid surgery

Transferable evidence

  • In a randomised study of elective perianal surgery, patients who received either a caudal injection of bupivacaine or diamorphine had better analgesia than patients receiving a control injection. Side-effects were less frequent with caudal diamorphine compared with caudal bupivacaine or control; 41% of patients treated with caudal bupivacaine experienced urinary retention and one patient required temporary catheterisation

Haemorrhoid surgery-specific evidence

  • On POD1, pain scores were significantly lower with caudal infiltration of bupivacaine versus lidocaine (p<0.05), morphine versus lidocaine (p<0.05), and morphine-lidocaine versus lidocaine (p<0.01). On POD2, pain scores were significantly lower with caudal infiltration of bupivacaine versus lidocaine (p<0.01), morphine versus lidocaine (p<0.05), and no injection versus lidocaine (p<0.01). There were no significant differences in pain scores between any other groups (
  • The proportion of patients requiring postoperative opiates was significantly fewer with the group receiving caudal infiltration of morphine and the group receiving caudal infiltration of morphine-lidocaine compared with the group receiving caudal injection of lidocaine (both p<0.05); there were no significant differences between any other groups (
  • Patients in a morphine caudal infiltration group and in a bupivacaine caudal infiltration group had a significantly longer duration of analgesia compared with patients receiving no injection (p<0.01), or patients in a lidocaine caudal infiltration group (p<0.01). Patients receiving caudal infiltration of morphine-lidocaine had a significantly longer duration of analgesia compared with those receiving no injection (p<0.05). There were no significant differences between any other groups (
  • The number of patients reporting no pain was significantly fewer with caudal injection compared with local infiltration on awakening (p<0.05) and at 3 and 6 h (both p<0.01), but not at 12, 24 and 48 h, on pack removal, or at first bowel action (
  • VAS pain scores were significantly lower with caudal injection compared with local infiltration on awakening, at 3 h (both p<0.05), at 6 h (p<0.01) and at first bowel action (p<0.05), but not at 12, 24 and 48 h or on pack removal (
  • The incidence of gastric upsets was significantly lower with caudal ketorolac versus IV ketorolac (p=0.0444) (
  • The incidence of bleeding disorders was significantly lower with caudal ketorolac compared with IV ketorolac (p=0.0098) (
  • The postoperative complication rate (including urinary retention, haemorrhage and infection) was similar with caudal injection and local infiltration (
  • There was no significant difference in the length of hospital stay with caudal injection and local infiltration (
  • The time to first bowel action was similar with caudal injection and local infiltration (
  • There were no significant differences between patients receiving caudal injection or local infiltration in number of patients requiring supplementary analgesia (IM papaveretum or oral coproxamol), the mean number of requests for analgesia, or the time to first analgesia (
  • There were no significant differences between groups receiving caudal or IV ketorolac in the proportion of patients requiring IV pethidine injection, the number of pethidine doses requested, or the time to first request for rescue analgesia (
  • There were no significant differences between groups receiving caudal or IV ketorolac in VAS pain scores when sitting or supine at any time-point assessed (i.e. at 1, 1.5, 2, 2.5, 3, 4, 5, 6, 10 and 24 h) (
  • The requirement for urinary catheterisation was higher with groups receiving a caudal injection compared with those receiving no injection, but no statistics were reported (
  • There were no significant differences in nausea or micturition scores between groups receiving a caudal injection of bupivacaine, lidocaine, morphine, morphine-lidocaine, or no injection (
  • Caudal LA injection versus local wound infiltration (GA in both groups)
  • Study details Pryn 1989 Click here for more information
  • Study details Yosry 2004 Click here for more information
  • Caudal NSAID versus IV NSAID
  • Study details Pybus 1983 Click here for more information
  • Caudal infiltration with or without opioid or LA, versus placebo (GA in all groups)

PROSPECT Recommendations

  • No recommendation can be made regarding the choice of anaesthetic technique (local anaesthesia versus spinal anaesthesia [appropriate ‘short-duration’ spinal] versus general anaesthesia), due to limited procedure-specific evidence
  • Addition of adjuncts to the spinal LA solution is not recommended (Grade D, LoE 4) due to potential side-effects

Clinical Practice

  • The type of spinal anaesthesia used should be appropriate for ambulatory procedures
  • As haemorrhoid surgery is performed on an outpatient basis, there may be safety concerns regarding administration of spinal opioids, such as the potential for delayed respiratory depression
  • Epinephrine is commonly used for LA infiltration, as it is often combined in a preparation with lidocaine and some other LAs
  • Perineal and pudendal nerve blocks require clinical experience, and their risks and benefits have not yet been evaluated in comparison with perianal LA infiltration
  • The questions around neurotoxicity of midazolam are not yet resolved and it should not be used spinally or epidurally in view of uncertain safety

Transferable Evidence

  • A randomised study reported similar pain scores, satisfaction scores and incidences of urinary retention and bleeding with regional anaesthesia (spinal or caudal) and with local perianal nerve block, in patients undergoing a variety of anorectal procedures (including haemorrhoidectomy, fistulectomy, lateral sphincterotomy, excision of anal polyps, and drainage of abscesses)
  • Spinal administration of strong opioids is associated with side-effects including pruritus, PONV, urinary retention, and respiratory depression (

Haemorrhoid surgery-specific evidence

  • The time to the first administration of pain medication was significantly longer with spinal bupivacaine + 1 mg midazolam and spinal bupivacaine + 2 mg midazolam compared with spinal bupivacaine + saline (both p<0.01), and significantly longer with spinal bupivacaine + 2 mg midazolam compared with spinal bupivacaine + 1 mg midazolam (p<0.05;
  • The number of administrations of oral analgesic tablets requested in 24 h was significantly fewer with spinal bupivacaine + 1 mg midazolam and spinal bupivacaine + 2 mg midazolam compared with spinal bupivacaine + saline (both p<0.01) (two paracetamol 300 mg + codeine 30 mg tablets taken every 4 h as needed) (
  • Fewer patients receiving spinal bupivacaine + morphine requested supplementary morphine (10 mg IM) compared with patients receiving spinal bupivacaine alone, but no statistics were reported (
  • Pain scores (assessed on a scale from 0–3) were significantly lower with spinal bupivacaine + morphine compared with spinal bupivacaine alone at 4 (p<0.05) and 6 h (p<0.001), but not at 2, 8, 10 or 12 h (
  • A significantly lower number of patients required urinary catheterisation with pudendal nerve block compared with spinal anaesthesia (p<0.001;
  • The time to first experiencing postoperative pain was significantly longer with pudendal nerve block compared with spinal anaesthesia (p<0.001;
  • The number of patients requiring analgesics and the total number of injections administered were significantly lower with pudendal nerve block compared with spinal anaesthesia (both p<0.001;
  • The maximal VAS pain score was significantly lower with pudendal nerve block compared with spinal anaesthesia (p<0.001;
  • The incidences of urinary retention, sedation and nausea/vomiting were similar with spinal bupivacaine + 1 mg midazolam, spinal bupivacaine + 2 mg midazolam, and spinal bupivacaine + saline (
  • The time to first self-voiding was similar with spinal bupivacaine + 1 mg midazolam, spinal bupivacaine + 2 mg midazolam, and spinal bupivacaine + saline (
  • VAS pain scores at the time of the first administration of pain medication were not significantly different between groups treated with spinal bupivacaine + 1 mg midazolam, spinal bupivacaine + 2 mg midazolam, and spinal bupivacaine + saline (
  • The incidence of urinary retention was similar with spinal bupivacaine + morphine and spinal bupivacaine alone (
  • The incidence of bleeding was not significantly different with local anaesthetic infiltration (n=1) and spinal anaesthesia (n=2) (
  • The incidence of urinary retention was not significantly different with local anaesthetic infiltration (n=0) and spinal anaesthesia (n=1) (
  • The number of days that patients required analgesics (paracetamol 1 g and codeine 16 mg every 6 h) was similar with local anaesthetic infiltration and spinal anaesthesia (
  • VAS pain scores at 6 and 24 h were not significantly different between patients undergoing local anaesthetic infiltration or spinal anaesthesia (
  • There were no significant differences in pain scores after infiltration of local anaesthetic or immediately after the operation in patients undergoing the Nivatvongs technique versus conventional LA infiltration (
  • The incidence of persistent pain or discomfort was similar with the Nivatvongs technique and conventional LA infiltration (
  • The incidence of fecal impaction was similar with the Nivatvongs technique and conventional LA infiltration (
  • Patient satisfaction with the anaesthesia and with the whole procedure were similar with the Nivatvongs technique and conventional LA infiltration (
  • Local anaesthetic infiltration versus spinal anaesthesia
  • Intra-anal injection (Nivatvongs technique) versus conventional local anaesthetic infiltration
  • Study details Roxas 2006 Click here for more information
  • Study details Kim 2001 Click here for more information
  • Spinal LA with or without midazolam
  • Pudendal nerve block versus spinal anaesthesia
  • Study details Ong 2005 Click here for more information
  • Study details Amanor-Boadu 1992 Click here for more information
  • Spinal LA with or without morphine
  • Study details Kim 2005 Click here for more information

Intra-operative analgesia

To ensure an adequate analgesic effect in the immediate postoperative period, it may be necessary to administer analgesic medication prior to the postoperative period, e.g. conventional NSAIDs, COX-2-selective inhibitors, paracetamol

PROSPECT Recommendations

  • Injection of botulinum toxin is not recommended (Grade D, LoE 4), due to inconsistent procedure-specific evidence for analgesic benefit in the postoperative period

Clinical Practice

  • The injection of botulinum toxin for pain after haemorrhoid surgery is not performed routinely in clinical practice

Transferable Evidence

  • None cited

Haemorrhoid surgery-specific evidence

  • Two out of two studies demonstrated a decrease in pain scores with Botox injection compared with placebo injection Davies 2003 Click here for more information
  • One study out of two showed a decrease in rescue analgesic consumption with Botox compared with placebo Patti 2005 Click here for more information
  • In one study out of one, the time to complete healing of wounds was significantly shorter with Botox compared with placebo (p<0.001;
  • In one study out of one, the time to return to work was significantly shorter in a Botox group versus a placebo group (p<0.05;
  • The time to first defecation was similar in groups receiving either Botox or placebo in two out of two studies (
  • In one study out of one, the incidence of anal incontinence was similar with Botox and placebo (
  • In one study out of one, the incidence of urinary retention was similar with Botox and placebo (
  • In two studies out of two, there was no significant difference in the length of hospital stay with Botox and placebo (
  • Study details Davies 2003 Click here for more information

PROSPECT Recommendations

  • Stapled haemorrhoid surgery is recommended (Grade A) based on reduced pain compared with other surgical techniques (procedure-specific evidence, LoE 1)
  • The choice of haemorrhoid operative techniques may depend on factors other than postoperative pain alone

Clinical Practice

  • The choice of haemorrhoid operative technique may depend on factors other than postoperative pain alone

Transferable Evidence

  • None cited

Haemorrhoid surgery-specific evidence

  • Closed versus open haemorrhoidectomy
  • Closed versus closed haemorrhoidectomy

PROSPECT Recommendations

  • No recommendation can be made regarding the choice of haemorrhoid dissection technique based on their effect on postoperative pain alone

Clinical Practice

  • None cited

Transferable Evidence

  • None cited

Haemorrhoid surgery-specific evidence

  • Summary of studies Click here for more information
  • Diathermy dissection versus conventional scissors dissection
  • Harmonic Scalpel™ dissection versus conventional scissors dissection
  • Dissection with radiofrequency bistoury versus conventional scissors dissection
  • Diathermy dissection versus Harmonic Scalpel™ dissection
  • LigaSure™ diathermy dissection versus conventional diathermy dissection
  • Cold scalpel dissection versus laser dissection

PROSPECT Recommendations

  • Lateral sphincterotomy as an adjunct to haemorrhoid surgery is not recommended for analgesia (Grade D, LoE 4) due to limited and inconsistent procedure-specific evidence
  • The use of an anal dilator as an adjunct to haemorrhoid surgery is not recommended for analgesia (Grade D, LoE 4) based on limited procedure-specific evidence

Clinical Practice

  • None cited

Transferable Evidence

  • None cited

Haemorrhoid surgery-specific evidence

  • Open haemorrhoidectomy, with or without lateral sphincterotomy
  • Closed haemorrhoidectomy, with or without lateral sphincterotomy
  • Diathermy haemorrhoidectomy, with or without lateral sphincterotomy
  • Anal dilator versus no treatment

Postoperative studies 

Data in this section are available from studies that assessed postoperative analgesia versus postoperative placebo, as well as those that assessed postoperative analgesia versus the same analgesia given pre-operatively or intra-operatively.

PROSPECT Recommendations

  • Postoperative gabapentinoids cannot be recommended (Grade D, LoE 4) because there is no procedure-specific evidence and because the benefit:risk ratio is not sufficiently favourable for this ambulatory procedure, despite analgesic efficacy in other procedures (transferable evidence, LoE 1)

Clinical Practice

  • None cited

Transferable Evidence

  • Three systematic reviews and a meta-analysis evaluated the use of gabapentinoids for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls (
  • Two systematic reviews (
  • Two systematic reviews (

Haemorrhoid surgery-specific evidence

  • None cited

PROSPECT Recommendations

  • Postoperative systemic conventional NSAIDs are recommended (Grade B) based on transferable evidence showing analgesic efficacy (LoE 1)
  • There is not enough evidence at this time to recommend the use of one NSAID over another
  • The use of conventional NSAIDs should depend upon assessment of individual patient risks (Grade B), including bleeding complications, actual or recent gastroduodenal ulcer history (transferable evidence, LoE 1), cardiovascular morbidity (LoE 4), aspirin-sensitive asthma, renal function and hepatic function (transferable evidence, LoE 3)

Clinical Practice

  • Conventional NSAIDs should be administered at the appropriate time to provide sufficient analgesia when the patient wakes

Transferable Evidence

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures (
  • One randomized study in patients undergoing colorectal resection demonstrated that patients receiving IV PCA morphine plus ketorolac required significantly less rescue analgesic than patients receiving IV PCA morphine alone (with comparable pain scores), although recovery of bowel function was not significantly different between the two groups
  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression (
  • Randomised endoscopic trials in healthy elderly volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use (
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo (
  • Meta-analyses of randomised controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls (
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease (
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported (with lumiracoxib;
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients (
  • Chronic administration of conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication (

Haemorrhoid surgery-specific evidence

  • The time to first bowel movement was significantly shorter in a group receiving diflunisal compared with a group receiving oral paracetamol + weak opioid (p<0.05;
  • Pain scores (rated on a scale from 0–3) were not significantly different in groups receiving either diflunisal or oral paracetamol + weak opioid, at any time point assessed (i.e. at 4 h intervals from 16–72 h) (
  • There were no significant differences between groups treated with either nimesulide or naproxen in VAS pain scores at any time point recorded (i.e. twice per day on POD 1, 2, 3, 4, 11, and 20) (
  • Pain scores (assessed using a verbal categorical scale, where 0=no pain, 1=mild pain, 2=moderate pain, and 3=severe pain) were higher with diclofenac compared with betamethasone, but no statistics were reported (
  • The proportion of patients requiring additional IM pethidine injections as rescue analgesia was similar with diflunisal and oral paracetamol + weak opioid (
  • A significantly higher proportion of patients required rescue analgesia (parenteral pethidine 50 mg) in a diclofenac group versus a betamethasone group (p<0.05;
  • More patients receiving betamethasone (75%) were discharged from hospital on the day of surgery compared with patients receiving diclofenac (0%), although no statistics were reported (
  • Global efficacy as assessed by patients and doctors was similar with nimesulide and naproxen (
  • Length of hospital stay was comparable with diflunisal and oral paracetamol + weak opioid (
  • Study details Madsen 1987 Click here for more information

PROSPECT Recommendations

  • Postoperative COX-2-selective inhibitors are recommended (Grade B) based on transferable evidence showing analgesic efficacy (LoE 1)
  • It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B) (cardiovascular morbidity (transferable evidence, LoE 1), renal function and hepatic function (transferable evidence, LoE 3) or actual or recent gastroduodenal ulcer history (LoE 4)

Clinical Practice

  • COX-2-selective inhibitors should be administered at the appropriate time to provide sufficient analgesia when the patient wakes
  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Transferable Evidence

  • Rofecoxib 50 mg and parecoxib 40 mg have an equipotent analgesic efficacy relative to traditional NSAIDs in postoperative pain after minor and major surgical procedures (
  • A systematic review to quantify the efficacy of single-dose oral valdecoxib and IV parecoxib demonstrated that both are effective treatments for acute postoperative pain, and show similar incidences of adverse effects
  • Randomised endoscopic trials in healthy elderly volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use (
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation or bleeding time compared with placebo Greenberg et al 2000 Click here for more information
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function (
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following non-cardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) (
  • Two clinical trials showed that in patients who had undergone CABG surgery, COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo (
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents (
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported (with lumiracoxib;
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients (
  • Chronic administration of COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication (

Haemorrhoid surgery-specific evidence

  • None cited

PROSPECT Recommendations

  • Ketamine cannot be recommended (Grade D, LoE 4) because there is no procedure-specific evidence at this time and because the benefit:risk ratio is not sufficiently favourable for this ambulatory procedure, despite analgesic efficacy in other procedures (transferable evidence, LoE 1)
  • Dextromethorphan is not recommended (Grade D, LoE 4) based on inconclusive procedure-specific and transferable evidence

Clinical Practice

  • Administration of IM dextromethorphan is not widely used in clinical practice

Transferable Evidence

  • Studies of ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain or opioid use when used as an adjunct to morphine (
  • Low-dose ketamine was associated with few and mild adverse effects, especially when administered in conjunction with general anaesthesia (
  • A systematic review found that dextromethorphan did not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases (
  • Two meta-analyses comparing pre-incisional and postincisional treatments found no significant analgesic benefit of pre-incisional administration of NMDA receptor antagonists (
  • Two systematic reviews of randomised controlled trials comparing magnesium with placebo demonstrated inconclusive results overall with regards to pain scores and supplemental analgesic use

Haemorrhoid surgery-specific evidence

  • In a group receiving IM dextromethorphan + CPM, the total pethidine consumption was significantly lower compared with a group receiving CPM alone (p<0.001). The proportion of patients who required pethidine injection was significantly fewer with IM dextromethorphan + CPM versus CPM alone (p<0.005;
  • The time to first pethidine injection was significantly longer with IM dextromethorphan + CPM compared with CPM alone (p=0.006;
  • The incidence of pethidine-related side-effects (such as nausea, vomiting, dizziness and headache) was significantly lower with IM dextromethorphan + CPM compared with CPM alone (p<0.025;
  • Worst pain scores in patients requesting pethidine were not significantly different with IM dextromethorphan + CPM compared with CPM alone (
  • Study details Chang 1999 Click here for more information

PROSPECT Recommendations

  • Strong opioids are recommended for moderate-to-high intensity postoperative pain (VAS>/= 30 mm) (Grade B), to supplement oral paracetamol and conventional NSAIDs/COX-2-selective inhibitors, based on transferable evidence for analgesic efficacy (LoE 1)

Clinical Practice

  • Strong opioids cause constipation, which may hinder recovery
  • Where possible, non-opioid analgesics should be used instead of opioids to avoid the risk of constipation

Transferable Evidence

  • Strong opioids are effective for reducing high- and moderate-intensity postoperative pain (
  • A systematic review comparing intravenous PCA opioids with intravenous, intramuscular or subcutaneous opioids by injection showed that PCA opioids were associated with greater pain relief, reduced supplemental analgesic requirements (analysis of eleven studies, total n=691), and more patients preferred PCA opioids (analysis of four trials, total n=352) compared with traditional opioid analgesia (
  • A quantitative systematic review showed that opioid by PCA provided better pain control and greater patient satisfaction than conventional opioid parenteral analgesia in a variety of surgical procedures (37/56 trials used IM analgesia in the control group) (
  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that combination of morphine plus NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression, compared with morphine alone (
  • A systematic review showed that patients using PCA consumed a greater quantity of opioids than those treated using conventional opioid parenteral analgesia, and had a higher incidence of pruritus, but a similar incidence of other side-effects, in a variety of surgical procedures. There was no difference between groups in the length of hospital stay (
  • Pethidine induced significantly higher sedation and respiratory depression compared with tramadol (both 100 mg intravenously) (n=48;
  • Strong opioids are associated with adverse effects, including nausea, vomiting, sedation, confusion, paralytic ileus and urinary retention (
  • One study comparing PCA with conventional pain therapy (CPT; IV piritramide or oral/IM tramadol) demonstrated an increased consumption of postoperative analgesic in the PCA group compared with the CPT group (p<0.01), although the PCA group reported a significantly greater satisfaction with pain therapy compared with the CPT group (p<0.01; n=42 patients)

Haemorrhoid surgery-specific evidence

  • None cited

PROSPECT Recommendations

  • Weak opioids are recommended for low-to-moderate intensity postoperative pain (VAS<50 mm) (Grade B), to supplement oral paracetamol and conventional NSAIDs/COX-2-selective inhibitors, based on transferable evidence for analgesic efficacy (LoE 1)

Clinical Practice

  • Weak opioids cause constipation, which may hinder recovery
  • Non-opioid analgesics should be used instead of opioids to avoid the risk of constipation
  • Tramadol causes less constipation than conventional opioids

Transferable Evidence

  • Tramadol was more effective than placebo for pain relief in a meta-analysis of post-surgical patients
  • The combination of tramadol and paracetamol enhances analgesic efficacy compared with either agent alone
  • A systematic review found that the combination of dextropropoxyphene 65 mg with paracetamol 650 mg showed similar efficacy to tramadol 100 mg
  • A systematic review found that the combination of codeine with paracetamol provided additional pain relief compared with paracetamol alone
  • A meta-analysis of randomised controlled trials found that the combination of codeine with ibuprofen caused an enhanced analgesic effect compared with ibuprofen alone, although the incidence of adverse effects was increased
  • Two studies found that codeine 30 mg + paracetamol 300 mg was associated with a higher incidence of constipation and vomiting than tramadol 37.5 mg + paracetamol 325 mg following arthroscopy
  • Adverse effects associated with tramadol include headache, nausea, vomiting, dizziness, and somnolence. A meta-analysis of individual patient data from randomised controlled trials found a dose-response of adverse effects with tramadol; postsurgical patients had fewer side-effects than dental patients
  • A systematic review found that the combination of codeine with paracetamol was associated with an increase in drowsiness and dizziness compared with paracetamol alone
  • A systematic review found an increased incidence of central nervous system adverse effects with paracetamol 650 mg plus dextropropoxyphene 65 mg compared with placebo, but the incidence of other adverse effects was reduced compared with tramadol 100 mg

Haemorrhoid surgery-specific evidence

  • None cited

PROSPECT Recommendations

  • Postoperative paracetamol is recommended (Grade B), based on transferable evidence (LoE 1) showing efficacy for low-moderate pain (VAS <50 mm)
  • Paracetamol alone is not recommended for high-intensity pain (VAS >/=50 mm) (Grade B), based on transferable evidence (LoE 1) showing a lack of analgesic efficacy

Clinical Practice

  • It is considered that paracetamol is ineffective as a single therapy for treatment of high-intensity pain (VAS>50 mm)

Transferable Evidence

  • Paracetamol is an effective analgesic for the treatment of postoperative pain of moderate intensity (
  • There is evidence that concurrent use of paracetamol and conventional NSAIDs improves pain relief compared with paracetamol alone, but there is no evidence for a superior analgesic effect of the combination compared with conventional NSAIDs alone

Haemorrhoid surgery-specific evidence

  • None cited

PROSPECT Recommendations

  • Injection of botulinum toxin is not recommended (Grade D, LoE 4), due to inconsistent procedure-specific evidence for analgesic benefit in the postoperative period

Clinical Practice

  • The injection of botulinum toxin for pain after haemorrhoid surgery is not performed routinely in clinical practice

Transferable Evidence

  • None cited

Haemorrhoid surgery-specific evidence

  • Overall pain at rest was significantly lower with Botox versus glyceryl trinitrate (GTN) ointment (p<0.01), although overall pain during defecation was similar between groups (
  • Significantly fewer nimesulide tablets (100 mg) were consumed by patients receiving Botox compared with those treated with GTN ointment (p<0.05;
  • The incidence of adverse events potentially related to drug treatment was significantly lower with Botox compared with GTN (p<0.03; 5 patients receiving GTN reported transient moderate-to-severe headaches) (
  • The time to complete healing of perianal wounds was similar with Botox and GTN ointment (
  • The time to first defecation was similar in groups treated with either Botox injection or GTN ointment (
  • The incidence of anal incontinence was comparable between groups receiving either Botox injection or GTN ointment (
  • The incidence of urinary retention was not significantly different between groups treated with either Botox injection or GTN ointment (
  • The time to return to work was similar with Botox and GTN (
  • There was no significant difference in the length of hospital stay in a Botox group versus a GTN group (
  • Study details Patti 2006 Click here for more information

PROSPECT Recommendations

  • Flavonoids are not recommended (Grade D, LoE 4) because of limited and inconclusive procedure-specific evidence

Clinical Practice

  • None cited

Transferable Evidence

  • None cited

Haemorrhoid surgery-specific evidence

PROSPECT Recommendations

  • Laxatives are recommended (Grade A) in the days prior to surgery, as an adjunct to analgesic therapy, based on procedure-specific evidence (LoE 1 and 2)

Clinical Practice

  • Stool softeners are an alternative to laxatives in clinical practice

Transferable Evidence

  • None cited

Haemorrhoid surgery-specific evidence

  • Two studies out of two demonstrated that laxatives caused a significant reduction in pain scores on defecation compared with placebo/control London 1987 Click here for more information
  • There was a significant reduction in VAS pain scores on day 10 with Plantago ovata compared with control (p<0.01), but not on day 20 (
  • In one study, oral paracetamol requirements after defecation were significantly lower with lactulose compared with placebo (p<0.01), although IM papaveretum consumption was not significantly different between groups, and analgesic requirements before defecation (papaveretum and paracetamol) were similar (
  • Two studies out of two demonstrated a shorter length of hospital stay with laxatives compared with placebo/control (
  • The tenesmus rate in patients in a Plantago ovata group was significantly lower than in patients in a control group (p<0.01;
  • The time to first bowel action was significantly shorter in patients receiving lactulose compared with patients receiving placebo (p=0.01), although the number of bowel actions in the first week was not significantly different between groups (p=0.05;
  • There were no significant differences between groups treated with lactulose and placebo in VAS or VRS pain scores in the 24 h preceding defecation on POD 1–3 (
  • Study details London 1987 Click here for more information

PROSPECT Recommendations

  • Oral metronidazole is recommended (Grade A) as an adjunct to analgesic therapy based on procedure-specific evidence (LoE 1)

Clinical Practice

  • None cited

Transferable Evidence

  • None cited

Haemorrhoid surgery-specific evidence

  • Three out of four studies demonstrated a reduction in pain scores with metronidazole compared with placebo/no treatment Click here for more information
  • In two out of three studies, the time to return to work or normal activities was significantly shorter with metronidazole compared with placebo/no treatment Click here for more information
  • In one study out of two, wound healing occurred significantly faster with metronidazole compared with placebo/no treatment; the second study also showed faster wound healing with metronidazole, but no statistics were reported Click here for more information
  • VAS pain scores were significantly lower with metronidazole + glyceryl trinitrate (GTN) + lactulose compared with placebo on days 2, 3 (both p<0.05), 6 and 7 (both p<0.01), but not at 24 h, or on days 4 and 5. Pain after defecation was significantly lower with metronidazole + GTN + lactulose compared with placebo after the 1st and 2nd defecations (both p<0.05), but not after the 3rd, 4th or 5th (
  • Time to return to work or normal activities was significantly shorter in patients receiving metronidazole + GTN + lactulose compared with those receiving placebo (p<0.05;
  • In four studies out of four, rescue analgesic requirements were not significantly different in groups receiving metronidazole or placebo/no treatment Click here for more information
  • Analgesic requirements (IV diclofenac 100 mg, then nimesulide 100 mg tablets as needed) were not significantly different between patients receiving metronidazole + GTN + lactulose compared with those receiving placebo (
  • Time to healing was not significantly different between patients receiving metronidazole + GTN + lactulose and those receiving placebo (
  • Metronidazole versus placebo/no treatment
  • Study details Click here for more information
  • Metronidazole + glyceryl trinitrate (GTN) + lactulose versus placebo
  • Study details Di Vita 2003 Click here for more information

PROSPECT Recommendations

  • The use of an anal sphincter relaxant is not recommended (Grade D, LoE 4) for analgesia based on limited procedure-specific evidence

Clinical Practice

  • Anal sphincter relaxants are not commonly used in clinical practice

Transferable Evidence

  • None cited

Haemorrhoid surgery-specific evidence

  • Pain scores at 4 h, maximum pain during the first 24 h after surgery, and pain scores on POD 2 were similar in patients receiving a trimebutine suppository and those receiving no suppository (
  • There were no significant differences in rescue analgesic requirements (number of ketoprofen tablets required and number of patients requiring IM pethidine injection) with or without a trimebutine suppository (
  • Study details Ho 1997a Click here for more information

PROSPECT Recommendations

  • Topical glyceryl trinitrate is not recommended (Grade D, LoE 4) due to inconsistent procedure-specific data
  • Topical calcium channel blocker is not recommended (Grade D, LoE 4) due to limited procedure-specific evidence
  • Calcium alginate dressings are not recommended (Grade D, LoE 4) due to limited procedure-specific evidence

Clinical Practice

  • Two studies involving the use of topical glyceryl trinitrate (GTN) showed an improvement in wound healing
  • Any effort to decrease postoperative oedema can be beneficial for postoperative analgesia

Transferable Evidence

  • None cited

Haemorrhoid surgery-specific evidence

  • Topical ointments
  • Haemostatic dressings

PROSPECT Recommendations

  • No recommendation can be made regarding postoperative local perianal infiltration, due to limited and inconsistent procedure-specific evidence (LoE 4)

Clinical Practice

  • Haemorrhoid surgery is a short procedure, and therefore the effects of LA infiltration may be most beneficial when administered pre-operatively
  • Epinephrine is commonly used for LA infiltration, as it is often combined in a preparation with lidocaine and some other LAs

Transferable Evidence

  • None cited

Haemorrhoid surgery-specific evidence

  • In one study out of one, the time to the first demand for IM opiate analgesia was significantly longer with perianal bupivacaine infiltration compared with placebo (p<0.01;
  • In one study out of one, complete wound healing at 6 weeks was observed in all patients treated with both perianal bupivacaine infiltration and placebo (
  • In one study out of two, there was no significant difference in pain scores between groups receiving perianal bupivacaine infiltration or placebo on POD 1 and 2 ( Marsh 1993 Click here for more information
  • In two out of two studies, there were no significant differences in rescue analgesic requirements in patients treated with either perianal bupivacaine infiltration or placebo Chester 1990 Click here for more information
  • In one study out of one, the time to first bowel movement was similar with perianal bupivacaine infiltration and placebo (
  • A similar incidence of urinary retention was reported with both perianal bupivacaine infiltration and placebo (
  • The length of hospital stay was not significantly different between groups undergoing perianal bupivacaine infiltration or placebo infiltration (
  • Patient satisfaction with analgesia was similar with perianal bupivacaine infiltration and placebo (
  • Study details Chester 1990 Click here for more information

Herniorraphy 2004

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Summary Recommendations 

  The recommendations of the PROSPECT Working Group are graded A–D, based on the level of evidence from the studies, which is in accordance with the Oxford Centre for Evidence-Based Medicine (CEBM website accessed Dec 2003, Sackett 2000). In the context of PROSPECT, recommendations based on procedure-specific evidence are grade A (randomised clinical trials), those based on transferable evidence are grade B (randomised clinical trials) or grade C (retrospective studies or case series) and those based on clinical practice are grade D (Click here for further information on levels of evidence and grades of recommendation). PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted.   The following pre-, intra- and postoperative interventions have been evaluated for the management of postoperative pain following herniorraphy:

Pre-operative

Recommended
Systemic 
  • Conventional NSAIDs (Grade A) or COX-2-selective inhibitors (Grade A) 
Local anaesthetic techniques
  • Inguinal nerve block/field block/infiltration, pre-operatively and/or intra-operatively (Grade A)
  • Long-acting local anaesthetics (Grade D)
Not recommended
Systemic
  • Clonidine (Grade D)
  • Corticosteroid (Grade D)
  • Gabapentin/pregabalin (Grade D)
  • Ketamine (Grade D)
Local anaesthetic techniques
  • Epinephrine (Grade A), dextran (Grade D) or corticosteroid (Grade D) as part of a local anaesthetic solution
  • Paravertebral nerve block (Grade D)
Other local analgesics
  • Wound infiltration with clonidine (Grade D)
  • Wound infiltration with conventional NSAIDs (Grade A)
  • Topical conventional NSAIDs (Grade D)

Intra-operative

Recommended 
Local anaesthetic techniques
  • Inguinal nerve block/field block/infiltration, pre-operatively and/or intra-operatively (Grade A)
  • Long-acting local anaesthetics (Grade D)
Operative anaesthetic techniques
  • Local anaesthesia ± sedation OR general anaesthesia in combination with local anaesthetic techniques (inguinal nerve block/field block/infiltration) (Grade A)
  • Long-acting local anaesthetics (Grade D)
Operative techniques
  • Open or laparoscopic surgery (Grade D)
  • Mesh techniques (Grade A) – no recommendations for one particular open mesh technique, prosthesis type or mesh fixation technique over another due to limited available pain data
Not recommended 
Systemic
  • Clonidine (Grade D)
  • Gabapentin/pregabalin (Grade D)
  • Ketamine (Grade D)
Local anaesthetic techniques
  • Epinephrine (Grade A), dextran (Grade D) or corticosteroid (Grade D) as part of a local anaesthetic solution
  • Local anaesthetic instillation (no needles) at closure (Grade D)
  • Extraperitoneal instillation of local anaesthetic during laparoscopic surgery (Grade A)
  • Paravertebral nerve block (Grade D)
Other local analgesics
  • Wound infiltration with clonidine (Grade D)
  • Wound infiltration with conventional NSAIDs (Grade A)
  • Wound infiltration with strong opioid (Grade A)
Operative anaesthetic techniques
  • Epidural anaesthesia (Grade D)
  • Spinal anaesthesia (Grade D)
Operative techniques
  • Open non-mesh surgery (Grade A)
Nerve section/cryoanalgesia techniques
  • Surgical division of the ilioinguinal nerve (Grade A)
  • Cryoanalgesia (Grade A)

Postoperative

Recommended 
Systemic
  • Conventional NSAIDs (grade A) or COX-2-selective inhibitors (grade A)
  • Paracetamol, for routine pain therapy in combination with conventional NSAIDs/COX-2-selective inhibitors (Grade B)
  • Weak opioids for moderate-intensity pain when conventional NSAIDs/COX-2-selective inhibitors plus paracetamol are not sufficient or are contraindicated (Grade B)
  • Strong opioids as rescue analgesia only (for high-intensity pain), in addition to non-opioid analgesia (Grade B)
Not recommended 
Systemic
  • Gabapentin/pregabalin (Grade D)
  • Ketamine (Grade D)
Local anaesthetic techniques
  • Continuous infusion with local anaesthetic by a catheter in the wound (Grade D)
  • Single/repeat dose of local anaesthetic by a catheter in the wound (Grade A)
  • Postoperative subcutaneous infiltration with local anaesthetic (Grade D)
Non-pharmacological techniques
  • TENS (Grade A)
See Overall PROSPECT recommendations for the overall strategy for managing pain after herniorraphy  

Overall PROSPECT Recommendations

Recommended
Pre-/intra-operative
  • Local anaesthesia ± sedation OR general anaesthesia in combination with local anaesthetic techniques (inguinal nerve block/field block/infiltration)
  • Long-acting local anaesthetics in preference to short-acting local anaesthetics
  • Open or laparoscopic surgery, depending on factors other than postoperative pain
  • Mesh techniques in preference to non-mesh techniques
Postoperative
0–6 hours (including the post anaesthetic care unit [PACU])
For postoperative analgesia in addition to that provided by intra-operative local anaesthetics:
  • Base medication: conventional NSAIDs or COX-2-selective inhibitors (use weak opioids when conventional NSAIDs/COX-2-selective inhibitors are contraindicated), combined with paracetamol
  • Add weak opioid when VAS>30<50*
  • Add strong opioid when VAS³50*
Postoperative Beyond 6 h
  • Continue base medication: conventional NSAIDs or COX-2-selective inhibitors (use weak opioids when conventional NSAIDs/COX-2-selective inhibitors are contraindicated), combined with paracetamol
  • Add weak opioid when VAS>30<50*
  • Add strong opioid when VAS³50*

* VAS³50, on a scale of 1–100 mm = high-intensity pain
VAS>30<50, on a scale of 1–100 mm = moderate-intensity pain
VAS£30, on a scale of 1–100 mm = low-intensity pain

Not recommended

  • Spinal anaesthesia
  • Epidural anaesthesia
  • Systemic clonidine, corticosteroid, gabapentin/pregabalin or ketamine
  • Epinephrine as part of a local anaesthetic solution
  • Intra-operative wound instillation with local anaesthetic
  • Paravertebral nerve block
  • Postoperative single/repeat wound injection, or postoperative continuous wound infusion, with local anaesthetic
  • Wound infiltration using conventional NSAIDs, clonidine or strong opioids
  • Topical conventional NSAIDs
  • Nerve section, cryoanalgesia techniques or TENS


 

Description of studies 
Literature search

Systematic review of the literature from 1966–January 2004 using MEDLINE and EmBASE, following the protocol of the Cochrane Collaboration:

  • Inclusion of randomised studies in English assessing analgesic interventions in herniorraphy in adults, and reporting pain on a linear analogue scale
  • Identification of 243 studies of peri-operative interventions for postoperative pain following herniorraphy
  • 122 studies included (Click here for further information)
  • 121 studies excluded (Click here for further information)
  • The most common reason for exclusion was the absence of postoperative pain scores (77 studies). Studies of analgesic interventions following laparoscopic herniorraphy (four studies) were excluded from the systematic review because there is evidence that laparoscopic herniorraphy is associated with a different postoperative pain profile to open herniorraphy (see Intra-operative, Operative techniques). These laparoscopic herniorraphy studies are presented as transferable evidence. (Click here for further information about excluded studies)

Transferable evidence

In PROSPECT, procedure-specific evidence is usually supplemented with transferable evidence (evidence from procedures with similar pain profiles). However, due to the nature of herniorraphy, evidence is not directly transferable from any other procedure; therefore this section includes studies and reviews of a variety of surgical procedures, where appropriate, to address information not covered in the systematic review. This section also includes a small number of studies of analgesic interventions following laparoscopic herniorraphy. 

Local Anaesthetic Techniques 

This section includes studies of local anaesthetics administered to provide postoperative analgesia (i.e. where each group received the same anaesthetic background). For studies of local anaesthesia versus other types of anaesthesia, see Intra-operative, Operative Anaesthetic Techniques

PROSPECT Recommendations

  • Local anaesthetic injection techniques (inguinal nerve block/field block/infiltration), administered pre-operatively or intra-operatively, or both, are recommended (Grade A) because they reduce early postoperative pain and supplementary analgesic use compared with placebo. The effect of pre-operative administration is comparable to post-incisional administration
  • There are insufficient data to recommend (Grade D) one injection technique (inguinal nerve block/field block/infiltration), or combination, in preference to another
  • Local anaesthetic instillation administered at closure cannot be recommended at this time, despite some evidence for its analgesic efficacy, because of limited data (grade D)
  • Long-acting local anaesthetics are recommended in preference to short-acting local anaesthetics (Grade D)
  • Addition of dextran or corticosteroid to local anaesthetic solution is not recommended (Grade D) because of limited procedure-specific evidence

Clinical Practice

  • Long-acting local anaesthetics are preferred to short-acting local anaesthetics for analgesia by local injection
  • In herniorraphy studies of local anaesthetic injection techniques, methodology is inconsistently described, and terminology is inconsistently used. In addition, studies directly comparing one local anaesthetic injection technique with another are lacking. For these reasons, no conclusion about the relative benefits of one technique, or combination of techniques (inguinal nerve block/field block/infiltration), can be made at this time

Transferable Evidence from Other Procedures

  • A systematic review of local anaesthesia infiltration showed inconclusive evidence of analgesic efficacy in hysterectomy, open cholecystectomy and a variety of other surgical procedures, but consistent and clinically relevant pain relief in herniorraphy Møiniche et al 1998
  • There is evidence from a variety of surgical procedures that the efficacy of local anaesthetics for postoperative analgesia is similar following pre-operative or post-incisional administration Møiniche et al 1998

Herniorraphy-Specific Evidence

PROSPECT Recommendations

  • Addition of epinephrine to local anaesthetic solution is not recommended because of a lack of additional or prolonged analgesic effect from limited procedure-specific data (Grade A)

Clinical Practice

  • Epinephrine may result in undesirable cardiovascular side-effects

Transferable Evidence from Other Procedures - Study information

Herniorraphy-Specific Evidence - Study information

  • Intra-operative wound instillation with epinephrine and local anaesthetic was of no significant benefit over local anaesthetic alone for reducing postoperative pain scores during 1–20 h, or for reducing analgesic requirements, for increasing the time to first analgesic request (n=17) Bays et al 1991

PROSPECT Recommendations

  • Paravertebral nerve block is not recommended (Grade D) because it has only a marginal analgesic benefit over other local anaesthetic techniques (nerve block/field block/infiltration) and is a more complex technique

Clinical Practice

  • Clinical experience with the paravertebral nerve block is not widespread. This technique is considered to be more complex, and thus it may be associated with a higher incidence of complications than other local anaesthetic techniques (nerve block/field block/infiltration)

Transferable Evidence from Other Procedures

  • [None cited]

Herniorraphy-Specific Evidence - Study information

  • Paravertebral nerve block was superior to peripheral nerve block for reducing the proportion of patients requiring supplementary analgesia in the PACU (p=0.002; n=46) Klein et al 2002
  • Paravertebral nerve block was superior to peripheral nerve block for reducing the incidence of PONV in the PACU (p<0.001; n=46) Klein et al 2002
  • Paravertebral nerve block and peripheral nerve block were not significantly different for VAS pain scores at rest, on movement and on coughing in the PACU, or at 2, 6, 12, 18, 24 and 48 h (n=46) Klein et al 2002
  • There was no significant difference between paravertebral nerve block and peripheral nerve block for the proportion of patients requiring supplementary analgesics in the 72-h follow-up period, or the time to first analgesic request (n=46) Klein et al 2002

PROSPECT Recommendations

  • Gabapentin/pregabalin cannot be recommended at this time due to the lack of procedure-specific evidence (Grade D), despite analgesic efficacy in other procedures

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Studies of gabapentin and pregabalin in mastectomy, abdominal surgery, laparoscopic cholecystectomy and spinal surgery showed reductions in postoperative pain and supplementary analgesic requirements for at least 24 h Dahl et al 2004

Herniorraphy-Specific Evidence

  • [None cited]

PROSPECT Recommendations

  • Pre-operative ketamine cannot be recommended at this time due to a lack of procedure-specific evidence, and due to associated side-effects that may hinder early ambulation (Grade D), despite some evidence of analgesic efficacy in other procedures

Clinical Practice

  • Ketamine is associated with a risk of adverse effects on the central nervous system

Transferable Evidence from Other Procedures

  • Studies of ketamine in abdominal, orthopaedic, gastric, hepatic and renal surgery showed a reduction in postoperative pain and opioid use when used as an adjuvant to morphine, either epidurally or intravenously Subramaniam et al 2004

Herniorraphy-Specific Evidence

  • [None cited]

 PROSPECT Recommendations

  • Pre-operative systemic clonidine is not recommended because of limited procedure-specific evidence and potential side-effects, which may delay early ambulation (Grade D)

Clinical Practice

  • Clonidine is associated with side-effects, including hypotension, sedation, dizziness and bradycardia

Transferable Evidence from Other Procedures

  • [None cited]

Herniorraphy-Specific Evidence

PROSPECT Recommendations

  • Pre-operative corticosteroid is not recommended due to limited procedure-specific evidence and because herniorraphy per se is not associated with a high incidence of PONV (Grade D)

Clinical Practice

  • Herniorraphy is not associated with a high incidence of PONV

Transferable Evidence from Other Procedures

  • Systemic corticosteroid administration is recommended to prevent PONV in procedures associated with high emetic effects Apfel et al 2004

Herniorraphy-Specific Evidence

  • Pre-operative intravenous dexamethasone showed no benefit over placebo for reducing VAS pain scores overall, and at 4, 8, 12, 16, 20 or 24 h (n=60) Tan et al 2001
  • Pre-operative intravenous dexamethasone was not significantly different from placebo for supplementary analgesic requirements or time to first analgesic request (n=60) Tan et al 2001
  • Pre-operative intravenous dexamethasone was of no benefit over placebo for reducing the incidence of PONV (n=60) Tan et al 2001

PROSPECT Recommendations

  • Pre-operative COX-2-selective inhibitors are recommended based on their analgesic efficacy (grade A) and, as with all analgesics, should be administered in time to secure sufficient analgesia following the procedure
  • Since pre-/intra-operative local anaesthetic techniques provide sufficient analgesia in the immediate postoperative period (grade A), COX-2-selective inhibitors can be initiated orally in the early (1-3 hours) postoperative period
  • COX-2-selective inhibitors may be preferred to conventional NSAIDs in the peri-operative setting, in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (grade B)
  • The use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (cardiovascular morbidity, actual or recent gastroduodenal ulcer history, renal function and hepatic function [grade B] or aspirin-sensitive asthma [grade D])

Clinical Practice

  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Transferable Evidence from Other Procedures

  • COX-2-selective inhibitors provide similar postoperative analgesia to conventional NSAIDs Rømsing et al 2004
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation Greenberg et al 2000
  • A randomised clinical trial showed that the COX-2-selective inhibitor rofecoxib was associated with significantly less intra-operative blood loss than the conventional NSAID diclofenac in patients undergoing abdominal or vaginal hysterectomy or breast surgery Hegi et al 2004
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) (in press, Anesthesiology)
  • Two clinical trials showed that in patients who had undergone CABG surgery, COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003

Herniorraphy-Specific Evidence

  • Oral rofecoxib administered pre- plus postoperatively significantly reduced postoperative pain scores, compared with placebo, at rest at 1 h (p<0.05) but there was no benefit at 30 min or at the time of first analgesic request (n=60) Ma et al 2004
  • Rofecoxib administered pre- plus postoperatively significantly reduced requirements for supplementary hydromorphone in the PACU (p<0.05) (n=60) Ma et al 2004
  • Rofecoxib administered pre- plus postoperatively did not significantly reduce the incidence of PONV compared with placebo (low incidence in both groups) (n=60) Ma et al 2004

PROSPECT Recommendations

  • Pre-operative conventional NSAIDs are recommended, based on their analgesic efficacy (grade A), and as with all analgesics should be administered in time to secure sufficient analgesia following the procedure
  • Since pre-/intra-operative local anaesthetic infiltration techniques provide sufficient analgesia in the immediate postoperative period (grade A), conventional NSAIDs can be initiated orally in the early (1-3 hours) postoperative period
  • Conventional NSAIDs are not recommended in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (grade B)
  • The use of conventional NSAIDs should depend upon assessment of individual patient risks (bleeding complications, cardiovascular morbidity, actual or recent gastroduodenal ulcer history, aspirin-sensitive asthma, renal function and hepatic function) (grade B)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Pre-operative ibuprofen was similar to intra-operative ketorolac for VAS pain scores over the first 24 h, at discharge and after discharge, and for the proportion of patients requiring postoperative supplementary analgesia (n=70) Mixter et al 1998
  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures Barden et al 2004
  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • A randomised clinical trial showed that the conventional NSAID diclofenac was associated with significantly greater intra-operative blood loss than the COX-2-selective inhibitor rofecoxib in patients undergoing abdominal or vaginal hysterectomy or breast surgery Hegi et al 2004
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004

Herniorraphy-Specific Evidence

  • Pre-operative conventional NSAIDs reduced postoperative pain scores compared with placebo or no treatment Ben-David et al 1996 Click here for more information
  • Pre-operative conventional NSAIDs reduced supplementary analgesic requirements compared with placebo or no treatment Dueholm et al 1989 Click here for more information
  • Tenoxicam 10 mg was not significantly different from 20 mg for pain scores at rest or on movement at 2, 9 and 24 h and for supplementary analgesic requirements (n=30) Lin et al 1998
  • Pre-operative intravenous ketorolac and rectal diclofenac were similar for pain scores at 2, 6 and 24 h and on day 3, for use of supplementary diclofenac, and for the incidence of PONV (n=108) Lau et al 2002
  • Intravenous and intramuscular ketorolac were superior to oral ketorolac for reducing pain scores and supplementary analgesic requirements, but there was no significant difference between intravenous and intramuscular ketorolac or between rectal and intramuscular diclofenac Ben-David et al 1996 Click here for more information

PROSPECT Recommendations

  • Wound infiltration with clonidine is not recommended because of limited procedure-specific data and because of potential side-effects, which may delay early ambulation (Grade D)

Clinical Practice

  • Clonidine is associated with side-effects, including hypotension, sedation, dizziness and bradycardia

Transferable Evidence from Other Procedures

  • [None cited]

Herniorraphy-Specific Evidence - Study information

  • Wound infiltration with clonidine showed a significant benefit for reducing pain scores compared with placebo at 2 h, but there was no significant difference at other times Connelly et al 1999 Click here for more information
  • Wound infiltration with clonidine was of no significant benefit for reducing supplementary analgesic requirements compared with placebo (n=30) Connelly et al 1999
  • Wound infiltration with clonidine was of no significant benefit over systemic administration for reducing pain scores or supplementary analgesic requirements Connelly et al 1999 Click here for more information

PROSPECT Recommendations

  • Pre-operative wound infiltration with conventional NSAIDs is not recommended (grade A) because of inconclusive evidence of an analgesic benefit, compared with systemic administration

Clinical Practice

  • The potential for conventional NSAIDs, administered by wound infiltration, to adversely affect platelet function and wound healing must be considered

Transferable Evidence from Other Procedures

  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987
  • A systematic review of the postoperative analgesic effect of local infiltration with conventional NSAIDs showed little difference between wound infiltration and systemic administration Rømsing et al 2000
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • A randomised clinical trial showed that the conventional NSAID diclofenac was associated with significantly greater intra-operative blood loss than the COX-2-selective inhibitor rofecoxib in patients undergoing abdominal or vaginal hysterectomy or breast surgery Hegi et al 2004

Herniorraphy-Specific Evidence - Study information

PROSPECT Recommendations

  • Pre-operative topical conventional NSAIDs cannot be recommended at this time (Grade D) because of limited procedure-specific data

Clinical Practice

  • The potential for conventional NSAIDs, administered topically, to adversely affect platelet function and wound healing must be considered

Transferable Evidence from Other Procedures

  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987
  • A systematic review of the postoperative analgesic effect of local infiltration with conventional NSAIDs showed little difference between wound infiltration and systemic administration Rømsing et al 2000
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • A randomised clinical trial showed that the conventional NSAID diclofenac was associated with significantly greater intra-operative blood loss than the COX-2-selective inhibitor rofecoxib in patients undergoing abdominal or vaginal hysterectomy or breast surgery Hegi et al 2004

Herniorraphy-Specific Evidence - Study information

  • Topical piroxicam was superior to placebo for reducing VAS pain scores during 0–4 h (p<0.05) but there was no significant difference during 4–24 h (n=27) O'Hanlon et al 1996
  • Topical piroxicam was superior to placebo for reducing postoperative supplementary analgesic requirements during 0–24 h (p<0.005) but not during 4–24 h, and piroxicam did not increase the time to first analgesia (n=27) O'Hanlon et al 1996
  • Topical application of NSAIDs was equally effective compared with inguinal nerve block for reducing 0–24 h pain scores at rest, reducing analgesic requirements and for increasing the time to first analgesic request (n=30) O'Hanlon et al 1996

PROSPECT Recommendations

  • Intra-operative clonidine is not recommended due to limited procedure-specific evidence and potential side-effects, which may delay early ambulation (Grade D)

Clinical Practice

  • Clonidine is associated with side-effects, including hypotension, sedation, dizziness and bradycardia

Transferable Evidence from Other Procedures

  • [None cited]

Herniorraphy-Specific Evidence - Study information

  • Clonidine significantly increased VAS pain scores compared with placebo at rest at 24 h (p<0.05), and there was no significant benefit in the PACU or at 6 h, or on coughing at any time (n=31) Elliott et al 1997
  • Intra-operative systemic clonidine was of no significant benefit over placebo for reducing postoperative analgesic requirements (n=31) Elliott et al 1997

PROSPECT Recommendations

  • Gabapentin/pregabalin cannot be recommended at this time due to the lack of procedure-specific evidence (Grade D), despite analgesic efficacy in other procedures

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Studies of gabapentin and pregabalin in mastectomy, abdominal surgery, laparoscopic cholecystectomy and spinal surgery showed reductions in postoperative pain and supplementary analgesic requirements for at least 24 h Dahl et al 2004

Herniorraphy-Specific Evidence

  • [None cited]

PROSPECT Recommendations

  • Intra-operative ketamine cannot be recommended at this time (Grade D) due to a lack of procedure-specific evidence, and due to associated side-effects that may hinder early ambulation, despite some evidence of analgesic efficacy in other procedures

Clinical Practice

  • Ketamine is associated with a risk of adverse effects on the central nervous system

Transferable Evidence from Other Procedures

  • Studies of ketamine in abdominal, orthopaedic, gastric, hepatic and renal surgery showed a reduction in postoperative pain and opioid use when used as an adjuvant to morphine, either epidurally or intravenously Subramaniam et al 2004

Herniorraphy-Specific Evidence

  • [None cited]

Local Anaesthetic Techniques 

This section includes studies of local anaesthetics administered to provide postoperative analgesia (i.e. where each group received the same anaesthetic background). For studies of local anaesthesia versus other types of anaesthesia, see Intra-operative, Operative Anaesthetic Techniques 

PROSPECT Recommendations

  • Local anaesthetic injection techniques (inguinal nerve block/field block/infiltration), administered pre-operatively or intra-operatively, or both, are recommended (Grade A) because they reduce early postoperative pain and supplementary analgesic use compared with placebo. The effect of pre-operative administration is comparable to post-incisional administration
  • There are insufficient data to recommend (Grade D) one injection technique (inguinal nerve block/field block/infiltration), or combination, in preference to another
  • Local anaesthetic instillation administered at closure cannot be recommended at this time, despite some evidence for its analgesic efficacy, because of limited data (Grade D)
  • Long-acting local anaesthetics are recommended in preference to short-acting local anaesthetics (Grade D)
  • Addition of dextran or corticosteroid to local anaesthetic solution is not recommended (Grade D) because of limited procedure-specific evidence

Clinical Practice

  • Long-acting local anaesthetics are preferred to short-acting local anaesthetics for analgesia by local injection
  • In herniorraphy studies of local anaesthetic injection techniques, methodology is inconsistently described, and terminology is inconsistently used. In addition, studies directly comparing one local anaesthetic injection technique with another are lacking. For these reasons, no conclusion about the relative benefits of one technique, or combination of techniques (inguinal nerve block/field block/infiltration), can be made at this time

Transferable Evidence from Other Procedures

  • A systematic review of local anaesthesia infiltration showed inconclusive evidence of analgesic efficacy in hysterectomy, open cholecystectomy and a variety of other surgical procedures, but consistent and clinically relevant pain relief in herniorraphy Møiniche et al 1998
  • There is evidence from a variety of surgical procedures that the efficacy of local anaesthetics for postoperative analgesia is similar following pre-operative or post-incisional administration Møiniche et al 1998

Herniorraphy-Specific Evidence - Study information

PROSPECT Recommendations

  • Addition of epinephrine to local anaesthetic solution is not recommended because of a lack of additional or prolonged analgesic effect from limited procedure-specific data (Grade A)

Clinical Practice

  • Epinephrine may result in undesirable cardiovascular side-effects

Transferable Evidence from Other Procedures - Study information

Herniorraphy-Specific Evidence - Study information

  • Intra-operative wound instillation with epinephrine and local anaesthetic was of no significant benefit over local anaesthetic alone for reducing postoperative pain scores during 1–20 h, for reducing analgesic requirements, or for increasing the time to first analgesic request (n=17) Bays et al 1991

PROSPECT Recommendations

  • Paravertebral nerve block is not recommended (Grade D) because it has only a marginal analgesic benefit over other local anaesthetic techniques (nerve block/field block/infiltration) and is a more complex technique

Clinical Practice

  • Clinical experience with the paravertebral nerve block is not widespread. This technique is considered to be more complex, and thus it may be associated with a higher incidence of complications than other local anaesthetic techniques (nerve block/field block/infiltration)

Transferable Evidence from Other Procedures

  • [None cited]

Herniorraphy-Specific Evidence - Study information

  • Paravertebral nerve block was superior to peripheral nerve block for reducing the proportion of patients requiring supplementary analgesia in the PACU (p=0.002; n=46) Klein et al 2002
  • Paravertebral nerve block was associated with a lower incidence of PONV in the PACU compared with peripheral nerve block (p<0.001; n=46) Klein et al 2002
  • Paravertebral nerve block and peripheral nerve block were not significantly different for VAS pain scores at rest, on movement and on coughing in the PACU, or at 2, 6, 12, 18, 24 and 48 h (n=46) Klein et al 2002
  • There was no significant difference between paravertebral nerve block and peripheral nerve block for the proportion of patients requiring supplementary analgesics in the 72-h follow-up period, or the time to first analgesic request (n=46) Klein et al 2002

PROSPECT Recommendations

  • Extraperitoneal instillation with local anaesthetic is not relevant for open herniorraphy
  • Extraperitoneal instillation with local anaesthetic is not recommended in laparoscopic herniorraphy because of a lack of analgesic effect (Grade A)

Clinical Practice

  • There is little clinical experience with extraperitoneal instillation and the technique is poorly defined

Transferable Evidence from Other Procedures - study information

Herniorraphy-Specific Evidence

  • – None cited for open herniorraphy– For data in laparoscopic herniorraphy, see the transferable evidence below

PROSPECT Recommendations

  • Wound infiltration with clonidine is not recommended due to limited procedure-specific data and potential side-effects that can delay early ambulation (Grade D)

Clinical Practice

  • Clonidine is associated with side-effects, including hypotension, sedation, dizziness and bradycardia

Transferable Evidence from Other Procedures 

  • [None cited]

Herniorraphy-Specific Evidence - Study information

  • Wound infiltration with clonidine was superior to intramuscular clonidine for reducing pain scores, but a significant benefit was only evident at 24 h; there was no significant benefit for reducing supplementary analgesic requirements Elliott et al 1997 Click here for more information
  • Wound infiltration with clonidine showed no significant benefit compared with placebo for reducing VAS pain scores at rest and on coughing in recovery, at 6 h and at 24 h (n=31) Elliott et al 1997
  • Wound infiltration with clonidine showed no significant benefit compared with placebo for reducing supplementary analgesic requirements (n=31) Elliott et al 1997

PROSPECT Recommendations

  • Intra-operative wound infiltration with conventional NSAIDs is not recommended (grade A) because of a limited analgesic benefit compared with systemic administration

Clinical Practice

  • The potential for conventional NSAIDs, administered by wound infiltration, to adversely affect platelet function and wound healing must be considered

Transferable Evidence from Other Procedures

  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987
  • A systematic review of the postoperative analgesic effect of local infiltration with conventional NSAIDs showed little difference between wound infiltration and systemic administration Rømsing et al 2000
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • A randomised clinical trial showed that the conventional NSAID diclofenac was associated with significantly greater intra-operative blood loss than the COX-2-selective inhibitor rofecoxib in patients undergoing abdominal or vaginal hysterectomy or breast surgery Hegi et al 2004

Herniorraphy-Specific Evidence -study information

PROSPECT Recommendations

  • Wound infiltration with strong opioids is not recommended because of conflicting procedure-specific evidence for its analgesic efficacy (Grade A). In addition, strong opioids are not recommended for routine analgesic treatment in herniorraphy because of potential side-effects (Grade D)

Clinical Practice

  • Strong opioids are associated with adverse effects, including respiratory depression, nausea, vomiting, sedation, confusion, paralytic ileus and urinary retention

Transferable Evidence from Other Procedures

  • [None cited]

Herniorraphy-Specific Evidence - study information

PROSPECT Recommendations

  • Local anaesthesia (inguinal nerve block/field block/infiltration techniques), with or without intravenous sedation, is recommended (Grade A) because it decreases postoperative pain and provides additional recovery benefits compared with spinal anaesthesia or general anaesthesia
  • Long-acting local anaesthetics are recommended (Grade D) in preference to short-acting local anaesthetics

Clinical Practice

  • Long-acting local anaesthetics are preferred to short-acting local anaesthetics
  • For all regional anaesthesia techniques, there are procedure-specific failure rates between 2 and 10%, and conversion to general anaesthesia may be required
  • Local practices and cultural differences influence the choice of anaesthetic technique for herniorraphy

Transferable Evidence from Other Procedures

  • [None cited]

Herniorraphy-Specific Evidence - study information

PROSPECT Recommendations

  • When general anaesthesia is used, its combination with local anaesthetic techniques is recommended to decrease postoperative pain (Grade A)
  • Spinal anaesthesia provides good anaesthesia and early postoperative analgesia. Spinal anaesthesia cannot be recommended for routine use (Grade D - majority vote from the prospect Working Group) because of postoperative side-effects that can delay early ambulation, such as urinary retention and hypotension
  • Epidural anaesthesia is not recommended (Grade D)
  • Local anaesthetic techniques (inguinal nerve block/field block/infiltration) are recommended (Grade A) because they provide good postoperative analgesia, rapid recovery, and few side-effects, but the need for intravenous sedation has to be considered (see Intra-operative anaesthetic techniques, Local anaesthesia)
  • Addition of clonidine or neostigmine to local anaesthetic solution for spinal anaesthesia is not recommended due to limited procedure-specific evidence. In addition, potential side-effects of clonidine (Grade D) and neostigmine (Grade A) may hinder early ambulation

Clinical Practice

  • For all regional anaesthesia techniques, there are procedure-specific failure rates between 2 and 10%, and conversion to general anaesthesia may be required
  • Local practices and cultural differences influence the choice of anaesthetic technique for herniorraphy
  • Clonidine is associated with side-effects, including hypotension, sedation, dizziness and bradycardia

Transferable Evidence from Other Procedures

  • [None cited]

Herniorraphy-Specific Evidence -study information

  • Spinal anaesthesia reduced pain scores compared with epidural anaesthesia, but did not reduce analgesic requirements during 0–24 h or the incidence of PONV Günal et al 2002 Click here for more information
  • Spinal anaesthesia (local anaesthetic) reduced the use of supplementary analgesics and the incidence of nausea compared with general anaesthesia, but data for a reduction in pain scores was inconclusive Tverskoy et al 1990 Click here for more information
  • Spinal anaesthesia (local anaesthetic plus strong opioid) significantly reduced supplementary opioid requirements and the incidence of PONV, compared with general anaesthesia, but there was no significant difference for pain scores or oral analgesic use Song et al 2000 Click here for more information
  • General anaesthesia was similar to epidural or spinal anaesthesia (mixed population) for VAS pain scores during the early postoperative period, at 8 days and at 30 days, for the duration of analgesic requirement but was associated with higher VAS nausea scores (n=407) Nordin et al 2003
  • General anaesthesia plus wound infiltration was superior to spinal anaesthesia for reducing dynamic pain scores, but not resting pain scores, and for increasing the time to first analgesic request Tverskoy et al 1990 Click here for more information
  • For spinal anaesthesia, bupivacaine 7.5 mg significantly reduced the proportion of patients requiring intra-operative fentanyl compared with bupivacaine 6 mg, but there was no significant difference in pain scores, supplementary analgesic requirements or the incidence of PONV Gupta et al 2003 Click here for more information
  • For spinal anaesthesia, local anaesthetic plus clonidine was of significant analgesic benefit compared with local anaesthetic alone during the early postoperative period, but did not reduce the risk of PONV Dobrydnjov et al 2003 Click here for more information
  • For spinal anaesthesia, local anaesthetic plus neostigmine showed significant benefit compared with local anaesthetic alone for reducing pain scores and increasing time to first analgesia  Tan et al 2000 Click here for more information
  • For spinal anaesthesia, neostigmine 50 µg and 100 µg were not significantly different for reducing VAS pain scores over 24 h, for reducing supplementary analgesic requirements, and for increasing the time to first analgesic request (n=40) Tan et al 2000
  • Tetracaine plus neostigmine caused a significantly higher rate of PONV than tetracaine alone (p<0.05) (two arms, n=60) Tan et al 2000
  • Pre- plus intra-operative epidural morphine plus postoperative naloxone did not significantly reduce postoperative analgesic requirements or VAS pain scores at rest at 6, 12, 24 or 48 h compared with placebo (n=36) Aida et al 1999

PROSPECT Recommendations

  • It is recommended (Grade D) that the choice of operative technique for herniorraphy (open versus laparoscopic) should be primarily based on factors other than the management of postoperative pain e.g. operative risk factors of the patient, risk of wound infection, availability of surgical expertise, risk of rare but serious complications, contraindications to general anaesthetic, recurrence rates, and cost
  • Laparoscopic herniorraphy is associated with less postoperative pain than open non-mesh herniorraphy (Grade A), but data are inconclusive for the relative analgesic effects of laparoscopic herniorraphy and open mesh herniorraphy  
  • A recommendation for pain management following laparoscopic herniorraphy cannot be made until further data are available 

Clinical Practice

Transferable Evidence from Other Procedures

  • [None cited]

Herniorraphy-Specific Evidence - study information

PROSPECT Recommendations

  • Open mesh procedures are recommended in preference to non-mesh procedures because of lower recurrence rates (Grade A); the recommendation cannot be based on the inconclusive acute pain data (Grade A)
  • There is not enough evidence, at this time, to recommend the following for the management of acute or chronic pain: – the plug-and-patch or the Prolene Hernia System® techniques in preference to the Lichtenstein patch technique (Grade D) – one type of mesh in preference to another (Grade D)  – one mesh fixation technique in preference to another (Grade D)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Herniorraphy-Specific Evidence - study information

  • A systematic review reported that open mesh herniorraphy is associated with a 50–75% reduction in the risk of hernia recurrence compared with open non-mesh herniorraphy Grant 2002
  • The Prolene Hernia System® procedure was superior to the Lichtenstein patch procedure for postoperative VAS pain scores at rest on day 0 (p<0.05) but there was no significant difference on days 1–14, or for the duration of requirement for postoperative analgesia (n=206) Kingsnorth et al 2002b
  • Two of three studies showed a significant benefit of the plug-and-patch procedure over the Lichtenstein open mesh procedure for reducing postoperative pain scores, and in all studies there was no significant difference in analgesic use Abu-Own A et al 2000 Click here for more information
  • The Stoppa procedure was not significantly different from the Lichtenstein patch procedure for VAS pain scores at rest on days 1, 2, 7 and 30, or on movement on days 7 and 30 (n=33) Malazgirt et al 2000
  • The smooth polypropylene mesh was superior to the monofile, rigid mesh for reducing VAS pain scores on day 1 and at 2, 4, 8 and 12 weeks (p<0.05), but there was no significant difference at 3 days or at 1 week (n=40) Langenbach et al 2003
  • A lightweight mesh was superior to a conventional mesh for reducing dynamic pain scores at 6 months but there was no significant difference in pain during the early postoperative period Post et al 2004 Click here for more information
  • Fixation by sutures for hernia repair was similar to fixation with staples for postoperative pain and supplementary analgesic requirements Leibl et al 2002 Click here for more information
  • Six out of ten studies showed no significant benefit of open mesh procedures compared with open non-mesh procedures for reducing pain scores Barth et al 1998 Click here for more information
  • Of eight studies that reported supplementary analgesic use, five showed no significant benefit for mesh procedures compared with non-mesh procedures for reducing analgesic requirements Barth et al 1998 Click here for more information

PROSPECT Recommendations

  • Open mesh procedures are recommended in preference to non-mesh procedures because of lower recurrence rates (Grade A); the recommendation cannot be based on the inconclusive acute pain data (Grade A, see Open Mesh Procedure)
  • There is not enough evidence to recommend one non-mesh repair technique in preference to another for the management of acute or chronic pain (Grade D)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Herniorraphy-Specific Evidence

  • Suture repair and no suture repair were similar for cumulative pain scores during the first week and for analgesic requirements (n=84) Callesen et al 1999
  • Moloney's darn repair was superior to the Shouldice repair for reducing postoperative VAS pain scores at 6, 12 and 24 h (p<0.05) and for reducing postoperative requirement for analgesia on days 1, 2 and 3 (p<0.05) (n=50) Thapar et al 2000
  • A systematic review reported that open non-mesh herniorraphy is associated with a 50–75% increase in the risk of hernia recurrence compared with open mesh herniorraphy Grant 2002

PROSPECT Recommendations

  • Nerve section/cryoanalgesia techniques are not recommended because of a lack of analgesic benefit (Grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Herniorraphy-Specific Evidence - Study information

  • Division of the ilioinguinal nerve was of no significant benefit over preservation of the nerve for VAS pain scores at 1 week, 1 or 6 months, 1 year or at telephone follow up (n=813) Picchio et al 2004
  • Cryoanalgesia was of no benefit for reducing VAS pain scores compared with no treatment or sham treatment in two studies (n=36) Khiroya et al 1986

PROSPECT Recommendations

  • Postoperative COX-2-selective inhibitors are recommended based on their analgesic efficacy (grade A)
  • Since pre-/intra-operative local anaesthetic infiltration techniques provide sufficient analgesia in the immediate postoperative period (grade A), COX-2-selective inhibitors can be initiated orally in the early (1-3 hours) postoperative period
  • COX-2-selective inhibitors may be preferred to conventional NSAIDs in the peri-operative setting, in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (grade B)
  • The use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (cardiovascular morbidity, actual or recent gastroduodenal ulcer history, renal function and hepatic function [grade B] or aspirin-sensitive asthma [grade D])

Clinical Practice

  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Transferable Evidence from Other Procedures

  • COX-2-selective inhibitors provide similar postoperative analgesia to conventional NSAIDs Rømsing et al 2004
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation Greenberg et al 2000
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) (in press, Anesthesiology)
  • Two clinical trials showed that in patients who had undergone CABG surgery, COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003

Herniorraphy-Specific Evidence - Study information

  • Oral rofecoxib administered pre- plus postoperatively significantly reduced postoperative pain scores, compared with placebo, at rest at 1 h (p<0.05) but there was no benefit at 30 min or at the time of first analgesic request (n=60) Ma et al 2004
  • Oral rofecoxib administered pre- plus postoperatively significantly reduced requirements for supplementary hydromorphone in the PACU (p<0.05) (n=60) Ma et al 2004
  • Oral rofecoxib administered pre- plus postoperatively did not significantly reduce the incidence of PONV compared with placebo (n=60) Ma et al 2004

PROSPECT Recommendations

  • Postoperative conventional NSAIDs are recommended based on their analgesic efficacy (grade A)
  • Since pre-/intra-operative local anaesthetic infiltration techniques provide sufficient analgesia in the immediate postoperative period (grade A), conventional NSAIDs can be initiated orally in the early (1-3 hours) postoperative period
  • Conventional NSAIDs are not recommended in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (grade B)
  • The use of conventional NSAIDs should depend upon assessment of individual patient risks (bleeding complications, cardiovascular morbidity, actual or recent gastroduodenal ulcer history, aspirin-sensitive asthma, renal function and hepatic function) (grade B)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures Barden et al 2004
  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004

Herniorraphy-Specific Evidence

  • Lysine acetyl salicylate and morphine were similar for verbal rating pain scores at 0, 0.5, 3, 6, 21 and 27 h, and for the proportion of patients requiring supplementary analgesia, but lysine acetyl salicylate was superior to morphine for reducing the incidence of nausea (p<0.05) (n=30) Cashman et al 1985
  • Lysine clonixinate and paracetamol/codeine were similar for VAS pain scores at rest or on coughing, sitting or applied pressure during the first 2 days, and for supplementary analgesic requirements (n=151) de los Santos et al 1998

PROSPECT Recommendations

  • Gabapentin/pregabalin cannot be recommended at this time (Grade D) due to the lack of procedure-specific evidence, despite analgesic efficacy in other procedures

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Studies of gabapentin and pregabalin in mastectomy, abdominal surgery, laparoscopic cholecystectomy and spinal surgery showed reductions in postoperative pain and supplementary analgesic requirements for at least 24 h Dahl et al 2004

Herniorraphy-Specific Evidence

  • [None cited]

PROSPECT Recommendations

  • Postoperative ketamine cannot be recommended at this time (Grade D) due to a lack of procedure-specific evidence, and due to associated side-effects that may hinder early ambulation, despite some evidence of analgesic efficacy in other procedures

Clinical Practice

  • Ketamine is associated with a risk of adverse effects on the central nervous system

Transferable Evidence from Other Procedures

  • Studies of ketamine in abdominal, orthopaedic, gastric, hepatic and renal surgery showed a reduction in postoperative pain and opioid use when used as an adjuvant to morphine, either epidurally or intravenously Subramaniam et al 2004

Herniorraphy-Specific Evidence

  • [None cited]

Opioids
Opioids, which can be naturally occurring, semisynthetic or synthetic compounds, produce analgesic effects by binding to opioid receptors in the central nervous system. Several different opioid receptors have been identified and, based on their interactions with these receptors, opioids fall into three main categories:
Pure agonists – drugs that bind to and stimulate opioid receptors, and are capable of producing a maximal response
Partial agonists – drugs that stimulate opioid receptors but have a ceiling effect, i.e. produce a submaximal response compared with an agonist
Mixed agonist-antagonists – drugs that are agonists for one opioid receptor but antagonise other opioid receptors.
Opioids are also classified as being ‘strong’ or ‘weak’, depending on the strength of their clinical effect, which has historically been measured against the effect of morphine.
Some opioids and their classifications are listed below:

Opioid

Agonist property

Clinical ‘strength’

Morphine

Pure

Strong

Oxycodone

Pure

Strong

Hydromorphone

Pure

Strong

Meperidine

Pure

Strong

Fentanyl

Pure

Strong

Methadone

Pure

Strong

Buprenorphine

Mixed

Strong

Nalbuphine

Mixed

Strong

Pentazocine

Mixed

Strong

Meptazinol

Partial

Strong

Tramadol

Partial

Weak

Codeine

Partial

Weak

PROSPECT Recommendations

  • Strong opioids are not recommended for first-line analgesia, despite evidence that they are effective, because of side-effects that may delay early ambulation (Grade D)
  • Strong opioids are recommended as rescue analgesia for severe pain in addition to the use of non-opioid agents (Grade B)

Clinical Practice

  • Strong opioids are not associated with a ceiling effect, and thus can provide effective analgesia for most types of surgical procedures
  • Strong opioids are available in a variety of preparations and routes of administration, enabling choice for onset, duration of action, and mode of delivery

Transferable Evidence from Other Procedures

  • Strong opioids are effective for reducing high- and moderate-intensity postoperative pain McQuay et al 1999
  • Strong opioids are associated with adverse effects, including nausea, vomiting, sedation, confusion, paralytic ileus and urinary retention Wheeler et al 2002

Herniorraphy-Specific Evidence - Study information

  • Postoperative sustained release morphine followed by dihydrocodeine was superior to dihydrocodeine plus paracetamol for reducing pain scores during days 0–5 (p=0.005, n=50) Fenton-Lee et al 1994
  • Postoperative papaveretum/aspirin provided no significant analgesic benefit over placebo, whether both groups received pre-operative inguinal field block or not (n=200) Nehra et al 1995
  • Postoperative papaveretum/aspirin was of no significant benefit over placebo for reducing the incidence of PONV (both groups received rescue opioid) (n=200) Nehra et al 1995
  • Sustained release morphine followed by dihydrocodeine was inferior to dihydrocodeine plus paracetamol for reducing postoperative nausea scores (n=50) Fenton-Lee et al 1994

PROSPECT Recommendations

  • Weak opioids are recommended based on their analgesic efficacy (Grade B), when conventional NSAIDs or COX-2-selective inhibitors plus paracetamol are not sufficient or are contraindicated

Clinical Practice

  • Tramadol is beneficial when conventional NSAIDs are contraindicated
  • The oral solution (drops) is useful as rescue medication when paracetamol/conventional NSAIDs/COX-2-selective inhibitor analgesic regimens are used
  • Tramadol is useful in the treatment of postoperative pain of moderate intensity (intravenous and oral administration), providing effective analgesia in the in-patient and ambulatory setting
  • Opioid adverse effects, especially nausea and dizziness, limit the usefulness of tramadol, but many of the effects are less than for strong opioids

Transferable Evidence from Other Procedures

  • The combination of tramadol and paracetamol enhances analgesic efficacy compared with either agent alone McQuay H et al 2003

Herniorraphy-Specific Evidence - Study information

  • Postoperative dihydrocodeine plus paracetamol was superior to sustained release morphine followed by dihydrocodeine for reducing postoperative nausea scores (n=50) Fenton-Lee et al 1994
  • Codeine plus paracetamol was of no significant benefit over lysine clonixinate for reducing postoperative VAS pain scores at rest or on coughing, sitting or applied pressure during the first 2 days, or supplementary analgesic requirements (n=151) de los Santos et al 1998
  • Dihydrocodeine plus paracetamol was inferior to sustained release morphine for reducing pain scores during days 0–5 (p=0.005, n=50) Fenton-Lee et al 1994

 PROSPECT Recommendations

  • Paracetamol is recommended for routine pain therapy in combination with conventional NSAIDs/COX-2-selective inhibitors or weak opioids based on evidence from other surgical procedures (Grade B)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Paracetamol is an effective analgesic for the treatment of postoperative pain of moderate intensity Hyllested et al 2002
  • Paracetamol combined with weak opioids (codeine, tramadol) is superior to weak opioids alone in a review of dental, gynaecological and orthopaedic surgery McQuay H et al 2003
  • [None cited]

Herniorraphy-Specific Evidence - Study information

  • Postoperative dihydrocodeine plus paracetamol was superior to sustained release morphine followed by dihydrocodeine for reducing postoperative VAS nausea scores (n=50) Fenton-Lee et al 1994
  • Paracetamol plus codeine was of no significant benefit over lysine clonixinate for reducing postoperative VAS pain scores at rest or on coughing, sitting or applied pressure during the first 2 days, or supplementary analgesic requirements (n=151) de los Santos et al 1998
  • Dihydrocodeine plus paracetamol was inferior to sustained release morphine followed by dihydrocodeine for reducing pain scores during days 0–5 (p=0.005, n=50) Fenton-Lee et al 1994

PROSPECT Recommendations

  • Postoperative continuous wound infusion with local anaesthetic cannot be recommended at this time, despite evidence for its analgesic efficacy, because of limited data (Grade D)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Herniorraphy-Specific Evidence

PROSPECT Recommendations

  • Postoperative single/repeat dose of local anaesthetic by catheter in the wound is not recommended because of a lack of analgesic effect (Grade A)
  • Postoperative subcutaneous infiltration cannot be recommended at this time because of limited data (Grade D)

Clinical Practice

  • [None specified]

Transferable Evidence from Other Procedures

  • [None cited]

Herniorraphy-Specific Evidence - Study information

  • Pre- plus intra- plus postoperative inguinal nerve block/field block/infiltration was superior to placebo for reducing pain scores on lying, sitting and walking at 8 h and on days 1–5 (p<0.05) but there was no significant difference at 10 or 30 days (n=70) Fischer et al 2000
  • Pre- plus intra- plus postoperative inguinal nerve block/field block/infiltration was superior to placebo for reducing the proportion of patients requiring supplementary ibuprofen at 0 and 2 days (p<0.05) (n=70) Fischer et al 2000
  • Postoperative wound instillation with bupivacaine in repeat doses via a catheter was similar to systemic conventional NSAIDs for reducing pain scores at 0–30 h, and for reducing use of supplementary metamizole (n=104) Zieren et al 1999
  • Postoperative single/repeat bolus of local anaesthetic by a catheter in the wound did not reduce pain scores compared with placebo or no such treatment Cameron et al 1985 Click here for more information
  • Postoperative single/repeat bolus of local anaesthetic by a catheter in the wound was of no benefit for reducing supplementary analgesic requirements compared with placebo or no such treatment (n=101) Cameron et al 1985
  • For postoperative wound instillation, ropivacaine and bupivacaine were similar for postoperative VAS pain scores at rest and on movement on days 0 and 1, for supplementary analgesic requirements, and for the incidence of PONV (n=51) Vintar et al 2002

PROSPECT Recommendations

  • Subfascial infiltration with local anaesthetics cannot be recommended in preference to subcutaneous infiltration at this time because of limited data (Grade D)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  •  [None cited]

Herniorraphy-Specific Evidence - Study information

  • Subfascial local anaesthetic showed a significant benefit over subcutaneous local anaesthetic for reducing pain scores during the first postoperative hour, but there was no difference in supplementary analgesic requirements Yndgaard et al 1994 Click here for more information

PROSPECT Recommendations

  • TENS is not recommended because of a lack of analgesic benefit (Grade A)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Herniorraphy-Specific Evidence - Study information

  • TENS was of no benefit compared with sham TENS for reducing VAS pain scores on days 1, 2 and 3 (n=40) Gilbert et al 1986
  • TENS was of no benefit compared with sham TENS for reducing postoperative analgesic requirements (n=40) Gilbert et al 1986

Laparoscopic Cholecystectomy 2005

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PROSPECT laparoscopic cholecystectomy update 2006 Subgroup

For each review, a Subgroup of the PROSPECT Working Group performs an initial evaluation of the evidence and also drafts clinical practice statements and recommendations, which are then discussed by the whole Working Group before a final consensus is reached. The Subgroup may sometimes include a non-Working Group member, to provide additional expertise in the procedure being reviewed. For the laparoscopic cholecystectomy update 2006 review, the Subgroup members were:
  • Mr Rory McCloy
  • Professor Edmund Neugebauer
  • Professor Stephan Schug

Grades of Recommendation

Recommendations are graded according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence: (Levels of evidence and grades of recommendation in PROSPECT reviews (from 2006)).   PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted.

Summary Recommendations

Pre-, intra- and postoperative interventions have been evaluated for the management of postoperative pain following laparoscopic cholecystectomy. Unless otherwise stated, ‘pre-operative’ refers to interventions applied before surgical incision, ‘intra-operative’ refers to interventions applied after incision and before wound closure, ‘postoperative’ refers to interventions applied at or after wound closure. The following peri-operative interventions for laparoscopic cholecystectomy have been reviewed: See Overall PROSPECT recommendations for the overall strategy for managing pain after laparoscopic cholecystectomy.

PROSPECT OVERALL RECOMMENDATIONS

PROSPECT overall recommendations for postoperative pain management following laparoscopic cholecystectomy:

DESCRIPTION OF STUDIES
Literature search

Study quality assessments, levels of evidence and grades of recommendation

Recommendations are graded according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence: (Levels of evidence and grades of recommendation in PROSPECT reviews (from 2006))

Click here for table of quality scores and levels of evidence for included procedure-specific studies:(Laparoscopic Cholecystectomy Update 2006 Quality Scoring + Levels of Evidence)

Transferable evidence

Transferable evidence of analgesic efficacy from comparable procedures or evidence of other outcomes, such as adverse effects, has been included to support the procedure-specific evidence where this is insufficient.


 

TOPICS FOR FUTURE RESEARCH

In certain circumstances, recommendations for a type of treatment cannot be made due to limited or conflicting evidence. Areas which have been identified as requiring further investigation in the future are as follows: 

  • Time of drug administration, e.g.:
    • pre- versus post-incisional administration of various agents, such as conventional NSAIDs, COX-2-selective inhibitors, paracetamol
    • IP LA instillation at the start of surgery versus administration at the end of surgery
  • IV LA infusion
  • Alpha-2-adrenergic receptor agonists
  • Dextromethorphan
  • Ketamine
  • Interpleural local anaesthetic
  • Intra-operative fluid management
  • Postoperative PCA IP local anaesthetic
  • Humidified and/or warmed pneumoperitoneum
  • Nitrous oxide pneumoperitoneum
  • Total size of trocar incision
  • Radially expanding trocars
  • Surgeon’s position
  • Subhepatic drains
  • Aspiration of the pneumoperitoneum gas

ABBREVIATIONS

FVC

forced vital capacity

FEV1

forced expiratory volume in 1 sec

PEF

peak expiratory flow

PEFR

peak expiratory flow rate

FEF

forced expiratory flow

FEFR

forced expiratory flow rate

FEFR25­–75

forced expiratory flow rate at 25–75% of the FVC

PCA

patient-controlled analgesia

PaO2

partial pressure of arterial oxygen

PaCO2

partial pressure of arterial carbon dioxide

IM

intramuscular

IV

intravenous

IP

intraperitoneal

Pre-op

pre-operatively

Intra-op

intra-operatively

Postop

postoperatively

VAS

visual analogue scale

VRS

verbal rating scale

LA

local anaesthetic

NRS

numerical rating scale

PROSPECT Recommendations

  • Pre-operative systemic clonidine is not recommended (Grade D) because procedure-specific evidence for analgesic efficacy is limited and because of potential adverse-effects, which may delay early ambulation (LoE 4)

Clinical Practice

  • The risk/benefit ratio for clonidine is unclear. Recognised side-effects include hypotension, sedation, dizziness and bradycardia

Transferable Evidence from Other Procedures

Laparoscopic Cholecystectomy-specific evidence

PROSPECT Recommendations

  • Pre-operative gabapentin is recommended (Grade B) for reducing postoperative pain and opioid use (procedure-specific and transferable evidence, LoE 1)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Two systematic reviews and a meta-analysis evaluated the use of gabapentin for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls Dahl et al 2004
  • One systematic review Ho et al 2006
  • One systematic review Ho et al 2006

Laparoscopic Cholecystectomy-specific evidence

  • Gabapentin significantly reduced VAS pain scores at rest over the first 24 h following surgery compared with placebo (p<0.05)  Pandey et al 2004
  • Gabapentin significantly reduced opioid consumption compared with placebo (p<0.05; 2 µg/kg IV fentanyl was given on request) Pandey et al 2004
  • Gabapentin significantly reduced VAS pain scores at rest compared with tramadol at 6–24 h postoperatively (p<0.05), but not at 0–6 h Pandey et al 2004
  • Gabapentin significantly decreased opioid consumption compared with tramadol in the first 24 h postoperatively (p<0.05; 2 µg/kg IV fentanyl was given on request) Pandey et al 2004
  • Gabapentin was associated with a lower incidence of respiratory depression than tramadol (p<0.05) Pandey et al 2004
  • The incidence of nausea/retching/vomiting, as well as of sedation, was significantly higher in the gabapentin group compared with the placebo group (p<0.05)  Pandey et al 2004
  • There were no significant differences between gabapentin and tramadol for the incidence of nausea/retching/vomiting or sedation Pandey et al 2004
  • Study details Pandey et al 2004 Click here for more information

PROSPECT Recommendations

  • Pre-operative conventional NSAIDs are not recommended (Grade B) (majority vote of the Working Group; 6:2). Although conventional NSAIDs reduce opioid use (procedure-specific evidence, LoE 1) and pain (transferable evidence, LoE 1) compared with placebo, they are associated with a risk of complications during surgical procedures (transferable evidence, LoE 1)
  • There is insufficient evidence that pre-operative administration is of greater analgesic benefit than intra- or postoperative administration (transferable evidence, LoE 1)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures Barden et al 2004
  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritis, urinary retention or respiratory depression Marret et al 2005
  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987
  • Two meta-analyses comparing pre-incisional and post-incisional NSAIDs/COX-2-selective inhibitors have found no significant benefit of pre-incisional administration for reducing pain scores Møiniche et al 2002
  • Randomised trials in healthy elderly volunteers have shown that conventional NSAIDs are associated with a higher incidence of upper gastrointestinal ulceration compared with COX-2-selective inhibitors for short-term use Harris et al 2001
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with control Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused reversible platelet dysfunction Niemi et al 1997
  • A large randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • A randomised clinical trial showed that the conventional NSAID diclofenac was associated with significantly greater intra-operative blood loss than the COX-2-selective inhibitor rofecoxib in patients undergoing abdominal or vaginal hysterectomy or breast surgery Hegi et al 2004
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • Conventional NSAIDs and COX-2 selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of conventional NSAIDs or COX-2 selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2 selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004

Laparoscopic Cholecystectomy-specific evidence

  • One study showed that pre-operative ketoprofen significantly increased the time to first analgesic demand compared with pre-operative propacetamol, but there was no significant difference between the agents given postoperatively  Boccara et al 2005
  • Compared with placebo, a regimen of conventional NSAID plus strong opioid, followed by LA infiltration, was associated with significantly reduced nausea scores in PACU (p<0.05), but there was no significant difference at any other time Michaloliakou et al 1996
  • Compared with placebo, a regimen of conventional NSAID plus strong opioid, followed by LA infiltration, was associated with a significantly shorter time to discharge from PACU (p<0.05), although the time to the first bowel movement was similar in both groups Michaloliakou et al 1996
  • Compared with placebo, a regimen of conventional NSAID plus strong opioid, followed by LA infiltration, was associated with a significantly reduced proportion of patients requiring postoperative analgesia (p<0.001; postoperative analgesia was 10–20 mg IV pethidine every 10 minutes, until pain relief established, followed by oral or IM ketorolac 10–30 mg) Michaloliakou et al 1996
  • Compared with placebo, a regimen of conventional NSAID plus strong opioid, followed by LA infiltration, was associated with a significantly longer time to first analgesic request (p<0.001) Michaloliakou et al 1996
  • Compared with placebo, a regimen of conventional NSAID plus strong opioid, followed by LA infiltration, was associated with a significantly greater proportion of patients without pain on arrival in PACU and with only mild pain at discharge (p<0.001 in each case)  Michaloliakou et al 1996
  • Compared with placebo, a regimen of conventional NSAID plus strong opioid, followed by LA infiltration, was associated with significantly lower VAS pain scores at 0, 0.5, 1, 2, 3 and 4 h after arrival in PACU, then at discharge and at 10 h (p<0.05 in each case) but not at 24 or 48 h; and also reduced VRS pain scores at all time points, except at 24 h (p<0.05) Michaloliakou et al 1996
  • One study showed that supplemental analgesia use and the number of patients requiring supplemental analgesia were significantly lower in the IV tenoxicam + IM dextromethorphan group compared with IV saline + IM dextromethorphan (p<0.05; p<0.001, respectively) (supplemental analgesia was IM pethidine 1 mg/kg on request) Yeh et al 2004
  • The time to first analgesic request was significantly longer in the IV tenoxicam + IM dextromethorphan group compared with IV saline + IM dextromethorphan (p<0.001) Yeh et al 2004
  • One study showed that pre-operative administration of IV tenoxicam + IM dextromethorphan was associated with significantly lower VAS pain scores than IV saline + IM dextromethorphan at 1 and 2 h at rest and at 1, 2 and 4 h on coughing (p<0.05 in each case), but not at other time points (data was collected at 1, 2, 4, 12, 24 and 48 h) Yeh et al 2004
  • Pre-operative ketoprofen significantly reduced opioid use compared with pre-operative propacetamol, but there was no significant difference between these agents given postoperatively Boccara et al 2005 Click here for more information
  • Pre-operative ketoprofen significantly reduced VAS pain scores compared with pre-operative propacetamol in one study, but two studies showed no significant difference for VAS pain scores between postoperative NSAIDs and postoperative propacetamol/paracetamol Boccara et al 2005 Click here for more information
  • Pre-operative ketoprofen significantly increased the time to first analgesic demand compared with postoperative ketoprofen (p<0.05) Boccara et al 2005
  • Pre-operative ketoprofen significantly reduced VAS pain scores compared with postoperative ketoprofen during the first 12 h following surgery (p<0.05), with the effect being most evident during the first 3 h (p=0.001), although there was no significant difference between the two groups at 24 h Boccara et al 2005
  • One study out of one showed that tenoxicam (20 mg) + ondansetron (4 mg), administered in 20 ml saline before induction of anaesthesia, significantly reduced the time to first flatus compared with ondansetron alone (p<0.05) Elhakim et al 1995
  • One study measured parameters of pulmonary function and found that the values of FEV1 and FEF25–75 were significantly higher at 4 h after surgery in the ketorolac group compared with the placebo group (p<0.05) Liu et al 1993
  • One study out of one showed that IM ketorolac (60 mg), administered intra-operatively pre-procedure (n=31), significantly increased the time to first analgesic request (p<0.05) compared with placebo (n=23) and IM ketorolac, administered intra-operatively post-procedure (n=20)  Lane et al 1996
  • Five studies out of ten showed a significant benefit of conventional NSAIDs compared with placebo or no treatment for reducing supplemental analgesic use Forse et al 1996 Click here for more information
  • Eight studies out of ten showed a significant benefit of conventional NSAIDs over placebo or no treatment for reducing VAS pain scores; in most cases the benefit was limited to the very early postoperative period Munro et al 1998 Click here for more information
  • One study out of one found no significant difference for the time to hospital discharge between IM diclofenac, administered after induction of anaesthesia (n=26), and placebo (n=23) Wilson et al 1994
  • One study out of one found no significant differences for the duration of hospital stay between IM ketorolac, administered intra-operatively pre- and post-procedure, and placebo Lane et al 1996
  • One study out of one found that the incidence of pethidine-related side-effects, such as nausea and vomiting, was similar in both the IV tenoxicam + IM dextromethorphan and the IV saline + IM dextromethorphan groups Yeh et al 2004
  • One study out of one found that VAS pain scores in the IV tenoxicam + IM chlorpheniramine group were significantly higher than those in the IV saline + IM dextromethorphan + IM chlorpheniramine group at 1 h at rest and at 2 and 4 h on coughing (p<0.05 in each case), but not at other time points (VAS pain scores were recorded at 1, 2, 4, 12, 24 and 48 h) Yeh et al 2004
  • One study out of one found that the time to first analgesic request, pethidine use and the incidence of pethidine-related side-effects were not significantly different between the IV tenoxicam + IM chlorpheniramine and the IM dextromethorphan groups + IM chlorpheniramine Yeh et al 2004
  • One study that compared IM ketorolac + glycerin suppository, administered after the induction of anaesthesia, with IM saline + indomethacin suppository, showed no significant difference in pain scores, opioid use and incidence of nausea/vomiting Forse et al 1996
  • There were no significant differences between ketoprofen and propacetamol for the incidence of nausea or vomiting, administered pre- or post-operatively Boccara et al 2005
  • There was no significant difference in the incidence of nausea or vomiting between pre-operative and postoperative administration of ketoprofen Boccara et al 2005
  • Pre-operative ketoprofen did not significantly reduce opioid use compared with postoperative ketoprofen Boccara et al 2005
  • Only two studies out of seven that recorded the incidence of nausea and/or vomiting showed that conventional NSAIDs significantly reduced the incidence of nausea and/or vomiting compared with placebo or no treatment Elhakim et al 1995 Click here for more information
  • The time to first analgesic request was similar between tenoxicam and placebo in two comparison arms of one study (arm 1: pre-operative IV tenoxicam + IM chlorpheniramine maleate (20 mg) versus IV saline + IM chlorpheniramine maleate (20 mg); arm 2: pre-operative IV tenoxicam + IM dextromethorphan + IM chlorpheniramine maleate (20 mg) versus IV saline + IM dextromethorphan + IM chlorpheniramine maleate (20 mg)) Yeh et al 2005
  • Table 1. Systemic conventional NSAIDs versus placebo or no treatment: Study details Elhakim et al 1995 Click here for more information
  • Study details Boccara et al 2005 Click here for more information

PROSPECT Recommendations

  • Pre-operative dexamethasone is recommended for its anti-emetic effects (Grade A), and potential analgesic effects (Grade B), based on procedure-specific evidence (LoE 1)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • A single prophylactic dose of corticosteroid is effective for preventing PONV in surgery associated with high emetic effects Henzi et al 2000

Laparoscopic Cholecystectomy-specific evidence

  • One of two studies showed that dexamethasone was associated with reduced postoperative pain scores compared with control Bisgaard et al 2003 Click here for more information
  • One of two studies showed that pre-operative dexamethasone was associated with reduced postoperative opioid use compared with control Bisgaard et al 2003 Click here for more information
  • Two studies showed that dexamethasone was associated with reduced incidence of PONV compared with control Bisgaard et al 2003 Click here for more information
  • Pre-operative dexamethasone significantly reduced the duration of convalescence compared with placebo (p=0.03) Bisgaard et al 2003
  • Pre-operative injection of dexamethasone (± ondansetron) did not reduce the duration of hospital stay compared with placebo or ondansetron alone Elhakim et al 2002
  • Pre-operative injection of dexamethasone (8 and 16 mg) + ondansetron did not significantly reduce antiemetic use compared with ondansetron alone Elhakim et al 2002
  • Pre-operative dexamethasone did not significantly affect pulmonary function (FVC, FEV1, PEF) compared with placebo Bisgaard et al 2003
  • There was no significant difference between the four doses of dexamethasone (2, 4, 8, 16 mg) for VAS pain scores at rest or with activity (each group received ondansetron 4 mg) Elhakim et al 2002
  • There was no significant difference between the four doses of dexamethasone (2, 4, 8, 16 mg) for opioid use at 12 and 24 h after surgery (each group received ondansetron 4 mg)  Elhakim et al 2002
  • There were no significant differences between the four doses of dexamethasone (2, 4, 8, 16 mg) for the incidence of PONV, antiemetic use and duration of hospital stay (each group received ondansetron 4 mg) Elhakim et al 2002
  • Study details Bisgaard et al 2003 Click here for more information

PROSPECT Recommendations

  • Pre-operative COX-2-selective inhibitors are recommended (Grade B), based on procedure-specific and transferable evidence for analgesic efficacy (LoE 1)
  • There is no procedure-specific evidence to suggest that pre-operative administration is of greater analgesic benefit than intra- or postoperative administration (transferable evidence, LoE 1)
  • It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B) (cardiovascular morbidity (transferable evidence, LoE 1), renal function and hepatic function (transferable evidence, LoE 3) or actual or recent gastroduodenal ulcer history (LoE 4)

Clinical Practice

  • The 200 mg dose of celecoxib used by Cheng et al 2004
  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Transferable Evidence from Other Procedures

  • Rofecoxib 50 mg and parecoxib 40 mg have an equipotent analgesic efficacy relative to traditional NSAIDs in postoperative pain after minor and major surgical procedures Rømsing et al 2004
  • Randomised trials in healthy elderly volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation or bleeding time Greenberg et al 2000 Click here for more information
  • A randomised clinical trial showed that the COX-2-selective inhibitor rofecoxib was associated with significantly less intra-operative blood loss than the conventional NSAID diclofenac in patients undergoing abdominal or vaginal hysterectomy or breast surgery Hegi et al 2004
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) Nussmeier et al 2006
  • Two meta-analyses comparing pre-incisional and post-incisional NSAIDs/COX-2-selective inhibitors have found no significant benefit of pre-incisional administration for reducing pain scores Møiniche et al 2002
  • Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003

Laparoscopic Cholecystectomy-specific evidence

  • Pre-operative parecoxib was associated with significantly reduced postoperative pain compared with placebo Joshi et al 2004 Click here for more information
  • One study (two reports) showed that parecoxib/valdecoxib were associated with significantly reduced pain compared with placebo Joshi et al 2004 Click here for more information
  • Parecoxib/valdecoxib significantly reduced supplemental analgesic use compared with placebo Joshi et al 2004 Click here for more information
  • Parecoxib/valdecoxib treatment resulted in significantly improved Patient and Physician/Nurse Global Evaluations compared with placebo (p<0.05)  Joshi et al 2004
  • One study showed that pre-operative celecoxib and placebo were similar for abdominal and trocar entry site VAS pain scores at rest and during coughing at 0–6 h, and 12 and 24 h; both groups were similar for shoulder pain VRS Cheng et al 2004
  • There was no significant difference between celecoxib and placebo for the cumulative morphine consumption over the first 24 h following surgery Cheng et al 2004
  • One study showed that patients in both celecoxib and placebo groups took a similar length of time for analgesic request and had a similar severity of nausea and vomiting Cheng et al 2004
  • Parecoxib/valdecoxib was associated with reduced incidence of vomiting at 24 h post-discharge (p<0.05) compared with placebo, but overall incidence of PONV throughout the study period was not reduced Gan et al 2004 Click here for more information
  • There was no significant difference for bleeding tendency between celecoxib and placebo Cheng et al 2004
  • Study details Cheng et al 2004 Click here for more information

PROSPECT Recommendations

  • IV LA infusion is not recommended (Grade D) because procedure-specific evidence for analgesic efficacy is limited

Clinical Practice

  • IV LA infusion is not commonly used in routine clinical practice

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

  • IV lidocaine infusion significantly reduced VAS pain scores on coughing compared with placebo for 12 h following surgery (p<0.05), but not at 24 or 48 h, and only for 2 h at rest  Wu CT et al 2005
  • Compared with placebo, IV lidocaine infusion + IM dextromethorphan significantly reduced VAS pain scores at rest for the first 12 h postoperatively (p<0.05), but not at 24 and 48 h, and on coughing for the first 24 h (p<0.05), but not at 48 h  Wu CT et al 2005
  • IV lidocaine infusion + IM dextromethorphan significantly reduced VAS pain scores at rest at 1 and 4 h (p<0.05), and on coughing for the first 24 h (p<0.05), compared with either agent alone, but not at other time points (VAS measured at 1, 4, 12, 24 and 48 h)  Wu CT et al 2005
  • Total pethidine consumption was significantly lower in the IV lidocaine infusion group compared with the placebo group (p<0.001), as was the proportion of patients requiring pethidine (p<0.01) Wu CT et al 2005
  • IV lidocaine infusion + IM dextromethorphan significantly increased the time to first pethidine request compared with placebo (p<0.001) Wu CT et al 2005
  • IV lidocaine infusion + IM dextromethorphan significantly increased the time to first pethidine request compared with lidocaine alone (p<0.05) but not compared with dextromethorphan alone Wu CT et al 2005
  • IV lidocaine infusion + IM dextromethorphan was associated with significantly reduced pethidine requirements compared with placebo or either agent alone Wu CT et al 2005 Click here for more information
  • The incidence of nausea and vomiting was significantly lower in the IV lidocaine infusion + IM dextromethorphan group compared with the placebo group (p<0.001) Wu CT et al 2005
  • IV lidocaine infusion + IM dextromethorphan was associated with a significantly reduced incidence of nausea and vomiting compared with lidocaine alone (p<0.05), but not compared with dextromethorphan alone Wu CT et al 2005
  • IV lidocaine infusion + IM dextromethorphan significantly reduced the time to first passage of flatus compared with placebo (p<0.001)  Wu CT et al 2005
  • IV lidocaine infusion + IM dextromethorphan significantly reduced the time to first passage of flatus compared with either agent alone (p<0.05 Wu CT et al 2005
  • The time to first opioid request was similar between IV lidocaine infusion and placebo groups (1 mg/kg IM pethidine was given if requested) Wu CT et al 2005
  • The incidence of nausea and vomiting and the time to the first passage of flatus were similar between IV lidocaine infusion and placebo groups Wu CT et al 2005
  • Study details Wu CT et al 2005 Click here for more information

PROSPECT Recommendations

  • Pre-operative dextromethorphan is not recommended (Grade D) because procedure-specific evidence for analgesic efficacy is limited and transferable evidence is inconclusive (LoE 4)
  • Pre-operative single dose ketamine is not recommended (Grade D) because procedure-specific evidence is limited, despite analgesic efficacy in other procedures (LoE 1)
  • Magnesium is not recommended (Grade B), due to lack of efficacy (LoE 1)

Clinical Practice

  • NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship; in addition, they are associated with adverse side-effects, e.g. ketamine is known for its CNS adverse effects, toxicity and for causing dysphoria

Transferable Evidence from Other Procedures

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine Bell et al 2006
  • A study in gynaecological surgery that compared magnesium with placebo (placebo group received saline, magnesium groups received 40 mg/kg at induction, followed by either, saline, or magnesium infusion 10 mg/kg or 20 mg/kg), showed that morphine consumption was higher in the placebo group compared with the magnesium groups (total n=80) Seyhan et al 2006
  • Preincisional dextromethorphan combined with thoracic epidural anesthesia and analgesia improved postoperative pain and bowel function in patients undergoing colonic surgery Yeh et al 2005
  • Preincisional dextromethorphan in patients undergoing upper abdominal surgery reduced postoperative pethidine consumption Helmy + Bali 2001
  • Dextromethorphan premedication reduced postoperative pain and morphine requirement in upper abdominal surgery Wu et al 2000
  • Pre-operative dextromethorphan reduced intra-operative but not postoperative morphine requirements after laparotomy Grace et al 1998
  • A systematic review found that dextromethorphan did not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases Duedahl et al 2006
  • In abdominal hysterectomy, NMDA-receptor antagonists provided no significant benefit over placebo for reducing postoperative pain scores, supplementary analgesic consumption or PONV in the majority of studies, but the results were mixed and were independent of the specific type of agent and timing of administration Burstal et al 2001 Click here for more information

Laparoscopic Cholecystectomy-specific evidence

  • IM dextromethorphan + IV lidocaine were associated with significantly reduced time to first passage of flatus compared with placebo (p<0.001), and compared with either agent alone (p<0.05) (all groups received IM chlorpheniramine maleate) Wu CT et al 2005
  • IV ketamine infusion significantly reduced VAS pain scores at rest compared with magnesium at 4 and 20 h (p<0.05 in both cases), but not at 0–4 h or at 8 h; ketamine also significantly reduced VRS pain scores compared with magnesium at 4 h ( p<0.05), but not at other time points Ayoglu et al 2005
  • Pre-incisional IV ketamine + ropivacaine infiltration significantly reduced the use of postoperative analgesics compared with placebo (p<0.05, postoperative analgesia: 50–100 mg diclofenac was given rectally, or 75 mg parenteral dextropropexyphene, if required; 50 mg IM pethidine was given if dextropropoxyphene was insufficient) Papaziogas et al 2001
  • Pre-incisional IV ketamine + ropivacaine infiltration was associated with a significantly longer time to first request compared with placebo (p<0.05) Papaziogas et al 2001
  • Pre-incisional IV ketamine + ropivacaine infiltration significantly reduced VAS pain scores compared with placebo at 0, 3 and 24 h (p<0.01 in each case), at 6 and 12 h (p<0.05 in both cases), but not at 48 h Papaziogas et al 2001
  • IV ketamine infusion significantly reduced cumulative opioid use compared with placebo at 2 and 3 h (p<0.05 in both cases), but not at 4 or 20 h (postoperative opioid was PCA bolus of 1 mg morphine, 10-minute lockout, maximum 4 h dose 20 mg) Ayoglu et al 2005
  • IV ketamine infusion significantly reduced pain compared with placebo: VAS pain scores at rest at 2–4 h (p<0.05 in each case), but not at 0, 1, 8 or 20 h; VRS pain scores at 2 and 3 h (p<0.05 in each case), but not at other time points Ayoglu et al 2005
  • Total pethidine consumption (1 mg/kg IM pethidine was given if requested) was significantly lower in the pre-operative IM dextromethorphan group compared with the intra-operative IM dextromethorphan group (p<0.0001) Wu et al 1999
  • Pre-operative IM dextromethorphan significantly increased the time to first pethidine request compared with intra-operative IM dextromethorphan Wu et al 1999
  • Pre-operative IM dextromethorphan significantly reduced the ‘worst pain’ score compared with intra-operative IM dextromethorphan Wu et al 1999
  • Pre-operative IM dextromethophan significantly reduced the bed rest time compared with placebo and intra-operative IM dextromethorphan (p<0.001) Wu et al 1999
  • IM dextromethorphan + IV lidocaine were associated with significantly reduced incidence of nausea and vomiting compared with placebo (p<0.001), and compared with lidocaine alone (p<0.05), but not compared with dextromethorphan alone (all groups received IM chlorpheniramine maleate) Wu CT et al 2005
  • IM dextromethorphan + IV lidocaine significantly reduced the time to first pethidine request compared with lidocaine alone (p<0.05), but not compared with dextromethorphan alone (all groups received IM chlorpheniramine maleate) Wu CT et al 2005
  • IM dextromethorphan + IV lidocaine + IM chlorpheniramine maleate significantly reduced total pethidine use, the number of patients requiring morphine, and the time to first request, compared with IM chlorpheniramine maleate alone (p<0.001) (1 mg/kg IM pethidine was given if requested Wu CT et al 2005
  • The time to first analgesic request was significantly longer in the IV tenoxicam + IM dextromethorphan + IM chlorpheniramine maleate group compared with IV saline + IM chlorpheniramine maleate (p<0.001) Yeh et al 2004
  • IM dextromethorphan + IV lidocaine significantly reduced supplementary analgesic requirements compared with either agent alone Wu CT et al 2005 Click here for more information
  • Pre-operative Wu et al 1999 Click here for more information
  • One study showed that supplemental analgesia use and the number of patients requiring supplemental analgesia were significantly lower in the IV tenoxicam + IM dextromethorphan + IM chlorpheniramine maleate group compared with IV saline + IM chlorpheniramine maleate (p<0.05; p<0.001, respectively) (supplemental analgesia was IM pethidine 1 mg/kg on request) Yeh et al 2004
  • In one study Wu CT et al 2005 Click here for more information
  • Compared with placebo, IM dextromethorphan + IV lidocaine significantly reduced VAS pain scores at rest for the first 12 h postoperatively (p<0.05), but not at 24 or 48 h, and on coughing for the first 24 h (p<0.05), but not at 48 h (each group received IM chlorpheniramine maleate) Wu CT et al 2005
  • In two out of two studies, pre-operative IM dextromethorphan + IM chlorpheniramine maleate was associated with significantly reduced VAS pain scores compared with IM chlorpheniramine maleate alone Wu CT et al 2005 Click here for more information
  • Pre-operative, but not intra-operative, IM dextromethorphan + IM chlorpheniramine maleate significantly reduced the ‘worst pain’ score compared with IM chlorpheniramine maleate alone (p<0.000001) Wu et al 1999
  • One study out of one found that VAS pain scores in the IM dextromethorphan + IM chlorpheniramine maleate + IV saline group were significantly lower than those in the IV tenoxicam + IM chlorpheniramine maleate group at 1 h at rest and at 2 and 4 h on coughing (p<0.05, in each case), but not at other time points (VAS pain scores were recorded at 1, 2, 4, 12, 24 and 48 h) Yeh et al 2004
  • One study showed that pre-operative administration of IV tenoxicam + IM dextromethorphan + IM chlorpheniramine maleate was associated with significantly lower VAS pain scores than IV saline + IM chlorpheniramine maleate at 1 and 2 h at rest and at 1, 2 and 4 h on coughing (p<0.05 in each case), but not at other time points recorded (i.e. at 1, 2, 4, 12, 24 or 48 h) Yeh et al 2004
  • IM dextromethorphan + IV lidocaine significantly reduced postoperative pain compared with either dextromethorphan or IV lidocaine alone Wu CT et al 2005 Click here for more information
  • IV ketamine and IV magnesium infusion and placebo were associated with a similar incidence of nausea and vomiting, and similar pulmonary function Ayoglu et al 2005
  • IV magnesium infusion did not significantly reduce VAS or VRS pain scores compared with placebo at any time during 0–20 h Ayoglu et al 2005
  • Postoperative, but not pre-operative, IV ketamine (bolus dose) reduced postoperative pain compared with placebo Mathisen et al 1999 Click here for more information
  • IV magnesium infusion did not significantly reduce cumulative opioid use compared with placebo at any time during 0–20 h (postoperative opioid was PCA bolus of 1 mg morphine, 10-minute lockout, maximum 4 h dose 20 mg) Ayoglu et al 2005
  • Pre-operative and postoperative (R)-ketamine (bolus dose) were similar to placebo for pethidine use in the first 4 h, and for use of paracetamol + codeine at 24 h and 7 days postoperatively (postoperative analgesia: bolus doses of 0.1 mg/kg pethidine, 5-minute lockout, for 4 h, and after discharge, 500 mg paracetamol + 30 mg codeine) Mathisen et al 1999
  • IV ketamine and IV magnesium infusion were associated with similar cumulative opioid use during 0–20 h (postoperative opioid was PCA bolus of 1 mg morphine, 10-minute lockout, maximum 4 h dose 20 mg) Ayoglu et al 2005
  • Pre-incisional IV ketamine + ropivacaine infiltration was similar to placebo for the incidence of nausea and vomiting Papaziogas et al 2001
  • There were no significant differences between pre-operative and intra-operative IM dextromethorphan treatment groups for the incidence of nausea or vomiting Wu et al 1999
  • In two out of three studies, the incidence of adverse effects, such as nausea and vomiting, was similar in the IM dextromethorphan + IM chlorpheniramine maleate + IV saline and the IM chlorpheniramine maleate + IV saline groups Wu et al 1999 Click here for more information
  • One study out of one found that the incidence of pethidine-related side-effects, such as nausea and vomiting, was similar in both the IV tenoxicam + IM dextromethorphan + IM chlorpheniramine maleate and the IM chlorpheniramine maleate + IV saline groups Yeh et al 2004
  • One study out of one found that the time to first analgesic request, pethidine use and the incidence of pethidine-related side-effects were not significantly different between the IV tenoxicam + IM chlorpheniramine maleate and the IM dextromethorphan + IM chlorpheniramine maleate + IV saline groups Yeh et al 2004
  • Study details Wu et al 1999 Click here for more information
  • Ketamine and magnesium
  • Dextromethorphan

PROSPECT Recommendations

  • Pre-operative strong opioids are not recommended (Grade B) for analgesia because of side-effects during recovery (transferable evidence, LoE 1)

Clinical Practice

  • Strong opioids are not associated with a ceiling effect, and thus can provide effective analgesia for most types of surgical procedures
  • Strong opioids may be used in a variety of preparations and routes of administration, enabling choice for onset, duration of action, and mode of delivery

Transferable Evidence from Other Procedures

  • Strong opioids are effective for reducing high- and moderate-intensity postoperative pain McQuay et al 1999
  • Strong opioids are associated with adverse effects, including nausea, vomiting, sedation, confusion, paralytic ileus and urinary retention Wheeler et al 2002

Laparoscopic Cholecystectomy-specific evidence

  • Fewer patients receiving pre-operative IV morphine requested ‘rescue’ opioid  compared with patients receiving placebo (unclear if significant for this particular comparison; 2–3 mg IV morphine was given when VAS pain 50 or greater) Munoz et al 2002
  • Immediately after surgery (i.e. at 0 h), sufentanil significantly reduced VRS pain scores compared with remifentanil (p=0.04), but there were no significant differences at all other time points (1–120 h)  Damen et al 2004
  • Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA infiltration, was associated with significantly lower VAS pain scores at 0, 0.5, 1, 2, 3 and 4 h after arrival in PACU, then at discharge and at 10 h (p<0.05 in each case) but not at 24 or 48 h; and also reduced VRS pain scores at all time points, except at 24 h (p<0.05) Michaloliakou et al 1996
  • Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA infiltration, was associated with a significantly greater proportion of patients without pain on arrival in PACU and with only mild pain at discharge (p<0.001 in each case) Michaloliakou et al 1996
  • Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA infiltration, was associated with a significantly longer time to first analgesic request (p<0.001) Michaloliakou et al 1996
  • Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA infiltration, was associated with a significantly reduced proportion of patients requiring postoperative analgesia (p<0.001; postoperative analgesia was 10–20 mg IV pethidine every 10 minutes, until pain relief established, followed by oral or IM ketorolac 10–30 mg) Michaloliakou et al 1996
  • Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA infiltration, was associated significantly shorter time to discharge from PACU (p<0.05), although the time to the first bowel movement was similar in both groups Michaloliakou et al 1996
  • Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA infiltration, was associated significantly reduced nausea scores in PACU (p<0.05), but there was no significant difference at any other time Michaloliakou et al 1996
  • There were no significant differences between pre-operative IV morphine and placebo for VAS pain scores at rest or on coughing at any time point (i.e. 0–180 minutes) Munoz et al 2002
  • There were no significant differences between groups receiving pre-operative, intra-operative or postoperative IV morphine for VAS pain scores at rest or on coughing at any time point Munoz et al 2002
  • Pre-operative IV morphine and placebo groups took a similar length of time to first analgesic request Munoz et al 2002
  • There was no significant difference between pre-operative IV morphine and placebo groups for the incidence of postoperative emesis, although this was higher in the morphine group Munoz et al 2002
  • There were no significant differences between groups receiving pre-operative, intra-operative or postoperative IV morphine for opioid use (2–3 mg IV morphine was given when VAS pain 50 or greater), the incidence of emesis, or the length of time for first analgesia request  Munoz et al 2002
  • There were no significant differences between the remifentanil and sufentanil treatment groups for the use of supplementary analgesia, this being low in both groups (10 mg morphine and 100 mg diclofenac were given on demand, up to 60 mg morphine and 200 mg diclofenac/day) Damen et al 2004
  • Remifentanil and sufentanil were similar for the incidence of vomiting and VRS nausea scores at all time points and they were also similar for the time to discharge Damen et al 2004
  • Study details Munoz et al 2002 Click here for more information

PROSPECT Recommendations

  • Pre-operative tramadol is not recommended (Grade B) for analgesia because of side-effects during recovery (transferable evidence, LoE 1)

Clinical Practice

  • Tramadol is a centrally acting analgesic with µ-opioid agonist (M1-metabolite) and aminergic mechanisms of action. For prescription purposes, it is considered a weak opioid or a non-narcotic in most countries
  • Tramadol is useful in the treatment of postoperative pain of moderate intensity (intravenous and oral administration), providing effective analgesia in the in-patient and ambulatory setting
  • The effects of weak opioids on gastrointestinal (transit, secretion) and sphincter function, are of a lesser magnitude than those of strong opioids
  • At recommended doses, tramadol has no clinically relevant effects on cardiovascular or respiratory parameters, thus the risk of respiratory depression is negligible
  • Tramadol is beneficial when conventional NSAIDs are contraindicated
  • The oral solution (drops) of tramadol is useful as rescue medication when paracetamol/conventional NSAIDs/COX-2-selective inhibitor analgesic regimens are used
  • Opioid adverse effects, especially nausea and dizziness, limit the usefulness of tramadol, but many of the effects are less than for strong opioids
  • When ondansetron is used for the treatment/prophylaxis of tramadol-induced nausea and vomiting, a decrease in analgesic efficacy has been reported

Transferable Evidence from Other Procedures

  • Tramadol was more effective than placebo for pain relief in a meta-analysis of post-surgical patients Moore et al 1997
  • The combination of tramadol and paracetamol enhances analgesic efficacy compared with either agent alone McQuay H et al 2003
  • A systematic review found that the combination of dextropropoxyphene 65 mg with paracetamol 650 mg showed similar efficacy to tramadol 100 mg but with a lower incidence of adverse effects Collins et al 2000
  • A systematic review found that the combination of codeine with paracetamol provided additional pain relief compared with paracetamol alone Moore et al 2000
  • Adverse effects associated with tramadol include headache, nausea, vomiting, dizziness, somnolence. A meta-analysis of individual patient data from randomised controlled trials found a dose-response of adverse effects with tramadol; postsurgical patients had fewer side-effects than dental patients Moore et al 1997
  • A systematic review found that the combination of codeine with paracetamol was associated with an increase in drowsiness and dizziness compared with paracetamol alone Moore et al 2000
  • A systematic review found an increased incidence of central nervous system adverse effects with paracetamol plus dextropropoxyphene compared with placebo Collins et al 2000

Laparoscopic Cholecystectomy-specific evidence

  • Oral tramadol significantly reduced VAS pain scores 0–24 h postoperatively compared with placebo (p<0.05)  Pandey et al 2004
  • Oral tramadol significantly reduced opioid use compared with placebo over the first 24 h following surgery (p<0.05; 2 µg/kg IV fentanyl was given on request)  Pandey et al 2004
  • The incidence of nausea/retching/vomiting was similar in both oral tramadol and placebo groups Pandey et al 2004
  • The incidence of nausea/retching/vomiting or sedation was similar in both oral tramadol and oral gabapentin groups Pandey et al 2004
  • The incidence of nausea and vomiting and of cardiovascular adverse events was similar in both the pre-operative IV tramadol + postoperative IV tramadol PCA group and pre-operative IV morphine + postoperative IV morphine PCA group Naguib et al 1998
  • Oral tramadol was associated with significantly higher VAS pain scores at rest compared with oral gabapentin at 6–24 h postoperatively (p<0.05), but not at 0–6 h Pandey et al 2004
  • Pre- and postoperative IV tramadol were associated with significantly higher VAS pain scores at 30, 45 and 90 minutes following surgery, but not at any other time during 2–24 h, compared with pre- and postoperative IV morphine (p<0.05); pain scores recorded by an observer were similar between groups Naguib et al 1998
  • Pre-operative oral tramadol was associated with significantly greater opioid use compared with pre-operative oral gabapentin (p<0.05; 2 µg/kg fentanyl was given on request) Pandey et al 2004
  • PCA drug consumption in the early postoperative period was significantly greater in the pre-operative IV tramadol + postoperative IV tramadol group compared with the pre-operative IV morphine + postoperative IV morphine PCA group Naguib et al 1998 Click here for more information
  • There were no significant differences between pre-operative IV tramadol + postoperative IV tramadol PCA and pre-operative IV morphine and postoperative IV morphine PCA groups for the time taken to the first analgesic demand or for the proportion of patients not requesting PCA analgesia Naguib et al 1998
  • The incidence of sedation and respiratory depression was significantly higher in the oral tramadol group compared with the placebo group (p<0.05 in both cases)  Pandey et al 2004
  • The incidence of respiratory depression was significantly higher in the oral tramadol group compared with the oral gabapentin group (p<0.05) Pandey et al 2004
  • Study details Pandey et al 2004 Click here for more information

PROSPECT Recommendations

  • Pre-operative paracetamol is not recommended (Grade B)
  • Limited evidence shows that pre-operative administration is of no greater analgesic benefit than postoperative administration (procedure-specific evidence, LoE 1)

Clinical Practice

  • Paracetamol is not effective for severe pain

Transferable Evidence from Other Procedures

  • Paracetamol is an effective analgesic for the treatment of postoperative pain of moderate intensity Rømsing et al 2002
  • Paracetamol combined with weak opioids (codeine, tramadol) is superior to weak opioids alone in a review of dental, gynaecological and orthopaedic surgery McQuay H et al 2003
  • A meta-analysis of randomised controlled trials showed that paracetamol combined with PCA morphine induced a significant morphine-sparing effect but did not change the incidence of morphine-related adverse effects in the postoperative period Remy 2005
  • There is evidence that concurrent use of paracetamol and conventional NSAIDs improves pain relief compared with paracetamol alone, but there is no evidence for a superior analgesic effect of the combination compared with conventional NSAIDs alone Altman 2004

Laparoscopic Cholecystectomy-specific evidence

  • The number of patients requiring supplemental nalbuphine, the total dose consumed and the time to first analgesic demand were similar in both pre-operative and postoperative propacetamol groups Boccara et al 2005
  • There were no significant differences between pre-operative ketoprofen and pre-operative propacetamol groups for the incidence of nausea or vomiting Boccara et al 2005
  • The incidence of nausea or vomiting was similar in both pre-operative and postoperative propacetamol groups Boccara et al 2005
  • Pre-operative propacetamol was associated with significantly higher VAS pain scores compared with pre-operative ketoprofen, but two studies showed no significant difference for VAS pain scores between postoperative NSAIDs and postoperative propacetamol/paracetamol Boccara et al 2005 Click here for more information
  • Pre-operative propacetamol was associated with a significantly shorter time to first analgesic demand compared with pre-operative ketoprofen (p<0.05) (p-value given for the overall 4-group comparison) Boccara et al 2005
  • Pre-operative propacetamol was associated with significantly greater opioid use compared with pre-operative ketoprofen, but there was no significant difference between these agents given postoperatively Boccara et al 2005 Click here for more information
  • Postoperative administration of propacetamol significantly reduced VAS pain scores between 2 and 5 h postoperatively compared with pre-operative administration (p<0.05); the number of patients with severe pain (VAS 50 mm or greater) was significantly lower in the postoperative administration group compared with the pre-operative administration group (p<0.05) Boccara et al 2005
  • Study details Boccara et al 2005 Click here for more information

PROSPECT Recommendations

  • Long-acting LA wound infiltration is recommended (Grade A) for reducing wound pain (procedure-specific evidence, LoE 1), but not for reducing shoulder pain (procedure-specific evidence, LoE 1)
  • There is evidence that pre-operative administration is of no greater analgesic benefit than intra- or postoperative administration (procedure-specific evidence, LoE 1)

Clinical Practice

  • Long-acting local anaesthetics are preferred to short-acting local anaesthetics for analgesia by local injection
  • Intra-operative wound infiltration is a well-established method of analgesia with a favourable safety profile
  • The dose of LA must be monitored to ensure that maximum dose limits are not exceeded, especially if both infiltration and IP LA techniques are used

Transferable Evidence from Other Procedures

  • A qualitative and quantitative systematic review of intraperitoneal, port-site infiltration and mesosalpinx block confirmed that intraperitoneal infiltration showed statistically significant but clinically questionable effect on postoperative pain; mesosalpinx local anaesthetic block, but not port-site infiltration, had some impact on postoperative pain after laparoscopy Møiniche et al 2000
  • A qualitative systematic review of incisional local anaesthesia for postoperative pain relief after abdominal operations showed that except for herniotomy, there was a lack of evidence for a beneficial effect of incisional local anaesthesia on postoperative pain Møiniche et al 1998
  • Two quantitative systematic reviews of studies performed in a variety of procedures found no significant analgesic benefit of pre-incisional local anaesthetic wound infiltration compared with similar post-incisional wound infiltration Møiniche et al 2002

Laparoscopic Cholecystectomy-specific evidence

  • There were no significant differences for VAS pain scores between pre-incisional LA and postoperative LA administration groups at any of the time points recorded (i.e. 1, 3, 5, 7 and 12 h in the Sarac et al 1996
  • Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA wound infiltration, was associated with a significantly shorter time to discharge from PACU (p<0.05), although the time to the first bowel movement was similar in both groups Michaloliakou et al 1996
  • Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA wound infiltration, was associated with a significantly reduced proportion of patients requiring postoperative analgesia (p<0.001; postoperative analgesia was 10–20 mg IV pethidine every 10 minutes, until pain relief established, followed by oral or IM ketorolac 10–30 mg) Michaloliakou et al 1996
  • Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA wound infiltration, was associated with a significantly longer time to first analgesic request (p<0.001) Michaloliakou et al 1996
  • Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA wound infiltration, was associated with a significantly greater proportion of patients without pain on arrival in PACU and with only mild pain at discharge (p<0.001 in each case) Michaloliakou et al 1996
  • Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA wound infiltration, was associated with significantly lower VAS pain scores at 0, 0.5, 1, 2, 3 and 4 h after arrival in PACU, then at discharge and at 10 h (p<0.05 in each case) but not at 24 or 48 h; and also reduced VRS pain scores at all time points, except at 24 h (p<0.05) Michaloliakou et al 1996
  • Infiltration with strong opioid ± LA was associated with significantly longer time to first analgesic request compared with placebo (p<0.05; 100 mg IV tramadol was given, on request) Zajaczkowska et al 2004
  • The consumption of analgesics was significantly lower in the IV ketamine + ropivacaine infiltration group compared to placebo group (p<0.05; 50–100 mg rectal diclofenac or 75 mg parenteral dextropropoxyphene, if required; 50 mg IM pethidine if pain relief insufficient) Papaziogas et al 2001
  • The time to first request for analgesics was significantly longer in the IV ketamine + ropivacaine infiltration group compared with the placebo group (p<0.05) Papaziogas et al 2001
  • IV ketamine + ropivacaine infiltration significantly decreased VAS pain scores compared with placebo at 6 and 12 h (p<0.05 in each case) as well as at 0, 3 and 24 h (p<0.01 in each case), but not at 48 h Papaziogas et al 2001
  • Pre-incisional ropivacaine significantly reduced NSAID (diclofenac) consumption (patients with VAS scores of 3 or greater were given 50–100 mg diclofenac, rectally) compared with pre-incisional levobupivacaine (p<0.001), but parenteral opioid use was similar between groups (patients with persistent pain were given parenteral opioids) Papagiannopoulou et al 2003
  • Pre-incisional levobupivacaine significantly reduced VAS pain scores compared with pre-incisional ropivacaine at 4 and 24 h postoperatively (p<0.001 in each case) but not at 2 h Papagiannopoulou et al 2003
  • Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA wound infiltration, was associated with a significantly reduced nausea scores in PACU (p<0.05), but there was no significant difference at any other time Michaloliakou et al 1996
  • Analgesic use (pethidine in the Sarac et al 1996
  • In one study out of one, the rate of same-day discharge was significantly higher in the LA wound infiltration (bupivacaine + epinephrine) group compared with the no infiltration group (p<0.05)  Dath and Park 1999
  • Six studies out of 11 reported that LA wound infiltration reduced analgesic consumption compared with placebo or no treatment, see Table 2a for details; each of those studies also showed significantly reduced VAS pain scores with LA wound infiltration Click here for more information
  • Two studies out of two found that LA wound infiltration significantly increased the time to first analgesic demand compared with placebo (p<0.05 in both cases) Papaziogas et al 2001
  • In one study out of one, the proportion of patients with no pain after 5 h was significantly higher in the pre-incisional LA infiltration group compared with the placebo group (p=0.03) Ure et al 1993
  • In one study out of one, the proportion of patients with most severe pain located to the right lower abdominal wall on day 2 was significantly lower in the pre-incisional LA (bupivacaine) infiltration group compared with the placebo group (p=0.012) Ure et al 1993
  • Nine out of 11 studies showed a significant benefit of LA wound infiltration over placebo or no treatment for reducing VAS pain scores, see Table 2a for details Click here for more information
  • There were no significant differences for VAS pain scores between the wound infiltration with strong opioid ± LA and placebo groups at 4, 8 and 12 h Zajaczkowska et al 2004
  • There were no significant differences between LA wound infiltration and placebo groups for the duration of hospital stay in two out of two studies Lepner et al 2003
  • The incidence of PONV was similar for LA wound infiltration and placebo or no treatment groups in five out of five studies Lee et al 2001 Click here for more information
  • The incidence of shoulder pain was similar in LA wound infiltration and placebo or no treatment groups in two out of two studies Lee et al 2001 Click here for more information
  • The incidence of nausea and vomiting was similar in both the ropivacaine infiltration + IV ketamine and the placebo group Papaziogas et al 2001
  • The incidence of nausea and vomiting was similar for infiltration with strong opioid ± LA and placebo groups Zajaczkowska et al 2004
  • Table 2a. Local anaesthetic (LA) wound infiltration versus placebo or no treatment: Study details and qualitative analysis Alexander et al 1996 Click here for more information
  • Study details Sarac et al 1996 Click here for more information
  • LA wound infiltration, miscellaneous studies
  • LA wound infiltration, time of administration
  • Local anaesthetic wound infiltration versus placebo or no treatment

PROSPECT Recommendations

  • Bilateral PV block with long-acting LA is not recommended (Grade D), due to limited evidence and poor risk:benefit ratios (LoE 4)

Clinical Practice

  • Clinical experience with the paravertebral nerve block is not widespread. This technique is considered to be more complex, and thus it may be associated with a higher incidence of complications than other local anaesthetic techniques (IP/infiltration)

Transferable Evidence from Other Procedures

  • Bilateral paravertebral block combined with general anaesthesia reduced pain scores, supplemental analgesic use, and the incidence of PONV, compared with general anaesthesia alone in ventral hernia repair (n=60) Naja et al 2002

Laparoscopic Cholecystectomy-specific evidence

  • General anaesthesia + paravertebral blockade significantly reduced VAS pain scores at rest and during activity compared with general anaesthesia alone at 6, 12, 24, 36 and 48 h (p<0.05 in each case), but not at 72 h; abdominal and shoulder VAS pain scores were significantly lower at 6 h only (p<0.05 in each case)  Naja et al 2004
  • General anaesthesia + paravertebral blockade significantly increased the proportion of patients who had VAS scores of less than 3 on movement, coughing and walking, up to 48 h postoperatively (p<0.05 in each case) Naja et al 2004
  • General anaesthesia + paravertebral blockade significantly reduced analgesic use compared with general anaesthesia alone at 0–36 h (p<0.05 in each case) (1 mg/kg IM pethidine was given in the first 12 hours if VAS 4 or greater; next 12 hours: 2 tablets oral dextropropoxyphene, every 6 hours, if VAS 4 or greater)  Naja et al 2004
  • The incidence of nausea, but not vomiting, was significantly reduced in the general anaesthesia + paravertebral blockade group compared with the general anaesthesia alone group at 6 and 12 h (p<0.05 in each case) Naja et al 2004
  • General anaesthesia/bilateral paravertebral blockade was not significantly different from general anaesthesia alone for the time taken to defecation or to passing bowel gas, or for the duration of recovery room or hospital ward stay Naja et al 2004
  • Study details Naja et al 2004 Click here for more information

PROSPECT Recommendations

  • Spinal LA + strong opioid reduces postoperative pain (procedure-specific evidence, LoE 1), but is not recommended (Grade D), due to a poor risk:benefit ratio (LoE 4)
  • Epidural analgesia is recommended in high-risk pulmonary patients (Grade D; LoE 4)

Clinical Practice

  • The risk of side-effects associated with spinal and epidural analgesia may outweigh the benefits of analgesia in routine laparoscopic cholecystectomy

Transferable Evidence from Other Procedures

  • Spinal and epidural administration of strong opioids is associated with side-effects including pruritis, PONV, urinary retention, and respiratory depression Chaney 1995

Laparoscopic Cholecystectomy-specific evidence

  • Pre-operative lumbar spinal LA + strong opioid was associated with significantly lower abdominal pain scores (at rest, on coughing, on first mobilisation) compared with placebo at all time points (i.e. at 2, 4, 6 and 20 h postoperatively; p<0.001 in each case) Motamed et al 2000
  • Pre-operative lumbar spinal LA + strong opioid was associated with significantly reduced cumulative IV morphine dose at 20 h after surgery compared with placebo (p<0.04), but not in the early postoperative period (postoperative IV morphine: bolus doses 1–3 mg every 5 minutes in recovery room, then PCA bolus doses 1 mg, 7-minute lockout) Motamed et al 2000
  • A study that compared pre-operative lumbar spinal LA + strong opioid with placebo showed that the incidence of nausea/vomiting and the duration of hospital stay were similar in both groups Motamed et al 2000
  • Study details Motamed et al 2000 Click here for more information

PROSPECT Recommendations

  • Pre-operative oral carbohydrate is not recommended (Grade A), due to a lack of analgesic efficacy (procedure-specific evidence, LoE 1) and inconsistent effects on the incidence of PONV (procedure-specific evidence, LoE 1)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

PROSPECT Recommendations

  • Intra-operative conventional NSAIDs are recommended at the end of surgery to ensure analgesia when the patient wakes up (Grade D), provided haemostasis is secured (LoE 4)
  • The use of conventional NSAIDs should depend upon assessment of individual patient risks (Grade B), including bleeding complications, actual or recent gastroduodenal ulcer history (transferable evidence, LoE 1), cardiovascular morbidity (LoE 4), aspirin-sensitive asthma, renal function and hepatic function (transferable evidence, LoE 3)
  • It is not possible to make a recommendation for one route of administration in preference to any other on the basis of the available evidence
  • It is not possible to make a recommendation for one NSAID in preference to any other on the basis of the available evidence

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures Barden et al 2004
  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritis, urinary retention or respiratory depression Marret et al 2005
  • Rofecoxib 50 mg and parecoxib 40 mg have an equipotent analgesic efficacy relative to traditional NSAIDs in postoperative pain after minor and major surgical procedures Rømsing et al 2004
  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987
  • Randomised trials in healthy elderly volunteers have shown that conventional NSAIDs are associated with a higher incidence of upper gastrointestinal ulceration compared with COX-2-selective inhibitors for short-term use Harris et al 2001
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with control Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused reversible platelet dysfunction Niemi et al 1997
  • A large randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • A randomised clinical trial showed that the conventional NSAID diclofenac was associated with significantly greater intra-operative blood loss than the COX-2-selective inhibitor rofecoxib in patients undergoing abdominal or vaginal hysterectomy or breast surgery Hegi et al 2004
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • Conventional NSAIDs and COX-2 selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of conventional NSAIDs or COX-2 selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2 selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004

Laparoscopic Cholecystectomy-specific evidence

  • Eight studies out of ten showed a significant benefit of conventional NSAIDs compared with placebo or no treatment for reducing VAS pain scores Munro et al 1998 Click here for more information
  • Five studies out of ten showed a significant benefit of conventional NSAIDs compared with placebo or no treatment for reducing supplementary analgesic use Forse et al 1996 Click here for more information
  • One study out of one showed that IM ketorolac (60 mg), administered intra-operatively pre-procedure (n=31), significantly increased the time to first analgesic request (p<0.05) compared with placebo (n=23) and IM ketorolac, administered intra-operatively post-procedure (n=20) Lane et al 1996
  • One study measured parameters of pulmonary function and found that the values of FEV1 and FEF25–75 were significantly higher at 4 h after surgery in the ketorolac group compared with the placebo group (p<0.05) Liu et al 1993
  • One study out of one showed that tenoxicam (20 mg) + ondansetron (4 mg), administered in 20 ml saline before induction of anaesthesia, significantly reduced the time to first flatus compared with ondansetron alone (p<0.05) Elhakim et al 1995
  • Two studies out of seven that recorded the incidence of nausea and/or vomiting, showed that conventional NSAIDs significantly reduced the incidence of nausea and/or vomiting compared with placebo or no treatment Elhakim et al 1995 Click here for more information
  • One study out of one found no significant difference for the duration of hospital stay between IM ketorolac, administered intra-operatively pre- and post-procedure, and placebo Lane et al 1996
  • One study out of one found no significant difference for the time to hospital discharge between IM diclofenac, administered after induction of anaesthesia (n=26), and placebo (n=23) Wilson et al 1994
  • One study which compared IM ketorolac with IM diclofenac, administered 30 min prior to end of surgery, showed that there was no significant difference in VAS pain scores, opioid use and incidence of nausea or vomiting between groups Fredman et al 1995
  • Study details Fredman et al 1995 Click here for more information
  • Table 1. Systemic conventional NSAIDs versus placebo or no treatment: Study details Elhakim et al 1995 Click here for more information

PROSPECT Recommendations

  • Intra-operative COX-2-selective inhibitors are recommended at the end of surgery to ensure analgesia when the patient wakes up (Grade D, LoE 4)
  • COX-2-selective inhibitors may be more appropriate than conventional NSAIDs in the peri-operative setting, in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (transferable evidence, LoE 1)
  • It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B) (cardiovascular morbidity (transferable evidence, LoE 1), renal function and hepatic function (transferable evidence, LoE 3) or actual or recent gastroduodenal ulcer history (LoE 4)

Clinical Practice

  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Transferable Evidence from Other Procedures

  • Rofecoxib 50 mg and parecoxib 40 mg have an equipotent analgesic efficacy relative to traditional NSAIDs in postoperative pain after minor and major surgical procedures Rømsing et al 2004
  • Randomised trials in healthy elderly volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation Greenberg et al 2000
  • A randomised clinical trial showed that the COX-2-selective inhibitor rofecoxib was associated with significantly less intra-operative blood loss than the conventional NSAID diclofenac in patients undergoing abdominal or vaginal hysterectomy or breast surgery Hegi et al 2004
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) Nussmeier et al 2006
  • Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003

Laparoscopic Cholecystectomy-specific evidence

  • [None cited]

PROSPECT Recommendations

  • Intra-operative dextromethorphan is not recommended (Grade D) because procedure-specific evidence for analgesic efficacy is limited and transferable evidence is inconclusive (LoE 4)
  • Intra-operative ketamine by infusion is not recommended (Grade D) because procedure-specific evidence is limited, despite some analgesic efficacy in other procedures (transferable evidence, LoE 1)
  • Intra-operative magnesium by infusion is not recommended (Grade B), because there is evidence for a lack of analgesic efficacy (procedure-specific evidence, LoE 1)

Clinical Practice

  • NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship; in addition, they are associated with adverse side-effects, e.g. ketamine is known for its CNS adverse effects, toxicity and for causing dysphoria

Transferable Evidence from Other Procedures

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genito-urinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine Bell et al 2006
  • Administration of intraoperative magnesium sulphate as an adjuvant analgesic in patients undergoing open cholecystectomy resulted in better pain relief and comfort in the first postoperative hour compared with placebo (sleep quality during first postoperative night was better in the magnesium group compared to placebo p< 0.05), but it did not significantly decrease the postoperative morphine requirement (total n=50) Bhatia et al 2004
  • A study in gynaecological surgery that compared magnesium with placebo (placebo group received saline, magnesium groups received 40 mg/kg at induction, followed by either, saline, or magnesium infusion 10 mg/kg or 20 mg/kg), showed that morphine consumption was higher in the placebo group compared with the magnesium groups (n=80) Seyhan et al 2006
  • A quantitative systematic review found that dextromethorphan does not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases Duedahl et al 2006
  • In abdominal hysterectomy, NMDA-receptor antagonists provided no significant benefit over placebo for reducing postoperative pain scores, supplementary analgesic consumption or PONV in the majority of studies, but the results were mixed and were independent of the specific type of agent and timing of administration Burstal et al 2001 Click here for more information

Laparoscopic Cholecystectomy-specific evidence

  • Intra-operative IM dextromethorphan + IM chlorpheniramine maleate significantly increased the time to first pethidine request compared with IM chlorpheniramine maleate alone (p<0.05) Wu et al 1999
  • IV ketamine infusion significantly reduced VAS pain scores at rest compared with magnesium at 4 and 20 h (p<0.05 in both cases), but not at 0–4 or at 8 h; ketamine also significantly reduced VRS pain scores compared with magnesium at 4 h (p<0.05), but not at other time points Ayoglu et al 2005
  • IV ketamine infusion significantly reduced cumulative opioid use compared with placebo at 2 and 3 h (p<0.05 in both cases), but not at other time points Ayoglu et al 2005
  • IV ketamine infusion significantly reduced pain compared with placebo: VAS pain scores at rest at 2–4 h (p<0.05 in each case) but not at 0, 1, 8 or 20 h; VRS pain scores at 2 and 3 h (p<0.05 in each case), but not at other time points Ayoglu et al 2005
  • There were no significant differences between pre-operative and intra-operative IM dextromethorphan treatment groups for the incidence of nausea and vomiting Wu et al 1999
  • IV ketamine and magnesium infusion were similar for the incidence of nausea and vomiting, and for pulmonary function parameters Ayoglu et al 2005
  • IV ketamine and IV magnesium infusion were associated with similar cumulative opioid use during 0–20 h (postoperative opioid was PCA bolus of 1 mg morphine, 10-minute lockout, maximum 4 h dose 20 mg) Ayoglu et al 2005
  • IV magnesium infusion did not significantly reduce cumulative opioid use compared with placebo at any time during 0–20 h (postoperative opioid was PCA bolus of 1 mg morphine, 10-minute lockout, maximum 4 h dose 20 mg) Ayoglu et al 2005
  • Ketamine, magnesium and placebo infusion were similar for the incidence of nausea and vomiting, and for pulmonary function parameters Ayoglu et al 2005
  • IV magnesium infusion did not significantly reduce VAS or VRS pain scores compared with placebo at any time during 0–20 h Ayoglu et al 2005
  • Intra-operative IM dextromethorphan was associated with significantly increased bed rest time compared with pre-operative IM dextromethorphan (p<0.001) Wu et al 1999
  • Total pethidine consumption (1 mg/kg IM pethidine was given if requested) was significantly higher in the intra-operative IM dextromethorphan group compared with the pre-operative IM dextromethorphan group (p<0.0001) Wu et al 1999
  • Pre-operative IM dextromethorphan significantly increased the time to first pethidine request compared with intra-operative IM dextromethorphan (p<0.05) Wu et al 1999
  • Intra-operative IM dextromethorphan + IM chlorpheniramine maleate and IM chlorpheniramine maleate alone groups were similar for the incidence of nausea and vomiting Wu et al 1999
  • Intra-operative IM dextromethorphan + IM chlorpheniramine maleate and IM chlorpheniramine maleate alone groups were similar for total pethidine consumption and the number of patients requiring pethidine (1 mg/kg IM pethidine was given if requested) Wu et al 1999
  • Intra-operative IM dextromethorphan significantly increased the ‘worst pain' score compared with pre-operative IM dextromethorphan (p<0.0001) Wu et al 1999
  • Intra-operative IM dextromethorphan + IM chlorpheniramine maleate did not significantly reduce the ‘worst pain' score compared with IM chlorpheniramine maleate alone Wu et al 1999
  • Study details Wu et al 1999 Click here for more information
  • Ketamine
  • Dextromethorphan

PROSPECT Recommendations

  • Short-acting strong opioids are recommended as part of the anaesthetic technique (Grade D, LoE 4)
  • Intra-operative longer-acting strong opioids are not recommended (Grade B) as part of the anaesthetic technique because of side effects during recovery (transferable evidence, LoE 1)

Clinical Practice

  • Strong opioids are not associated with a ceiling effect, and thus can provide effective analgesia for most types of surgical procedures
  • Strong opioids may be used in a variety of preparations and routes of administration, enabling choice for onset, duration of action, and mode of delivery

Transferable Evidence from Other Procedures

  • Strong opioids are effective for reducing high- and moderate-intensity postoperative pain McQuay et al 1999
  • Strong opioids are associated with adverse effects, including nausea, vomiting, sedation, confusion, paralytic ileus and urinary retention Wheeler et al 2002

Laparoscopic Cholecystectomy-specific evidence

  • IM pethidine significantly reduced opioid use in the recovery room (0.25 mg/kg IV pethidine was given every 10 minutes, as needed, up to 4 doses in the first hour postoperatively) compared with placebo (p<0.05) Lane et al 1996
  • Fewer patients receiving IV morphine requested rescue opioid (2–3 mg/kg IV pethidine was given every 10 minutes, as needed, up to 4 doses in the first hour postoperatively) compared with patients receiving placebo (unclear if significant for this particular comparison Munoz et al 2002
  • There were no significant differences between IV morphine and placebo for VAS pain scores at rest or on coughing at any time point (0–180 min) and both groups took a similar length of time to first analgesic request Munoz et al 2002
  • There were no significant differences in VAS pain scores between IM pethidine and placebo groups over the first 24 h following surgery Lane et al 1996
  • There were no significant differences between groups receiving pre-operative, intra-operative or postoperative IV morphine for VAS pain scores at rest or on coughing at any time point (0–180 min) Munoz et al 2002
  • There was no significant difference between the IV morphine and placebo groups for the incidence of postoperative emesis Munoz et al 2002
  • There were no significant differences between groups receiving pre-operative, intra-operative or postoperative IV morphine for opioid use or the incidence of emesis. All IV morphine groups took similar length of time for first analgesia request Munoz et al 2002
  • IM pethidine and placebo groups took a similar length of time to first analgesic request Lane et al 1996
  • There was no significant difference between the IM pethidine and placebo groups for the duration of hospital stay Lane et al 1996
  • Study details Lane et al 1996 Click here for more information

PROSPECT Recommendations

  • Long-acting LA wound infiltration is recommended (Grade A) for reducing wound pain (procedure-specific evidence, LoE 1), but not for reducing shoulder pain (procedure-specific evidence, LoE 1)
  • There is no evidence that intra-operative administration is of greater analgesic benefit than pre- or postoperative administration

Clinical Practice

  • Long-acting local anaesthetics are preferred to short-acting local anaesthetics for analgesia by local injection
  • Intra-operative wound infiltration is a well-established method of analgesia with a favourable safety profile
  • The dose of LA must be monitored to ensure that maximum dose limits are not exceeded, especially if both infiltration and IP LA techniques are used

Transferable Evidence from Other Procedures

  • A qualitative and quantitative systematic review of intraperitoneal, port-site infiltration and mesosalpinx block showed that port-site infiltration did not reduce postoperative pain after laparoscopy, while intraperitoneal infiltration was associated with a statistically significant but clinically questionable effect on postoperative pain, and mesosalpinx local anaesthetic block reduced postoperative pain to some extent after laparoscopy Møiniche et al 2000
  • A qualitative systematic review of incisional local anaesthesia for postoperative pain relief after abdominal operations showed that except for herniotomy, there was a lack of evidence for a beneficial effect of incisional local anaesthesia on postoperative pain Møiniche et al 1998
  • Two quantitative systematic reviews of studies performed in a variety of procedures found no significant benefit of preincisional LA wound infiltration compared with similar postincisional wound infiltration for reducing pain scores Møiniche et al 2002

Laparoscopic Cholecystectomy-specific evidence

  • In one study out of one, the rate of same-day discharge was significantly higher in the LA wound infiltration (bupivacaine + epinephrine) group compared with the placebo group (p<0.05) Dath and Park 1999
  • There were no significant differences between IP LA and intrawound LA for VAS pain scores at 1, 2, 4 or 8 h postoperatively, or at discharge, or for total analgesic use (postoperative analgesia was IM Cyclimorph or 2 x co-proxamol tablets, as required) Johnson et al 1999
  • Six studies out of 11 reported that LA wound infiltration reduced analgesic consumption compared with placebo or no treatment, see Table 2a for details; each of those studies also showed significantly reduced VAS pain scores with LA wound infiltration Click here for more information
  • Two studies out of two found that LA wound infiltration significantly increased the time to first analgesic demand compared with placebo (p<0.05 in both cases) Papaziogas et al 2001
  • In one study out of one, the proportion of patients with no pain after 5 h was significantly higher in the LA wound infiltration group compared with the placebo group (p=0.03) Ure et al 1993
  • In one study out of one, the proportion of patients with most severe pain located to the right lower abdominal wall on day 2 was significantly lower in the LA (bupivacaine) infiltration group compared with the placebo group (p=0.012) Ure et al 1993
  • Nine out of 11 studies showed a significant benefit of LA wound infiltration over placebo or no treatment for reducing VAS pain scores, see Table 2a for details Click here for more information
  • The incidence of shoulder pain was similar for LA wound infiltration and placebo or no treatment groups in two out of two studies Lee et al 2001 Click here for more information
  • The incidence of PONV was similar for LA wound infiltration and placebo or no treatment in five out of five studies Lee et al 2001 Click here for more information
  • There were no significant differences between LA wound infiltration and placebo groups for the duration of hospital stay in two out of two studies Lepner et al 2003
  • There were no significant differences for VAS pain scores between pre-incisional and postoperative LA administration groups at any of the time points recorded (i.e. 1, 3, 5, 7 and 12 h in the Sarac et al 1996
  • Analgesic use (pethidine in the Sarac et al 1996
  • Study details Sarac et al 1996 Click here for more information
  • Table 2a. Local anaesthetic (LA) infiltration versus control or no treatment: Study details and qualitative outcomes Alexander et al 1996 Click here for more information
  • LA wound infiltration versus placebo or no treatment
  • LA infiltration, time of administration
  • Intrawound LA versus IP LA

PROSPECT Recommendations

  • Combined LA wound infiltration/IP LA techniques are recommended (Grade A) for analgesic efficacy (procedure-specific evidence, LoE 1), provided the dose is monitored to prevent toxicity (Grade D, LoE 4)

Clinical Practice

  • Long-acting local anaesthetics are preferred to short-acting local anaesthetics for analgesia by local injection
  • Intra-operative wound infiltration is a well-established method of analgesia with a favourable safety profile
  • The dose of LA must be monitored to ensure that maximum dose limits are not exceeded, especially if both infiltration and IP LA techniques are used

Transferable Evidence from Other Procedures

  • A qualitative and quantitative systematic review of intraperitoneal, port-site infiltration and mesosalpinx block showed that port-site infiltration did not reduce postoperative pain after laparoscopy, while intraperitoneal infiltration was associated with a statistically significant but clinically questionable effect on postoperative pain, and mesosalpinx local anaesthetic block reduced postoperative pain to some extent after laparoscopy Møiniche et al 2000
  • A qualitative systematic review of incisional local anaesthesia for postoperative pain relief after abdominal operations showed that except for herniotomy, there was a lack of evidence for a beneficial effect of incisional local anaesthesia on postoperative pain Møiniche et al 1998

Laparoscopic Cholecystectomy-specific evidence

PROSPECT Recommendations

  • IP LA techniques are recommended (Grade A) for reducing wound pain (procedure-specific evidence, LoE 1), but not for reducing shoulder pain (procedure-specific evidence, LoE 1)
  • IP LA + epinephrine is not recommended over IP LA alone (Grade B), as epinephrine provides no additional analgesic benefit (limited procedure-specific evidence, LoE 1)
  • IP instillation at the start of surgery is more favourable than administration at the end of surgery (procedure-specific evidence, LoE 1), although this is from limited evidence and requires confirmation from further studies before a recommendation can be made

Clinical Practice

  • Long-acting local anaesthetics are preferred to short-acting local anaesthetics
  • The dose of LA must be monitored to ensure that maximum dose limits are not exceeded, especially if both infiltration and IP LA techniques are used

Transferable Evidence from Other Procedures

  • A qualitative and quantitative systematic review of intraperitoneal, port-site infiltration and mesosalpinx block showed that intraperitoneal infiltration was associated with a statistically significant but clinically questionable reduction of postoperative pain, and mesosalpinx local anaesthetic block, but not port-site infiltration, reduced postoperative pain to some extent after laparoscopy Møiniche et al 2000
  • IP LA administration is an effective method for controlling postoperative pain in gynaecological laparoscopy Narchi 1995
  • A randomised placebo controlled study in laparoscopic tubal ligation comparing intraperitoneal ropivacaine with placebo, showed that ropivacaine reduced pain scores 2 hours postoperatively (p<0.05) and fentanyl requirement (p<0.02) (total n=19) Dreher et al 2000
  • One study indicates that intraperitoneal application of tramadol, tenoxicam and bupivacaine is effective for reducing pain after laparoscopic gynaecological operations (total n=80) Karsli et al 2003
  • A study in patients undergoing laparoscopic gynaecological surgery showed that prophylactic IP administration of bupivacaine and/or morphine does not significantly improve postoperative analgesia Keita et al 2003

Laparoscopic Cholecystectomy-specific evidence

  • IP LA + IP NSAID and IP LA + IV NSAID significantly reduced VAS pain scores compared with placebo in two studies Jabbour-Khoury et al 2005 Click here for more information
  • Administration of IP bupivacaine at the start and end of surgery sugnificantly reduced VRS pain scores at 0, 4, 8 and 12 h compared with administration at the end of surgery alone (in all cases, p<0.05) but not at 24 h postoperatively in one study Pasqualucci et al 1994
  • Administration of IP bupivacaine at the start and end of surgery was significantly superior to administration at the start of surgery alone for reducing VAS pain scores at 0 and 4 h (in both cases, p<0.05) Pasqualucci et al 1996
  • Administration of IP bupivacaine at the start and end of surgery was significantly superior to administration at the start of surgery alone for reducing VRS pain scores at 0 h (p<0.05) Pasqualucci et al 1996
  • Administration of IP bupivacaine at the start of surgery significantly reduced analgesic use (30 mg IV ketorolac was given, as necessary) compared with IP bupivacaine administration at the end of surgery (p<0.05) Pasqualucci et al 1996
  • Administration of IP bupivacaine at the start and end of surgery significantly reduced analgesic (30 mg IV ketorolac was given, as necessary) requirement compared with administration at the end of surgery alone (p<0.05) Pasqualucci et al 1994
  • The incidence of nausea and vomiting was lower in the start of surgery IP LA administration group compared with the end of surgery IP LA administration group, although p values were not given Pasqualucci et al 1996
  • Administration of IP bupivacaine at the start and end of surgery reduced the incidence of nausea and vomiting compared with administration at the end of surgery alone Pasqualucci et al 1994
  • IP LA + IP NSAID and IP LA + IV NSAID reduced opioid consumption over the first 24 h postoperatively, but the difference was significant only for the IP LA + IP NSAID versus placebo comparison Elhakim et al 2000a
  • Administration of IP bupivacaine at the start and end of surgery was significantly superior to administration at the end of surgery alone for reducing VAS pain scores at 0, 4, 8 and 24 h following surgery (p<0.05 in each case) but not at 12 h in one study Pasqualucci et al 1994
  • One of two studies showed that IP LA + IP NSAID and IP LA + IV NSAID significantly reduced shoulder VAS pain scores compared with placebo at 0 and 6 h and at 0, 1 and 6 h, respectively (p<0.05, in all cases) Jabbour-Khoury et al 2005
  • Incisional and intra-abdominal VAS pain scores at rest and during coughing were significantly reduced in the IP LA + IV strong opioid group compared with the placebo group at 1 and 2 h following surgery (p<0.05, in all cases), but not at other time points (4, 6, 12 or 24 h postoperatively); shoulder-tip pain VAS scores and VRS pain relief scores were also similar Hernandez-Palazon et al 2001
  • Abdominal and shoulder VAS pain scores were significantly lower in the IP LA + saline lavage and suction group compared with the placebo group (p<0.05) Tsimoyiannis et al 1998
  • Adding ketamine or magnesium to IP bupivacaine resulted in a significant reduction in VAS shoulder pain scores compared with both IP LA alone and placebo (p<0.05 in each case) Abdel-Raouf + Amer 2004
  • One out of two studies showed that IP LA + IP NSAID and IP LA + IV NSAID treatment increased the time to first analgesic request compared with placebo, although p values were not presented Elhakim et al 2000a
  • Adding ketamine or magnesium to IP bupivacaine resulted in a significantly longer time to first analgesic request compared with both IP LA alone and placebo (p<0.05 in each case) Abdel-Raouf + Amer 2004
  • The number of patients needing rescue analgesics was significantly lower in the IP LA + IV NSAID group, but not the IP LA + IP NSAID group, compared with the placebo group Jabbour-Khoury et al 2005
  • Administration of IP bupivacaine at the start of surgery significantly reduced VAS pain scores compared with IP bupivacaine administration at the end of surgery at 8, 12 and 24 h following surgery (p<0.05 in each case), but not at 0 or 4 h, and VRS pain scores at 4, 8 and 24 h (p<0.05 in each case), but not at 0 or 12 h Pasqualucci et al 1996
  • Postoperative PCA metamizol use was significantly lower in the IP LA + IP strong opioid group compared with the placebo group 0–6 h postoperatively (p<0.05), and significantly lower in the IP LA + IV strong opioid group compared with the placebo group 0–24 h following surgery (p<0.05) Hernandez-Palazon et al 2003
  • IP LA + saline lavage and suction reduced supplemental analgesic requirements compared with placebo Tsimoyiannis et al 1998 Click here for more information
  • Adding ketamine or magnesium to IP bupivacaine resulted in a significant reduction in supplemental analgesic use compared with both IP LA alone and placebo at all time points (0–6, 6–12, 12–18, 18–24 and 0–24 h) (postoperative analgesia was PCA IV morphine boluses, 1 mg increments, 10 min lockout, 10 mg max dose/h) (p<0.05 in each case) Abdel-Raouf + Amer 2004
  • The proportion of patients requiring no analgesia was significantly lower in the IP LA group compared with the saline lavage + suction group (p<0.05) Tsimoyiannis et al 1998
  • In one of two studies, the incidence of vomiting was significantly lower in the IP LA + IV NSAID group, but not the IP LA + IP NSAID group, compared with the placebo group (p<0.05) Jabbour-Khoury et al 2005
  • The incidence of nausea and vomiting was significantly lower in the IP LA + saline lavage and suction group compared with the placebo group (p<0.05, in both cases) Tsimoyiannis et al 1998
  • The incidence of nausea and vomiting and the duration of hospital stay were not significantly different between the IP LA group and the saline lavage and suction group Tsimoyiannis et al 1998
  • In one study, patients receiving IP tenoxicam (20 mg) and 200 ml lidocaine (0.1%) + 2 ml IV saline, administered at the end of surgery, took significantly less time to bowel recovery compared with the placebo group (p<0.05) Elhakim et al 2000a
  • Three systematic reviews of local anaesthesia in laparoscopic cholecystectomy have found some evidence that intraperitoneal LA reduces pain after surgery, although the overall quality of the studies was not high and there were some conflicting results Bisgaard 2006
  • In one study, the same day discharge rate was significantly higher in all groups receiving intraperitoneal LA (15 ml 0.5% bupivacaine) compared with the placebo group (p<0.02) Paulson et al 2003
  • Four studies out of six showed a significant benefit of intraperitoneal LA over placebo for reducing VRS pain scores, see Table 3 for details
  • Fourteen studies out of 23 showed a significant benefit of intraperitoneal LA over placebo or no treatment for reducing VAS pain scores, see Table 3 for details; in two out of nine studies that did not find significant differences between groups, the comparator was IV strong opioid Click here for more information
  • There were no significant differences between IP LA and intrawound LA for VAS pain scores at 1, 2, 4 or 8 h postoperatively, or at discharge, or for total analgesic use (postoperative analgesia was IM Cyclimorph or 2 x co-proxamol tablets, as required) Johnson et al 1999
  • IP LA was associated with significantly increased abdominal and shoulder VAS pain scores compared with the saline lavage + suction group (p<0.05) Tsimoyiannis et al 1998
  • One study showed that the addition of epinephrine to IP LA solution did not reduce the duration of hospital stay Scheinin et al 1995
  • There were no significant differences between IP ropivacaine doses groups [20 ml (300 mg) 0.75% and 20 ml (100 mg) 0.25%], administered once at the start of surgery and once at the end of surgery, for visceral or parietal VAS pain scores at rest, during coughing or during mobilisation Labaille et al 2002
  • One study showed that the addition of epinephrine to IP LA solution did not confer any benefit for reducing pain scores: VRS pain score at rest or on movement; the incidence of shoulder pain and the proportion of patients with strong or unbearable pain Scheinin et al 1995
  • One study that compared two different doses of ropivacaine, 20 ml (300 mg) 0.75% ropivacaine with 20 ml (100 mg) 0.25% ropivacaine, administerd once at the start and once at the end of surgery, showed that both dose groups consumed similar amounts of opioids (see Table 2.1 for details) Labaille et al 2002
  • One study that compared bupivacaine (0.125%) with bupivacaine (0.25%), both regimens administered at the end of surgery, showed no significant difference for VAS pain scores at rest, on deep inspiration or on coughing Raetzel et al 1995
  • One study that compared bupivacaine (0.125%) with bupivacaine (0.25%), both regimens administered at the end of surgery, showed that both dose groups consumed similar amounts of opioids Raetzel et al 1995
  • One study compared 0.25% IP bupivacaine + 2 mg IP or IV morphine, administered at the end of surgery, with placebo showed that there was no significant difference between the groups for incidence of nausea/vomiting Hernandez-Palazon et al 2003
  • One study that compared bupivacaine (0.125%) with bupivacaine (0.25%), both regimens administered at the end of surgery, showed no significant difference between both dose groups for incidence of nausea and vomiting Raetzel et al 1995
  • A study that compared 125% IP bupivacaine with 0.25% IP bupivacaine, both regimens adminstered at the end of surgery showed that FVC was significantly more impaired in the group receiving the higher dose of bupivacaine (0.25%) compared with the lower dose (0.125%) Raetzel et al 1995
  • One study showed that the addition of epinephrine to IP LA solution did not reduce supplemental analgesic requirements Scheinin et al 1995 Click here for more information
  • A study that compared IP LA + IP or IV NSAID versus control showed that the duration of hospital stay was similar in all groups Elhakim et al 2000a
  • A study that compared IP LA + saline lavage and suction with control showed no significant difference between groups for the duration of hospital stay Tsimoyiannis et al 1998
  • There were no significant differences between the IP LA + IP strong opioid group compared with the placebo group at any time (i.e. at 1, 2, 4, 6, 12 or 24 h postoperatively) for incisional, intra-abdominal or shoulder VAS pain scores, at rest or during coughing, or for VRS pain relief scores Hernandez-Palazon et al 2003
  • In three out of five studies, there were no significant differences between the IP LA and control groups for respiratory function parameters; see Table 3 for details Rademaker et al 1994 Click here for more information
  • In six out of six studies, there were no significant differences between IP LA and control groups for the duration of hospital stay (see Table 3 for details) Click here for more information
  • In seven out of nine studies, the incidence of nausea and/or vomiting was similar in both IP LA and control groups (in one study the comparator used was IV strong opioid); in the remaining two studies Pasqualucci et al 1994 Click here for more information
  • Thirteen out of 20 studies showed no significant benefit of intraperitoneal LA over control or no treatment for reducing supplemental use of analgesia, see Table 3 for details Elhakim et al 2000 Click here for more information
  • Two out of three studies found that IP LA treatment did not increase the time to first analgesic request compared with placebo; see Table 3
  • In one study that compared IP bupivacaine or bupivacaine + epinephrine with placebo or no treatment, the proportion of patients with strong or unbearable pain was found to be similar in the three groups Scheinin et al 1995
  • Five out of six studies found no benefit of IP LA for reducing the incidence of shoulder pain compared with placebo; see Table 3 Elhakim et al 2000 Click here for more information
  • Table 3. IP LA versus placebo, no treatment or IV analgesia: Study details and qualitative outcomes Busley et al 1999 Click here for more information
  • Study details Busley et al 1999 Click here for more information
  • IP LA, miscellaneous studies
  • IP local anaesthetic, timing of administration
  • IP LA versus placebo, no treatment or IV analgesia

PROSPECT Recommendations

  • Interpleural LA is not recommended (Grade D), because there is limited procedure-specific evidence (LoE 1) for analgesic efficacy

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

PROSPECT Recommendations

  • IP opioids are not recommended due to limited evidence for analgesic benefit (Grade D)

Clinical Practice

  • Since pethidine has an additional local anaesthetic action, which morphine does not, it can be expected to be more efficacious than morphine when given intraperitoneally

Transferable Evidence from Other Procedures

  • One study found that the combination of intraperitoneal bupivacaine and intraperitoneal pethidine was better than the combination of IP bupivacaine and IM pethidine for postoperative analgesia in patients undergoing laparoscopic tubal ligation; pain scores were significantly lower in the group receiving IP pethidine both at rest (p<0.01) and with movement (p<0.05) (n=100) Colbert et al 2000
  • A study in patients undergoing laparoscopic gynaecological surgery Keita et al 2003

Laparoscopic Cholecystectomy-specific evidence

  • A study that compared IP strong opioid (pethidine) versus IM/IV strong opioid (pethidine) on a background of IP LA showed that IP pethidine significantly reduced VAS pain scores at rest and on movement compared with IM pethidine at all time points (i.e. 30 minutes, 2, 4, 8 and 24 h postoperatively) (p<0.001 in all cases) O'Hanlon et al 2002
  • A study that compared IP strong opioid (pethidine) with IM/IV strong opioid (pethidine) on a background of IP LA showed that total PCA opioid consumption during the first 24 h after surgery was significantly lower in the IP pethidine group compared with the IM pethidine group (p<0.001) O'Hanlon et al 2002
  • A study that compared IP morphine with IM/IV morphine on a background of IP LA, found that incisional and intra-abdominal VAS pain scores were significantly lower in the IV morphine group compared with the IP morphine group at 1 and 2 h following surgery (in both cases, p<0.05), but not at 4, 6, 12 or 24 h Hernandez-Palazon et al 2003
  • A study that compared IP strong opioid (morphine) with IM/IV strong opioid (morphine) on a background of IP LA, showed that postoperative PCA metamizol use was significantly lower in the IV morphine group compared with the IP morphine group in the first 24 h following surgery (p<0.05) Hernandez-Palazon et al 2003
  • One of two studies that compared IP strong opioid with IM/IV strong opioid on a background of IP LA showed that IP strong opioid increased nausea scores compared with parenteral strong opioid O'Hanlon et al 2002 Click here for more information
  • Study details O'Hanlon et al 2002 Click here for more information

PROSPECT Recommendations

  • Interpleural strong opioids are not recommended (Grade B), because of limited procedure-specific evidence (LoE 1) showing no effect

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

PROSPECT Recommendations

  • CEGA (combined epidural/general anaesthesia) is not recommended (Grade D) for routine anaesthetic management, due to poor risk:benefit ratio (LoE 4)
  • CEGA (combined epidural/general anaesthesia) is recommended in high-risk pulmonary patients (Grade D; LoE 4)

Clinical Practice

  • Combined epidural/general anaesthesia (CEGA) may be utilised in certain patients at high risk of pulmonary complications, although the surgical procedure does not justify the use of this anaesthetic technique in most patients where the risk of side-effects associated with the epidural technique may outweigh the potential benefits.
  • Prophylactic anti-emetics, such as ondansetron or dexamethasone, may be administered intravenously before emergence from anaesthesia
  • Total intravenous anaesthesia (TIVA) or balanced anaesthesia with inhalational agents (avoid halothane), short-acting opioids (fentanyl, alfentanil, remifentanil), and muscle relaxants may be used
  • TIVA offers an alternative to inhalational anaesthesia, and whilst rapid recovery from anaesthesia and reduction in nausea and vomiting are recognised benefits, the analgesic components of TIVA have a very short duration and do not contribute to improved postoperative analgesia

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

  • Combined epidural/general anaesthesia was significantly superior to total intravenous anaesthesia for reducing VAS pain scores at 2, 3 and 4 h (p<0.05 in each case), but not at 0–1 h; the incidence of abdominal and shoulder pain was similar in both groups Luchetti et al 1996
  • The incidence of nausea, but not vomiting, was significantly reduced in the remifentanil + propofol group compared with the remifentanil + desflurane group (p<0.05) Grundmann et al 2001
  • Remifentanil + propofol significantly reduced the total amount of IV piritramide used compared with remifentanil + desflurane (p<0.05) (postoperative analgesia was PCA IV piritramide, dose not specified + titrated IV loading dose if required) Grundmann et al 2001
  • Remifentanil + propofol significantly increased the time to first analgesic request compared with remifentanil + desflurane (p<0.05)  Grundmann et al 2001
  • The time to tracheal extubation and to eye opening was significantly reduced in the 1.2% end-tidal isoflurane-fentanyl group compared with the 1.8% group (p<0.05)  Munoz et al 2005
  • The time to tracheal extubation and to eye opening was significantly reduced in the 0.6% end-tidal isoflurane-fentanyl group compared with the other two groups (1.2% and 1.8%) (p<0.001), although the times to spontaneous breathing and to discharge to the ward were similar in all three groups Munoz et al 2005
  • A study that compared three different doses (0.6%, 1.2% and 1.8%) of isoflurane-fentanyl combination with isoflurane alone for maintenance anaesthesia, showed that the time to tracheal extubation and to eye opening was significantly reduced in the 0.6% end-tidal isoflurane-fentanyl group compared with the isoflurane alone group (p<0.01), although the times to spontaneous breathing and to discharge to the ward were similar in all groups Munoz et al 2005
  • The time to first rescue analgesic (1.5 mg/kg IV tramadol hydrochloride was given to patients complaining of moderate to severe pain) was significantly longer in the butorphanol group compared with the fentanyl group (p<0.05)  Usmani et al 2004
  • IV butorphanol was associated with a significantly lower proportion of patients with moderate-severe pain on the VRS scale compared with IV fentanyl (p<0.05; both administered 2 minutes before induction of anaesthesia)  Usmani et al 2004
  • The recovery score (Steward test) was significantly superior in the combined epidural/general anaesthesia group compared with the total intravenous anaesthesia group at 4 and 6 minutes (p<0.05, in both cases), but not at other times Luchetti et al 1996
  • In a study that compared combined epidural/general anaesthesia with total intravenous anaesthesia, there were no significant differences between groups for the incidence of nausea or vomiting Luchetti et al 1996
  • IV butorphanol and IV fentanyl administered 2 minutes before induction of ananesthesia were associated with similar incidence of nausea and vomiting, time to orientation and discharge, and the incidence of excessive drowsiness were similar in both groups Usmani et al 2004
  • There were no significant differences between different doses (0.6%, 1.2% and 1.8%) of isoflurane-fentanyl combination and isoflurane alone for VAS pain scores at rest or on coughing at any of the time points recorded (i.e. at 0, 15, 30, 45, 60, 90 or 120 minutes postoperatively) Munoz et al 2005
  • There were no significant differences between the remifentanil + propofol and remifentanil + desflurane groups for reducing VAS pain scores (both groups had lower pain scores at 30–90 minutes after arrival in PACU than at arrival in PACU) Grundmann et al 2001
  • The proportion of patients requiring opioid and the amount of opioid used were similar between different doses of isoflurane-fentanyl combination (0.6%, 1.2% and 1.8%) and isoflurane alone Munoz et al 2005
  • There were no significant differences between three different doses (0.6%, 1.2% and 1.8%) of isoflurane-fentanyl combination and isoflurane alone for Apfels' risk score for PONV and the incidence of nausea and vomiting was also similar in both groups Munoz et al 2005
  • Study details Munoz et al 2005 Click here for more information

PROSPECT Recommendations

  • Gasless laparoscopic cholecystectomy cannot be recommended (Grade A), due to lack of analgesic efficacy (procedure-specific evidence, LoE 1)

Clinical Practice

  • The gasless technique requires additional equipment (currently no proven cost:benefit ratio), operating time may be increased and surgical view of the cholecystectomy may be compromised

Transferable Evidence from Other Procedures

  • One study found that there were no clinically important differences in cardiovascular and systemic responses between patients undergoing CO2 or gasless laparoscopy for colonic disease (n=17) Schulze et al 1999
  • A study comparing gasless and CO2 pneumoperitoneum in patients undergoing laparoscopic tubal ligation showed that, although gasless pneumoperitoneum maintained stable ventilatory and haemodynamic parameters, it caused more technical difficulty, poorer visualization, longer operating time and was also associated with greater postoperative pain and nausea, compared with CO2 pneumoperitoneum (n=18) Johnson et al 1997
  • A study showed that patients undergoing laparoscopic tubal ligation experience similar postoperative pain with both gasless laparoscopy and traditional laparoscopy (total n=67) Guido et al 1998

Laparoscopic Cholecystectomy-specific evidence

  • In one out of the two studies, the incidence of shoulder pain was significantly lower (p<0.05) in the gasless or minimal CO2 insufflation pneumoperitoneum group compared with the conventional CO2 pneumoperitoneum group Lindgren et al 1995 Click here for more information
  • In one study out of one, the number of patients with no pain in the recovery room was significantly higher in the gasless CO2 insufflation pneumoperitoneum group compared with the conventional CO2 pneumoperitoneum group Uen et al 2002
  • In one out of one study, the duration of drowsiness was significantly lower (p<0.001) in the minimal CO2 insufflation pneumoperitoneum group compared with the conventional CO2 pneumoperitoneum group  Lindgren et al 1995
  • In three out of the three studies, there were no significant differences between gasless or minimal CO2 insufflation pneumoperitoneum and conventional CO2 pneumoperitoneum groups for VAS pain scores (see Table 4 for details)
  • There were no significant differences between gasless laparoscopic cholecystectomy and low-pressure laparoscopic cholecystectomy for VAS pain scores at any time point (VAS pain scores recorded at 4, 8, 12 and 24 h postoperatively and then each morning, for 1 week) Vezakis et al 1999
  • The incidence of shoulder pain was significantly greater in the gasless laparoscopic cholecystectomy group compared with the low-pressure laparoscopic cholecystectomy group (p<0.05) Vezakis et al 1999
  • In three out of three studies, analgesic use was similar in both gasless or minimal CO2 insufflation pneumoperitoneum and conventional CO2 pneumoperitoneum groups (see Table 4 for details); in one study out of one the length of time to complete pain relief was also similar in both groups Larsen et al 2001
  • Analgesic use was similar in both gasless pneumoperitoneum and low-pressure pneumoperitoneum group Vezakis et al 1999
  • One out of the three studies reported that PONV requiring droperidol was significantly reduced in the minimal CO2 insufflation pneumoperitoneum group compared with the conventional CO2 pneumoperitoneum group (p<0.05) Lindgren et al 1995
  • There was no significant difference between gasless pneumoperitoneum and low-pressure pneumoperitoneum groups for the incidence of nausea or vomiting Vezakis et al 1999
  • In two studies out of two, there were no significant differences between the gasless pneumoperitoneum and conventional carbon dioxide (CO2) pneumoperitoneum groups for the duration of hospital stay Larsen et al 2001 Click here for more information
  • The duration of hospital stay was similar in gasless pneumoperitoneum and low-pressure pneumoperitoneum groups Vezakis et al 1999
  • Study details Vezakis et al 1999 Click here for more information
  • Table 4. Gasless pneumoperitoneum versus conventional CO2 pneumoperitoneum: Study Details and Qualitative Outcomes Larsen et al 2001 Click here for more information

PROSPECT Recommendations

  • Low-pressure (<10 mmHg) CO2 pneumoperitoneum is recommended (Grade A) on the basis of evidence for analgesic benefit (procedure-specific evidence, LoE 1)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

  • Three studies out of four found that low pressure CO2 pneumoperitoneum significantly reduced VAS pain scores compared with conventional CO2 pneumoperitoneum, see Table 5 for details
  • In two out of three studies, the incidence of shoulder pain was significantly lower in the low pressure CO2 pneumoperitoneum group compared with the conventional CO2 pneumoperitoneum group Barczynski and Herman 2003 Click here for more information
  • The incidence of shoulder pain was significantly lower in the low-pressure laparoscopic cholecystecomy group compared with the gasless laparoscopic cholecystectomy group (p<0.05)  Vezakis et al 1999
  • In two studies out of four, analgesic use was significantly reduced in the low pressure CO2 pneumoperitoneum group compared with the conventional CO2 pneumoperitoneum group, see Table 5 for details Barczynski and Herman 2003
  • In one study out of one, low pressure CO2 pneumoperitoneum was significantly superior to conventional CO2 pneumoperitoneum in terms of pulmonary function and duration of hospital stay Wallace et al 1997
  • There were no significant differences between gasless laparoscopic cholecystectomy and low-pressure laparoscopic cholecystectomy for VAS pain scores at any time point (VAS pain scores recorded at 4, 8, 12 and 24 h postoperatively and then each morning, for 1 week) Vezakis et al 1999
  • Analgesic use was similar in both gasless pneumoperitoneum and low-pressure pneumoperitoneum group Vezakis et al 1999
  • In two out of two studies, the incidence of nausea and vomiting was similar in both low-pressure CO2 pneumoperitoneum and conventional CO2 pneumoperitoneum groups  Barczynski and Herman 2003 Click here for more information
  • There was no significant difference between gasless pneumoperitoneum and low-pressure pneumoperitoneum groups for the incidence of nausea or vomiting Vezakis et al 1999
  • The duration of hospital stay was similar in both gasless pneumoperitoneum and low-pressure pneumoperitoneum groups Vezakis et al 1999
  • The time to passage of flatus was similar in both the minimal CO2 insufflation pneumoperitoneum group and the conventional CO2 pneumoperitoneum group  Uen et al 2002
  • Study details Vezakis et al 1999 Click here for more information
  • Table 5. Low CO2 pneumoperitoneum versus conventional CO2 pneumoperitoneum: Study Details and Qualitative Outcomes Barczynski and Herman 2003 Click here for more information

PROSPECT Recommendations

  • Humidified CO2 is not recommended (Grade D) based on limited available procedure-specific evidence (LoE 2)
  • Warmed CO 2 is not recommended (Grade A) based on procedure-specific evidence of a lack of analgesic benefit (LoE 1)

Clinical Practice

Transferable Evidence from Other Procedures

  • A study showed that heated, 95% humidified CO2 pneumoperitoneum effectively decreases postoperative pain  and narcotics usage (p<0.05) compared with heated, dry CO2 pneumoperitoneum in patients undergoing laparoscopic surgery (total n=89) Beste et al 2006
  • One study showed that heated and humidified pneumoperitoneum increases tolerance of awake laparoscopy and decreases the frequency and duration of shoulder pain (total n=40) Demco 2001
  • A reduction in pain by warmed CO2 pneumoperitoneum was reported in two studies Ott et al 2003
  • A study showed that humidified and heated CO2 pneumoperitoneum did not reduce postoperative pain or intra-operative analgesic requirements compared to standard dry, cold CO2 pneumoperitoneum in gynaecological laparoscopic surgery (total n=90) Kissler et al 2004

Laparoscopic Cholecystectomy-specific evidence

  • Humidified CO2 insufflation was significantly superior to standard CO2 insufflation for reducing VAS pain scores at 6 h (p=0.02; n=32), on day 1 (p=0.03; n=27), day 2 (p=0.04, n=11) and day 3 (p=0.005; n=5) postoperatively, and also at follow-up, on day 1 (p=0.02; n=31) Mouton et al 1999
  • One study Farley et al 2004
  • Postoperative opioid requirement (IM morphine sulphate was given, as required, up to 10 mg/4 h) was not significantly different between humidified CO2 insufflation group and standard CO2 insufflation Mouton et al 1999
  • There were no significant differences between the humidified and standard CO2 groups for the duration of hospital stay Mouton et al 1999
  • Two studies out of three found no significant differences between warmed CO2 and conventional CO2 for VAS pain scores, see Table 6 for details Click here for more information
  • One study Slim et al 1999
  • Two studies out of four found no significant differences between warmed CO2 and conventional CO2 for analgesia use, see Table 6 for details; the remaining two studies had mixed results Farley et al 2004 Click here for more information
  • Study details Mouton et al 1999 Click here for more information
  • Table 6. Warmed CO2 versus conventional CO2: Study Details and Qualitative Outcomes Farley et al 2004 Click here for more information

PROSPECT Recommendations

  • The use of N2O pneumoperitoneum is not recommended (Grade D), because of limited evidence and inconclusive results in procedure-specific evidence (LoE 4)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • A prospective randomised clinical trial comparing N2O and CO2 pneumoperitoneum for laparoscopic surgery, showed that patients receiving N2O pneumoperitoneum had less pain at 2 h postoperatively (p<0.05), 4 h postoperatively (p<0.01), and on 1 day postoperatively (p<0.01) compared with patients receiving CO2 pneumoperitoneum (n=103) Tsereteli et al 2002
  • In patients undergoing peritoneoscopy under local anaesthesia, compared to N2O pneumoperitoneum, CO2 pneumoperitoneum was more uncomfortable as perceived by the patient (p=0.02), the physician (p=0.0006), and objectively assessed by degree of abdominal splinting (p=0.006) (total n= 46) Sharp et al 1982
  • One study showed no significant differences in intra-operative and postoperative pain between N2O and CO2 pneumoperitoneum for laparoscopic sterilization (total n=105) Lipscomb et al 1994

Laparoscopic Cholecystectomy-specific evidence

  • N2O pneumoperitoneum significantly reduced VAS pain scores compared with CO2 pneumoperitoneum at 1 h (p<0.04), 6 h (p<0.017), 23 h (p<0.002) and 24 h (p<0.026) following surgery, but not at 2, 3, 4, 5, 7, 8, 9 or 10 h postoperatively; the intensity of postoperative pain and the incidence of shoulder pain, as recorded by nurses, was similar in both groups Aitola et al 1998
  • CO2 pneumoperitoneum caused respiratory acidosis while N2O pneumoperitoneum did not (p<0.05) Aitola et al 1998
  • Opioid use (0.1 mg/kg IM oxycodone was given as required and then 0.075 mg/kg on request, up to every 2 h) was not significantly different between the N2O group and the CO2 group Aitola et al 1998
  • The incidence of emesis, as recorded by nurses, was similar in N2O and conventional CO2 pneumoperitoneum groups Aitola et al 1998
  • Study details Aitola et al 1998 Click here for more information

PROSPECT Recommendations

  • The use of helium pneumoperitoneum is not recommended (Grade B), because there is no procedure-specific evidence and transferable evidence for a lack of analgesic benefit (LoE 1)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • One study showed no significant benefit of helium versus CO2 pneumoperitoneum for reducing VAS scores and use of supplemental analgesics in laparoscopic surgery (total n=173) O'Boyle et al 2002

Laparoscopic Cholecystectomy-specific evidence

  • [None cited]

PROSPECT Recommendations

  • A smaller total size of trocar incision is not recommended to reduce postoperative pain (Grade D, LoE 4) because of inconsistent procedure-specific evidence for analgesic benefit

Clinical Practice

  • [None cited]

Transferable evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

  • Seven out of 12 studies found that a smaller total size of trocar incision significantly reduced VAS pain scores compared with conventional total size of trocar incision (25 mm or greater), see Table 7 for details
  • For VRS pain scores, a smaller total size of trocar incision was associated with significantly less pain in two out of three studies compared with conventional total size of trocar incision Bisgaard et al 2000 Click here for more information
  • In one study Sarli et al 2003
  • Five out of 13 studies found that a smaller total size of trocar incision significantly reduced analgesic use compared with conventional total size of trocar incision (25 mm or greater), see Table 7 for details; of those five studies, three also showed significantly lower VAS pain scores with smaller total size of trocar incision Bresadola et al 1999 Click here for more information
  • Two studies out of three found no significant differences between the smaller total size and conventional (25 mm or greater) total size of trocar incision groups for the incidence of nausea and vomiting Ainslie et al 2003
  • In four out of four studies, pulmonary function values were similar in both the smaller total size and conventional (25 mm or greater) total size of trocar incision groups Ainslie et al 2003
  • There were no significant differences between the smaller total size of trocar incision and the conventional (25 mm or greater) total size of trocar incision groups for the duration of hospital stay in eight studies out of eight; see Table 7 for details Click here for more information
  • In one study out of one, the time taken to resume stool passage was similar in both the smaller total size of trocar incision and conventional (25 mm or greater) total size of trocar incision groups Sarli et al 2003
  • Study details Click here for more information
  • Table 7. Total size of trocar incision: Study Details and Qualitative Outcomes Click here for more information

PROSPECT Recommendations

  • Radially expanding trocars are not recommended for reducing postoperative pain (Grade D) because of limited evidence (procedure-specific evidence, LoE 2)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • A randomised prospective study of radially expanding trocars showed that radially expanding trocars are safe and effective, and less likely than conventional trocars to result in intra-operative or postoperative complications Bhoyrul et al 2000 Click here for more information
  • In patients undergoing laparoscopic adnexal surgery, compared with the conventional trocar, the radially expanding access device was associated with significant reduction in severity (p<0.001) and duration (p<0.001) of postoperative wound pain, shorter wound scars (p<0.001), lower incidence of wound induration (p<0.01), and a higher patient satisfaction score (p<0.001) (n=34) Yim + Yuen 2001

Laparoscopic Cholecystectomy-specific evidence

  • Epigastric wound VAS pain scores were significantly lower in the radially expanding trocar group compared with the conventional trocar group from day 1 to day 3 following surgery (p<0.05, in all cases); subumbilical VAS pain scores over the same period were similar Lam et al 2000
  • Study details Lam et al 2000 Click here for more information

PROSPECT Recommendations

  • No recommendation for surgeon’s position can be made because of limited procedure-specific evidence (LoE 1)

Clinical Practice

  • The ‘French’ technique is associated with a better display of the anatomy of Calot’s triangle
  • The ‘American’ technique has a lower trajectory for instrument contact with the bowel and may increase the rate of perforation of the bowel

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

  • VRS pain scores were significantly lower in the 'French' technique group compared with the 'American' technique group at 48 h following surgery (lying VAS p=0.034; sitting VAS p=0.021), but not at 6 or 24 h Kum et al 1996
  • One study Kum et al 1996
  • One study that compared the 'French' and 'American' technique showed that FEV1 was significantly greater in the 'French' technique group compared with the 'American' technique group at 6, 24 and 48 h postoperatively (p=0.001 in all cases) Kum et al 1996
  • One study Kum et al 1996
  • There were no significant differences between the 'French' and 'American' techniques for opioid or NSAID consumption (postoperative analgesia was IV tramadol or enteral ibuprofen, on request; doses not specified) Kum et al 1996
  • Study details Kum et al 1996 Click here for more information

PROSPECT Recommendations

  • No recommendation can be made for one form of dissection over another on the basis of impact on pain

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

  • In one study out of two, postoperative VAS pain scores were significantly lower in the ultrasonic shears group compared with the electrocautery group at 4 and 24 h (p=0.002; p=0.003, respectively), but not at 1 and 2 h Cengiz et al 2005
  • One out of two studies found that postoperative nausea scores (VAS) were significantly reduced in the ultrasonic shears group compared with the electrocautery group at 2, 4 and 24 h (p=0.023; p=0.002; p<0.001, respectively), but not at 1 h Cengiz et al 2005
  • In one study Tsimoyiannis et al 1998c
  • The length of sick leave was significantly shorter in the ultrasonic shears group compared with the electrocautery group (p<0.001) Cengiz et al 2005
  • There were no significant differences between the laser dissection and the diathermy dissection groups for VAS pain scores at 24 h postoperatively (only time assessed) Scott et al 1992
  • Postoperative analgesia use was similar in both the ultrasonic shears and electrocautery groups (postoperative analgesia was rofecoxib 50 mg tablets and oral paracetamol 1 g tablets as required) Cengiz et al 2005
  • Postoperative analgesia use was similar in both laser dissection and diathermy dissection groups (type, dose and route not specified) Scott et al 1992
  • There were no significant differences between the laser dissection and the diathermy dissection groups for the duration of hospital stay Scott et al 1992
  • Study details Scott et al 1992 Click here for more information

PROSPECT Recommendations

  • Use of saline lavage, followed by suction of the saline, is recommended (Grade A) based on evidence for a reduction in postoperative abdominal and shoulder pain, as well as a reduction in supplementary analgesic use (procedure-specific evidence, LoE 1)
  • Use of a subhepatic drain is not recommended (Grade D) because of inconsistent evidence for an analgesic benefit (LoE 4)
  • Aspiration of the pneumoperitoneum gas is not recommended (Grade D) because of limited procedure-specific evidence (LoE 1)

Clinical Practice

  • [None cited]

Transferable evidence from Other Procedures

  • A study showed that patients undergoing laparoscopic-assisted vaginal hysterectomy and receiving closed-suction drains, had lower oral analgesic requirement compared to patients without drain (total n=160) Shen et al 2002
  • A study that compared saline peritoneal lavage with no lavage during laparoscopic surgery observed that less pain was found in the group undergoing saline peritoneal lavage at 4 and 24 h (total n=173) O'Boyle et al 2002

Laparoscopic Cholecystectomy-specific evidence

  • The proportion of patients not requiring analgesia was significantly greater in the saline lavage group compared with the control group (p<0.05) Tsimoyiannis et al 1998
  • Saline lavage + suction significantly decreased abdominal and shoulder VAS pain scores at rest in the first 48 h postoperatively (both arms) (p<0.05, in all cases) Tsimoyiannis et al 1998 Click here for more information
  • The proportion of patients not requiring analgesia was significantly higher in the saline lavage + suction group compared with the control group (with or without subhepatic drain in both groups) (p<0.05, in both cases) Tsimoyiannis et al 1998 Click here for more information
  • Saline + suction was associated with significantly reduced supplemental analgesic requirements compared with control Barczynski and Herman 2004 Click here for more information
  • Saline + suction was associated with significantly reduced postoperative pain scores compared with control Barczynski and Herman 2004 Click here for more information
  • The incidence of vomiting was similar in both groups but the incidence of nausea was significantly lower in the saline lavage group compared with the control group in one study (p<0.05) Tsimoyiannis et al 1998
  • The number of suppositories required (400 mg 4-acetylamino-phenol with 20 mg codeine phosphate + 50 mg caffeine was given rectally, as required), and the proportion of patients requiring parenteral pethidine (one 50 mg dose was given if the suppositories failed) were significantly lower in the saline lavage group compared with the control group (p<0.05, in both cases) Tsimoyiannis et al 1998
  • Abdominal and shoulder VAS pain scores were significantly lower in the saline lavage group compared with the control group at 2–48 h  (p<0.05, in all cases), but not at 72 h Tsimoyiannis et al 1998
  • PCA opioid demands (1 mg/ml bolus doses of morphine were given, to a maximum of 6 mg/h) were significantly lower in the active aspiration group compared with the control group (p<0.05); but there was no significant difference between groups for total morphine use Fredman 1994
  • One study Tsimoyiannis et al 1998 Click here for more information
  • Two studies found that drain + saline lavage + saline suction was associated with significantly reduced supplemental analgesic use compared with control Tsimoyiannis et al 1998 Click here for more information
  • The incidence of nausea was significantly lower in the drainage + saline lavage + suction group compared with the control group in both studies (p<0.05, in both cases) Tsimoyiannis et al 1998 Click here for more information
  • VAS pain scores appear to be not significantly different between saline lavage + suction and saline lavage with no suction, at 2, 6, 12, 24, 48 or 72 h, though statistics are not clear Tsimoyiannis et al 1998
  • Three out of four studies found no significant difference between drain and control for postoperative nausea and vomiting Tsimoyiannis et al 1998 Click here for more information
  • Supplemental analgesic requirements were not significantly different between the saline lavage + suction and saline lavage with no suction groups Tsimoyiannis et al 1998 Click here for more information
  • Three studies out of five found no significant differences for VAS pain scores for drainage compared with control, see Table 8b for details; in addition, the number of patients with abdominal and shoulder pain, as well as the duration of postoperative and shoulder pain were similar in both groups in one study out of one Hawasli and Brown 1994 Click here for more information
  • The incidence of nausea, vomiting and blood loss and the duration of hospital stay were similar in both saline + suction and control groups (with or without subhepatic drain in both groups), although quantitative analysis shows a benefit of saline + suction for reducing PONV  Tsimoyiannis et al 1998 Click here for more information
  • The incidence of nausea and vomiting and the duration of hospital stay were similar in both saline lavage + suction and saline lavage with no suction groups Tsimoyiannis et al 1998
  • Analgesia use (see Table 8b for details) was similar in both groups in three out of three studies Nursal et al 2003
  • Saline + suction was similar to control for the duration of hospital stay Barczynski and Herman 2004
  • Saline + suction was similar to control for the incidence of nausea and vomiting Barczynski and Herman 2004
  • There were no significant differences between the saline lavage and control groups for the duration of hospital stay Tsimoyiannis et al 1998
  • The duration of hospital stay was similar in both drain and control groups in one study out of one Tsimoyiannis et al 1998
  • There were no significant differences for VAS pain scores between the two groups at any time point (i.e. 1–4 h) Fredman 1994
  • There were no significant differences between drain + saline lavage + saline suction and control groups for the duration of hospital stay in either study Tsimoyiannis et al 1998 Click here for more information
  • Table 8a. Comparison groups: Suction, lavage and drainage Fredman 1994 Click here for more information
  • Table 8c. Comparison groups in Tsimoyiannis 1998 studies Tsimoyiannis et al 1998 Click here for more information
  • Table 8b. Drain versus control: Study details and qualitative outcomes Hawasli and Brown 1994 Click here for more information
  • Study details Fredman 1994 Click here for more information
  • Drain versus control
  • Saline lavage + suction versus saline lavage without suction
  • Saline lavage + suction versus control (IP LA +/- subhepatic closed drain in both groups)
  • Saline lavage + suction versus control
  • Saline lavage versus control
  • Drain + saline lavage + saline suction versus control
  • Gas suction versus control

PROSPECT Recommendations

  • No recommendation regarding intra-operative fluid management can be made because of limited procedure-specific evidence (LoE 1)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

  • There were no significant differences between the restrictive fluid administration and liberal fluid administration groups for reducing VAS pain scores in the early (i.e 0–4 h after surgery) or late (from the evening on the day of surgery to the evening on the third postoperative day) postoperative periods Holte et al 2004
  • In one study Holte et al 2004
  • In one study Holte et al 2004
  • FVC and FEV1 were significantly reduced in the restrictive fluid administration group compared with the liberal fluid administration group at 2 h postoperatively for FVC, and 2 and 4 h postoperatively for FEV1 (p<0.05, in all cases); PEF was similar in both groups Holte et al 2004
  • Study details Holte et al 2004 Click here for more information

PROSPECT Recommendations

  • Conventional NSAIDs are recommended (Grade A) because they reduce pain and opioid use (procedure-specific evidence, LoE 1)
  • The use of conventional NSAIDs should depend upon assessment of individual patient risks (Grade B), including bleeding complications, actual or recent gastroduodenal ulcer history (transferable evidence, LoE 1), cardiovascular morbidity (LoE 4), aspirin-sensitive asthma, renal function and hepatic function (transferable evidence, LoE 3)
  • It is not possible to make a recommendation for one route of administration in preference to any other on the basis of the available evidence
  • It is not possible to make a recommendation for one NSAID in preference to any other on the basis of the available evidence

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures Barden et al 2004
  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritis, urinary retention or respiratory depression Marret et al 2005
  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987
  • Randomised trials in healthy elderly volunteers have shown that conventional NSAIDs are associated with a higher incidence of upper gastrointestinal ulceration compared with COX-2-selective inhibitors for short-term use Harris et al 2001
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with control Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused reversible platelet dysfunction Niemi et al 1997
  • A large randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • Conventional NSAIDs and COX-2 selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of conventional NSAIDs or COX-2 selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2 selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004

Laparoscopic Cholecystectomy-specific evidence

  • Eight studies out of ten showed a significant benefit of conventional NSAIDs over placebo or no treatment for reducing VAS pain scores Munro et al 1998 Click here for more information
  • Five studies out of ten showed a significant benefit of conventional NSAIDs compared with placebo or no treatment for reducing supplementary analgesic use Forse et al 1996 Click here for more information
  • One study measured parameters of pulmonary function and found that the values of FEV1 and FEF25–75 were significantly higher at 4 h after surgery in the ketorolac group compared with the placebo group (p<0.05) Liu et al 1993
  • One study out of one showed that tenoxicam (20 mg) + ondansetron (4 mg), administered in 20 ml saline before induction of anaesthesia, significantly reduced the time to first flatus compared with ondansetron alone (p<0.05) Elhakim et al 1995
  • One study showed that IP NSAID + IP LA significantly reduced abdominal VAS pain scores at 0, 1, 2 and 6 h compared with placebo, but not at 12 or 24 h, whereas IV NSAID + IP LA significantly reduced VAS pain scores at all time points (p<0.05, in all cases); IP NSAID + IP LA and IV NSAID + IP LA also significantly reduced shoulder VAS pain scores at 0 and 6 h and at 0, 1 and 6 h, respectively (p<0.05, in all cases) Jabbour-Khoury et al 2005
  • One study showed that the number of patients needing rescue analgesics (type, dose and time of administration not stated) was significantly lower in the IV NSAID + IP LA group, but not the IP NSAID + IP LA group, compared with the placebo group (p<0.05) Jabbour-Khoury et al 2005
  • The incidence of vomiting was significantly lower in the IV NSAID + IP LA group, but not the IP NSAID + IP LA group, compared with the placebo group (p<0.05) Jabbour-Khoury et al 2005
  • IV tenoxicam significantly reduced the time to bowel recovery compared with IP tenoxicam Elhakim et al 2000a
  • One study out of one found no significant difference for the duration of hospital stay between IM ketorolac, administered intra-operatively pre- and post-procedure, and placebo Lane et al 1996
  • There were no significant differences between postoperative ketoprofen and postoperative propacetamol, for the incidence of nausea or vomiting Boccara et al 2005
  • One study showed that there was no significant difference between postoperative ketoprofen and postoperative propacetamol for the time to first analgesic demand Boccara et al 2005
  • Pre-operative ketoprofen significantly reduced opioid use compared with pre-operative propacetamol, but there was no significant difference between these agents given postoperatively Boccara et al 2005 Click here for more information
  • One study that compared IM ketorolac + glycerin suppository (n=17), administered after the induction of anaesthesia, with IM saline + indomethacin suppository, showed no significant difference in pain scores, opioid use and incidence of nausea/vomiting Forse et al 1996
  • A study which compared IV tenoxicam + intraperitoneal (IP) lidocaine + IP saline with IP tenoxicam + IP lidocaine + IV saline, administered at the end of surgery, showed no significant difference between IV and IP administration of tenoxicam for VAS pain scores, opioid use, incidence of nausea or vomiting and length of hospital stay  Elhakim et al 2000a
  • One study showed no significant difference between IV and IP administration of tenoxicam for VAS pain scores (at rest, on movement or on coughing), opioid use (postoperative opioid was 20 mg IM nalbuphine, every 4 h, or on request), incidence of nausea or vomiting and length of hospital stay  Elhakim et al 2000a
  • One study out of one showed that IM ketorolac (60 mg), administered intra-operatively post-procedure (n=20) significantly decreased the time to first analgesic request (p<0.05) compared with IM ketorolac, administered intra-operatively pre-procedure (n=31)  Lane et al 1996
  • Postoperative ketoprofen did not significantly reduce opioid use compared with pre-operative ketoprofen Boccara et al 2005
  • Postoperative ketoprofen significantly decreased the time to first analgesic demand compared with pre-operative ketoprofen (p<0.05) Boccara et al 2005
  • Postoperative ketoprofen significantly increased VAS pain scores compared with pre-operative ketoprofen during the first 12 h following surgery (p<0.05), with the effect being most evident during the first 3 h (p=0.001), although there was no significant difference between the two groups at 24 h Boccara et al 2005
  • One study out of one found no significant difference for the time to hospital discharge between IM diclofenac, administered after induction of anaesthesia (n=26), and control (n=23) Wilson et al 1994
  • Two studies out of seven that recorded the incidence of nausea and/or vomiting showed that conventional NSAIDs significantly reduced the incidence of nausea and/or vomiting compared with placebo or no treatment Elhakim et al 1995 Click here for more information
  • Study details Boccara et al 2005 Click here for more information
  • Table 1. Systemic conventional NSAIDs versus placebo or no treatment: Study details Elhakim et al 1995 Click here for more information

PROSPECT Recommendations

  • Postoperative COX-2-selective inhibitors are recommended (Grade A) because they reduce pain, opioid use and opioid side-effects (procedure-specific evidence, LoE 1)
  • COX-2-selective inhibitors may be more appropriate than conventional NSAIDs in the peri-operative setting, in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (transferable evidence, LoE 1)
  • It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B) (cardiovascular morbidity (transferable evidence, LoE 1), renal function and hepatic function (transferable evidence, LoE 3) or actual or recent gastroduodenal ulcer history (LoE 4)

Clinical Practice

  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Transferable Evidence from Other Procedures

  • Rofecoxib 50 mg and parecoxib 40 mg have an equipotent analgesic efficacy relative to traditional NSAIDs in postoperative pain after minor and major surgical procedures Rømsing et al 2004
  • Randomised trials in healthy elderly volunteers have shown that COX-2 selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation or bleeding time Greenberg et al 2000 Click here for more information
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) Nussmeier et al 2006
  • Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Short-term use of COX-2 selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2 selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • COX-2 selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003

Laparoscopic Cholecystectomy-specific evidence

PROSPECT Recommendations

  • Postoperative ketamine by bolus or infusion is not recommended (Grade D) because procedure-specific evidence is limited, despite some analgesic efficacy in other procedures (LoE 1)
  • Postoperative magnesium by infusion is not recommended (Grade B), because there is evidence for a lack of analgesic efficacy (procedure-specific evidence, LoE 1)

Clinical Practice

  • NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship; in addition, they are associated with adverse side-effects, e.g. ketamine is known for its CNS adverse effects, toxicity and for causing dysphoria

Transferable Evidence from Other Procedures

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine Bell et al 2006
  • A study in gynaecological surgery that compared magnesium with placebo (placebo group received saline, magnesium groups received 40 mg/kg at induction, followed by either saline, or magnesium infusion 10 mg/kg or 20 mg/kg), showed that morphine consumption was higher in the placebo group compared with the magnesium groups (total n=80) Seyhan et al 2006
  • A quantitative systematic review found that dextromethorphan does not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases Duedahl et al 2006
  • In abdominal hysterectomy, NMDA-receptor antagonists provided no significant benefit over placebo for reducing postoperative pain scores, supplementary analgesic consumption or PONV in the majority of studies, but the results were mixed and were independent of the specific type of agent and timing of administration Burstal et al 2001 Click here for more information

Laparoscopic Cholecystectomy-specific evidence

  • IV ketamine infusion significantly reduced pain compared with placebo: VAS pain scores at rest at 2–4 h (p<0.05 in each case), but not at 0, 1, 8 or 20 h; VRS pain scores at 2 and 3 h (p<0.05 in both cases), but not at other time points Ayoglu et al 2005
  • Postoperative, but not pre-operative, IV ketamine (bolus dose) reduced postoperative pain compared with placebo Mathisen et al 1999 Click here for more information
  • IV ketamine infusion significantly reduced VAS pain scores at rest compared with magnesium at 4 and 20 h (p<0.05 in both cases), but not at 0–4 h or at 8 h; ketamine also significantly reduced VRS pain scores compared with magnesium at 4 h (p<0.05), but not at other time points Ayoglu et al 2005
  • IV ketamine infusion significantly reduced cumulative opioid use compared with placebo at 2 and 3 h (p<0.05 in both cases), but not at 4 or 20 h (postoperative opioid was PCA bolus of 1 mg morphine, 10-minute lockout, maximum 4 h dose 20 mg) Ayoglu et al 2005
  • IV ketamine reduced the amount of rescue tramadol used and the number of patients requesting rescue tramadol compared with tramadol (p values not given) (a rescue dose was administered when VAS >5 on the 0–10 scale) Launo et al 2004
  • IV ketamine and tramadol were equally effective for reducing VAS pain scores 0–24 h after surgery; there were no significant differences between the two treatment groups for VRS pain scores Launo et al 2004
  • IV magnesium infusion did not significantly reduce VAS or VRS pain scores compared with placebo at any time during 0–20 h Ayoglu et al 2005
  • IV magnesium infusion did not significantly reduce cumulative opioid use compared with placebo at any time during 0–20 h (postoperative opioid was PCA bolus of 1 mg morphine, 10-minute lockout, maximum 4 h dose 20 mg) Ayoglu et al 2005
  • Pre-operative and postoperative (R)-ketamine (bolus dose) were similar to placebo for pethidine use in the first 4 h, and for use of paracetamol + codeine at 24 h and 7 days postoperatively (postoperative analgesia: bolus doses of 0.1 mg/kg pethidine, 5-minute lockout, for 4 h, and after discharge, 500 mg paracetamol + 30 mg codeine) Mathisen et al 1999
  • IV ketamine and IV magnesium infusion were associated with similar cumulative opioid use during 0–20 h (postoperative opioid was PCA bolus of 1 mg morphine, 10-minute lockout, maximum 4 h dose 20 mg)
  • IV ketamine and IV magnesium infusion and placebo were associated with a similar incidence of nausea and vomiting, and similar pulmonary function Ayoglu et al 2005
  • IV ketamine increased the incidence of nausea compared with tramadol (p value not given)  Launo et al 2004
  • Study details Mathisen et al 1999 Click here for more information

PROSPECT Recommendations

  • Strong opioids are not recommended for routine analgesia (Grade B) because of side-effects during recovery (transferable evidence, LoE 1)
  • Strong opioids are recommended for rescue analgesia (high-intensity pain) in addition to the use of other agents (Grade D, LoE 4)

Clinical Practice

  • Regular administration, titrated for pain intensity, is generally accepted as an effective method of administering strong opioids
  • Strong opioids are not associated with a ceiling effect, and thus can provide effective analgesia for most types of surgical procedures
  • Strong opioids may be used in a variety of preparations and routes of administration, enabling choice for onset, duration of action, and mode of delivery
  • Most clinical trials showing benefits of intramuscular strong opioids use nurse-administered regimens. In regular clinical practice, full adherence to nurse-administered regimens is not usually achievable, and the full analgesic benefits of intramuscular strong opioids are also not achieved
  • Intramuscular administration of strong opioids is considered to be more painful than intravenous administration; however, the dose and rapidity of intravenous administration should be assessed to minimise the risk of respiratory depression

Transferable Evidence from Other Procedures

  • Strong opioids are effective for reducing high- and moderate-intensity postoperative pain McQuay et al 1999
  • A systematic review comparing intravenous PCA opioids with intravenous, intramuscular or subcutaneous opioids by injection showed that PCA opioids were associated with greater pain relief, reduced supplementary analgesic requirements (analysis of eleven studies, total n=691), and more patients preferred PCA opioids (analysis of four trials, total n=352) compared with traditional opioid analgesia Walder et al 2001
  • Strong opioids are associated with adverse effects, including nausea, vomiting, sedation, confusion, paralytic ileus and urinary retention Wheeler et al 2002

Laparoscopic Cholecystectomy-specific evidence

  • Two studies showed that parenteral strong opioids reduced supplemental analgesic requirements compared with placebo Munoz et al 2002 Click here for more information
  • There were no significant differences between IV morphine and placebo for VAS pain scores at rest or on coughing at any time point (i.e. 0–180 minutes) Munoz et al 2002
  • There were no significant differences between groups receiving pre-operative, intra-operative or postoperative IV morphine for VAS pain scores at rest or on coughing at any time point Munoz et al 2002
  • Systemic opioid and placebo groups took a similar length of time to first analgesic request Munoz et al 2002
  • There was no significant difference between IV morphine and placebo for the incidence of postoperative emesis Munoz et al 2002
  • There was no significant difference between the IM pethidine and placebo groups for the duration of hospital stay Lane et al 1996
  • There were no significant differences between groups receiving pre-operative, intra-operative or postoperative IV morphine for opioid use or the incidence of emesis. All IV morphine groups took a similar length of time for first analgesia request Munoz et al 2002
  • Study details Munoz et al 2002 Click here for more information

PROSPECT Recommendations

  • Postoperative weak opioids are not recommended (Grade B) for routine analgesia because of side-effects during recovery (transferable evidence, LoE 1)
  • Weak opioids are recommended for rescue analgesia (low- to moderate-intensity pain) in addition to the use of other agents (Grade D, LoE 4)

Clinical Practice

  • Tramadol is a centrally acting analgesic with µ-opioid agonist (M1-metabolite) and aminergic mechanisms of action. For prescription purposes, it is considered a weak opioid or a non-narcotic in most countries
  • Tramadol is useful in the treatment of postoperative pain of moderate intensity (intravenous and oral administration), providing effective analgesia in the in-patient and ambulatory setting
  • The opioid-like effects of tramadol on gastrointestinal (transit, secretion) and sphincter function, are of a lesser magnitude than those of strong opioids
  • At recommended doses, tramadol has no clinically relevant effects on cardiovascular or respiratory parameters, thus the risk of respiratory depression is negligible
  • Tramadol is beneficial when NSAIDs are contraindicated
  • The oral solution (drops) of tramadol is useful as rescue medication when paracetamol/NSAID analgesic regimens are used
  • Opioid adverse effects, especially nausea and dizziness, limit the usefulness of tramadol, but many of the effects are less than for strong opioids
  • When ondansetron is used for the treatment/prophylaxis of tramadol-induced nausea and vomiting, a decrease in analgesic efficacy has been reported

Transferable Evidence from Other Procedures

  • Tramadol was more effective than placebo for pain relief in a meta-analysis of post-surgical patients Moore et al 1997
  • The combination of tramadol and paracetamol enhances analgesic efficacy compared with either agent alone McQuay H et al 2003
  • A systematic review found that the combination of dextropropoxyphene 65 mg with paracetamol 650 mg showed similar efficacy to tramadol 100 mg but with a lower incidence of adverse effects Collins et al 2000
  • A systematic review found that the combination of codeine with paracetamol provided additional pain relief compared with paracetamol alone Moore et al 2000
  • Adverse effects associated with tramadol include headache, nausea, vomiting, dizziness, somnolence. A meta-analysis of individual patient data from randomised controlled trials found a dose-response of adverse effects with tramadol; postsurgical patients had fewer side-effects than dental patients Moore et al 1997
  • A systematic review found that the combination of codeine with paracetamol was associated with an increase in drowsiness and dizziness compared with paracetamol alone Moore et al 2000
  • A systematic review found an increased incidence of central nervous system adverse effects with paracetamol plus dextropropoxyphene compared with placebo Collins et al 2000

Laparoscopic Cholecystectomy-specific evidence

  • Compared with placebo, tramadol significantly reduced VAS pain scores at 30, 45 and 60 minutes postoperatively (in all cases, p=0.01), but not at any other time point in the first 24 h (i.e. at 2, 4, 6, 8, 10, 12, 18 or 24 h Naguib et al 2000
  • Tramadol treatment was significantly superior to placebo treatment for reducing pain scores recorded by an observer at 30 and 45 minutes following surgery (p=0.01, in both cases)  Naguib et al 2000
  • Tramadol treatment significantly increased the time to first analgesic request and the proportion of patients not requesting PCA analgesia (postoperative PCA analgesia was 16 mg tramadol, 5-minute lockout; 4-h limit: 400 mg) compared with placebo (p<0.03) Naguib et al 2000
  • Tramadol significantly reduced supplementary tramadol use only at 30, 45 and 60 minutes postoperatively compared with placebo (p<0.03), but not at any other time point in the first 24 h Naguib et al 2000
  • One study that compared pre-operative IV tramadol + postoperative IV tramadol PCA with pre-operative IV morphine + postoperative IV morphine PCA, showed that morphine significantly reduced VAS pain scores at 30, 45 and 90 minutes following surgery compared with tramadol (in all cases, p<0.05), but not at any other time (recorded every 2 h until 24 h) or for pain scores recorded by an observer; but not at any other time  Naguib et al 1998
  • PCA drug consumption was significantly greater in the pre-operative IV tramadol + postoperative tramadol PCA group at 90 minutes and 4 h postoperatively, compared with the pre-operative IV morphine + postoperative morphine PCA group Naguib et al 1998 Click here for more information
  • There were no significant differences between pre-operative IV tramadol + postoperative IV tramadol PCA group and pre-operative IV morphine + postoperative IV morphine group for the time taken to the first analgesic demand or for the proportion of patients not requesting PCA analgesia Naguib et al 1998
  • The incidence of nausea and vomiting, as well as respiratory rate were similar in both tramadol and placebo groups Naguib et al 2000
  • The incidence of nausea and vomiting and cardiovascular adverse effects was similar in both pre-operative IV tramadol + postoperative IV tramadol PCA group and pre-operative IV morphine + postoperative IV morphine PCA group Naguib et al 1998
  • Study details Naguib et al 2000 Click here for more information

PROSPECT Recommendations

  • Paracetamol is recommended (Grade A) because analgesic efficacy is comparable with that of NSAIDs, based on procedure-specific evidence (LoE 1)

Clinical Practice

  • Paracetamol is not effective for severe pain

Transferable Evidence from Other Procedures

  • Paracetamol is an effective analgesic for the treatment of postoperative pain of moderate intensity Rømsing et al 2002
  • Paracetamol combined with weak opioids (codeine, tramadol) is superior to weak opioids alone in a review of dental, gynaecological and orthopaedic surgery McQuay H et al 2003
  • A meta-analysis of randomised controlled trials showed that paracetamol combined with PCA morphine induced a significant morphine-sparing effect but did not change the incidence of morphine-related adverse effects in the postoperative period Remy 2005
  • There is evidence that concurrent use of paracetamol and conventional NSAIDs improves pain relief compared with paracetamol alone, but there is no evidence for a superior analgesic effect of the combination compared with conventional NSAIDs alone Altman 2004

Laparoscopic Cholecystectomy-specific evidence

  • Postoperative administration of propacetamol significantly reduced VAS pain scores between 2 and 5 h postoperatively compared with pre-operative administration (p<0.05); the number of patients with severe pain (VAS 50 mm or greater) was significantly lower in the postoperative administration group compared with the pre-operative administration group (p<0.05) Boccara et al 2005
  • Two studies showed no significant difference for VAS pain scores between postoperative NSAIDs and postoperative propacetamol/paracetamol but pre-operative propacetamol was associated with significantly higher VAS pain scores compared with pre-operative ketoprofen Boccara et al 2005 Click here for more information
  • Ibuprofen sustained-release tablets and paracetamol were associated with similar VRS pain scores all time points (i.e. days 1–7) Owen et al 1997
  • Pre-operative propacetamol was associated with significantly greater opioid use compared with pre-operative ketoprofen, but there was no significant difference between these agents given postoperatively Boccara et al 2005 Click here for more information
  • The number of patients requiring supplemental nalbuphine, the total dose consumed and the time to first analgesic demand were similar in both pre-operative and postoperative propacetamol groups Boccara et al 2005
  • The incidence of nausea or vomiting was similar in both pre-operative and postoperative propacetamol groups Boccara et al 2005
  • There were no significant differences between the paracetamol + codeine and codeine alone groups for VAS pain scores (recorded at 0.5–4 h, then 3 times/day, until 48 h) Chung et al 2004
  • Supplemental opioid consumption, the time of onset of analgesia and the overall level of pain relief were similar in both paracetamol + codeine and codeine alone groups Chung et al 2004
  • There were no significant differences between the paracetamol + codeine and codeine alone groups for postoperative nausea; the time to discharge was also similar in both groups Chung et al 2004
  • Study details Boccara et al 2005 Click here for more information

PROSPECT Recommendations

  • Postoperative PCA IP LA is not recommended (Grade D) because of limited procedure-specific evidence (LoE 1)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

  • One study that compared ropivacaine injected into the bed of the gall bladder and in all portals after surgery and then as intermittent self-administered postoperative PCA versus placebo, showed that ropivacaine significantly decreased VAS pain scores (deep intra-abdominal and coughing pain) compared with placebo, up to 4 hours postoperatively, but not at 8, 12, 16 or 20 h or between 1–7 days following surgery Gupta et al 2002
  • One study that compared ropivacaine injected into the bed of the gall bladder and in all portals after surgery and then as intermittent self-administered PCA versus placebo showed that opioid consumption 0–20 h postoperatively, and the total amount of analgesics consumed during the first week following surgery were similar in both groups Gupta et al 2002
  • One study that compared ropivacaine injected into the bed of the gall bladder and in all portals after surgery and then as intermittent self-administered postoperative PCA versus placebo, showed that there were no significant differences between the two groups for the incidence of nausea and vomiting Gupta et al 2002
  • A study that compared ropivacaine injected into the bed of the gall bladder and in all portals after surgery and then as intermittent self-administered postoperative PCA versus placebo, showed that the time to discharge and also the time to defecate were similar in both groups Gupta et al 2002
  • Study details Gupta et al 2005 Click here for more information
  • PCA IP local anaesthetic versus placebo

PROSPECT Recommendations

  • Epidural LA + strong opioid reduces postoperative pain (procedure-specific evidence, LoE 1), but is not recommended (Grade D), due to high cost and poor risk:benefit ratio (LoE 4)
  • Epidural analgesia is recommended in high-risk pulmonary patients (Grade D; LoE 4)

Clinical Practice

  • Epidural analgesia may be effective in open cholecystectomy
  • The risk of side-effects associated with epidural analgesia may outweigh the benefits of analgesia in laparoscopic cholecystectomy

Transferable Evidence from Other Procedures

  • A meta-analysis of randomised controlled trials found that both continuous epidural infusion and PCEA analgesia provided superior postoperative analgesia compared with intravenous PCA analgesia Wu et al 2005
  • A meta-analysis of randomised controlled trials found that compared with systemic opioids, epidural opioids significantly decreased the incidence of atelectasis and had a weak tendency to reduce the incidence of pulmonary infections and pulmonary complications overall, while epidural LAs significantly increased PaO2 and decreased the incidence of pulmonary infections and pulmonary complications overall Ballantyne et al 1998
  • Epidural administration of strong opioids is associated with side-effects including pruritis, PONV, urinary retention, and respiratory depression Chaney 1995

Laparoscopic Cholecystectomy-specific evidence

  • Epidural LA + strong opioid significantly reduced VAS pain scores at 24 h compared with placebo (p<0.05), but there were no differences between groups at 48 h Fujii et al 1998
  • Epidural LA + strong opioid significantly reduced analgesic use compared with placebo (50 mg indomethacin was given rectally, on request) at 0–24 h (p<0.05), but not at 24–48 h Fujii et al 1998
  • A study that compared postoperative epidural LA + strong opioid with placebo showed that the incidence of nausea and vomiting was similar in both groups Fujii et al 1998
  • Study details Fujii et al 1998 Click here for more information

PROSPECT Recommendations

  • Postoperative pain is not increased by early discharge (<24 hours) (procedure-specific evidence, LoE 1), which is recommended for other reasons (Grade D)

Clinical Practice

  • Early discharge is associated with greater patient satisfaction and reduced cost

Transferable evidence from Other Procedures

  • A study comparing costs and outcomes of inpatient versus outpatient hernia repair, showed that outpatient hernia repair was associated with lower costs and apparent absence of adverse outcomes; although there were no detectable differences between inpatients and outpatients for outcomes such as complication rates, deaths and hernia recurrence, the re-admission rates were higher for inpatients (n=27,036) Mitchell + Harrow 1994

Laparoscopic Cholecystectomy-specific evidence

  • Three out of three studies showed no significant differences between outpatient and inpatient management groups for reducing VAS pain scores Curet et al 2002 Click here for more information
  • In one study, VRS pain/discomfort at 1 week and 6 weeks follow-up was similar in the daycare and clinical observation groups Keulemans et al 1998
  • The outpatient management group consumed significantly more oral analgesic (oxycodone + paracetamol) compared with the inpatient management group prior to PACU discharge (p<0.05), but there were no significant differences between groups for total analgesia used (fentanyl, narcotics, oxycodone + paracetamol; details not given) Curet et al 2002
  • There were no significant differences in outpatient and inpatient management groups for analgesic consumption (a single dose of 5–10 mg IM morphine was given on request; 500 mg paracetamol + 20 mg codeine was given up to 6 times/day; 500 mg naproxen was also given, up to 3 times/day) during the first 48 h postoperatively Keulemans et al 1998
  • In two out of two studies, the incidence of PONV (assessed at 4 h and 24 h) Curet et al 2002
  • In one study out of one, there were no significant differences between inpatient and outpatient management groups for bowel movement Young and O'Connell 2001
  • Study details Curet et al 2002 Click here for more information

Non-cosmetic Breast Surgery 2006

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PROSPECT Non-cosmetic Breast Surgery Subgroup

For each review, a Subgroup of the prospect Working Group performs an initial evaluation of the evidence and also drafts clinical practice statements and recommendations, which are then discussed by the whole Working Group before a final consensus is reached. The Subgroup may sometimes include a non-Working Group member, to provide additional expertise in the procedure being reviewed. For the non-cosmetic breast surgery review, the Subgroup members were:
  • Professor Francis Bonnet (PROSPECT Working Group member)
  • Professor Frederic Camu (PROSPECT Working Group member)
  • Dr Emmanuel Barranger (Service de Gynecologue-Obstétrique, Hopital Lariboisiere, Paris)

Grades of Recommendation

Recommendations are graded according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence: Levels of evidence and grades of recommendation in PROSPECT reviews (from 2006) PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted.

Summary Recommendations

Pre-, intra- and postoperative interventions have been evaluated for the management of postoperative pain following non-cosmetic breast surgery. Unless otherwise stated, ‘pre-operative’ refers to interventions applied before surgical incision, ‘intra-operative’ refers to interventions applied after incision and before wound closure, ‘postoperative’ refers to interventions applied at or after wound closure. The following peri-operative interventions for non-cosmetic breast surgery have been reviewed: See Overall PROSPECT recommendations for the overall strategy for managing pain after non-cosmetic breast surgery.

PROSPECT overall recommendations for postoperative pain management following breast cancer surgery:

Description of studies

Literature search

Systematic review of the literature from 1966–May 2006 using MEDLINE and EmBASE, following the protocol of the Cochrane Collaboration: Non-cosmetic Breast Surgery search terms

  • Inclusion of randomised studies in English, assessing analgesic interventions in non-cosmetic breast surgery in adults, and reporting pain on a linear analogue, verbal or numerical rating scale
  • Primary outcome measure: postoperative pain scores
  • Secondary outcome measure: supplemental analgesic requirements, other recovery outcomes (adverse effects, functional recovery)
  • Identification of 99 studies of peri-operative interventions for postoperative pain following breast surgery
  • 42 studies included: Non-cosmetic Breast Surgery Included References
  • 57 studies excluded
  • The most common reasons for exclusion were that pain scores were not reported (29 studies), or the study combined data from mixed surgery groups (10 studies) without an identifiable breast surgery subgroup, or the type of surgery was inappropriate (8 studies): Table 1: Non-cosmetic Breast Surgery Reasons for Exclusion

Study quality assessments, levels of evidence and grades of recommendation

Recommendations are graded according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence: Levels of evidence and grades of recommendation in PROSPECT reviews (from 2006)

Click here for quality scores and levels of evidence for included procedure-specific studies: Table 3: Non-cosmetic Breast Surgery May 2006 Quality Scoring + Levels of Evidence

Quantitative analyses

Overall, few meta-analyses could be performed that used data from more than two studies. This is because there are a limited number of studies of homogeneous design that report similar outcome measures. Therefore, the majority of the procedure-specific evidence was assessed only qualitatively.

Transferable evidence

Transferable evidence of analgesic efficacy from comparable procedures or evidence of other outcomes, such as adverse effects, has been included to support the procedure-specific evidence where this is insufficient to formulate the recommendations.

Several studies that were identified in the literature search included patients undergoing undefined or cosmetic breast surgery, or reported data pooled from patients undergoing mixed surgical procedures including breast surgery. Such studies are excluded from the procedure-specific systematic review, but have been used as additional transferable evidence in cases where the Working Group considered it appropriate.

Major breast surgery

Mastectomy:

  • Total or simple - the whole breast, including the nipple and areola, is removed, but not the axillary lymph nodes
  • Partial or segmental - removal of a portion of the breast tissue and a surrounding area of normal breast tissue (usually removes less tissue than a quandrantectomy but more than a lumpectomy or wide excision)
  • Radical - removal of the breast tissue, skin, nipple, areola, underlying chest wall muscles (pectorals) and varying numbers of axillary lymph nodes
  • Modified radical – removal of the whole breast, nipple/areolar region, and most of the axillary lymph nodes, but not the chest wall muscles
  • Unilateral – on one side only

Quadrantectomy - removes a quarter of the breast, including the skin and breast fascia

Axillary lymph node dissection (or resection or clearance), or axillary lymphadenectomy - surgical removal of the axillary lymph nodes

Breast reconstruction:

  • Transverse rectus abdominis musculocutaneous (TRAM) flap breast reconstruction - uses muscle, skin, and fat from the patient’s abdominal wall to reconstruct the breast
  • Latissimus dorsi breast reconstruction - uses skin and muscle from the patient’s back  

 

Minor breast surgery

Lumpectomy, breast lump excision, breast biopsy, breast-conserving therapy, wide local excision, breast tumour resection or breast surgery resection - removal of the breast cancer tumor and a surrounding area of normal breast tissue

Radioisotope-guided (sentinel) lymph node biopsy or sentinel node procedure – involves the removal of only 1–3 sentinel lymph nodes (the first nodes in the lymphatic chain). A radioactive tracer and/or blue dye is injected into an area of the tumor and is taken up by the sentinel nodes, thus enabling the surgeon to identify the lymph node most likely to be cancerous if the disease has spread from its original source

Cosmetic breast surgery

Reduction mammoplasty - breast reduction surgery

Breast augmentation - breast enlargement operation that usually involves placing an artificial implant either under the breast tissue, or under the chest muscle behind the breast.

Topics for future research

In certain circumstances, recommendations for a type of treatment cannot be made due to limited or conflicting evidence. Areas which have been identified as requiring further investigation in the future are listed:

  • Studies reporting pain on movement or chronic postmastectomy pain syndrome
  • Paravertebral block: single injection versus continuous infusion
  • Local wound infiltration and infusion
  • Axillary versus breast infiltration
  • Intercostal block
  • Gabapentin and other alpha-2-delta subunit ligands (gabapentinoids)
  • NMDA antagonists
  • Topical administration of local anaesthetics for minor breast surgery
  • Different surgical techniques e.g. laser surgery, electrocautery
  • Electro-acupoint stimulation

Abbreviations

ALND

axillary lymph node dissection

CFF

Critical Flicker Frequency test

CPM

chlorpheniramine maleate

EMLA

Eutectic Mixture of Local Anaesthetic

GA

general anaesthetic

ICB

intercostal nerve block

IM

intramuscular

Intra-op

intra-operative

IV

intravenous

LA

local anaesthetic

NRS

numerical rating scale

PACU

post-anaesthesia care unit

PCA

patient-controlled analgesia

PCEA

patient-controlled epidural analgesia

PCRA

patient-controlled regional analgesia

POD

postoperative day

PONV

postoperative nausea and vomiting

Postop

postoperative

Pre-op

pre-operative

PVB

paravertebral block

SDS

simple descriptive scale

TEA

thoracic epidural anaesthesia

TRAM

transverse rectus abdominis musculocutaneous

VAS

visual analogue scale

VIS

visual intensity scale

VRS

verbal rating scale

Pre-operative analgesia

To ensure an adequate analgesic effect in the immediate postoperative period, it may be necessary to administer analgesic medication prior to the postoperative period.

Data in this section are available from studies that assessed pre-operative analgesia versus pre-operative placebo, as well as those that assessed pre-operative analgesia versus the same analgesia given postoperatively (to examine the concept of pre-emptive – or preventive – analgesia). Where certain analgesics have been administered at various time points in studies (pre-operatively, intra-operatively or postoperatively), then these studies may be presented together in the same section to simplify the interpretation of the overall data (e.g. studies of pre- or intra-operative corticosteroid are presented together in both the Pre- and Intra-operative sections).

A meta-analysis of studies comparing pre-operative interventions with similar postoperative interventions in various procedures (including breast surgery) found that pre-operative epidural analgesia resulted in improvements in pain scores, analgesic consumption and time to first rescue analgesic request, whereas pre-operative NSAIDs and local anaesthetic wound infiltration improved analgesic consumption and time to first rescue analgesic request, but not pain scores. Evidence did not support an improvement in postoperative analgesia following administration of pre-operative NMDA antagonists and opioids (Ong 2005).

A previous systematic review of pre-emptive analgesia for acute or chronic postoperative pain relief in a variety of surgical procedures — such as orthopaedic, dental, gynaecological and abdominal — has concluded that there is no benefit of pre-emptive over postoperative administration (Møiniche 2002).

PROSPECT Recommendations

  • Gabapentinoids are recommended in major breast surgery (Grade A) based on procedure-specific (LoE 1) and transferable (LoE 1) evidence for reducing postoperative pain and opioid use compared with control
  • Gabapentinoids are not recommended for minor breast surgery (Grade D, LoE 4) because pain intensity is commonly not severe enough to justify an adjuvant to the usual analgesic agents
  • Transferable evidence (LoE 1) suggests that gabapentinoids are associated with sedation, and it is recommended (Grade D) that this side-effect should be considered when determining the dose that will be administered
  • Gabapentinoids cannot be recommended at this time (Grade D, LoE 4) for the prevention of chronic pain after breast surgery, because there is conflicting procedure-specific and transferable evidence

Clinical practice

  • Limited procedure-specific evidence supports an effect of gabapentinoids on chronic pain after breast surgery but transferable evidence from lower limb amputation showed no effect of gabapentin on chronic pain. Further studies are required to investigate the mechanisms of post-surgical chronic pain and the effects of gabapentin on the development of chronic pain after breast surgery

Transferable evidence

  • Three systematic reviews and a meta-analysis evaluated the use of gabapentinoids for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls Dahl et al 2004
  • Two systematic reviews Ho et al 2006
  • Two systematic reviews Ho et al 2006
  • A randomised study found that gabapentin administered in the first 30 days after lower limb amputation did not reduce the incidence or intensity of stump and phantom pain compared with placebo Nikolajsen 2006

Breast surgery-specific evidence

  • In one study out of two, VAS pain scores at rest were significantly lower with oral gabapentin compared with placebo on postoperative day 3 (p<0.05), but not in the first 24 h, or on days 1, 2, or 4–10 after surgery Fassoulaki 2002 Click here for more information
  • VAS pain scores at rest were significantly lower with oral gabapentin + regional block + LA cream compared with placebo in the PACU (p=0.001) and on PODs 1, 3 and 5 (p=0.04, p<0.02, p<0.05, respectively) Fassoulaki et al 2005
  • Two studies out of two demonstrated significantly lower VAS pain scores during movement with gabapentin compared with placebo Dirks ET AL 2002 Click here for more information
  • VAS pain scores on movement were significantly lower following oral gabapentin + regional block + LA cream administration compared with placebo in the PACU (p=0.001) and on PODs 2, 4 and 8 (p<0.03, p=0.007 and p<0.04, respectively) Fassoulaki et al 2005
  • Two out of two studies reported significantly lower rescue analgesic requirements with oral gabapentin compared with placebo Dirks ET AL 2002 Click here for more information
  • Rescue analgesic use was significantly lower with oral gabapentin + regional block + LA cream compared with placebo Fassoulaki et al 2005 Click here for more information
  • At 3 months postoperatively, the incidence of chronic burning pain was significantly lower with oral gabapentin compared with placebo (p<0.04). The incidence of pain in the chest, axilla or arm, and the incidence of abnormal sensation were similar in both groups Fassoulaki 2002
  • After 3 months, fewer patients required analgesics, and the number of patients experiencing total chronic pain was significantly lower with oral gabapentin + regional block + LA cream compared with placebo (p<0.05 and p<0.03, respectively), although neither measure was significant at 6 months Fassoulaki et al 2005
  • There was no significant difference between groups receiving oral gabapentin + regional block + LA cream versus placebo for the time to first request for rescue analgesics Fassoulaki et al 2005
  • There was no significant difference in the incidence of nausea with oral gabapentin versus placebo Dirks ET AL 2002
  • Study details Dirks ET AL 2002 Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • Conventional NSAIDs are not recommended pre-operatively (Grade B) for major breast surgery due to inconsistent procedure-specific (LoE 1) and transferable (LoE 1) evidence for the analgesic effects of pre-operative versus postoperative administration, and due to an increased risk of bleeding versus control (transferable evidence; LoE 1) and versus COX-2-selective inhibitors (procedure-specific evidence, LoE 1)
  • Pre-operative administration of conventional NSAIDs is not recommended (Grade D, LoE 4)) for minor breast surgery, as transferable and procedure-specific evidence shows inconsistent results for pre- versus postoperative administration
  • As with all analgesics, it is recommended (Grade D, LoE 4) that conventional NSAIDs should be administered at the appropriate time to provide sufficient analgesia in the early recovery period
  • The use of conventional NSAIDs should depend upon assessment of individual patient risks (Grade B), including bleeding complications, actual or recent gastroduodenal ulcer history (transferable evidence, LoE 1), cardiovascular morbidity (LoE 4), aspirin-sensitive asthma, renal function and hepatic function (transferable evidence, LoE 3)

Clinical practice

  • The risk of bleeding complications in breast cancer surgery is about 2–5%. Conventional NSAIDs carry the risk of increased bleeding, therefore it may be preferable to use COX-2-selective inhibitors as an alternative analgesic intervention in major breast surgery

Transferable evidence

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures Barden et al 2004
  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression Marret et al 2005
  • One randomised trial in patients undergoing vaginal hysterectomy or breast surgery showed that diclofenac was as effective as rofecoxib in terms of postoperative analgesia, but was associated with greater use of anti-emetics Hegi et al 2004
  • Two meta-analyses comparing pre-incisional and post-incisional NSAIDs/COX-2-selective inhibitors have found no significant benefit of pre-incisional administration for reducing pain scores Møiniche et al 2002
  • Randomised endoscopic trials in healthy elderly volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported (with lumiracoxib; Shi 2008
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Chronic administration of conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Pain relief with oral paracetamol plus ibuprofen was inferior to patient-controlled incisional regional analgesia and was associated with more frequent side-effects, after ambulatory breast augmentation Rawal 2006

Breast surgery-specific evidence

  • VAS pain scores were significantly lower in a group receiving pre-operative IM diclofenac compared with a placebo group at 60 min (p=0.05) and cumulatively over 48 h postoperatively (p=0.002), but not at 30 or 120 min postoperatively Chan et al 1996
  • Observer-recorded VAS pain scores were significantly lower with pre-operative IV ketoprofen compared with intra-operative IV ketoprofen at all time intervals until 10 h after surgery (p=0.00001 at 1, 1.5, 2, 4 and 6 h, p=0.001 at 8 and 10 h) Priya et al 2002
  • The number of patients requiring postoperative analgesia (IV tramadol 100 mg) was lower with pre-operative IV ketoprofen compared with intra-operative IV ketoprofen at 2, 4, 6, 8 and 10 h after surgery (at 2, 4, 8 and 10 h, p<0.0001; at 6 h, p<0.003) Priya et al 2002
  • The time to first request for rescue analgesia was significantly longer following pre-operative IV ketoprofen compared with intra-operative IV ketoprofen (p<0.0001) Priya et al 2002
  • There were significantly fewer patients with PONV in a pre-operative IV ketoprofen group compared with an intra-operative IV ketoprofen group (p<0.00001) Priya et al 2002
  • There were no significant differences in VAS pain scores with pre-operative compared with postoperative IM diclofenac, with or without wound infiltration, at any time point recorded (30, 60 and 120 min postoperatively and at discharge) Chan et al 1996
  • There were no significant differences between groups receiving pre-operative IM diclofenac group versus placebo with regards to the number of patients requiring rescue analgesia (IV fentanyl 50 µg) or the number of analgesic tablets consumed in the 48 h following surgery Chan et al 1996
  • There were no significant differences with pre-operative versus postoperative IM diclofenac, with or without wound infiltration, with regards to the number of patients requiring rescue analgesia (IV fentanyl 50 µg) or the number of analgesic tablets consumed in the 48 h following surgery Chan et al 1996
  • One randomised trial in patients undergoing breast surgery showed that diclofenac was associated with significantly greater intra-operative blood loss compared with rofecoxib (p=0.01). This study did not report separate pain score analyses for the breast surgery subgroup for diclofenac versus rofecoxib, and therefore is not included as part of the systematic review for postoperative pain management Hegi et al 2004
  • Study details Chan et al 1996 Click here for more information
  • Minor and major breast surgery

PROSPECT Recommendations

  • Corticosteroids are not recommended for analgesia in minor or major breast surgery (Grade D, LoE 4) due to insufficient procedure-specific evidence (LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • Dexamethasone significantly reduced pain scores compared with placebo following laparoscopic cholecystectomy Bisgaard 2003
  • Dexamethasone was shown to prevent postoperative nausea and vomiting after surgery in a systematic review Carlisle 2006b
  • A single prophylactic dose of dexamethasone (4–8 mg) is effective for preventing PONV in surgery associated with high emetic effects Henzi et al 2000
  • In one randomised placebo-controlled study, parecoxib and methylprednisolone had comparable analgesic and rescue analgesic sparing effects in breast augmentation surgery, although only methylprednisolone reduced nausea, vomiting, and fatigue Romundstad 2006

Breast surgery-specific evidence

  • Incidences of nausea (p<0.009) and vomiting (p<0.000005) were significantly lower with dexamethasone compared with placebo Abou Zeid 2002
  • Rescue anti-emetic consumption (dolasetron) was significantly lower with dexamethasone compared with placebo (p<0.001) Abou Zeid 2002
  • VAS pain scores were not significantly with dexamethasone compared with placebo at all time points assessed (on arrival in the recovery room, at 30 and 60 mins, on leaving the recovery room, and at 4 hours) Abou Zeid 2002
  • Consumption of postoperative diclofenac was comparable in patients receiving dexamethasone and patients receiving placebo Abou Zeid 2002
  • Study details Abou Zeid 2002 Click here for more information
  • Major and minor breast surgery

PROSPECT Recommendations

  • As with all analgesics, it is recommended (Grade D, LoE 4) that COX-2-selective inhibitors should be administered at the appropriate time to provide sufficient analgesia in the early recovery period. Therefore, in short breast surgery procedures, pre-operative administration of COX-2-selective inhibitors is recommended (Grade D, LoE 4)
  • For prolonged breast surgery procedures, pre-operative administration of COX-2-selective inhibitors is not recommended (Grade D, LoE 4), as there is transferable evidence (LoE 1) showing inconsistent benefit of pre- versus postoperative administration, and there is no procedure-specific evidence
  • It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B) (cardiovascular morbidity (transferable evidence, LoE 1), renal function and hepatic function (transferable evidence, LoE 3) or actual or recent gastroduodenal ulcer history (LoE 4)

Clinical practice

  • The risk of bleeding complications in breast cancer surgery is about 2–5%. Conventional NSAIDs carry the risk of increased bleeding, therefore it may be preferable to use COX-2-selective inhibitors as an alternative analgesic intervention
  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Transferable evidence

  • One randomised trial in patients undergoing vaginal hysterectomy or breast surgery showed that rofecoxib was as effective as diclofenac in terms of postoperative analgesia, but was associated with less use of anti-emetics Hegi et al 2004
  • In one study, parecoxib and methylprednisolone had comparable analgesic and rescue analgesic sparing effects in breast augmentation surgery, although only methylprednisolone reduced nausea, vomiting, and fatigue Romundstad 2006
  • Rofecoxib 50 mg and parecoxib 40 mg have an equipotent analgesic efficacy relative to traditional NSAIDs in postoperative pain after minor and major surgical procedures Rømsing et al 2004
  • A systematic review to quantify the efficacy of single-dose oral valdecoxib and IV parecoxib demonstrated that both are effective treatments for acute postoperative pain, and show similar incidences of adverse effects Barden 2003
  • Randomised endoscopic trials in healthy elderly volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation or bleeding time compared with placebo Greenberg et al 2000 Click here for more information
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following non-cardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) Nussmeier et al 2006
  • Two meta-analyses comparing pre-incisional and post-incisional NSAIDs/COX-2-selective inhibitors have found no significant benefit of pre-incisional administration for reducing pain scores Møiniche et al 2002
  • Two clinical trials showed that in patients who had undergone CABG surgery, COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported (with lumiracoxib; Shi 2008
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Chronic administration of COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004

Breast surgery-specific evidence

  • One randomised trial in patients undergoing breast surgery showed that rofecoxib was associated with significantly less intra-operative blood loss compared with diclofenac (p=0.01). This study did not report separate pain score analyses for the breast surgery subgroup for diclofenac versus rofecoxib, and therefore is not included as part of the systematic review for postoperative pain management Hegi et al 2004

PROSPECT Recommendations

  • Dextromethorphan is not recommended (Grade D, LoE 4) due to limited procedure-specific evidence, despite transferable evidence showing some marginal effects
  • No recommendations can be made at this time regarding the use of ketamine due to insufficient procedure-specific evidence, despite opioid-sparing effects in other procedures (transferable evidence, LoE 1)
  • Magnesium is not recommended for analgesia (Grade B) due to transferable evidence showing a lack of analgesic effect (LoE 1)
  • There is transferable evidence (LoE 1) to show that pre-incisional administration of NMDA antagonists is of no significant analgesic benefit compared with postincisional administration

Clinical practice

  • None cited

Transferable evidence

  • Studies of ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain or opioid use when used as an adjunct to morphine Bell et al 2006
  • Low-dose ketamine was associated with few and mild adverse effects, especially when administered in conjunction with general anaesthesia Bell et al 2006
  • A systematic review found that dextromethorphan did not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases Duedahl et al 2006
  • Two meta-analyses comparing pre-incisional and postincisional treatments found no significant analgesic benefit of pre-incisional administration of NMDA receptor antagonists Møiniche et al 2002
  • Two systematic reviews of randomised controlled trials comparing magnesium with placebo demonstrated inconclusive results overall with regards to pain scores and supplemental analgesic use Lysakowski 2007

Breast surgery-specific evidence

  • Total IM pethidine consumption during the 48 h after surgery was significantly lower with dextromethorphan + chlorpheniramine maleate (CPM) compared with CPM alone (p<0.001). Significantly fewer patients receiving dextromethorphan + CPM required pethidine within 48 h compared with those receiving CPM alone (p<0.005). The time to first IM pethidine injection was significantly longer with dextromethorphan + CPM compared with CPM alone (p<0.001) Wong et al 1999
  • Frequency of side-effects (including nausea and vomiting) was significantly lower with dextromethorphan + CPM compared with CPM alone (p<0.05) Wong et al 1999
  • Average bedrest time was significantly shorter following dextromethorphan + CPM compared with CPM alone (p<0.001) Wong et al 1999
  • There were no significant differences in VAS pain scores between groups receiving pre- versus postoperative IV ketamine at any time point (on arrival in recovery room, or at 1–6, 8, 12, 16, 20 or 24 h after surgery) Adam et al 1999
  • There were no significant differences between groups receiving dextromethorphan + CPM and CPM alone in observer-assessed VAS pain scores at the time of the first pethidine injection (n=7 and n=25 for the dextromethorphan + CPM and the CPM alone groups, respectively, as not all patients required a pethidine injection) Wong et al 1999
  • Cumulative PCA morphine use was significantly higher with pre-operative IV ketamine compared with postoperative IV ketamine at 1 (p<0.009) and 2 h (p<0.04), but not at 2–24 h (PCA morphine: bolus 0.5 mg on demand, lockout 5 min). The time to first request for rescue analgesic was not significantly different between the pre- and postoperative ketamine groups Adam et al 1999
  • The incidence of PONV was similar with IV ketamine, whether administered pre- or postoperatively Adam et al 1999
  • There was no significant difference in the level of patient satisfaction with pre- versus postoperative IV ketamine Adam et al 1999
  • Study details Wong et al 1999 Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • Pre-incisional administration of strong opioids is not recommended (Grade D, LoE 4) because there is no procedure-specific evidence of an analgesic benefit of pre-incisional administration over post-incisional administration

Clinical practice

  • Routine administration of strong opioids should be avoided in minor breast surgery due to the risk of PONV
  • As with all types of analgesia for postoperative pain, strong opioids should be instituted in time to secure sufficient analgesia when the patient wakes

Transferable evidence

  • Strong opioids are effective for reducing high- and moderate-intensity postoperative pain McQuay et al 1999
  • Pethidine induced significantly higher sedation and respiratory depression compared with tramadol (both 100 mg intravenously) (n=48) Tarradell et al 1996
  • Strong opioids are associated with adverse effects, including nausea, vomiting, sedation, confusion, paralytic ileus and urinary retention Wheeler et al 2002
  • One study comparing PCA with conventional pain therapy (CPT; IV piritramide or oral/IM tramadol) demonstrated an increased consumption of postoperative analgesic in the PCA group compared with the CPT group (p<0.01), although the PCA group reported a significantly greater satisfaction with pain therapy compared with the CPT group (p<0.01) (n=42 patients; Forst J et al 1999

Breast surgery-specific evidence

  • Observer-rated VAS pain scores at rest were significantly lower with oral oxycodone compared with placebo at 16 (p=0.04) and 24 h (p=0.03) postoperatively, but not at 0, 4 or 8 h after surgery. Observer-rated VAS pain scores on movement were not significantly different between the oral oxycodone versus placebo groups during the assessment period (i.e. at 0–24 h) Kampe et al 2004
  • Consumption of IV PCA piritramide (1.5 mg bolus doses, 6 min lockout, 30 mg limit over 4 h) was significantly lower with oral oxycodone group compared with placebo at 0 (loading dose), 4, 16, and 24 h (p<0.001, p<0.04, p=0.01, and p=0.005, respectively), but not at 8 h postoperatively. The cumulative IV PCA piritramide consumption was also significantly lower following oral oxycodone compared with placebo (p=0.002) Kampe et al 2004
  • The number of patients experiencing nausea was similar with oral oxycodone and placebo Kampe et al 2004
  • The overall quality of pain management as judged by the patients was not deemed significantly different between those receiving oral oxycodone and those receiving placebo Kampe et al 2004
  • Study details Kampe et al 2004 Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • As with all analgesics, it is recommended (Grade D, LoE 4) that paracetamol should be administered at the appropriate time to provide sufficient analgesia in the early recovery period. Therefore, in short breast surgery procedures, pre-operative administration of paracetamol is recommended (Grade B) based on transferable evidence showing efficacy for treating pain of moderate intensity (LoE 1)
  • For prolonged breast surgery procedures, pre-operative administration of paracetamol is not recommended (Grade D, LoE 4), as there is no procedure-specific or transferable evidence to show whether pre-operative administration has any analgesic benefit compared with postoperative administration

Clinical practice

  • Many studies include the use of paracetamol, but as a supplemental analgesic for all patients
  • It is considered that paracetamol is ineffective as a single therapy for treatment of high-intensity pain (VAS >/=50 mm)

Transferable evidence

  • Paracetamol is an effective analgesic for the treatment of postoperative pain of moderate intensity Rømsing et al 2002
  • There is evidence that concurrent use of paracetamol and conventional NSAIDs improves pain relief compared with paracetamol alone, but there is no evidence for a superior analgesic effect of the combination compared with conventional NSAIDs alone Altman 2004
  • A study of propacetamol administered after breast surgery or thyroidectomy (n=119) showed that pain relief and supplemental injection of morphine were not statistically different between groups treated with propacetamol systematically or propacetamol on demand, and adverse effects were rare Farhat 1995
  • Pain relief with oral paracetamol plus ibuprofen was inferior to patient-controlled incisional regional analgesia and was associated with more frequent side-effects, after ambulatory breast augmentation Rawal 2006

Breast surgery-specific evidence

  • None cited

PROSPECT Recommendations

  • PVB is recommended for postoperative analgesia following major breast surgeries (Grade A), based on procedure-specific evidence (LoE 1) showing a reduction in pain and opioid use
  • PVB is not recommended for minor breast surgeries (Grade D, LoE 4), because the risk of complications may outweigh the benefits for analgesia
  • There are currently no procedure-specific data to show whether continuous infusion is more beneficial than single injection

Clinical practice

  • PVB is an invasive technique, and the risk of complications (e.g. pneumothorax) may outweigh the benefits in minor procedures that result in mild pain
  • While there is good evidence for the use of PVB in breast surgery, it is not commonly used for anaesthesia in clinical practice

Transferable evidence

  • One study found that PVB reduced pain scores and incidence of PONV compared with general anaesthesia following cosmetic breast surgery (n=30) Klein et al 2002b
  • A review of locoregional analgesic techniques after breast surgery (including cosmetic breast surgery) concluded that single injection thoracic paravertebral block was more effective for analgesia and PONV than wound infiltration Marret 2006
  • Two retrospective studies of patients undergoing breast cancer surgery showed benefits of PVB over general anaesthesia, in terms of pain control, side-effects and quality of recovery Coveney 1998
  • A review of 15 patients undergoing surgery for breast cancer concluded that ambulatory surgical management of breast carcinoma using PVB is a safe procedure associated with high patient satisfaction and minimal postoperative complications Weltz 1995
  • A prospective study in 367 paediatric and adult patients receiving thoracic or lumbar PVB showed that the frequency of hypotension was 4.6% Lönnqvist 1995
  • A non-randomised study of 3450 patients receiving PVB for breast cancer surgery reported 17 episodes of epidural spreads leading to increased length of PACU stay, and 3 incidences of pre-seizure excitation caused by partial accidental intravascular injection Ganapathy 2005

Breast surgery-specific evidence

  • Rescue morphine requirements in the PACU were significantly lower with PVB compared with PCA IV opioid (p=0.04) Buggy et al 2004
  • One study out of one showed that duration of hospital stay was significantly shorter following PVB compared with GA (p<0.01) Naja et al 2003
  • One study out of one reported that patient satisfaction scores were significantly higher following PVB versus GA (p=0.008) Terheggen et al 2002
  • Tissue oxygen tension values in the latissimus dorsi flap tissue were significantly higher in the PVB group compared with the PCA IV opioid group at 2–20 h (p<0.05) Buggy et al 2004
  • Mean intra-operative blood loss was significantly lower with PVB versus PCA IV opioid (p=0.04) Buggy et al 2004
  • Two out of three studies reporting PONV outcomes reported superior results with PVB compared with GA Naja et al 2003 Click here for more information
  • In the PACU, the number of anti-emetic doses administered was significantly lower with bupivacaine PVB versus placebo (p<0.05), although VAS PONV scores at 6, 12 or 24 h after surgery were comparable between groups Kairaluoma et al 2004
  • In two out of two studies, the incidence of PONV was significantly lower with PVB compared with placebo/GA Kairaluoma et al 2004 Click here for more information
  • The time to first request for rescue analgesic was significantly longer with bupivacaine PVB compared with placebo (p<0.02) Kairaluoma et al 2004
  • Postoperative rescue analgesic requirements were significantly lower with PVB compared with GA in three out of three studies Terheggen et al 2002 Click here for more information
  • In the PACU, opioid consumption (IV oxycodone, 2–3 mg [0.04 mg/kg] every 5 min until pain VAS and NRS <3) was significantly lower with bupivacaine PVB versus placebo (p=0.004); however, the difference in opioid consumption was not significant after discharge from the PACU at any time point assessed (up to 6 h, 6–12, and 12–24 h) Kairaluoma et al 2004
  • One study out of one reported that radiograph pain (rated using verbal numeric score 0–5) was significantly lower with PVB compared with GA (p=0.0001) Terheggen et al 2002
  • One study out of one reported that significantly less painful restricted movement was observed with PVB at all time points assessed (i.e. at 1, 6, and 24 h after surgery), compared with GA (p<0.05 in all cases) Pusch et al 1999
  • The minimal pain experienced by patients receiving bupivacaine PVB was significantly lower than that experienced by patients receiving placebo over 24 h (p<0.03). The number of patients with pain at rest, evaluated using NRS, was significantly lower with bupivacaine PVB versus placebo (p=0.007), although there was no significant difference between groups in the number of patients with pain on movement. The number of patients with continuous aching pain (NRS) was significantly lower with bupiv Kairaluoma et al 2004
  • VAS pain scores during movement were significantly lower in patients receiving PVB compared with PCA IV opioid (p<0.05) at all time points recorded (1, 3, 12 and 24 h) Buggy et al 2004
  • Three out of three studies reported significantly lower VAS pain scores with PVB compared with GA in minor and major breast surgery Terheggen et al 2002 Click here for more information
  • Observer-recorded VAS pain scores were significantly lower with bupivacaine paravertebral block (PVB) compared with placebo at 30, 60, 90, 120 min and 6 h (p<0.02, 0.03, 0.02, 0.02 and 0.02, respectively), but not at 12 h or 24 h, or at the time of first rescue analgesic intake. There were no significant differences between the bupivacaine PVB and placebo groups in NRS pain scores at the time of interview on POD1, or the maximal NRS pain score over 24 h Kairaluoma et al 2004
  • The amount of IV ketoprofen administered to patients was similar with ropivacaine paravertebral block and bupivacaine paravertebral block. The time to first request for rescue analgesic was not significantly different between the two groups Hura et al 2006
  • One study out of one reported no significant difference between a group receiving PVB and a group receiving GA with regards to duration of PACU stay Terheggen et al 2002
  • There was no significant difference in blood loss between groups receiving bupivacaine PVB versus placebo Kairaluoma et al 2004
  • There were no significant differences in NRS pain scores between groups receiving ropivacaine paravertebral block versus bupivacaine paravertebral block at any time point postoperatively (at 0, 30, 60, or 120 min, or at 24 h). Patient satisfaction did not differ between the two groups Hura et al 2006
  • Minor and major breast surgery
  • Study details Kairaluoma 2004 Click here for more information

PROSPECT Recommendations

  • Thoracic epidural analgesia is not recommended (Grade D, LoE 4) since the risk of rare but serious complications outweighs the benefits of analgesia, and usually only unilateral block is required for breast cancer surgery

Clinical practice

  • Epidural analgesia is associated with a relatively high degree of patient monitoring, due to the invasiveness of the technique, and serious (although rare) major complications (e.g. haematoma)
  • Bilateral block is not required for mastectomy, therefore PVB is preferred to epidural analgesia/anaesthesia
  • Haemostatic disturbances due to chemotherapy are contra-indications for epidural techniques

Transferable evidence

  • A review of case studies reporting spinal haematomas associated with epidural anaesthesia over a 10-year period suggested an incidence of haematoma in 1:190,000 epidurals, with coagulopathies or anticoagulant therapy being the predominant risk factors Wulf 1996
  • Epidural administration of strong opioids is associated with side-effects including pruritus, PONV, urinary retention, and respiratory depression Chaney 1995

Breast surgery-specific evidence

  • Worst VAS pain scores, recorded at the time of the first dose of pethidine (1 mg/kg IM on demand), were significantly lower with TEA compared with GA (p<0.01) Yeh et al 1999
  • Significantly fewer patients receiving TEA + regional block compared with GA experienced substantial pain, as assessed by a VRS scale, in the PACU and at 12 h postoperatively (p<0.001 in both cases), but not at 24 h Sundarathiti et al 2005
  • Total IM pethidine consumption was significantly lower with TEA versus GA (p<0.001) during the 2-day study period Yeh et al 1999
  • The number of patients requiring postoperative rescue analgesia was significantly lower following TEA + regional block compared with GA, both in the PACU (p=0.002) and on the ward (p<0.001) Sundarathiti et al 2005 Click here for more information
  • The time to first pethidine injection was significantly longer with TEA compared with GA (p<0.001) Yeh et al 1999
  • Frequency of side-effects (including nausea and vomiting) was lower with TEA compared with GA (p<0.0001) Yeh et al 1999
  • Sedation score in the PACU was significantly lower following TEA + regional block compared with GA (p=0.003) Sundarathiti et al 2005
  • Average bedrest time was significantly shorter with TEA compared with GA (p<0.01) Yeh et al 1999
  • Overall satisfaction scores were significantly higher following TEA compared with GA (p<0.01) Yeh et al 1999
  • Patient satisfaction scores were significantly higher with TEA + regional block compared with GA (p<0.02) Sundarathiti et al 2005
  • There was no significant difference in the incidence of nausea and vomiting between patients receiving TEA + regional block and GA Sundarathiti et al 2005
  • Study details Yeh et al 1999 Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • Electro-acupoint stimulation is not recommended for analgesia (Grade D, LoE 4), due to limited procedure-specific and transferable data (LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • A randomised study in patients undergoing gynaecologic lower abdominal surgery demonstrated reduced morphine consumption with preoperative electroacupuncture (EA) compared with placebo or postoperative EA in the early postoperative period, although VAS pain scores were not significantly different between groups Sim 2002

Breast surgery-specific evidence

  • VRS pain scores were significantly lower with electro-acupoint stimulation compared with sham (p=0.01). The number of patients experiencing severe pain (VRS >5 of 10) was also significantly lower with electro-acupoint stimulation compared with sham (p=0.02) Gan 2004
  • Incidence of nausea was significantly lower with electro-acupoint stimulation versus sham (p<0.0001) Gan 2004
  • Rescue anti-emetic requirement (dexamethasone 8 mg) in a group receiving electro-acupoint stimulation was significantly lower than in a group receiving sham (p=0.04) Gan 2004
  • The complete response rate (no nausea, emesis or use of rescue anti-emetic) was significantly higher with electro-acupoint stimulation compared with sham at 2 h (p=0.01) and 24 h (p=0.006) Gan 2004
  • Nausea scores at 30, 60, 90 and 120 min (p=0.03, p=0.005, p=0.0004, p=0.003, respectively) and the worst nausea score (p=0.0001) were significantly lower with electro-acupoint stimulation compared with sham Gan 2004
  • Patient satisfaction scores were higher with electro-acupoint stimulation compared with sham (p=0.007) Gan 2004
  • Postoperative analgesic consumption (IV fentanyl 25 µg) was similar with electro-acupoint stimulation and sham (p=0.01) Gan 2004
  • The incidence of emesis in groups receiving electro-acupoint stimulation and sham was not significantly different at 2 or 24 h Gan 2004
  • Study details Gan 2004 Click here for more information
  • Major breast surgery

Intra-operative analgesia

To ensure an adequate analgesic effect in the immediate postoperative period, it may be necessary to administer analgesic medication prior to the postoperative period. Data included this section are from studies that assessed intra-operative analgesia versus intra-operative placebo, as well as those that assessed intra-operative analgesia versus the same analgesia given pre- or postoperatively. Where certain analgesics have been administered at various time points in studies (pre-operatively, intra-operatively or postoperatively), then these studies may be presented together in the same section to simplify the interpretation of the overall data (e.g. studies of pre- or intra-operative corticosteroid are presented together in both the Pre- and Intra-operative sections).

PROSPECT Recommendations

  • Corticosteroids are not recommended for analgesia in minor or major breast surgery (Grade D, LoE 4) due to insufficient procedure-specific evidence, but may be used to prevent PONV (procedure-specific and transferable evidence, both LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • Dexamethasone significantly reduced pain scores compared with placebo following laparoscopic cholecystectomy Bisgaard 2003
  • Dexamethasone was shown to prevent postoperative nausea and vomiting after surgery in a systematic review Carlisle 2006b
  • A single prophylactic dose of dexamethasone (4–8 mg) is effective for preventing PONV in surgery associated with high emetic effects Henzi et al 2000
  • In one randomised placebo-controlled study, parecoxib and methylprednisolone had comparable analgesic and rescue analgesic sparing effects in breast augmentation surgery, although only methylprednisolone reduced nausea, vomiting, and fatigue Romundstad 2006

Breast surgery-specific evidence

  • Incidences of nausea (p<0.009) and vomiting (p<0.000005) were significantly lower with dexamethasone compared with placebo Abou Zeid 2002
  • Rescue anti-emetic consumption (dolasetron) was significantly lower with dexamethasone compared with placebo (p<0.001) Abou Zeid 2002
  • VAS pain scores were not significantly different with dexamethasone compared with placebo at all time points assessed (on arrival in the recovery room, at 30 and 60 mins, on leaving the recovery room, and at 4 hours) Abou Zeid 2002
  • Consumption of postoperative diclofenac was comparable in patients receiving dexamethasone and patients receiving placebo Abou Zeid 2002
  • Study details Abou Zeid 2002 Click here for more information
  • Major and minor breast surgery

PROSPECT Recommendations

  • Adenosine is not recommended for analgesia (Grade D, LoE 4) due to limited procedure-specific and transferable evidence (LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • None cited

Breast surgery-specific evidence

  • Fewer patients receiving IV adenosine experienced wound pain on regaining consciousness compared with placebo (p<0.02) Segerdahl et al 1995
  • Opioid requirements (morphine or cetobemidone) during the first 24 h postoperatively were significantly lower with IV adenosine compared with placebo (p<0.03) Segerdahl et al 1995
  • Peri-operative blood loss was lower with IV adenosine compared with placebo (p<0.02) Segerdahl et al 1995
  • There were no significant differences in observer-assessed VAS wound pain between groups receiving IV adenosine versus placebo at 0–3 h or 18–24 h Segerdahl et al 1995
  • There were no significant differences in the incidence of spontaneous vomiting or nausea scores between groups receiving IV adenosine versus placebo Segerdahl et al 1995
  • There were no significant differences in the CFF test or VAS sedation scores between the groups receiving IV adenosine versus placebo at 30 min or 3 h Segerdahl et al 1995
  • Study details Segerdahl et al 1995 Click here for more information
  • Major breast surgery (and reduction mammoplasty)

PROSPECT Recommendations

  • Intercostal nerve block is not recommended for postoperative analgesia in minor or major breast surgery due to insufficient procedure-specific data (Grade D, LoE 4)

Clinical practice

  • The combination of ICB with brachial plexus block is not common practice
  • There is no study comparing intercostal nerve block alone with placebo in breast surgery
  • ICB is an invasive technique, and should not be used for minor breast surgery due to the risk of complications

Transferable evidence

  • The incidence of pneumothorax following intercostal nerve block in thoracic and upper abdominal surgery has been reported in the range of 0.073% to 19% Shanti et al 2001

Breast surgery-specific evidence

  • In one study out of one, there were no significant differences between groups receiving ropivacaine intercostal nerve block versus bupivacaine intercostal nerve block for the incidence of PONV Pakhira et al 2004
  • Rescue analgesic requirements (tramadol) and the time to first request for rescue analgesic were similar with ropivacaine and bupivacaine intercostal nerve block Pakhira et al 2004
  • Two out of two studies reported significantly lower VAS pain scores at rest with intercostal nerve block plus other regional techniques compared with placebo Fassoulaki et al 2001 Click here for more information
  • One study out of two reported a significant reduction in postoperative rescue analgesia with intercostal nerve block plus other regional techniques compared with placebo Pakhira et al 2004 Click here for more information
  • One study reported that the duration of analgesia (time when the observer rated VAS pain scores at >/=40 mm and administered rescue analgesia) was significantly longer with ropivacaine intercostal nerve block and bupivacaine intercostal nerve block, plus other regional techniques, compared with placebo (p<0.01) Pakhira et al 2004
  • There were no significant differences between groups receiving 1.5% lidocaine + 3.75 µg/ml epinephrine versus 2% lidocaine + 5 µg/ml epinephrine versus 0.5% bupivacaine intercostal nerve block with regards to the number of patients requiring postoperative analgesia (paracetamol on demand, then morphine if necessary), time to first request for rescue analgesia, or the total consumption of paracetamol in the first 24 h Atanassoff et al 1994
  • There were no significant differences in VAS pain scores between groups receiving ropivacaine intercostal nerve block versus bupivacaine intercostal nerve block at 1–12 or at 24 h Pakhira et al 2004
  • VAS pain scores were significantly lower with 0.5% bupivacaine intercostal nerve block compared with 2% lidocaine + 5 µg/ml epinephrine intercostal nerve block from 90–120 min (p<0.05), but not at any other time points assessed (i.e. on admission to the recovery room, every 15 min until 2 h, then every 30 min until 4 h postoperatively) Atanassoff et al 1994
  • VAS pain scores were significantly lower with intercostal nerve block compared with GA for the first 45, 60 and 90 minutes following surgery (p<0.05) Atanassoff et al 1994
  • Significantly fewer patients required postoperative analgesia following intercostal nerve block compared with GA (paracetamol on demand, plus morphine if necessary; p<0.05), although total consumption of paracetamol in the first 24 h was not significantly different between groups Atanassoff et al 1994
  • The time to first request for rescue analgesia was significantly longer with intercostal nerve block compared with GA (p<0.05) Atanassoff et al 1994
  • One out of one study showed no significant differences between groups receiving ropivacaine intercostal nerve block plus other regional techniques versus placebo in the frequency of chronic pain in the chest, axilla or arm, or in the overall pain frequency or intensity, at 3 months postoperatively Fassoulaki et al 2001
  • One study out of one showed that the time to first request for rescue analgesic was similar with ropivacaine intercostal nerve block plus other regional techniques and placebo Fassoulaki et al 2001
  • One study out of one reported no significant differences between groups receiving ropivacaine intercostal nerve block plus other regional techniques, bupivacaine intercostal nerve block plus other regional techniques, and placebo for the incidence of PONV Pakhira et al 2004
  • Minor breast surgery
  • Minor and major breast surgery
  • Study details Atanassoff et al 1994 Click here for more information
  • Intercostal nerve block: LA versus other LA
  • Intercostal nerve block plus other regional techniques versus placebo (GA in both groups)
  • Study details Atanassoff et al 1994 Click here for more information
  • Intercostal nerve block (no GA) versus GA
  • Minor and major breast surgery
  • Study details Fassoulaki et al 2001 Click here for more information

PROSPECT Recommendations

  • High concentrations of oxygen cannot be recommended for postoperative analgesia (Grade B) due to negative procedure-specific evidence (LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • None cited

Breast surgery-specific evidence

  • There was no significant difference in pain scores (measured on a linear scale) between treatment groups receiving different concentrations of oxygen Purhonen et al 2006
  • There was no significant difference between treatment groups receiving varying oxygen concentrations in postoperative rescue analgesic consumption (IM or IV oxycodone), or the time to first request for rescue analgesia Purhonen et al 2006
  • There was no significant difference in the incidence of vomiting between groups receiving 30% versus 80% oxygen Purhonen et al 2006
  • There was no significant difference between groups receiving different concentrations of oxygen with regards to consumption of rescue anti-emetics, incidence of nausea, number of emetic episodes, nausea scores, time from the end of surgery to the first PONV, and time to first request for rescue ondansetron Purhonen et al 2006
  • One study reported no significant difference in the incidence of total response (no vomiting or retching and a nausea score of 0), between groups receiving 30% versus 80% oxygen Purhonen et al 2006
  • There was no significant difference in postoperative blood loss between patients receiving 30% and 80% oxygen Purhonen et al 2006
  • One study reported no significant difference in patient satisfaction scores between groups receiving 30% and 80% oxygen Purhonen et al 2006
  • Study details Purhonen et al 2006 Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • There is insufficient procedure-specific evidence at this time to make a recommendation about the use of drains based on their effect on postoperative pain. The use of drains should depend on factors other than analgesia

Clinical practice

  • The use of drains is related to the prevention of axillary seroma

Transferable evidence

  • None cited

Breast surgery-specific evidence

  • The mean duration of drainage in patients with a drain was significantly shorter than the mean duration of aspiration in patients without a drain (p=0.0067, n=23/14 for drain/no drain) Zavotsky 1998
  • Pain scores (rated on a scale of 1–10) were significantly higher in patients with a drain versus patients receiving no drain at postoperative week 0 (p=0.0062, n=18/16 for drain/no drain), but not at weeks 1, 2 or 3 Zavotsky 1998
  • Haematoma incidence was not significantly different between patients with a drain compared with patients receiving no drain Zavotsky 1998
  • The incidence of infection was not significantly different between drain and no drain groups Zavotsky 1998
  • VAS pain scores were significantly higher in patients with a suction drain versus patients receiving no drain + sealant or no drain + no sealant at 24 and 48 h (p<0.001, p=0.002, respectively) (the two groups without drains were reported as combined for this comparison) Jain et al 2004
  • The duration of hospital stay was significantly longer in patients with a suction drain compared with patients receiving no drain + sealant or no drain + no sealant (p<0.001) (the two groups without drains were reported as combined for this comparison) Jain et al 2004
  • There was no significant difference in the overall incidence of seromas between groups with a suction drain, a suction drain + sealant, and no drain + no sealant Jain et al 2004
  • Total volume of fluid aspirated from seromas was significantly greater in patients with no drain + no sealant compared with patients receiving a suction drain (p=0.008) and patients receiving no drain + sealant (p<0.02). The frequency of aspiration was significantly higher with no drain + no sealant compared with a suction drain (p<0.03) but not versus no drain + sealant Jain et al 2004
  • Drain versus no drain
  • Study details Zavotsky 1998 Click here for more information
  • Major breast surgery
  • Drain versus sealant versus no drain + no sealant
  • Study details Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • There is insufficient procedure-specific evidence at this time to make a recommendation about surgical techniques based on their effect on postoperative pain. The type of surgical technique should depend on factors other than analgesia

Clinical practice

  • None cited

Transferable evidence

  • None cited

Breast surgery-specific evidence

  • One out of two studies showed a benefit of laser surgery for reducing pain versus conventional surgery Ansanelli etal 1996 Click here for more information
  • Two out of two studies reported significantly reduced peri-operative blood loss with laser surgery compared with conventional scalpel surgery (p<0.001, Wyman et al 1993
  • In one study out of one, drain removal occurred significantly earlier following CO2 laser surgery versus conventional scalpel surgery (p<0.003), and total in-hospital drainage was significantly lower with CO2 laser surgery compared with conventional scalpel surgery (p<0.02) Ansanelli etal 1996
  • One out of two studies showed a benefit of laser surgery for reducing the length of hospital stay versus conventional surgery Ansanelli etal 1996 Click here for more information
  • There were no significant differences in VAS or VRS pain scores between groups undergoing electrocautery and scalpel surgery Chan et al 1997
  • PCA morphine consumption was similar with electrocautery and scalpel surgery (PCA system set to deliver 1 mg/ml) Chan et al 1997
  • One study out of one reported no significant differences between groups receiving laser scalpel surgery and conventional scalpel surgery in the time taken for useful shoulder mobility to return, in the total postoperative wound drainage volume, or the incidence of axillary seroma Wyman et al 1993
  • The length of postoperative hospital stay, peri-operative blood loss, and total drainage were all similar with electrocautery and scalpel surgery Chan et al 1997
  • Study details Ansanelli etal 1996 Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • Electro-acupoint stimulation is not recommended for analgesia (Grade D, LoE 4), due to limited procedure-specific and transferable evidence

Clinical practice

  • None cited

Transferable evidence

  • A randomised study in patients undergoing gynaecologic lower abdominal surgery demonstrated reduced morphine consumption with pre-operative electroacupuncture (EA) compared with placebo or postoperative EA in the early postoperative period, although VAS pain scores were not significantly different between groups Sim 2002

Breast surgery-specific evidence

  • VRS pain scores were significantly lower with electro-acupoint stimulation compared with sham (p=0.01). The number of patients experiencing severe pain (VRS >5 of 10) was also significantly lower with electro-acupoint stimulation compared with sham (p=0.02) Gan et al 2004
  • Incidence of nausea was significantly lower with electro-acupoint stimulation versus sham (p<0.0001) Gan et al 2004
  • Rescue anti-emetic requirement (dexamethasone 8 mg) in a group receiving electro-acupoint stimulation was significantly lower than in a group receiving sham (p=0.04) Gan et al 2004
  • The complete response rate (no nausea, emesis or use of rescue anti-emetic) was significantly higher with electro-acupoint stimulation compared with sham at 2 h (p=0.01) and 24 h (p=0.006) Gan et al 2004
  • Nausea scores at 30, 60, 90 and 120 min (p=0.03, p=0.005, p=0.0004, p=0.003, respectively) and the worst nausea score (p=0.0001) were significantly lower with electro-acupoint stimulation compared with sham Gan et al 2004
  • Patient satisfaction scores were higher with electro-acupoint stimulation compared with sham (p=0.007) Gan et al 2004
  • Postoperative analgesic consumption (IV fentanyl 25 µg) was similar with electro-acupoint stimulation and sham (p=0.01) Gan et al 2004
  • The incidence of emesis in groups receiving electro-acupoint stimulation and sham was not significantly different at 2 or 24 h Gan et al 2004
  • Study details Gan et al 2004 Click here for more information
  • Major breast surgery

Postoperative studies

Data in this section are available from studies that assessed postoperative analgesia versus postoperative placebo, as well as those that assessed postoperative analgesia versus the same analgesia given pre-operatively or intra-operatively. Where certain analgesics have been administered at various time points in studies (pre-operatively, intra-operatively or postoperatively), then these studies may be presented together in the same section to simplify the interpretation of the overall data (e.g. studies of pre- or peri-operative gabapentin are presented together in both the Pre- and Postoperative sections)

PROSPECT Recommendations

  • No recommendation can be made regarding repeated postoperative administration of gabapentinoids in major breast surgery because of insufficient procedure-specific and transferable evidence
  • Gabapentinoids are not recommended for minor breast surgery (Grade B) based on transferable evidence (LoE 1) because pain intensity is commonly not severe enough to justify an adjuvant to the usual analgesic agents
  • Transferable evidence (LoE 1) suggests that gabapentinoids are associated with sedation, and it is recommended (Grade D) that this side-effect should be considered when determining the dose that will be administered
  • Gabapentinoids cannot be recommended at this time (Grade D, LoE 4) for the prevention of chronic pain after breast surgery, because there is conflicting procedure-specific and transferable evidence

Clinical practice

  • Limited procedure-specific evidence supports an effect of gabapentinoids on chronic pain after breast surgery but transferable evidence from lower limb amputation showed no effect of gabapentin on chronic pain. Further studies are required to investigate the mechanisms of post-surgical chronic pain and the effects of gabapentin on the development of chronic pain after breast surgery

Transferable evidence

  • Three systematic reviews and a meta-analysis evaluated the use of gabapentinoids for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls Dahl et al 2004
  • Two systematic reviews Ho et al 2006
  • Two systematic reviews Ho et al 2006
  • A randomised study found that gabapentin administered in the first 30 days after lower limb amputation did not reduce the incidence or intensity of stump and phantom pain compared with placebo Nikolajsen 2006

Breast surgery-specific evidence

  • In one study out of two, VAS pain scores at rest were significantly lower with oral gabapentin compared with placebo on postoperative day 3 (p<0.05), but not in the first 24 h, or on days 1, 2, or 4–10 after surgery Fassoulaki 2002 Click here for more information
  • VAS pain scores at rest were significantly lower with oral gabapentin + regional block + LA cream compared with placebo in the PACU (p=0.001) and on PODs 1, 3 and 5 (p=0.04, p<0.02, p<0.05, respectively) Fassoulaki et al 2005
  • Two studies out of two demonstrated significantly lower VAS pain scores during movement with gabapentin compared with placebo Dirks ET AL 2002 Click here for more information
  • VAS pain scores on movement were significantly lower following oral gabapentin + regional block + LA cream administration compared with placebo in the PACU (p=0.001) and on PODs 2, 4 and 8 (p<0.03, p=0.007 and p<0.04, respectively) Fassoulaki et al 2005
  • Two out of two studies reported significantly lower rescue analgesic requirements with oral gabapentin compared with placebo Dirks ET AL 2002 Click here for more information
  • Rescue analgesic use was significantly lower with oral gabapentin + regional block + LA cream compared with placebo Fassoulaki et al 2005 Click here for more information
  • At 3 months postoperatively, the incidence of burning, chronic pain was significantly lower with oral gabapentin compared with placebo (p<0.04). The incidence of pain in the chest, axilla or arm, and the incidence of abnormal sensation were similar in both groups Fassoulaki 2002
  • After 3 months, fewer patients required analgesics, and the number of patients experiencing total chronic pain was significantly lower with oral gabapentin + regional block + LA cream compared with placebo (p<0.05 and p<0.03, respectively), although neither measure was significant at 6 months Fassoulaki et al 2005
  • There was no significant difference between groups receiving oral gabapentin + regional block + LA cream versus placebo for the time to first request for rescue analgesics Fassoulaki et al 2005
  • There was no significant difference in the incidence of nausea with oral gabapentin versus placebo Dirks ET AL 2002
  • Study details Dirks ET AL 2002 Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • Postoperative conventional NSAIDs are recommended (Grade A) for postoperative analgesia following major and minor breast surgery based on procedure-specific evidence (LoE 1) showing a reduction in pain scores compared with placebo
  • The use of conventional NSAIDs should depend upon assessment of individual patient risks (Grade B), including bleeding complications, actual or recent gastroduodenal ulcer history (transferable evidence, LoE 1), cardiovascular morbidity (LoE 4), aspirin-sensitive asthma, renal function and hepatic function (transferable evidence, LoE 3)

Clinical practice

  • The risk of bleeding complications in breast cancer surgery is about 2–5%. Conventional NSAIDs carry the risk of increased bleeding, therefore it may be preferable to use COX-2-selective inhibitors as an alternative analgesic intervention

Transferable evidence

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures Barden et al 2004
  • One randomised trial in patients undergoing vaginal hysterectomy or breast surgery showed that diclofenac was as effective as rofecoxib in terms of postoperative analgesia, but was associated with greater use of anti-emetics Hegi et al 2004
  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression Marret et al 2005
  • Randomised endoscopic trials in healthy elderly volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported (with lumiracoxib; Shi 2008
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Chronic administration of conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Pain relief with oral paracetamol plus ibuprofen was inferior to patient-controlled incisional regional analgesia and was associated with more frequent side-effects, after ambulatory breast augmentation Rawal 2006

Breast surgery-specific evidence

  • Three out of three studies reported lower VAS pain scores with conventional NSAID compared with placebo Bosek et al 1996 Click here for more information
  • One out of two studies reported a significant reduction in PCA morphine consumption with conventional NSAID compared with placebo Legeby et al 2005 Click here for more information
  • One study out of one reported significantly less wound drainage following IV ketorolac administration compared with placebo at 6 h postoperatively (p</=0.05), but not at any other time point (60 min, 12 and 18 h) Bosek et al 1996
  • There were no significant differences between groups receiving postoperative IM diclofenac versus placebo with regards to the number of patients requiring rescue analgesia (IV fentanyl 50 µg) or the number of analgesic tablets consumed in the 48 h following surgery Chan et al 1996
  • Two out of two studies reported no significant differences between systemic NSAID (IV ketorolac, Bosek et al 1996
  • One study out of one reported that postoperative blood loss was significantly greater with rectal diclofenac compared with placebo (p<0.01), with the difference being more pronounced in patients with ALND Legeby et al 2005
  • Study details Bosek et al 1996 Click here for more information
  • Major and minor breast surgery

PROSPECT Recommendations

  • Postoperative COX-2-selective inhibitors are recommended (Grade B) for major and minor breast surgery, based on transferable evidence for analgesic efficacy (LoE 1)
  • It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B) (cardiovascular morbidity (transferable evidence, LoE 1), renal function and hepatic function (transferable evidence, LoE 3) or actual or recent gastroduodenal ulcer history (LoE 4)

Clinical practice

  • The risk of bleeding complications in breast cancer surgery is about 2–5%. Conventional NSAIDs carry the risk of increased bleeding, therefore it may be preferable to use COX-2-selective inhibitors as an alternative analgesic intervention
  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Transferable evidence

  • One randomised trial in patients undergoing vaginal hysterectomy or breast surgery showed that rofecoxib was as effective as diclofenac in terms of postoperative analgesia, but was associated with less use of anti-emetics Hegi et al 2004
  • In one study, parecoxib and methylprednisolone had comparable analgesic and rescue analgesic sparing effects in breast augmentation surgery, although only methylprednisolone reduced nausea, vomiting, and fatigue Romundstad 2006
  • Rofecoxib 50 mg and parecoxib 40 mg have an equipotent analgesic efficacy relative to traditional NSAIDs in postoperative pain after minor and major surgical procedures Rømsing et al 2004
  • A systematic review to quantify the efficacy of single-dose oral valdecoxib and IV parecoxib demonstrated that both are effective treatments for acute postoperative pain, and show similar incidences of adverse effects Barden 2003
  • Randomised endoscopic trials in healthy elderly volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation or bleeding time compared with placebo Greenberg et al 2000 Click here for more information
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following non-cardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) Nussmeier et al 2006
  • Two clinical trials showed that in patients who had undergone CABG surgery, COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported (with lumiracoxib; Shi 2008
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Chronic administration of COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004

Breast surgery-specific evidence

  • None cited

PROSPECT Recommendations

  • Mexiletine is not recommended at this time for analgesia in minor or major breast surgery (Grade D, LoE 4) due to limited and conflicting procedure-specific evidence (LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • None cited

Breast surgery-specific evidence

PROSPECT Recommendations

  • No recommendations can be made at this time regarding the use of ketamine due to insufficient procedure-specific evidence, despite opioid-sparing effects in other procedures (transferable evidence, LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • Studies of ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain or opioid use when used as an adjunct to morphine Bell et al 2006
  • Low-dose ketamine was associated with few and mild adverse effects, especially when administered in conjunction with general anaesthesia Bell et al 2006

Breast surgery-specific evidence

  • There were no significant differences in VAS pain scores between groups receiving pre- versus postoperative IV ketamine at any time point (on arrival in recovery room, or at 1–6, 8, 12, 16, 20 or 24 h after surgery) Adam et al 1999
  • Cumulative PCA morphine use was significantly lower with postoperative IV ketamine compared with pre-operative IV ketamine at 1 (p<0.009) and 2 h (p<0.04), but not at 2–24 h (PCA morphine: bolus 0.5 mg on demand, lockout 5 min) Adam et al 1999
  • The time to first request for rescue analgesic was not significantly different between the pre-operative IV ketamine and postoperative IV ketamine groups Adam et al 1999
  • The incidence of PONV was similar with pre-operative IV ketamine and postoperative IV ketamine Adam et al 1999
  • There was no significant difference in the level of patient satisfaction with pre-operative IV ketamine and postoperative IV ketamine Adam et al 1999
  • Study details Adam et al 1999 Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • Postoperative strong opioids (oral, IV or PCA) are recommended to treat high-intensity pain (VAS >/=50 mm) in the early postoperative period (Grade B) based on analgesic efficacy in procedure-specific (LoE 1) and transferable evidence (LoE 1)
  • Strong opioids are not recommended (Grade B) for moderate- to low-intensity pain (VAS<50 mm), because of the risk of emetic and other side-effects (transferable evidence, LoE 1). Non-opioid analgesics are recommended in preference to strong opioids for moderate- to low-intensity pain (Grade D, LoE 4)
  • IM administration is not recommended (Grade B) because of unfavourable pharmacokinetics, injection-associated pain (LoE 4) and patient dissatisfaction (transferable evidence, LoE 1)

Clinical practice

  • Routine administration of strong opioids should be avoided in minor breast surgery due to the risk of PONV
  • As with all types of analgesia for postoperative pain, strong opioids should be instituted in time to secure sufficient analgesia when the patient wakes
  • Oral opioids are preferable to parenteral opioids
  • Regular administration, titrated for pain intensity, is generally accepted as an effective method of administering strong opioids
  • Most clinical trials showing benefits of intramuscular strong opioids use nurse-administered regimens. In regular clinical practice, full adherence to nurse-administered regimens is not usually achievable, and the full analgesic benefits of intramuscular strong opioids are also not achieved

Transferable evidence

  • Strong opioids are effective for reducing high- and moderate-intensity postoperative pain McQuay et al 1999
  • A systematic review comparing intravenous PCA opioids with intravenous, intramuscular or subcutaneous opioids by injection showed that PCA opioids were associated with greater pain relief, reduced supplemental analgesic requirements (analysis of eleven studies, total n=691), and more patients preferred PCA opioids (analysis of four trials, total n=352) compared with traditional opioid analgesia Walder et al 2001
  • A quantitative systematic review showed that opioid by PCA provided better pain control and greater patient satisfaction than conventional opioid parenteral analgesia in a variety of surgical procedures (37/56 trials used IM analgesia in the control group) Hudcova et al 2005
  • A systematic review showed that patients using PCA consumed a greater quantity of opioids than those treated using conventional opioid parenteral analgesia, and had a higher incidence of pruritus, but a similar incidence of other side-effects, in a variety of surgical procedures. There was no difference between groups in the length of hospital stay Hudcova et al 2005
  • Pethidine induced significantly higher sedation and respiratory depression compared with tramadol (both 100 mg intravenously) (n=48) Tarradell et al 1996
  • Strong opioids are associated with adverse effects, including nausea, vomiting, sedation, confusion, paralytic ileus and urinary retention Wheeler et al 2002
  • One study comparing PCA with conventional pain therapy (CPT; IV piritramide or oral/IM tramadol) demonstrated an increased consumption of postoperative analgesic in the PCA group compared with the CPT group (p<0.01), although the PCA group reported a significantly greater satisfaction with pain therapy compared with the CPT group (p<0.01) (n=42 patients; Forst J et al 1999

Breast surgery-specific evidence

  • Observer-rated VAS pain scores at rest were significantly lower with oral oxycodone compared with placebo at 16 (p=0.04) and 24 h (p=0.03) postoperatively, but not at 0, 4 or 8 h after surgery. Observer-rated VAS pain scores on movement were not significantly different between the oral oxycodone versus placebo groups during the assessment period (i.e. at 0–24 h) Kampe et al 2004
  • Consumption of IV PCA piritramide (1.5 mg bolus doses, 6 min lockout, 30 mg limit over 4 h) was significantly lower with oral oxycodone group compared with placebo at 0 (loading dose), 4, 16, and 24 h (p<0.001, p<0.04, p=0.01, and p=0.005, respectively), but not at 8 h postoperatively. The cumulative IV PCA piritramide consumption was also significantly lower following oral oxycodone compared with placebo (p=0.002) Kampe et al 2004
  • The number of patients experiencing nausea was similar with oral oxycodone and placebo Kampe et al 2004
  • The overall quality of pain management as judged by the patients was not deemed significantly different between those receiving oral oxycodone and those receiving placebo Kampe et al 2004
  • Study details Kampe et al 2004 Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • Weak opioids are recommended for minor and major breast surgery (Grade B) based on transferable evidence for analgesic efficacy (LoE 1), and should be used as rescue analgesics for moderate- or low-intensity pain (VAS <50 mm), if conventional NSAIDs or COX-2-selective inhibitors are insufficient or are contraindicated (Grade D, LoE 4)
  • Recommendations regarding choice of weak opioid cannot be made at this time due to limited procedure-specific data

Clinical practice

  • It is considered that weak opioids are inappropriate as a single therapy for postoperative pain following breast surgery, and are ineffective for treatment of high-intensity pain (VAS >/=50 mm)
  • Common side-effects of tramadol include nausea and vomiting
  • The use of the anti-emetic ondansetron increases the amount of tramadol required to provide analgesia

Transferable evidence

  • Tramadol was more effective than placebo for pain relief in a meta-analysis of post-surgical patients Moore et al 1997
  • The combination of tramadol and paracetamol enhances analgesic efficacy compared with either agent alone McQuay H et al 2003
  • A systematic review found that the combination of dextropropoxyphene 65 mg with paracetamol 650 mg showed similar efficacy to tramadol 100 mg Collins et al 2000
  • A systematic review found that the combination of codeine with paracetamol provided additional pain relief compared with paracetamol alone Moore et al 2000
  • Two studies found that codeine 30 mg + paracetamol 300 mg was associated with a higher incidence of constipation and vomiting than tramadol 37.5 mg + paracetamol 325 mg following arthroscopy Bourne et al 2005
  • Adverse effects associated with tramadol include headache, nausea, vomiting, dizziness, and somnolence. A meta-analysis of individual patient data from randomised controlled trials found a dose-response of adverse effects with tramadol; postsurgical patients had fewer side-effects than dental patients Moore et al 1997
  • A systematic review found that the combination of codeine with paracetamol was associated with an increase in drowsiness and dizziness compared with paracetamol alone Moore et al 2000
  • A systematic review found an increased incidence of central nervous system adverse effects with paracetamol 650 mg plus dextropropoxyphene 65 mg compared with placebo, but the incidence of other adverse effects was reduced compared with tramadol 100 mg Collins et al 2000

Breast surgery-specific evidence

  • Observer-rated VAS pain scores during movement were significantly higher following oral tramadol administration compared with placebo administration at 24 h (p=0.04), but not at any other time point assessed, and not at rest Thienthong et al 2004
  • The proportion of patients reporting VAS pain scores >30 mm during movement was significantly higher with oral tramadol group compared with placebo at 24 h (p=0.04), but not at any other time point recorded (i.e. at admission to PACU or at 2, 6, or 12 h after surgery) Thienthong et al 2004
  • There were no significant differences in cumulative IV PCA morphine consumption between groups receiving oral tramadol versus placebo (PCA morphine: 1 mg bolus, 5 min lockout) Thienthong et al 2004
  • The percentage of patients experiencing nausea and vomiting was significantly higher with oral tramadol compared with placebo (p=0.02) Thienthong et al 2004
  • Study details Thienthong et al 2004 Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • Paracetamol alone or in combination with other analgesics (e.g. conventional NSAIDs or COX-2-selective inhibitors) is recommended for low-to-moderate intensity pain (VAS <50 mm) following minor or major breast surgery (Grade B), based on transferable evidence (LoE 1) showing efficacy for treating pain of moderate intensity
  • Paracetamol is recommended to be used in combination with opioid analgesics for high-intensity pain (Grade D, LoE 4)
  • Paracetamol alone is not recommended for high-intensity pain (VAS >/=50 mm) (Grade B), based on transferable evidence (LoE 1)

Clinical practice

  • Many studies include the use of paracetamol, but as a supplemental analgesic for all patients
  • It is considered that paracetamol is ineffective as a single therapy for treatment of high-intensity pain (VAS >/=50 mm)

Transferable evidence

  • Paracetamol is an effective analgesic for the treatment of postoperative pain of moderate intensity Rømsing et al 2002
  • There is evidence that concurrent use of paracetamol and conventional NSAIDs improves pain relief compared with paracetamol alone, but there is no evidence for a superior analgesic effect of the combination compared with conventional NSAIDs alone Altman 2004
  • A study of propacetamol administered after breast surgery or thyroidectomy (n=119) showed that pain relief and supplemental injection of morphine were not statistically different between groups treated with propacetamol systematically or propacetamol on demand, and adverse effects were rare Farhat 1995
  • Pain relief with oral paracetamol plus ibuprofen was inferior to patient-controlled incisional regional analgesia and was associated with more frequent side-effects, after ambulatory breast augmentation Rawal 2006

Breast surgery-specific evidence

  • None cited

PROSPECT Recommendations

  • Antibiotics are not recommended for analgesic purposes (Grade D, LoE 4) due to inconsistent results from limited procedure-specific evidence

Clinical practice

  • None cited

Transferable evidence

  • None cited

Breast surgery-specific evidence

  • One study out of two reported less pain with antibiotic treatment compared with placebo/no treatment Chow et al 2000 Click here for more information
  • One study out of one reported that the frequency of analgesic consumption was significantly lower with oral clarithromycin compared with a group receiving no treatment (p<0.005; analgesics were oral acetaminophen and IV propoxyphene hydrochloride, given as needed every 4 h) Chow et al 2000
  • One study out of one showed that postoperative functional status (range of abduction and range of flexion) was significantly greater with oral clarithromycin compared with a group receiving no treatment (both p<0.05) Chow et al 2000
  • In one study out of one, there was no significant difference in the total volume of wound drainage between groups receiving tetracycline versus placebo Rice et al 2000
  • Wound seromas occurred more frequently with tetracycline compared with placebo 2 weeks after surgery (p=0.01). There were no significant differences in seroma incidence, wound infection, or necrosis of skin flaps at 1 month postoperatively Rice et al 2000
  • Study details Chow et al 2000 Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • Continuous PVB cannot be recommended at this time for postoperative analgesia following major breast surgeries (Grade D, LoE 4), because of limited procedure-specific evidence
  • Continuous PVB is not recommended for minor breast surgeries (Grade D, LoE 4), because the risk of complications may outweigh the benefits for analgesia

Clinical practice

  • PVB is an invasive technique, and the risk of complications (e.g. pneumothorax) may outweigh the benefits in minor procedures that result in mild pain
  • While there is good evidence for the use of PVB in breast surgery, it is not commonly used for anaesthesia in clinical practice

Transferable evidence

  • One study found that PVB reduced pain scores and incidence of PONV compared with general anaesthesia following cosmetic breast surgery (n=30) Klein et al 2000
  • Two retrospective studies of patients undergoing breast cancer surgery showed benefits of PVB over general anaesthesia, in terms of pain control, side-effects and quality of recovery Coveney 1998
  • A review of 15 patients undergoing surgery for breast cancer concluded that ambulatory surgical management of breast carcinoma using PVB is a safe procedure associated with high patient satisfaction and minimal postoperative complications Weltz 1995
  • A systematic review reported a similar level of pain relief with PVB and epidural analgesia following thoracotomy, although PVB was associated with fewer side-effects and a reduced risk of pulmonary complications Davies et al 2006
  • A prospective study in 367 paediatric and adult patients receiving thoracic or lumbar PVB showed that the frequency of hypotension was 4.6% Lönnqvist 1995
  • A non-randomised study of 3450 patients receiving PVB for breast cancer surgery reported 17 episodes of epidural spreads leading to increased length of PACU stay, and 3 incidences of preseizure excitation caused by partial accidental intravascular injection Ganapathy 2005

Breast surgery-specific evidence

  • VAS pain scores during movement were significantly lower in patients receiving paravertebral block (PVB) compared with PCA IV opioid (p<0.05) at all time points recorded (1, 3, 12 and 24 h) Buggy et al 2004
  • Rescue morphine requirements in the PACU were significantly lower with PVB compared with PCA IV opioid (p=0.04) Buggy et al 2004
  • Mean intra-operative blood loss was significantly lower with PVB versus PCA IV opioid (p=0.04) Buggy et al 2004
  • Tissue oxygen tension values in the latissimus dorsi flap tissue were significantly higher in the PVB group compared with the PCA IV opioid group at 2–20 h (p<0.05) Buggy et al 2004
  • Study details Buggy et al 2004 Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • Continuous thoracic epidural analgesia is not recommended (Grade D, LoE 4) since the risk of rare but serious complications outweighs the benefits of analgesia, and usually only unilateral block is required for breast cancer surgery

Clinical practice

  • Epidural analgesia is associated with a relatively high degree of patient monitoring, due to the invasiveness of the technique, and serious (although rare) major complications (e.g. haematoma)
  • Bilateral block is not required for mastectomy, therefore PVB is preferred to epidural analgesia/anaesthesia
  • Haemostatic disturbances due to chemotherapy are contra-indications for epidural techniques

Transferable evidence

  • A review of case studies reporting spinal haematomas associated with epidural anaesthesia over a 10-year period suggested an incidence of haematoma in 1:190,000 epidurals, with coagulopathies or anticoagulant therapy being the predominant risk factors
  • Epidural administration of strong opioids is associated with side-effects including pruritus, PONV, urinary retention, and respiratory depression

Breast surgery-specific evidence

  • Observer-rated VAS pain scores at rest were significantly lower with epidural morphine + PCEA compared with PCEA only, at all time points recorded (i.e. at 6, 12, 24 and 48 h; p<0.001 in all cases). Verbal pain scores during the 48 h after surgery were significantly lower with epidural morphine + PCEA compared with PCEA only (p<0.001) Aida et al 1999
  • VAS pain scores were significantly lower with epidural morphine compared with PCA IV morphine at POD1 (morning), and POD2 (morning and evening) (p<0.05 in all cases) Correll ET AL 2001
  • Significantly fewer patients receiving TEA compared with GA experienced substantial pain, as assessed by a VRS scale, in the PACU and at 12 h postoperatively (p<0.001 in both cases), but not at 24 h Sundarathiti et al 2005
  • Cumulative epidural PCA morphine consumption was significantly lower following epidural morphine + PCEA compared with PCEA only, at every time point observed (i.e. at 6, 12, 24 and 48 h; p<0.001 in all cases; PCA morphine bolus 0.2 mg on demand, lockout 15 min))
  • The number of patients requiring postoperative rescue analgesia was significantly lower following TEA compared with GA, both in the PACU (p=0.002) and on the ward (p<0.001) Sundarathiti et al 2005 Click here for more information
  • Length of hospital stay was significantly shorter with epidural morphine compared with PCA IV morphine (p<0.05)
  • Patient satisfaction scores were significantly higher with TEA compared with GA (p<0.02)
  • Nausea scores were similar in patients receiving epidural morphine and PCA IV morphine
  • There was no significant difference in the incidence of nausea and vomiting between patients receiving TEA and those receiving GA
  • Sedation score in the PACU was significantly lower following TEA compared with GA (p=0.003)
  • There were no significant differences between groups receiving epidural morphine versus PCA IV morphine for time to first audible bowel sounds, tolerance of liquid or solid food, time to passage of first flatus, first bowel movement, time to first ambulation or incidence of pruritus
  • Study details Aida et al 1999 Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • No recommendations can be made at this time regarding the use of local wound infiltration or infusion due to insufficient procedure-specific evidence and heterogeneity in study design

Clinical practice

  • Long-acting local anaesthetics are preferred to short-acting local anaesthetics for analgesia by local injection
  • Axillary infiltration may be more effective for functional pain control, but more studies are needed to verify this. Existing studies provide insufficient data regarding pain on movement after surgery

Transferable evidence

  • There is evidence from a variety of surgical procedures that the efficacy of local anaesthetics for postoperative analgesia is similar following pre-operative or post-incisional administration
  • Pre-operative tumescent infiltration with lidocaine resulted in reduced pain and lower postoperative opioid requirements compared with placebo following reduction mammoplasty
  • A study of local anaesthesia infiltration in patients undergoing either breast augmentation or breast reduction showed comparable analgesic effects of ropivacaine and bupivacaine
  • Pain relief with oral paracetamol plus ibuprofen was inferior to patient-controlled incisional regional analgesia and was associated with more frequent side-effects, after ambulatory breast augmentation
  • A systematic review of continuous administration of local anaesthetics via wound catheters reported a consistent reduction in pain scores/opioid use across a variety of surgical procedures, with a global reduction in PONV, increased patient satisfaction, and decreased length of stay
  • A systematic review of local anaesthesia infiltration showed inconclusive evidence of analgesic efficacy in hysterectomy, open cholecystectomy and a variety of other surgical procedures, but consistent and clinically relevant pain relief in herniorraphy

Breast surgery-specific evidence

  • LA wound infiltration versus placebo
  • LA wound infiltration (with or without opioid) versus systemic opioid
  • Opioid wound infiltration versus placebo or systemic opioid
  • Post-operative LA wound infiltration with pre- or postoperative IM NSAID
  • LA wound infusion versus placebo

PROSPECT Recommendations

  • Topical application of local anaesthetics is not recommended (Grade D, LoE 4) due to inconsistent procedure-specific data

Clinical practice

  • None cited

Transferable evidence

  • None cited

Breast surgery-specific evidence

  • Chronic pain intensity at 3 months, measured using the verbal intensity scale (VIS), was significantly lower in patients receiving topical application of EMLA cream compared with placebo (p=0.003) (
  • Incidence of pain in the chest wall and axilla was significantly lower with topical application of EMLA cream compared with placebo (p=0.004 and p<0.03 for the chest wall and axilla, respectively). Incidence of pain in one or more location, and total incidence of chronic pain, were significantly lower in the EMLA cream group compared with the placebo group (p=0.002 in both cases). There was no significant difference between the groups in the incidence of pain in arm, or in the loss of sensati
  • The time to first request for rescue analgesic was significantly longer with topical application of EMLA cream compared with placebo (p=0.04) (
  • VAS pain scores at rest and on movement were not significantly different between patients receiving topical application of EMLA cream versus placebo at any time point recorded (i.e. at 0, 3, 6, 9 or 24 h, or on POD2–6) (
  • Quantitative outcomes: when topical application was combined with two studies of local wound infiltration, there was a benefit over placebo for VAS pain scores at rest at 18–24 h (three studies, WMD -4.14 mm [-8.17, -0.12], p=0.04), but not at 0–1 h (WMD 5.99 mm [-0.37, 12.35], p=0.06), 2–3 h (WMD 0.48 mm [-5.42, 6.37], p=0.87), 6 h (WMD 0.88 mm [-6.00, 7.76], p=0.8) or 9–12 h (WMD 1.94 mm [-0.25, 4.12], p=0.08)
  • There were no significant differences between groups receiving LA topical wound dressing versus no treatment in VAS pain scores at rest at 0, 1, 2, 4, 6, 8, 12 or 20 h postoperatively (
  • There was no significant difference between groups receiving topical application of EMLA cream versus placebo in IM analgesic consumption (75 mg IM propoxyphene and 600 mg IM paracetamol) in the first 24 h postoperatively. Oral analgesic consumption from POD2–5 was significantly lower in the EMLA cream group versus the placebo group (p=0.004 and p=0.001 for paracetamol and codeine, respectively) (
  • There was no significant difference in hydroxyzine consumption between groups receiving topical application of EMLA cream and placebo (
  • There was no significant difference in morphine consumption following LA topical wound dressing compared with no treatment from 0–20 h after surgery ( Pettersson et al 2001 Click here for more information
  • Study details Fassoulaki et al 2000 Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • Wound application of conventional NSAID via a drain is not recommended (Grade B), because of procedure-specific (LoE 1) evidence showing a lack of analgesic benefit

Clinical practice

  • None cited

Transferable evidence

  • None cited

Breast surgery-specific evidence

  • VAS pain scores were significantly lower with ketorolac administered via a drain compared with placebo during the first 60 min (p</=0.05), but not at 6, 12 and 18 h postoperatively
  • The incidence of nausea during the first 60 min was lower with ketorolac administered via a drain compared with placebo (p</=0.05)
  • Significantly less wound drainage was observed following ketorolac administered via a drain compared with placebo at 6 h postoperatively (p</=0.05), but not at any other time point (60 min, 12 and 18 h)
  • There were no significant differences in VAS pain scores between groups receiving ketorolac via a drain versus IV ketorolac at any time points (60 min, 6, 12 and 18 h postoperatively)
  • IV PCA morphine consumption was similar with ketorolac administered via a drain and placebo
  • There were no significant differences in IV PCA morphine consumption between groups receiving ketorolac via a drain and IV ketorolac
  • There were no significant differences in the incidence of nausea between groups receiving ketorolac via a drain and IV ketorolac
  • There were no significant differences in wound drainage observed between groups receiving ketorolac via a drain versus IV ketorolac at any time point after surgery (60 min, 6, 12 and 18 h)
  • Study details Bosek et al 1996 Click here for more information
  • Major breast surgery

PROSPECT Recommendations

  • High concentrations of oxygen cannot be recommended for postoperative analgesia (Grade B), due to negative procedure-specific evidence (LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • None cited

Breast surgery-specific evidence

  • There was no significant difference in pain scores (measured on a linear scale) between treatment groups receiving different concentrations of oxygen
  • There was no significant difference between treatment groups receiving varying oxygen concentrations in postoperative rescue analgesic consumption (IM or IV oxycodone), or the time to first request for rescue analgesia
  • There was no significant difference in the incidence of vomiting between groups receiving 30% versus 80% oxygen
  • There was no significant difference between groups receiving different concentrations of oxygen with regards to consumption of rescue anti-emetics, incidence of nausea, number of emetic episodes, nausea scores, time from the end of surgery to the first PONV, and time to first request for rescue ondansetron
  • One study reported no significant difference in the incidence of total response (no vomiting or retching and a nausea score of 0), between groups receiving 30% versus 80% oxygen (
  • There was no significant difference in postoperative blood loss between patients receiving 30% or 80% oxygen
  • One study reported no significant difference in patient satisfaction scores between groups receiving 30% or 80% oxygen
  • Study details Purhonen et al 2006 Click here for more information
  • Major breast surgery

Radical Prostatectomy 2012

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Notes on PROSPECT recommendations

PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted. Grades of recommendation (GoR) are assigned according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence.

Summary table: Grades of recommendation (GoR) based on source and level of evidence (LoE)

 
Study type LoE GoR (based on overall LoE, considering balance of clinical practice information and evidence)
Procedure-specific Transferable
Systematic review with homogeneous results 1 A B
Randomised controlled trial (RCT) – high quality 1

A

(based on two or more studies or a single large, well-designed study)

 B
RCT – with limitations in methodology or reporting 2

B

(or extrapolation from one procedure-specific LoE 1 study)

 C
Non-systematic review, cohort study, case study; (e.g. some adverse effects evidence) 3 C
Clinical practice information (expert opinion); inconsistent evidence 4

D

An explanation of how study quality assessments are performed to determine the LoE and GoR can be found in Radical Prostatectomy: Evidence Review Process. The AGREE II instrument (Brouwers 2010) is used internationally to assess the methodological rigour and transparency of practice guidelines. As far as possible, the methodology of the PROSPECT Radical Prostatectomy review meets the requirements of ‘Domain 3: Rigour of development’ of the AGREE II instrument:
  • Systematic methods were used to search for evidence.
  • The criteria for selecting the evidence are clearly described.
  • The strengths and limitations of the body of evidence are clearly described.
  • The methods for formulating the recommendations are clearly described.
  • The health benefits, side effects, and risks have been considered in formulating the recommendations.
  • There is an explicit link between the recommendations and the supporting evidence.
  • The guideline has been externally reviewed by experts prior to its publication. [The evidence and recommendations will be submitted for peer-review after publication on the PROSPECT website]
  • A procedure for updating the guideline is provided. [Methodology is provided so that the systematic review can be updated as required]
 

Interventions that are recommended for radical prostatectomy

Pre-operative interventions that are recommended for radical prostatectomy

Note: Unless otherwise stated, ‘pre-operative’ refers to interventions applied before surgical incision

Note: All analgesics should be administered at the appropriate time
(pre- or intra-operatively) to provide sufficient analgesia in the early recovery period

COX-2-selective inhibitors

·         As with all analgesics, COX-2-selective inhibitors should be administered at the appropriate time (pre- or intra-operatively) to provide sufficient analgesia in the early recovery period (GoR B), based on transferable evidence from diverse procedures showing analgesic efficacy (LoE 1)

Dexamethasone

·         Pre-operative dexamethasone is recommended both for its analgesic and anti-emetic effects (GoR B), based on transferable evidence from multiple procedures (LoE 1), despite lack of procedure-specific evidence

Gabapentinoids

·         Pre-operative gabapentinoids are recommended (GoR B) based on transferable evidence from multiple procedures showing analgesic efficacy (LoE 1), despite lack of procedure-specific evidence

Intra-operative interventions that are recommended for radical prostatectomy

Note:

- Unless otherwise stated, ‘intra-operative’ refers to interventions applied after incision and before wound closure

- All analgesics should be administered at the appropriate time
(pre- or intra-operatively) to provide sufficient analgesia in the early recovery period

- All intra-operative anaesthetic and/or analgesic interventions are considered in the postoperative section.

Postoperative interventions that are recommended for radical prostatectomy

Note: ‘Postoperative’ refers to interventions applied at or after wound closure

COX-2-selective inhibitors

·         COX-2-selective inhibitors are recommended (GoR B) based on transferable evidence from multiple procedures showing analgesic efficacy (LoE 1), despite a lack of procedure-specific evidence

Systemic lidocaine

·         Lidocaine infusion is recommended for radical prostatectomy (GoR B), due to transferable evidence from multiple procedures showing analgesic efficacy (LoE 1) despite limited procedure-specific evidence

Systemic strong opioids

·         Systemic strong opioids are recommended following prostatectomy (GoR B), based on transferable evidence from multiple procedures, for their efficacy in reducing high-intensity postoperative pain (VAS >/=50 mm) (LoE 1), with the following considerations:

·         Systemic strong opioids should be used in combination with COX-2-selective inhibitors and paracetamol to reduce opioid use and its associated side-effects (GoR D)

·         IV PCA strong opioids are recommended (GoR B) based on greater patient satisfaction compared with regular (fixed-interval) or PRN dosing (transferable evidence, LoE 1); however, fixed-interval IV administration titrated to pain intensity is also recognised as an effective mode of administration (LoE 4)

Systemic weak opioids

·         Weak opioids are recommended to be used for moderate- or low-intensity pain if non-opioid analgesia is insufficient or is contra-indicated (GoR B), based on transferable evidence (LoE 1) showing analgesic efficacy in multiple surgical procedures

·         Weak opioids are recommended to be used in combination with non-opioid analgesics (GoR B), based on transferable evidence (LoE 1) showing analgesic efficacy in combination regimens

Paracetamol

·         Paracetamol is recommended (GoR B) due to strong transferable evidence from multiple procedures showing analgesic efficacy (LoE 1) despite lack of procedure-specific evidence

·         Paracetamol should be administered at the appropriate time (pre- or intraoperatively) to provide sufficient analgesia in the early recovery period (GoR D)

Alternative analgesics

·         Muscarinic receptor antagonists (oxybutynin, tolterodine) are recommended (GoR B) to prevent bladder discomfort based on procedure-specific (LoE 1) and transferable evidence from various procedures (LoE 2)

Wound infiltration or infusion

·         For open prostatectomy local anaesthetic wound infiltration administered at the end of surgery is recommended (GoR B) because transferable evidence from hernia repair shows analgesic efficacy (LoE1) and because it is a convenient technique with a favourable safety profile, despite limited procedure-specific evidence

·         For video-assisted prostatectomy local anaesthetic port-site infiltration administered at the end of surgery is recommended (GoR B) because transferable evidence from laparoscopic cholecystectomy shows analgesic efficacy (LoE 1) despite lack of procedure-specific evidence

·         Long-acting local anaesthetics are recommended in preference to short-acting local anaesthetics (GoR D)

 

Interventions that are NOT recommended for radical prostatectomy

Alternative analgesics: Pre-operative belladonna and opium suppository, melatonin, amantadine, or clonidine

Not recommended (GoR D) due to limited procedure-specific evidence

Intra- and postoperative conventional NSAIDs

Not recommended (GoR B) based on limited procedure-specific (LoE 2) and strong transferable evidence from multiple procedures concerning an increased risk of bleeding (LoE 1)

Intra- or postoperative ketamine

Not recommended for routine use (GoR D) because of conflicting procedure-specific evidence (LoE 4), despite favourable transferable evidence from more painful surgical procedures (LoE 1)

Lidocaine patch

Not recommended (GoR B) based on limited procedure-specific evidence

IM strong opioids

Not recommended because of the pain associated with these injections (GoR D)

Transdermal nicotine and intravenous magnesium

Not recommended (GoR D) due to limited procedure-specific and transferable evidence

Epidural analgesia

Not recommended for prostatectomy (GoR D) despite some procedure-specific evidence (LoE 1) of analgesic benefit, due to adverse risk:benefit profile

Paravertebral analgesia

Not recommended (GoR D) due to limited procedure-specific evidence

TAP-blocks

Not recommended (GoR D) due to lack of procedure-specific and limited transferable evidence

Intrathecal opioid anaesthesia and analgesia

Not recommended (GoR B) despite procedure-specific evidence (LoE 1) of analgesic benefit, due to adverse risk:benefit profile (intrathecal anaesthesia is also not recommended). This statement is supported by transferable evidence (LoE 1) from patients undergoing major surgery

Continuous local anaesthetic wound infusion

Not recommended (GoR B) based on procedure-specific evidence (LoE 2) showing lack of analgesic efficacy

Magnesium sulfate wound infiltration

Not recommended (GoR D) due to limited procedure-specific evidence


PROSPECT Radical Prostatectomy Subgroup and Working Group process

For each review, a Subgroup of the PROSPECT Working Group performs an initial evaluation of the evidence and also drafts clinical practice statements and recommendations, which are then discussed by the whole Working Group before a final consensus is reached.

For the Radical Prostatectomy review, the Subgroup members were:
  • Professor Girish Joshi (PROSPECT Working Group member)
  • Professor Francis Bonnet (PROSPECT Working Group member)
Dr Thomas Jaschinski (IFOM - Institut für Forschung in der Operativen Medizin, Universität Witten/Herdecke, Köln, Germany) provided support in conducting the literature search, preparing the evidence summary and coordinating the Subgroup and Working Group reviews of the evidence to prepare the final recommendations.

The recommendations for postoperative pain management in Radical Prostatectomy were voted on by eight Working Group members to show the strength of consensus. The results of each vote are indicated within the PROSPECT recommendations sub-folders.

Literature search


Radical Prostatectomy: Sources and levels of evidence (LoE) determine the grades of recommendation (GoR)

Sources of evidence in PROSPECT

The evidence for prospect is derived from three separate sources, and this evidence is taken into consideration by the prospect Working Group to determine the prospect recommendations:
  • Procedure-specific evidence derived from the systematic reviews of the literature
  • Transferable evidence from comparable procedures, or from other relevant sources, identified by the members of the prospect Working Group
  • Current practice – A commentary on the interventions from the members of the prospect Working Group
  • Practical prospect recommendations are based on all the information

Study quality assessment

For the Radical Prostatectomy review, the quality of procedure-specific evidence has been assessed according to NICE methodology, to determine the possibility of selection bias, performance bias, attrition bias and detection bias (www.nice.org.uk/media/615/64/The_guidelines_manual_2009.pdf).

Any limitations in the reporting of cited procedure-specific studies are described in the evidence tables within each Procedure-Specific Evidence folder.

GoR are assigned according to the overall LoE, which is determined by the quality of studies cited, the consistency of evidence and the source of evidence (as indicated in the Table below).

Quality indicators used to determine the LoE of individual studies:
  • Allocation concealment: indicates whether there was adequate prevention of foreknowledge of treatment assignment by those involved in recruitment (in the table below, A=adequate, B=unclear, C=inadequate, D=not used). Empirical research has shown that trials with inadequate or unclear allocation concealment report significantly greater estimates of treatment effect than those trials in which concealment was adequate (Chalmers 1983, Schulz 1995, Moher 1998). Allocation concealment was found to be more important for preventing bias than other aspects of study quality, such as generation of the allocation sequence and double-blinding (Chalmers 1983, Schulz 1995, Moher 1998, HigginsandGreen 2005: Section 6.3. http://www.cochrane.org/resources/handbook/hbook.htm)
  • Statistical analyses and patient follow-up: indicates whether statistical analyses were reported, and whether patient follow-up was greater or less than 80%.
  • Numerical scores (total 1–5) for study quality: assigned using the method proposed by Jadad 1996, to indicate whether a study reports appropriate randomisation, double-blinding and statements of possible withdrawals. Empirical research found that low-quality trials were associated with an increased estimate of treatment benefit than high-quality trials (Moher 1998)

Table: Relationship between quality and source of evidence, levels of evidence and grades of recommendation in PROSPECT

 

 

Study quality assessments

Level of Evidence (LoE)

Grade of recommendation
(based on overall LoE, considering balance of clinical practice information and evidence)
Study type

Statistical analyses and patient follow-up assessment

 

Allocation concealment

Jadad scores

Additional assessment of overall study quality required to judge LoE

 

Procedure-specific

Transferable

Systematic review with homogeneous results

N/A

 

N/A

N/A

N/A

1

A

B

Randomised controlled trial (RCT)

Statistics reported
and >80%
follow-up

AND

A

(1-5)

N/A

1

A

(based on two or more studies or a single large, well-designed study)

B

OR

B

(3-5)

N/A

OR

B

(1-2)

Yes

RCT

Statistics not reported or questionable or <80% follow-up

AND/OR

B

(1-2)

Yes

2

B

(or extrapolation from one procedure-specific
LoE 1 study)

C

OR

C

(1-5)

N/A

OR

D

(1-5)

N/A

Non-systematic review, cohort study,
case study;

 (e.g. some adverse effects evidence)

N/A

 

N/A

3

C

Clinical practice information (expert opinion); inconsistent evidence

N/A

 

N/A

4

D

 



Quantitative analyses

No meta-analyses were performed due to a limited number of studies of homogeneous design that reported similar outcome measures. Therefore, the procedure-specific evidence was only assessed qualitatively.

Transferable evidence

Transferable evidence has been included to support the procedure-specific evidence where this is insufficient to formulate the recommendations.

Transferable evidence includes evidence of analgesic efficacy from a variety of procedures that have some similarity to radical prostatectomy in terms of pain pathology, including abdominal surgery, laparoscopic colonic resection, laparoscopic cholecystectomy, open or laparoscopic hysterectomy, herniorraphy, percutaneous nephrolithotomy surgery and urologic surgery. Systematic reviews of pain management for multiple surgical procedures are also cited.

Transferable evidence of other outcomes, such as adverse effects, is included from a variety of surgical procedures.

Topics for future research

Many of the studies included in this systematic review of postoperative pain management in radical prostatectomy have methodological shortcomings. Therefore, further high-quality randomised clinical trials are required.

List of abbreviations

 

BMI

body mass index

CCT

clinical controlled trial

CG

control group

E-LRPE

extraperitoneal laparoscopic radical prostatectomy

GA

general anesthesia

IG

intervention group

ITT

intention to treat (statistical method for analysis)

i.t.

intrathecal

i.m. or IM

intramuscular

i.v. or IV

intravenous

IQR

interquartile range

LRP

laparoscopic radical prostatectomy

LOS

length of stay

LN-SV-TPP

laparoscopic pelvic lymph node dissection (PLND), laparoscopically assisted seminal vesicle mobilization, and total perineal prostatectomy

n

absolute value

NPS

numeric pain score

O-RPE

open extraperitoneal radical prostatectomy

PACU

post-anesthesia care unit

PCA

patient controlled analgesia

PCEA

patient-controlled epidural analgesia

POD

postoperative day

PONV

postoperative nausea and vomiting

POSAS

patient and observer scar assessment scale

p.o.

per os

PRN

pro re nata (as needed)

QoL

quality of life

RALRP

robot-assisted laparoscopic radical prostatectomy

RCT

randomised controlled trial

rg

range

RRP

radical retropubic prostatectomy

SD

standard deviation

SEM

standard error of mean

SpA

spinal anesthesia

TAP block

transversus abdominis plane block

TEA

thoracic epidural analgesia

TRUS

transrectal prostatic ultrasound

T-LRPE

transperitoneal laparoscopic radical prostatectomy

VAS

visual analogue scale

VIP

Vattikuti Institute prostatectomy

VNS

verbal numeric scale

VRS

verbal rating scale

yr.

years

PROSPECT Recommendations

  • As with all analgesics, COX-2-selective inhibitors should be administered at the appropriate time (pre- or intra-operatively) to provide sufficient analgesia in the early recovery period (GoR B), based on transferable evidence from diverse procedures showing analgesic efficacy (LoE 1)
  • Voting for: 8; voting against: 0; abstentions: 0

Clinical Practice

  • Rofecoxib and valdecoxib have been withdrawn from the market
  • The use of COX-2-selective inhibitors should depend upon assessment of individual patient risks, cardiovascular morbidity, actual or recent gastroduodenal ulcer history, renal function and hepatic function

Transferable Evidence

  • Intravenous parecoxib (40 mg bid for 3 days) followed by oral celecoxib (0.2 g bid for 4 days) was as effective as intravenous tramadol (0.1 g tid for 3 days) with continued oral tramadol (0.1 g tid for 4 days) for reducing pain intensity during leg raising from the fourth day after major abdominal surgery in a randomised study (n=112) Xu et al 2013 Click here for more information
  • A retrospective cohort study showed that the COX-2-selective inhibitors rofecoxib and celecoxib were associated with a lower risk of acute kidney infection than less-selective NSAIDs Lafrance and Miller 2009
  • A meta-analysis that included data from 17 parecoxib and 15 valdecoxib placebo-controlled trials in non-cardiac surgery showed that there was no significant association between short-term treatment with parecoxib and/or valdecoxib and an increase in cardiovascular thromboembolic adverse events, compared with placebo (n=8511 overall) Schug et al 2009
  • A review concluded that COX-2-selective inhibitors were as effective as conventional NSAIDs for treatment of postoperative pain in various surgical models, and offer a number of other advantages including: reduced incidence of gastrointestinal ulceration, no inhibitory effect on platelet function (and thereby a reduced risk of blood loss) and no induction of bronchospasm in patients with aspirin-sensitive asthma Schug 2006
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) Nussmeier et al 2006
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A randomised clinical trial showed that the COX-2-selective inhibitor rofecoxib was associated with significantly less intra-operative blood loss than the conventional NSAID diclofenac in patients undergoing abdominal or vaginal hysterectomy or breast surgery Hegi et al 2004
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation compared with placebo Noveck et al 2001
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • A systematic review including sixty studies of major surgery concluded that compared with placebo, COX-2-selective inhibitors provide similar reduction in 24-hour PCA morphine consumption to conventional NSAIDs and paracetamol Maund et al 2011
  • COX-2-selective inhibitors provide similar postoperative analgesia to conventional NSAIDs Rømsing et al 2004
  • In a randomized, double-blind study in ambulatory surgery, ibuprofen (1200 mg/day) and celecoxib (400 mg/day) significantly decreased the need for rescue analgesic medication after discharge, improved the quality of recovery scores and patient satisfaction with postoperative pain management, and decreased the incidence of postoperative constipation vs placebo (p<0.05 for all comparisons) White et al 2011
  • A systematic review including eight randomised studies concluded that single-dose oral celecoxib is an effective analgesic for postoperative pain relief Derry and Moore 2012
  • Two meta-analyses comparing pre-incisional and post-incisional NSAIDs/COX-2-selective inhibitors have found no significant benefit of pre-incisional administration for reducing pain scores Møiniche et al 2002
  • Two clinical trials showed that in patients who had undergone coronary artery bypass graft surgery, COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Harris 2002
  • Although there is some concern COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003

Radical Prostatectomy-Specific Evidence

PROSPECT Recommendations

  • Pre-operative dexamethasone is recommended both for its analgesic and anti-emetic effects (GoR B), based on transferable evidence from multiple procedures (LoE 1), despite lack of procedure-specific evidence
  • Voting for: 8; voting against: 0; abstentions: 0

Clinical Practice

  • None cited

Transferable Evidence

  • A systematic review including forty-five studies (n= 5796) concluded that a single IV perioperative dose of dexamethasone had small but statistically significant analgesic benefits vs placebo or anti-emetic (reduced pain scores at 2 and 24 hours, reduced opioid use, increased time to first analgesic, and reduced duration of PACU stay) Waldron et al 2013
  • A meta-analysis of twenty-four studies including 2751 subjects concluded that dexamethasone at doses >0.1 mg/kg is effective as a part of multimodal pain management for reduction of postoperative pain at rest and movement and reduction of opioid consumption after surgery. Pre-operative administration of dexamethasone appeared to produce a more consistent analgesic effect vs intraoperative administration Waldron et al 2013
  • A single prophylactic dose of corticosteroid is effective for preventing PONV in surgery associated with high emetic effects Henzi et al 2000
  • A review of major abdominal surgery, a randomised study of patients at high-risk of nausea and vomiting undergoing surgery, and a systematic review of drugs that prevent PONV, all showed that corticosteroids decrease PONV Apfel et al 2004

Radical Prostatectomy-Specific Evidence

  • None cited

PROSPECT Recommendations

  • Pre-operative gabapentinoids are recommended (GoR B) based on transferable evidence from multiple procedures showing analgesic efficacy (LoE 1), despite lack of procedure-specific evidence
  • Voting for: 8; voting against: 0; abstentions: 0

Clinical Practice

  • None cited

Transferable Evidence

  • Four systematic reviews and three meta-analyses evaluated the use of gabapentinoids for postoperative analgesia and demonstrated significant reductions in postoperative pain and/or supplementary analgesic requirements compared with inactive controls Ho et al 2006
  • Two systematic reviews and two meta-analyses showed a significant reduction in the incidence of nausea and/or vomiting with gabapentin compared with inactive controls, although a meta-analysis and a systematic review of studies of pre-operative gabapentin, showed no significant difference in the incidence of side-effects Ho et al 2006
  • Two systematic reviews showed a significant increase in the incidence of sedation with gabapentin compared with inactive controls, and one meta-analysis found a non-significant increase in risk of sedation with gabapentin, although found no significant difference between pregabalin and placebo/control Peng et al 2007
  • One systematic review found a significant increase in the risk of visual disturbance with pregabalin and one meta-analysis found a significant increase in dizziness with gabapentin compared with placebo/control Peng et al 2007

Radical Prostatectomy-Specific Evidence

  • None cited

PROSPECT Recommendations

  • Belladonna and opium suppository (and melatonin, amantadine and clonidine) are not recommended (GoR D) due to limited procedure-specific evidence
  • Voting for: 8; voting against: 0; abstentions: 0

Clinical Practice

  • None cited

Transferable Evidence

  • None cited

Radical Prostatectomy-Specific Evidence

PROSPECT Recommendations

  • No recommendation can be made at the present time regarding particular surgical techniques, due to limited procedure-specific evidence
  • It is recommended that surgical requirement rather than pain management should be the main consideration in choosing the surgical procedure (GoR D)
  • Voting for: 8; voting against: 0; abstentions: 0

Clinical Practice

  • None cited

Transferable Evidence

  • None cited

Radical Prostatectomy-Specific Evidence

PROSPECT Recommendations

  • COX-2-selective inhibitors are recommended (GoR B) based on transferable evidence from multiple procedures showing analgesic efficacy (LoE 1), despite a lack of procedure-specific evidence
  • Voting for: 8; voting against: 0; abstentions: 0

Clinical Practice

  • Rofecoxib and valdecoxib have been withdrawn from the market
  • The use of COX-2-selective inhibitors should depend upon assessment of individual patient risks, cardiovascular morbidity, actual or recent gastroduodenal ulcer history, renal function and hepatic function

Transferable Evidence

  • Intravenous parecoxib (40 mg bid for 3 days) followed by oral celecoxib (0.2 g bid for 4 days) was as effective as intravenous tramadol (0.1 g tid for 3 days) with continued oral tramadol (0.1 g tid for 4 days) for reducing pain intensity during leg raising from the fourth day after major abdominal surgery in a randomised study (n=112) Xu et al 2013 Click here for more information
  • A retrospective cohort study showed that the COX-2-selective inhibitors rofecoxib and celecoxib were associated with a lower risk of acute kidney infection than less-selective NSAIDs Lafrance and Miller 2009
  • A meta-analysis that included data from 17 parecoxib and 15 valdecoxib placebo-controlled trials in non-cardiac surgery showed that there was no significant association between short-term treatment with parecoxib and/or valdecoxib and an increase in cardiovascular thromboembolic adverse events, compared with placebo (n=8511 overall) Schug et al 2009
  • A review concluded that COX-2-selective inhibitors were as effective as conventional NSAIDs for treatment of postoperative pain in various surgical models, and offer a number of other advantages including: reduced incidence of gastrointestinal ulceration, no inhibitory effect on platelet function (and thereby a reduced risk of blood loss) and no induction of bronchospasm in patients with aspirin-sensitive asthma Schug 2006
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) Nussmeier et al 2006
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation Greenberg et al 2000
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • A systematic review including sixty studies of major surgery concluded that compared with placebo, COX-2-selective inhibitors provide similar reduction in 24-hour PCA morphine consumption to conventional NSAIDs and paracetamol Maund et al 2011
  • COX-2-selective inhibitors provide similar postoperative analgesia to conventional NSAIDs Rømsing et al 2004
  • In a randomized, double-blind study in ambulatory surgery, ibuprofen (1200 mg/day) and celecoxib (400 mg/day) significantly decreased the need for rescue analgesic medication after discharge, improved the quality of recovery scores and patient satisfaction with postoperative pain management, and decreased the incidence of postoperative constipation vs placebo (p<0.05 for all comparisons) White et al 2011
  • A systematic review including eight randomised studies concluded that single-dose oral celecoxib is an effective analgesic for postoperative pain relief Derry and Moore 2012
  • Two clinical trials showed that in patients who had undergone coronary artery bypass graft surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Although there is some concern COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003

Radical Prostatectomy-Specific Evidence

  • None cited

PROSPECT Recommendations

  • Intra- and postoperative conventional NSAIDs are not recommended (GoR B) based on limited procedure-specific (LoE 2) and strong transferable evidence from multiple procedures concerning an increased risk of bleeding (LoE 1)
  • Voting for: 8; voting against: 0; abstentions: 0

Clinical Practice

  • The use of conventional NSAIDs should depend upon assessment of individual patient risks, including bleeding complications, actual or recent gastroduodenal ulcer history, cardiovascular morbidity, aspirin-sensitive asthma, renal function and hepatic function

Transferable Evidence

  • A systematic review including sixty studies of major surgery concluded that compared with placebo, conventional NSAIDs provide similar reduction in 24-hour PCA morphine consumption to COX-2-selective inhibitors and paracetamol Maund et al 2011
  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression Marret et al 2005
  • In laparoscopic colonic resection, postoperative IV ketorolac was superior to placebo for reduction of: VAS pain scores during walking on Days 1 (p<0.001), 2 (p<0.05) and 3 (p<0.001), but not on Day 4; postoperative PCA morphine requirement (p=0.011); time to first flatus (p=0.005); and time to return to full diet (p=0.033) (n=44) Schlachta et al 2007 Click here for more information
  • Conventional NSAIDs were superior to placebo for reducing morphine consumption in abdominal hysterectomy but did not consistently reduce pain scores in two studies (PROSPECT systematic review) Ng et al 2002a Click here for more information
  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987
  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures Barden et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls Marret et al 2003
  • Conventional NSAIDs were associated with a significant increase in the risk of surgical bleeding and severe surgical bleeding compared with placebo in a meta-analysis of randomised trials in a variety of surgical procedures (nine trials reporting on surgical bleeding complications) Elia et al 2005
  • A systematic review identified six studies comparing conventional NSAIDs with placebo in major surgery that reported on surgical bleeding, and found that overall 2.4% of patients receiving conventional NSAIDs experienced surgical-related bleeding compared with 0.4% receiving placebo Maund et al 2011
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Conventional NSAIDs and placebo were not significantly different for the incidence of PONV (all groups received background strong opioid) in patients undergoing abdominal surgery Blackburn et al 1995 Click here for more information

Radical Prostatectomy-Specific Evidence

PROSPECT Recommendations

  • Intra- or postoperative ketamine is not recommended for routine use (GoR D) because of conflicting procedure-specific evidence (LoE 4), despite favourable transferable evidence from more painful surgical procedures (LoE 1)
  • Voting for: 8; voting against: 0; abstentions: 0

Clinical Practice

  • None cited

Transferable Evidence

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine Laskowski et al 2011
  • A systematic review found that intravenous ketamine was associated with analgesic benefit particularly in painful procedures, including upper abdominal, thoracic, and major orthopedic surgeries Laskowski et al 2011
  • Low-dose ketamine was associated with few and mild adverse effects, especially when administered in conjunction with general anaesthesia Bell et al 2006

Radical Prostatectomy-Specific Evidence

PROSPECT Recommendations

  • Lidocaine patch is not recommended (GoR B) based on limited procedure-specific evidence
  • Lidocaine infusion is recommended for radical prostatectomy (GoR B), due to transferable evidence from multiple procedures showing analgesic efficacy (LoE 1) despite limited procedure-specific evidence
  • Voting for: 7; voting against: 1; abstentions: 0

Clinical Practice

  • None cited

Transferable Evidence

  • A meta-analysis of randomised clinical trials performed to evaluate the effect of continuous IV lidocaine infusion during and after abdominal surgery, reported that lidocaine significantly reduced postoperative VAS pain scores, duration of postoperative ileus, incidence of PONV and length of hospital stay, compared with the controls Marret et al 2008
  • In laparoscopic colonic resection, continuous intra-/postoperative IV lidocaine was superior to placebo for reducing: postoperative pain scores; opioid consumption; time to first flatus and first bowel movement; and length of hospital stay (n=40) Kaba et al 2007 Click here for more information
  • A meta-analysis concluded that systemic lidocaine may be a useful adjunct for postoperative analgesia after abdominal surgery, associated with decreased postoperative pain intensity and opioid consumption, improved GI function, and shortened hospital stay compared with controls Sun et al 2012

Radical Prostatectomy-Specific Evidence

PROSPECT Recommendations

  • Systemic strong opioids are recommended following prostatectomy (GoR B), based on transferable evidence from multiple procedures, for their efficacy in reducing high-intensity postoperative pain (VAS >/=50 mm) (LoE 1), with the following considerations:
  • Systemic strong opioids should be used in combination with COX-2-selective inhibitors and paracetamol to reduce opioid use and its associated side-effects (GoR D)
  • IV PCA strong opioids are recommended (GoR B) based on greater patient satisfaction compared with regular (fixed-interval) or PRN dosing (transferable evidence, LoE 1); however, fixed-interval IV administration titrated to pain intensity is also recognised as an effective mode of administration (LoE 4)
  • IM strong opioids are not recommended because of the pain associated with these injections (GoR D)
  • Voting for: 8; voting against: 0; abstentions: 0

Clinical Practice

  • None cited

Transferable Evidence

  • Strong opioids are effective for reducing high- and moderate-intensity postoperative pain McQuay et al 1999
  • Opioids administered by PCA improved analgesia, decreased the risk of pulmonary complications and patients preferred them compared with regular IM, IV or SC opioid treatment, as determined in a quantitative systematic review of randomised trials in various surgical procedures Walder et al 2001
  • Strong opioids are associated with adverse effects, including nausea, vomiting, sedation, confusion, paralytic ileus and urinary retention Wheeler M et all 2002

Radical Prostatectomy-Specific Evidence

PROSPECT Recommendations

  • Weak opioids are recommended to be used for moderate- or low-intensity pain if non-opioid analgesia is insufficient or is contra-indicated (GoR B), based on transferable evidence (LoE 1) showing analgesic efficacy in multiple surgical procedures
  • Weak opioids are recommended to be used in combination with non-opioid analgesics (GoR B), based on transferable evidence (LoE 1) showing analgesic efficacy in combination regimens

Clinical Practice

  • Dextropropoxyphene has been withdrawn from several markets due to concern regarding its adverse events profile

Transferable Evidence

  • Tramadol was more effective than placebo for pain relief in a meta-analysis of post-surgical patients Moore et al 1997
  • The combination of tramadol and paracetamol enhances analgesic efficacy compared with either agent alone McQuay H et al 2003
  • A systematic review found that the combination of dextropropoxyphene 65 mg with paracetamol 650 mg showed similar efficacy to tramadol 100 mg but with a lower incidence of adverse effects Collins et al 2000
  • A systematic review found that the combination of codeine with paracetamol provided additional pain relief compared with paracetamol alone Moore et al 2000
  • Adverse effects associated with tramadol include headache, nausea, vomiting, dizziness, somnolence. A meta-analysis of individual patient data from randomised controlled trials found a dose-response of adverse effects with tramadol; postsurgical patients had fewer side-effects than dental patients Moore et al 1997
  • A systematic review found that the combination of codeine with paracetamol was associated with an increase in drowsiness and dizziness compared with paracetamol alone Moore et al 2000
  • A systematic review found an increased incidence of central nervous system adverse effects with paracetamol plus dextropropoxyphene compared with placebo Collins et al 2000

Radical Prostatectomy-Specific Evidence

  • None cited

PROSPECT Recommendations

  • Paracetamol is recommended (GoR B) due to strong transferable evidence from multiple procedures showing analgesic efficacy (LoE 1) despite lack of procedure-specific evidence
  • Paracetamol should be administered at the appropriate time (pre- or intraoperatively) to provide sufficient analgesia in the early recovery period (GoR D)
  • Voting for: 8; voting against: 0; abstentions: 0

Clinical Practice

  • None cited

Transferable Evidence

  • Paracetamol is an effective analgesic for the treatment of postoperative pain of moderate intensity Rømsing et al 2002
  • A systematic review including sixty studies of major surgery concluded that compared with placebo, paracetamol provides similar reduction in 24-hour PCA morphine consumption to COX-2-selective inhibitors and conventional NSAIDs Maund et al 2011
  • Paracetamol combined with weak opioids (codeine, tramadol) is superior to weak opioids alone in a review of dental, gynaecological and orthopaedic surgery McQuay H et al 2003
  • A meta-analysis of randomised controlled trials showed that paracetamol combined with PCA morphine induced a significant morphine-sparing effect but did not change the incidence of morphine-related adverse effects in the postoperative period Remy 2005
  • There is evidence that concurrent use of paracetamol and conventional NSAIDs improves pain relief compared with paracetamol alone, but there is no evidence for a superior analgesic effect of the combination compared with conventional NSAIDs alone Altman 2004
  • In a systematic review, paracetamol plus NSAID conferred no significant benefit over NSAID alone for reducing pain scores in orthopaedic and gynaecological operations. However, a significant benefit was seen in the lower-intensity pain associated with dental operations Rømsing et al 2002

Radical Prostatectomy-Specific Evidence

PROSPECT Recommendations

  • Transdermal nicotine and intravenous magnesium are not recommended (GoR D) due to limited procedure-specific and transferable evidence
  • Muscarinic receptor antagonists (oxybutynin, tolterodine) are recommended (GoR B) to prevent bladder discomfort based on procedure-specific (LoE 1) and transferable evidence from various procedures (LoE 2)
  • Voting for: 8; voting against: 0; abstentions: 0

Clinical Practice

  • None cited

Transferable Evidence

  • Pre-treatment with either 5 mg oxybutynin or 2 mg tolterodine compared with placebo in patients undergoing percutaneous nephrolithotomy surgery reduced the incidence and severity of catheter-related bladder discomfort (p<0.05) (N=234; Agarwal 2006) Agarwal et al 2006
  • The administration of 2 mg tolterodine compared with placebo in patients undergoing urologic surgery was superior in reducing the incidence and severity of catheter-related bladder discomfort (p<0.05) (N=215; Agarwal 2005) Agarwal et al 2005
  • The administration of 10 mg oxybutynin or 200 mg phenazopyridine compared with placebo in patients who received a unilateral stent after ureteroscopy showed no significant difference in bothersome score among the groups for flank pain, suprapubic pain, urinary frequency, urgency, and dysuria (N=52; Norris 2008) Norris et al 2008
  • Two systematic reviews of randomised controlled trials comparing magnesium with placebo demonstrated inconclusive results overall with regards to pain scores and supplemental analgesic use Lysakowski 2007

Radical Prostatectomy-Specific Evidence

PROSPECT Recommendations

  • Epidural analgesia is not recommended for prostatectomy (GoR D) despite some procedure-specific evidence (LoE 1) of analgesic benefit, due to adverse risk:benefit profile
  • Voting for: 8; voting against: 0; abstentions: 0

Clinical Practice

  • Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications

Transferable Evidence

  • In a quantitative meta-analysis of studies in abdominal hysterectomy, epidural analgesia had a statistically significant, and marginally clinically significant, benefit over systemic analgesia for reducing postoperative pain scores at 4 h (PROSPECT systematic review) Hindsholm et al 1993 Click here for more information
  • In abdominal hysterectomy, epidural analgesia provided a significant benefit over IV administration for reducing analgesic consumption over 24 h (PROSPECT systematic review) Eriksson-Mjoberg et al 1997b Click here for more information
  • In abdominal hysterectomy, epidural analgesia was associated with a significantly lower incidence of PONV compared with systemic analgesia(PROSPECT systematic review) Camu et al 1991 Click here for more information
  • In laparoscopic cholecystectomy, epidural LA + strong opioid significantly reduced VAS pain scores at 24 h compared with placebo (p<0.05), but there were no differences between groups at 48 h; epidural LA + strong opioid significantly reduced analgesic use compared with placebo (50 mg indomethacin was given rectally, on request) at 0–24 h (p<0.05), but not at 24–48 h Fujii et al 1998
  • A study in laparoscopic cholecystectomy that compared postoperative epidural LA + strong opioid with placebo showed that the incidence of nausea and vomiting was similar in both groups Fujii et al 1998
  • A meta-analysis of randomised controlled trials found that both continuous epidural infusion and PCEA analgesia provided superior postoperative analgesia compared with intravenous PCA analgesia Wu et al 2005
  • Epidural analgesia using local anaesthetic was superior to systemic strong opioid for reducing postoperative pain scores in six studies identified in a systematic review of abdominal surgery Jorgensen et al 2000b
  • Epidural analgesia using a combination of local anaesthetic and strong opioid was superior to local anaesthetic alone for reducing postoperative pain – 15 mm reduction in VAS score on a 100-mm scale – in a meta-analysis of five studies in abdominal surgery Jorgensen et al 2000b
  • Epidural analgesia using local anaesthetics was superior to epidural opioids or systemic opioids for reducing the incidence of postoperative gastrointestinal paralysis, in a systematic review in abdominal surgery Jorgensen et al 2000b
  • Epidural administration of strong opioids is associated with side-effects including pruritis, PONV, urinary retention, and respiratory depression Chaney 1995

Radical Prostatectomy-Specific Evidence

  • The epidural administration of 1 mg/ml ropivacaine, 2 µg/ml fentanyl and 2 µg/ml adrenaline at 10 ml/h for 48 hours compared with placebo was superior in pain reduction for the first 24 postoperative hours but patients in the intervention group more frequently required antiemetics (p<0.05), in RRP Gupta et al 2006 Click here for more information
  • The epidural administration of ropivacaine and fentanyl (5 ml bolus consisting of 0.2% ropivacaine and 1 µg/kg fentanyl; continuous infusion of same solution) was superior to morphine i.v. (initial bolus of 3-5 mg; intravenous continuous infusion, max 40 mg/day) in reducing pain on movement for the first 72 postoperative hours and for pain at rest for the first 6 postoperative hours in RRP Maestroni et al 2007 Click here for more information
  • Epidural PCA (0.15% ropivacaine and 10 µg/ml fentanyl) significantly reduced dynamic pain but not pain at rest compared with intravenous PCA (10 µg/ml fentanyl), in RALRP Hong et al 2009 Click here for more information
  • Patients who received epidural fentanyl or bupivacaine prior to surgical incision (preemptive analgesia) experienced 33% less pain when compared with patients in the control group (postoperative epidural analgesia only) for POD 1 to POD 4 (p=0.007) in RRP Gottschalk et al 1998 Click here for more information
  • Peri-operative epidural analgesia reduced pain scores, analgesic requirements, and blood loss compared with postoperative epidural analgesia. However, epidural administration of 1 µg/ml sufentanil (in addition to 0.3% ropivacaine) during surgery was not superior to administration of 0.3% ropivacaine alone for pain reduction in RRP Hong et al 2011 Click here for more information
  • Epidural administration of 1 mg/ml ropivacaine, 2 µg/ml fentanyl and 2 µg/ml epinephrine at a constant rate of 10 ml/h for 48 hours was superior to 10 ml of ropivacaine 2 mg/ml via intra-abdominal catheter for 48 hours in reducing pain at the incision site at 4-24 hours and in deep pain and pain on coughing at 4-48 hours, in RRP Fant et al 2011 Click here for more information
  • Epidural administration of 20 ml bupivacaine 0.125% and continuous infusion of 8 ml/h (option 1) or 20 mg tramadol with 20 ml bupivacaine 0.125% and infusion of 1 mg/ml tramadol in 20 ml bupivacaine 0.125% combination with a rate of 8 ml/h (option 2) compared with 20 mg tramadol with a continuous infusion of 1 mg/ml tramadol at a rate of 8 ml/h (option 3) showed significantly better results in reducing pain at 12 and 24 hours Aribogan et al 2003 Click here for more information
  • The comparison of epidural with intravenous PCA hydromorphone showed no significant differences in pain at rest and after coughing or in PONV, in RRP Liu et al 1995 Click here for more information
  • The comparison between epidural anaesthesia with ropivacaine, paracetamol, injected morphine or oral dextropropoxyphene on demand (group EDA); and infiltration of bupivacaine into the wound, oral oxycodone hydrochloride, paracetamol, and oral morphine on demand (group OXY) showed no significant difference in postoperative pain or vomiting, in RRP Hohwu et al 2006 Click here for more information
  • The comparison of epidural anaesthesia, combined epidural and general anaesthesia, and general anaesthesia showed no significant difference in mean pain scores in the first 5 POD in RRP Shir et al 1994 Click here for more information
  • The comparison between epidural administration of 15 ml 0.25% bupivacaine and 15 ml 0.5% ropivacaine showed no significant differences in pain scores in RRP Heid et al 2007 Click here for more information
  • Epidural analgesia versus systemic analgesia: Study details
    Click here for more information
  • Peri-operative epidural analgesia versus postoperative epidural analgesia: Study details Click here for more information
  • Epidural analgesia versus local infiltration analgesia: Study details Click here for more information
  • Components of epidural anaesthesia and analgesia: Study details Click here for more information

PROSPECT Recommendations

  • Paravertebral analgesia is not recommended (GoR D) due to limited procedure-specific evidence
  • TAP-blocks are not recommended (GoR D) due to lack of procedure-specific and limited transferable evidence
  • Voting for: 8; voting against: 0; abstentions: 0

Clinical Practice

  • None cited

Transferable Evidence

  • A systematic review including eighteen randomised trials of TAP block in various surgical procedures found analgesic benefit was reported in patients undergoing laparotomy for colorectal surgery, laparoscopic cholecystectomy, and open and laparoscopic appendectomy. However, the authors were unable to definitively identify the surgical procedures, dosing, techniques, and timing that provide optimal analgesia following TAP block Abdallah et al 2012
  • A systematic review of TAP block vs placebo in abdominal surgery included nine studies (n=413) and found a reduction in cumulative morphine use at 24 hours (p<0.0001), a reduction in the incidence of PONV (p=0.003) and a non-significant reduction in VAS pain scores Johns et al 2012
  • In laparoscopic hysterectomy, a 3-arm study compared preoperative ultrasound-guided TAP block plus wound infiltration using two concentrations of ropivacaine (5.0 mg/ml, n=22 and 2.5 mg/ml, n=21) or saline (n=23). NRS pain scores in the PACU were lower for ropivacaine versus saline (p<0.001). 24-hour cumulative opioid consumption was lower with 5.0mg/ml ropivacaine group versus saline (p=0.003) De Oliveira, Milad et al 2011
  • In laparoscopic hysterectomy, a study compared TAP block with 20 ml of 5.0mg/ml ropivacaine (n= 28) performed at the end of the surgical procedure with no block (n=29). NRS pain scores and opioid requirements were similar between groups Kane et al 2012

Radical Prostatectomy-Specific Evidence

PROSPECT Recommendations

  • Intrathecal opioid analgesia is not recommended (GoR B) despite procedure-specific evidence (LoE 1) of analgesic benefit, due to adverse risk:benefit profile (intrathecal anaesthesia is also not recommended). This statement is supported by transferable evidence (LoE 1) from patients undergoing major surgery
  • Voting for: 7; voting against: 1; abstentions: 0

Clinical Practice

  • Spinal analgesia (LA + opioid) has a limited duration of action
  • Spinal morphine may produce some postoperative pain relief but also produces risk of PONV and prolongation of postoperative ileus

Transferable Evidence

  • A meta-analysis of randomized trials included 27 studies comparing intrathecal morphine (dose range 100–4000 µg; without local anaesthetic) with control (placebo/sham injection/no injection) for patients undergoing major surgery with general anaesthesia (n=645). Intrathecal morphine decreased pain scores and opioid requirement up to 24 hours postoperatively Meylan et al 2009
  • A meta-analysis found that intrathecal morphine was associated with increased risk of respiratory depression and pruritis compared with control for patients undergoing major surgery with general anaesthesia (n=645) Meylan et al 2009

Radical Prostatectomy-Specific Evidence

  • Intra-operative intrathecal administration of 4 µg/kg morphine compared with intravenous postoperative morphine by PCA alone (1 mg bolus, 7 min lockout) was superior in reducing pain at 0-18 hours, in RRP. There were no significant differences in PONV Andrieu et al 2009 Click here for more information
  • Patients receiving spinal anaesthesia with sedation had lower pain scores, shorter surgery and less blood loss than patients receiving general anaesthesia Salonia et al 2004 Click here for more information
  • Intra-operative intrathecal administration of bupivacaine (15 mg isobaric, 0.75%), clonidine (75 µg) and morphine (0.2 mg) compared with intravenous bolus of 4 µg/kg fentanyl followed by continuous infusion was superior in significantly reducing pain scores only on the day of surgery, in RRP. Pruritus was significantly greater in the intrathecal group (p<0.001) Brown et al 2004 Click here for more information
  • Study details Click here for more information

PROSPECT Recommendations

  • For open prostatectomy local anaesthetic wound infiltration administered at the end of surgery is recommended (GoR B) because transferable evidence from hernia repair shows analgesic efficacy (LoE1) and because it is a convenient technique with a favourable safety profile, despite limited procedure-specific evidence.
  • For video-assisted prostatectomy local anaesthetic port-site infiltration administered at the end of surgery is recommended (GoR B) because transferable evidence from laparoscopic cholecystectomy shows analgesic efficacy (LoE 1) despite lack of procedure-specific evidence
  • Long-acting local anaesthetics are recommended in preference to short-acting local anaesthetics (GoR D)
  • Continuous local anaesthetic wound infusion is not recommended (GoR B) based on procedure-specific evidence (LoE 2) showing lack of analgesic efficacy
  • Magnesium sulfate wound infiltration is not recommended (GoR D) due to limited procedure-specific evidence
  • Voting for: 8; voting against: 0; abstentions: 0

Clinical Practice

  • Wound infiltration should be used whenever appropriate and possible

Transferable Evidence

  • In herniorraphy, group analysis of all pre-operative local anaesthetic injection techniques (inguinal nerve block/field block/infiltration) showed that they were superior to no treatment or placebo for reducing postoperative pain scores and supplementary analgesic requirements (PROSPECT systematic review) Bugedo et al 1990 Click here for more information
  • In herniorraphy, group analysis of all intra-operative (± pre-operative) local anaesthetic injection techniques (inguinal nerve block/field block/infiltration) showed that they were more effective than placebo for reducing pain scores during the early postoperative period and supplementary analgesic requirements (PROSPECT systematic review) Dierking et al 1994 Click here for more information
  • In herniorraphy, pre-operative local anaesthetic injection was similar to the same regimen given at-closure for pain scores and analgesic use (PROSPECT systematic review) Dierking et al 1992 Click here for more information
  • In laparoscopic cholecystectomy, nine out of 11 studies showed a significant benefit of LA wound infiltration over placebo or no treatment for reducing VAS pain scores (PROSPECT systematic review) Click here for more information
  • A systematic review including 31 studies in laparoscopic cholecystectomy found that local injection of local anaesthetics provided benefits for pain relief but not analgesic consumption for up to 24 h postoperatively. Some studies reported patients with toxic plasma levels of local anaesthetic, without symptoms, and the authors concluded that the dose should be monitored carefully to avoid toxicity (Gupta 2005) Gupta A.
  • In abdominal hysterectomy, there is mixed evidence for a benefit of intra-operative wound infiltration for reducing postoperative pain scores, and the benefits are of marginal clinical significance (PROSPECT systematic review) Cobby et al 1997 Click here for more information
  • A qualitative and quantitative systematic review of intraperitoneal, port-site infiltration and mesosalpinx block showed that port-site infiltration did not reduce postoperative pain after laparoscopy, while intraperitoneal infiltration was associated with a statistically significant but clinically questionable effect on postoperative pain, and mesosalpinx local anaesthetic block reduced postoperative pain to some extent after laparoscopy Møiniche et al 2000

Radical Prostatectomy-Specific Evidence

  • Wound infiltration with 20 ml of 0.5% bupivacaine during surgical closure and 3 ml 75 mg diclofenac (i.m.) compared to saline was superior in reducing pain scores (p<0.001) and cumulative PCA tramadol consumption at 24 h (p<0.001), in RRP Bilgin et al 2011 Click here for more information
  • Infiltration of the incision site with 25% magnesium sulfate 80 mg/kg (Group M), or with the same volume of saline (Group P), under remifentanil-based anaesthesia, or with the same volume of saline under desflurane based anaesthesia (Group D) resulted in significantly higher pain scores in Group P than in Group M for 24 h and Group D for 12 h after surgery, in RALP Lee et al 2011 Click here for more information
  • Co-administration of magnesium sulfate with ropivacaine for postoperative infiltration analgesia produced a significant reduction in tramadol requirements (p<0.001) but showed no significant decrease in pain scores (p=0.40) compared with magnesium sulfate IV 30 min after induction of anaesthesia followed by postoperative infiltration with ropivacaine, in RRP Tauzin-Fin et al 2009 Click here for more information
  • The administration of either 0.5% bupivacaine or normal saline into the wound at a rate of 2 ml/h until discharge on postoperative day 3 resulted in no significant differences in pain scores and PONV, in RRP Wu et al 2005 Click here for more information
  • The comparison between epidural anaesthesia with ropivacaine, paracetamol, injected morphine or oral dextropropoxyphene on demand (group EDA); and infiltration of bupivacaine into the wound, oral oxycodone hydrochloride, paracetamol, and oral morphine on demand (group OXY) showed no significant difference in postoperative pain or vomiting, in RRP Hohwu et al 2006 Click here for more information
  • Wound infiltration or infusion vs placebo: Study details Click here for more information
  • Wound infiltration or infusion vs other: Study details Click here for more information
  • Components of wound infiltration or infusion: Study details Click here for more information

Thoracotomy 2004

ASA American Association of Anesthesiologists
ANOVA Analysis of variance
BPI Brief Pain Inventory
CPTP Chronic post-thoracotomy pain
CeT Effect compartment concentration
EA Epidural anaesthesia
FEF Forced expiratory flow
FEFR Forced expiratory flow rate
FEV1 Forced expiratory volume in 1 sec
FVC Forced vital capacity
GoR Grade of recommendation
HR Heart rate
h Hour(s)
IQR Interquartile range
IM Intramuscular
Intraop Intraoperative
IT Intrathecal
ITO Intrathecal opioid
IV Intravenous
iPCA Intravenous patient controlled analgesia
LoE Level of evidence
LA Local anaesthetic
LVRS Lung volume reduction surgery
MAP Mean arterial pressure
MEFR Mid-expiratory flow rate
NSAIDs Non-steroidal anti-inflammatory drugs
NRS Numerical rating scale
PaCO2 Partial pressure of arterial carbon dioxide
PaO2 Partial pressure of arterial oxygen
PSS Patient satisfaction score
PCA Patient-controlled analgesia

DESCRIPTION OF STUDIES
Literature search

  • Systematic review of the literature from 1966–May 2004 using MEDLINE and EmBASE, following the protocol of the Cochrane Collaboration (Thoracotomy search terms)
  • Inclusion of randomised studies in English assessing analgesic interventions in thoracotomy in adults, and reporting pain on a linear analogue scale
  • Identification of 332 studies of peri-operative interventions for postoperative pain following thoracotomy
  • 169 studies included (Thoracotomy included references)
  • 163 studies excluded (Thoracotomy excluded references)
  • The most common reason for exclusion was that the study was not a randomised, comparative clinical trial (60 studies). (Thoracotomy reasons for exclusion)
  • Where procedure-specific evidence regarding a particular intervention was lacking in the systematic review but relevant information was available from more recent studies, the additional information was added with a note that the publication date was after the defined cut-off date for the systematic review

Transferable evidence
This section includes studies and reviews from a variety of surgical procedures to address, where appropriate, information about analgesic efficacy and adverse effects of the available interventions, which are not covered in the systematic review.

Quality of studies
Despite the large number of studies included in the review, the methodological quality of the studies of analgesia for thoracotomy was found to be generally quite poor, and patient numbers were often small.

PROSPECT Recommendations

  • Conventional NSAIDs are not recommended pre-operatively in thoracotomy due to the risk of bleeding (transferable evidence, Grade B) and because pre-operative administration is of no additional benefit compared with postoperative administration alone (Grade A)

Clinical Practice

  • Caution is required when conventional NSAIDs are used in patients receiving epidural analgesia concomitantly with medications for thromboprophylaxis, due to the risk of spinal haematoma

Transferable Evidence from Other Procedures

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures Barden et al 2004
  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritis, urinary retention or respiratory depression Marret et al 2005
  • Randomised trials in healthy volunteers have shown that conventional NSAIDs are associated with a higher incidence of upper gastrointestinal ulceration compared with COX-2 selective inhibitors for short-term use Harris et al 2001
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with control Marret et al 2003
  • Pre-operative conventional NSAIDs significantly increased peri-operative blood loss in patients undergoing total hip arthroplasty compared with other analgesic agents in four out of five studies An et al 1991 Click here for more information
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused reversible platelet dysfunction Niemi et al 1997
  • A large randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • A randomised clinical trial showed that the conventional NSAID diclofenac was associated with significantly greater intra-operative blood loss than the COX-2-selective inhibitor rofecoxib in patients undergoing abdominal or vaginal hysterectomy or breast surgery Hegi et al 2004
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • Conventional NSAIDs and COX-2 selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of conventional NSAIDs or COX-2 selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2 selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Conventional NSAIDs and COX-2 selective inhibitors have been associated with impaired bone healing in various animal models and in vitro studies Gajraj 2003

Thoracotomy-specific Evidence

PROSPECT Recommendations

  • Pre-operative systemic clonidine is not recommended because limited evidence from thoracotomy shows no analgesic benefit (Grade A), transferable evidence shows inconsistent analgesic benefit (Grade B), and because of potential side-effects (Grade D)
  • Despite positive transferable evidence, pre-operative systemic dexmedetomidine is not recommended at this time because procedure-specific evidence is lacking, and because of potential side-effects (Grade D)

Clinical Practice

  • The risk/benefit ratio for clonidine and dexmedetomidine is unclear. Potential side effects include hypotension, sedation, dizziness and bradycardia

Transferable Evidence from Other Procedures

  • Intravenous clonidine given before skin incision, or before peritoneal incision, was superior to fentanyl given before skin incision for postoperative analgesic outcomes in open colonic resection De Kock et al 1994 Click here for more information
  • Intravenous dexmedetomidine administered before hand or abdominal surgery reduced intra- and/or postoperative analgesic requirements compared with control in four studies (n=40, n=30, n=30, n=60) Esmaoglu et al 2005
  • Pre-operative clonidine provided no consistent significant benefit over placebo for reducing postoperative pain scores in abdominal hysterectomy; and results for other postoperative pain outcomes were mixed Dimou et al 2003 Click here for more information
  • Intravenous dexmedetomidine administered before hand or abdominal surgery did not significantly reduce pain scores compared with control in two studies (n=30, n=60) Jacobson et al 1983
  • In one study, intravenous dexmedetomidine administered before hand surgery induced decreases in blood pressure and heart rate that were mainly abolished within 4 h of surgery (n=30) Jaakola 1994
  • Study Information Dimou et al 2003 Click here for more information

Thoracotomy-specific Evidence

PROSPECT Recommendations

  • Despite positive transferable evidence on reduction of pain and PONV from other procedures, pre-operative corticosteroids are not recommended for thoracotomy due to limited procedure-specific evidence (Grade D)

Clinical practice

  • Much of the transferable evidence for efficacy of corticosteroids in reduction of PONV and for pain relief is based on short-stay surgery

Transferable Evidence from Other Procedures

  • A single prophylactic dose of corticosteroid is anti-emetic compared with placebo, when there is a high risk of PONV, in a wide range of surgical procedures Henzi et al 2000
  • Pre-operative dexamethasone (8 mg) reduced pain, fatigue, nausea and vomiting, and duration of convalescence, compared with placebo in patients undergoing laparoscopic cholecystectomy Bisgaard et al 2003
  • Intravenous methylprednisolone (125 mg) given one day after orthopaedic surgery reduced pain and opioid consumption compared with placebo (n=50) Romundstad et al 2004

Thoracotomy-specific Evidence

  • A pre-operative intravenous bolus of methylprednisolone reduced VAS pain scores compared with placebo at rest at 4 h and day 1, and on coughing at 4 and 8 h and day 2, (p<0.05), but not on days 3 and 4 (n=36) Bigler et al 1996
  • A pre-operative intravenous bolus of methylprednisolone was associated with similar pulmonary function (FVC, FEV, PEF) compared with placebo (n=36) Bigler et al 1996
  • Study details Bigler et al 1996 Click here for more information

PROSPECT Recommendations

  • COX-2-selective inhibitors are not recommended pre-operatively because there is no procedure-specific evidence that pre-operative administration is of more benefit than postoperative administration (Grade D)

Clinical Practice

  • None cited

Transferable Evidence from Other Procedures

  • Peri-operative use of rofecoxib (50 mg at 24 h and at 1 to 2 h before total knee arthroplasty, followed by 50 mg daily for 5 days postoperatively, and 25 mg for another 8 days), as part of a multi-analgesic regimen, reduced pain, opioid use, vomiting, sleep disturbance and improved knee range of motion, compared with placebo (n=68) Buvanendran et al 2003
  • COX-2-selective inhibitors provide similar postoperative analgesia to conventional NSAIDs Rømsing et al 2004
  • Randomised trials in healthy volunteers have shown that COX-2 selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2 selective inhibitors had no effect on platelet aggregation Greenberg et al 2000
  • Pre-operative administration of oral rofecoxib 25 mg once daily did not increase intra- or postoperative blood loss when compared with placebo, in patients undergoing total knee arthroplasty Reuben et al 2002
  • A randomised clinical trial showed that the COX-2-selective inhibitor rofecoxib was associated with significantly less intra-operative blood loss than the conventional NSAID diclofenac in patients undergoing abdominal or vaginal hysterectomy or breast surgery Hegi et al 2004
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) Nussmeier et al 2006
  • Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Conventional NSAIDs and COX-2 selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of COX-2 selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • COX-2 selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003
  • Conventional NSAIDs and COX-2 selective inhibitors have been associated with impaired bone healing in various animal models and in vitro studies Gajraj 2003

Thoracotomy-specific Evidence

  • None cited

PROSPECT Recommendations

  • Low-dose ketamine cannot be recommended at this time due to a lack of procedure-specific evidence (Grade D), although analgesic data from other procedures are promising

Clinical Practice

  • Ketamine may be of benefit for prevention of chronic pain conditions following thoracotomy, where 40–60% patients may develop chronic pain and/or allodynia. Additionally, it may be of benefit in patients who have opioid tolerance. Ketamine is most often used after induction of GA, but before incision (pre-operatively)

Transferable Evidence from Other Procedures

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitor-urinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine Bell et al 2005

Thoracotomy-specific Evidence

  • Pre-operative intramuscular ketamine reduced PCEA morphine use, but not PCEA bupivacaine use, compared with placebo (p<0.001) (n=40) Ozyalcin et al 2004
  • Pre-operative intramuscular ketamine reduced the areas of pin-prick hyperalgesia at 1 month (p=0.008), brush allodynia at 2 and 15 days and at 1 month (p<0.05), and pressure hyperalgesia at 2 days (p<0.05), compared with placebo (n=40) Ozyalcin et al 2004
  • Study details Ozyalcin et al 2004 Click here for more information

PROSPECT Recommendations

  • Gabapentin/pregabalin cannot be recommended at this time due to a lack of procedure-specific evidence (Grade D), although analgesic data from other procedures are promising

Clinical Practice

  • Gabapentin may be of benefit for prevention of chronic pain conditions following thoracotomy, where 40–60% of patients may develop chronic pain and/or allodynia

Transferable Evidence from Other Procedures

  • Studies of gabapentin and pregabalin in mastectomy, abdominal surgery, laparoscopic cholecystectomy, spinal surgery, knee surgery, ear-nose-throat surgery, and nephrectomy showed reductions in postoperative pain and supplementary analgesic requirements for at least 24 h Dahl et al 2004
  • One study showed no significant benefit of gabapentin 800 mg for reducing pain or opioid use compared with placebo in spinal surgery (n=60) Radhakrishnan et al 2005

Thoracotomy-specific Evidence

  • None cited

PROSPECT Recommendations

  • Systemic strong opioids are not recommended as premedication to provide postoperative analgesia, based on evidence for a lack of postoperative analgesic benefit (Grade A), and because of potential side-effects (Grade B)

Clinical Practice

  • None cited

Transferable Evidence from Other Procedures

  • Strong opioids are associated with adverse effects, including nausea, vomiting, sedation, confusion, paralytic ileus and urinary retention Wheeler et al 2002

Thoracotomy-specific Evidence

PROSPECT Recommendations

  • Pre- and intra-operative thoracic epidural LA plus strong opioid is recommended based on a reduction in pain compared with postoperative administration alone (Grade A)
  • Thoracic epidural LA plus strong opioid is recommended as a pre-operative bolus followed by an infusion continued for 2–3 days postoperatively, based on a reduction in pain compared with systemic analgesia (Grade A, see Postoperative Epidural Analgesia section)
  • There are not enough data to recommend one specific combination of LA and opioid over another
  • There are not enough data to recommend a specific concentration or volume of LA and strong opioid
  • There are not enough data to recommend lipophilic opioids in preference to hydrophilic opioids or vice versa, in combination with LA

Clinical Practice

  • Thoracic epidural strong opioid alone may be used when there is a contra-indication for thoracic epidural LA, such as hypotension due to excessive blood loss
  • Thoracic epidural LA alone may be used when opioid-associated side-effects are a problem
  • Use of heparin or conventional NSAIDs may increase the risk of spinal haematoma due to epidural analgesia

Transferable Evidence from Other Procedures

  • A meta-analysis of randomised controlled trials found that both continuous epidural infusion and PCEA analgesia provided superior postoperative analgesia compared with intravenous PCA analgesia Wu et al 2005
  • A meta-analysis found that continuous epidural infusion provided superior analgesia and reduced the incidence of pruritis compared with PCEA analgesia, but was associated with a higher incidence of PONV and motor block Wu et al 2005
  • A meta-analysis of randomised controlled trials found that epidural analgesia significantly decreased the incidence of pulmonary morbidity compared with systemic opioids Ballantyne et al 1998 Click here for more information
  • Epidural administration of strong opioids is associated with side effects including pruritis, PONV, urinary retention, and respiratory depression Chaney 1995

Thoracotomy-specific Evidence

  • Four of six studies showed that pre-/intra-operative thoracic epidural LA ± strong opioid reduced pain scores compared with control Neustein et al 2002 Click here for more information
  • Pre-operative thoracic epidural sufentanil was superior to intravenous sufentanil for reducing pain scores at 1 h (p<0.005) and 2 h (p<0.025) (n=22) Rosseel et al 1988
  • Pre-operative thoracic epidural sufentanil was superior to intravenous sufentanil for reducing the dose of sufentanil required during surgery (p<0.005) but not for reducing the number of sufentanil doses required (n=22) Rosseel et al 1988
  • Pre-operative thoracic epidural sufentanil was superior to intravenous sufentanil for extending the time until first analgesic request (p<0.05) (n=22) Rosseel et al 1988
  • Two studies reported that pre-/intra-operative thoracic epidural bupivacaine plus morphine was similar to control for the incidence of: vomiting (all patients received postoperative epidural analgesia) (n=46) Senturk et al 2002
  • Pre-operative thoracic epidural sufentanil was associated with lower PaCO compared with intravenous sufentanil, at 2 h (p<0.025) but not at 1 h (n=22) Rosseel et al 1988
  • Three of five studies reported that pre-/intra-operative thoracic epidural LA ± strong opioid was similar to control for the rate of epidural infusion required or indomethacin use Aguilar et al 1996 Click here for more information
  • Intra-operative thoracic epidural bupivacaine plus fentanyl was not associated with an increase in physical activity after discharge compared with control (both groups received postoperative epidural analgesia; n=120) Ochroch et al 2002
  • Pre-operative thoracic epidural sufentanil was similar to intravenous sufentanil for the incidence of PONV (n=22) Rosseel et al 1988
  • Study details Aguilar et al 1996 Click here for more information

PROSPECT Recommendations

  • Pre-operative lumbar epidural strong opioid is not recommended as the first choice of epidural technique, based on evidence that the thoracic epidural route is more effective for pain relief following thoracotomy (Grade A, see Postoperative Epidural Analgesia). However, there is procedure specific evidence that lumbar epidural hydrophilic strong opioid reduces pain compared with systemic analgesia (see Postoperative Epidural Analgesia)

Clinical Practice

  • Infusion techniques are more convenient for use in clinical practice and adequate analgesia is more likely to be maintained than with bolus administration of lumbar epidural strong opioid
  • Use of heparin or conventional NSAIDs may increase the risk of spinal haematoma due to epidural analgesia

Transferable Evidence

  • A meta-analysis of randomised controlled trials found that both continuous epidural infusion and PCEA analgesia provided superior postoperative analgesia compared with intravenous PCA analgesia Wu et al 2005
  • A meta-analysis found that continuous epidural infusion provided superior analgesia and reduced the incidence of pruritis compared with PCEA analgesia, but was associated with a higher incidence of PONV and motor block Wu et al 2005
  • A meta-analysis of randomised controlled trials found that epidural analgesia significantly decreased the incidence of pulmonary morbidity compared with systemic opioids Ballantyne et al 1998 Click here for more information
  • Epidural administration of strong opioids is associated with side effects including pruritis, PONV, urinary retention, and respiratory depression Chaney 1995

Thoracotomy-specific Evidence

  • Pre-incisional administration of lumbar epidural fentanyl was not significantly different from post-incisional administration for reducing pain scores at 2, 4, 12, 24 and 48 h; pre-incision administration was superior only at 6 h (p<0.04) (n=30) Katz et al 1992
  • Pre-incisional administration of lumbar epidural fentanyl was superior to post-incisional administration for reducing PCA morphine requirements during 12–24 h (p<0.008), but there was no significant difference during 0–12 h and 24–48 h (n=30) Katz et al 1992
  • Study details Katz et al 1992 Click here for more information

PROSPECT recommendations

  • Thoracic epidural corticosteroid is not recommended because there are limited data (Grade D)
  • Epidural epinephrine is recommended if a low dose of epidural LA and/or opioid is used (Grade B)

Clinical Practice

  • None cited

Transferable Evidence from Other Procedures

  • Three studies in major thoracic or abdominal surgery showed that addition of epinephrine 1.5–2 µg/ml to thoracic epidural local anaesthetic plus strong opioid reduced pain intensity Niemi et al 1998 Click here for more information
  • Epinephrine 1.5–2 µg/ml was associated with reduced frequency of pruritis (p<0.002; n=36) Niemi et al 2003

Thoracotomy-specific evidence

  • Addition of epinephrine to thoracic epidural strong opioid was superior to epidural strong opioid alone for reducing use of epidural fentanyl, and for extending the duration of analgesia Baron et al 1996 Click here for more information
  • Postoperative epidural methylprednisolone did not significantly reduce pain scores at rest and on mobilisation, or total morphine requirement over 48 h, compared with placebo (n=24) Blanloeil et al 2001
  • Postoperative epidural methylprednisolone did not significantly reduce the incidence of PONV compared with placebo (n=24) Blanloeil et al 2001
  • Addition of epinephrine to postoperative thoracic epidural strong opioid did not significantly reduce pain scores compared with epidural strong opioid alone Baron et al 1996 Click here for more information
  • Addition of epinephrine to postoperative thoracic epidural strong opioid did not significantly reduce the incidence of PONV compared with epidural strong opioid alone (n=34; n=23) Baron et al 1996
  • Addition of epinephrine to postoperative thoracic epidural strong opioid was associated with similar pulmonary function to epidural strong opioid alone: FEV (n=23) Baron et al 1996
  • Study details Blanloeil et al 2001 Click here for more information

PROSPECT Recommendations

  • A pre-operative single bolus of spinal strong opioid is recommended as part of a multi-analgesic regimen (Grade A), when epidural analgesia or paravertebral block are not possible for any reason (Grade D)
  • Spinal opioids are recommended in preference to intravenous PCA opioids, based on a greater reduction in pain for up to 24 hours, with no difference in respiratory function (Grade A)
  • Thoracic epidural LA plus opioid is recommended in preference to spinal strong opioid based on evidence that the analgesic effect of thoracic epidural analgesia has a longer duration than 24 h (Grade A, see Postoperative Epidural Analgesia)

Clinical Practice

  • Hydrophilic opioids provide a longer duration of analgesia than lipophilic opioids

Transferable Evidence

  • A meta-analysis of randomised controlled trials in coronary artery bypass surgery found that spinal analgesia combined with general anaesthesia decreased pain scores and systemic morphine use compared with general anaesthesia alone Liu et al 2004
  • Spinal administration of strong opioids is associated with side effects including pruritis, PONV, urinary retention, and respiratory depression Chaney 1995
  • A meta-analysis found that spinal analgesia combined with general anaesthesia in coronary artery bypass surgery increased the incidence of pruritis compared with general anaesthesia alone Liu et al 2004
  • In a systematic review, spinal morphine in patients undergoing caesarean section was shown to increase the relative risk of postoperative pruritis, nausea and vomiting compared with control; increasing the dose of morphine increased the relative risk of postoperative nausea and vomiting Dahl et al 1999

Thoracotomy-specific Evidence

  • Pre-operative single bolus spinal sufentanil was superior to control for reducing pain scores: at rest at 0 and 2 h (p<0.05), but not during 4–24 h; and on coughing during 0–4 h (p<0.05) (one treatment arm; n=29) Liu et al 2001
  • Four studies showed that pre-operative single bolus spinal morphine was superior to control for reducing pain scores Cohen et al 1993 Click here for more information
  • Two studies showed that pre-operative single bolus spinal sufentanil plus morphine was superior to control for reducing pain scores Liu et al 2001 Click here for more information
  • Pre-operative single bolus spinal sufentanil was superior to control for reducing supplementary analgesic requirements: titrated morphine dose and total 24-h morphine dose (p<0.05) (one treatment arm; n=29) Liu et al 2001
  • Pre-operative single bolus spinal morphine was superior to control for reducing supplementary analgesic requirements Liu et al 2001 Click here for more information
  • Single bolus spinal strong opioid (lipophilic and hydrophilic combined) was superior to control for reducing supplementary analgesic requirements Liu et al 2001 Click here for more information
  • Pre-operative spinal morphine was associated with similar or superior pulmonary function compared with control Bowler et al 2002 Click here for more information
  • Pre-operative single bolus spinal strong opioid (lipophilic and hydrophilic combined) did not significantly increase the time to first use of PCA analgesia compared with control (n=30) Mason et al 2001
  • Pre-operative single bolus spinal sufentanil did not reduce the incidence of PONV compared with control (one treatment arm; n=29) Liu et al 2001
  • Pre-operative single bolus spinal morphine did not reduce the incidence of PONV compared with control (one treatment arm, n=29) Liu et al 2001
  • Pre-operative single bolus spinal strong opioid (lipophilic and hydrophilic combined) did not reduce the incidence of PONV compared with control (one treatment arm; n=29) Liu et al 2001
  • Pre-operative single bolus spinal strong opioid (lipophilic and hydrophilic combined) was similar to placebo for outcomes of pulmonary function tests: PEFR, FEV, FVC (n=30) Mason et al 2001
  • Study details Liu et al 2001 Click here for more information

PROSPECT Recommendations

  • Paravertebral block with LA is recommended as an alternative to thoracic epidural LA plus strong opioid, based on evidence that the technique provides comparable postoperative analgesia and may be associated with fewer adverse effects (Grade A; see also Postoperative Paravertebral Block)

Clinical Practice

  • A paravertebral block can be used in combination with other analgesic techniques, as part of a multimodal analgesic regimen
  • Paravertebral LA may be administered as a bolus before surgery
  • Paravertebral block is used less frequently than epidural analgesia in clinical practice

Transferable Evidence from Other Procedures

  • Paravertebral block improved pain relief, reduced opioid use and was associated with improved pulmonary function compared with placebo in pleurectomy Mozell et al 1991
  • Four studies in breast surgery found that paravertebral block was associated with analgesic benefits compared with control Kairaluoma et al 2004 Click here for more information
  • Bilateral paravertebral block combined with general anaesthesia reduced pain scores, supplementary analgesic use, and the incidence of PONV, compared with general anaesthesia alone in laparoscopic cholecystectomy (n=60) Naja et al 2004

Thoracotomy-specific Evidence

  • Pre-operative paravertebral block was superior to control for reducing pain scores during 0–48 h (no statistical analyses) (seven treatment arms; n=56) Richardson et al 1994
  • Pre-operative paravertebral block was superior to control for reducing supplementary opioid use during 0–24 h (no statistical analysis) (seven treatment arms; n=56) Richardson et al 1994
  • Pre-operative paravertebral block was associated with superior pulmonary function (FVC, FEV1 and PEFR) compared with control (no statistical analysis) (seven treatment arms; n=56) Richardson et al 1994
  • Pre-operative multi-analgesic regimens including paravertebral bupivacaine were superior to analgesic regimens including only systemic morphine or diclofenac with no paravertebral bupivacaine for reducing pain scores during 0–48h and the use of supplementary opioids during 0–24 h (no statistical analysis) (n=56) Richardson et al 1994
  • Pre-operative multi-analgesic regimens including paravertebral bupivacaine were superior to systemic morphine or diclofenac, alone or in combination, and were associated with superior pulmonary function (FVC, FEV1 and PEFR) to no pre-operative treatment (n=56) Richardson et al 1994
  • Study details Richardson et al 1994 Click here for more information

PROSPECT Recommendations

  • Single pre-operative injection with LA for intercostal nerve block is not recommended based on limited evidence (Grade D)

Clinical Practice

  • Infusion techniques for intercostal nerve blocks are more convenient for use in clinical practice and adequate analgesia is more likely to be maintained than with intermittent bolus administration

Transferable Evidence

  • Two studies in open cholecystectomy and one study in upper abdominal surgery showed that intercostal nerve block did not significantly reduce pain scores compared with control (n=37, n=40, n=66) Maidatsi et al 1998
  • In open cholecystectomy, intercostal nerve block reduced supplementary opioid use compared with control in one study (n=37) Maidatsi et al 1998
  • A meta-analysis found that intercostal nerve block tended to reduce the incidence of pulmonary complications, but these differences did not achieve statistical significance. There were no significant differences in surrogate measures of pulmonary function (FEV1, FVC, and PEFR) Ballantyne et al 1998
  • The incidence of pneumothorax following intercostal nerve block in thoracic and upper abdominal surgery has been reported in the range of 0.073% to 19% Shanti et al 2001

Thoracotomy-specific Evidence

  • Intercostal bupivacaine pH 4.1 and pH 6.9 were similar for pain scores and supplementary morphine use during 0–36 h (n=20) Swann et al 1991
  • Pre-operative administration of an analgesic regimen including intercostal LA was superior to postoperative administration for reducing pain scores Doyle et al 1998 Click here for more information
  • Pre-operative and postoperative administration of an analgesic regimen including intercostal LA were similar for postoperative supplementary analgesic requirements Doyle et al 1998 Click here for more information
  • Intramuscular morphine plus rectal indomethacin plus intercostal bupivacaine did not significantly reduce pain scores at rest or on movement compared with placebo (n=30) Kavanagh et al 1994
  • Intramuscular morphine plus rectal indomethacin plus intercostal bupivacaine significantly reduced PCA morphine use during 0–6 h (p<0.03) but increased cumulative morphine use during 0–72 h (p<0.05), compared with placebo (n=30) Kavanagh et al 1994
  • Intramuscular morphine plus rectal indomethacin plus intercostal bupivacaine was associated with similar pulmonary function parameters to placebo (FVC, FEV1 and PaCO2) (n=30) Kavanagh et al 1994
  • Pre-operative and postoperative administration of an analgesic regimen including systemic morphine and diclofenac plus intercostal bupivacaine were similar for the duration of hospital stay (n=30) Doyle et al 1998
  • Study details Swann et al 1991 Click here for more information

PROSPECT Recommendations

  • Intercostal clonidine, in combination with LA, is not recommended, due to limited evidence (Grade D)

Clinical Practice

  • Clonidine may prolong the intercostal nerve block
  • Clonidine is not routinely used because it is associated with an increased risk of hypotension, sedation, dizziness and bradycardia

Transferable Evidence

  • None cited

Thoracotomy-specific Evidence

  • Intercostal LA plus clonidine significantly reduced pain scores compared with LA alone, during 1–4 h after arrival in the PACU (p<0.05), but there was no significant difference during 5–8 h (n=26) Tschernko et al 1998
  • Intercostal LA plus clonidine was superior to LA alone, for reducing PCA piritramide requirements during 1–5 h after arrival in PACU (p<0.05), but not during 6–8 h, and total opioid use at 24 h (p<0.005), but there was no significant difference at 48 h (n=26) Tschernko et al 1998
  • Intercostal LA plus clonidine was associated with increased PaO2 during 1–4 h (p<0.05), but not during 5–8 h, compared with LA alone (n=26) Tschernko et al 1998
  • Study details Tschernko et al 1998 Click here for more information

PROSPECT Recommendations

  • Pre-operative LA injection in the planned site of incision is not recommended based on procedure-specific evidence that shows a lack of analgesic efficacy (Grade A)

Clinical Practice

  • None cited

Transferable Evidence

  • None cited

Thoracotomy-specific Evidence

PROSPECT Recommendations

  • Conventional NSAIDs are not recommended during the procedure in thoracotomy due to the risk of bleeding (transferable evidence, Grade B). However, see Postoperative conventional NSAIDs.

Clinical Practice

  • Caution is required when conventional NSAIDs are used in patients receiving epidural analgesia concomitantly with medications for thromboprophylaxis, due to the risk of spinal haematoma

Transferable Evidence

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures Barden et al 2004
  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritis, urinary retention or respiratory depression Marret et al 2005
  • Randomised trials in healthy volunteers have shown that conventional NSAIDs are associated with a higher incidence of upper gastrointestinal ulceration compared with COX-2 selective inhibitors for short-term use Harris et al 2001
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with control Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused reversible platelet dysfunction Niemi et al 1997
  • A large randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with impaired bone healing in various animal models and in vitro studies Gajraj 2003

Thoracotomy-specific Evidence

PROSPECT Recommendations

  • COX-2-selective inhibitors are not recommended intra-operatively because there is a lack of procedure-specific evidence that intra-operative administration is of more benefit than postoperative administration (Grade D); see Postoperative COX-2-selective inhibitors.

Clinical Practice

  • The potential side-effects of pre- or intra-operative COX-2-selective inhibitors may have greater consequences in this procedure, due to the typically poor condition of the patient, due to potential for greater blood and fluid loss, and renal complications
  • Thoracic surgery patients may frequently have coronary artery disease or cardiac contra-indications

Transferable Evidence from Other Procedures

  • COX-2-selective inhibitors provide similar postoperative analgesia to conventional NSAIDs Rømsing et al 2004
  • Randomised trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation Greenberg et al 2000
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) Nussmeier et al 2006
  • Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with impaired bone healing in various animal models and in vitro studies Gajraj 2003

Thoracotomy-specific Evidence

  • None cited

PROSPECT Recommendations

  • Low-dose ketamine cannot be recommended at this time due to a lack of procedure-specific evidence (Grade D), although analgesic data from other procedures are promising

Clinical Practice

  • Ketamine may be of benefit for prevention of chronic pain conditions following thoracotomy, where 40–60% patients may develop chronic pain and/or allodynia. Additionally, it may be of benefit in patients who have opioid tolerance. Ketamine is most often used after induction of GA, but before incision (pre-operatively)

Transferable Evidence

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genito-urinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine Bell et al 2005

Thoracotomy-specific Evidence

  • None cited

PROSPECT Recommendations

  • Gabapentin/pregabalin cannot be recommended at this time due to a lack of procedure-specific evidence (Grade D), although analgesic data from other procedures are promising

Clinical Practice

  • Gabapentin may be of benefit for prevention of chronic pain conditions following thoracotomy, where 40–60% of patients may develop chronic pain and/or allodynia

Transferable Evidence

  • Studies of gabapentin and pregabalin in mastectomy, abdominal surgery, laparoscopic cholecystectomy, spinal surgery, knee surgery, ear-nose-throat surgery, and nephrectomy showed reductions in postoperative pain and supplementary analgesic requirements for at least 24 h Dahl et al 2004
  • One study showed no significant benefit of gabapentin 800 mg for reducing pain or opioid use compared with placebo in spinal surgery (n=60) Radhakrishnan et al 2005

Thoracotomy-specific Evidence

  • None cited

PROSPECT Recommendations

  • Intra-operative thoracic epidural LA plus strong opioid is recommended based on a reduction in pain compared with postoperative administration alone (Grade A)
  • Intra-operative thoracic epidural LA plus strong opioid is recommended as an infusion continued for 2–3 days postoperatively, based on a reduction in pain compared with systemic analgesia (Grade A, see Postoperative Epidural Analgesia)
  • There are not enough data to recommend one specific combination of LA and opioid over another
  • There are not enough data to recommend a specific concentration or volume of LA and strong opioid
  • There are not enough data to recommend lipophilic opioids in preference to hydrophilic opioids or vice versa, in combination with LA

Clinical Practice

  • Thoracic epidural strong opioid alone may be used when there is a contra-indication for thoracic epidural LA, such as hypotension due to excessive blood loss
  • Thoracic epidural LA alone may be used when opioid-associated side-effects are a problem
  • Use of heparin or conventional NSAIDs may increase the risk of spinal haematoma due to epidural analgesia

Transferable Evidence

  • A meta-analysis of randomised controlled trials found that both continuous epidural infusion and PCEA analgesia provided superior postoperative analgesia compared with intravenous PCA analgesia Wu et al 2005
  • A meta-analysis found that continuous epidural infusion provided superior analgesia and reduced the incidence of pruritis compared with PCEA analgesia, but was associated with a higher incidence of PONV and motor block Wu et al 2005
  • A meta-analysis of randomised controlled trials found that epidural analgesia significantly decreased the incidence of pulmonary morbidity compared with systemic opioids Ballantyne et al 1998 Click here for more information
  • Epidural administration of strong opioids is associated with side effects including pruritis, PONV, urinary retention, and respiratory depression Chaney 1995

Thoracotomy-specific Evidence

  • Four of six studies showed that pre-/intra-operative thoracic epidural LA ± strong opioid reduced pain scores compared with control Neustein et al 2002 Click here for more information
  • Two studies reported that pre-/intra-operative thoracic epidural bupivacaine plus morphine was similar to control for the incidence of: vomiting (all patients received postoperative epidural analgesia) (n=46) Senturk et al 2002
  • Three of five studies reported that pre-/intra-operative thoracic epidural LA ± strong opioid was similar to control for the rate of epidural infusion required or indomethacin use Aguilar et al 1996 Click here for more information
  • Intra-operative plus postoperative thoracic epidural bupivacaine plus fentanyl was not associated with an increase in physical activity after discharge compared with postoperative epidural alone (n=120) Ochroch et al 2002
  • Study details Aguilar et al 1996 Click here for more information

PROSPECT Recommendations

  • Lumbar epidural strong opioid is not recommended as the first choice of epidural technique, based on evidence that the thoracic epidural route is more effective for pain relief following thoracotomy (Grade A, see Postoperative Epidural Analgesia). However, there is procedure-specific evidence that lumbar epidural hydrophilic strong opioid reduces pain compared with systemic analgesia (see Postoperative Epidural Analgesia)

Clinical Practice

  • Infusion techniques are more convenient for use in clinical practice and adequate analgesia is more likely to be maintained than with bolus administration of lumbar epidural strong opioid
  • Use of heparin or conventional NSAIDs may increase the risk of spinal haematoma due to epidural analgesia

Transferable Evidence

  • A meta-analysis of randomised controlled trials found that both continuous epidural infusion and PCEA analgesia provided superior postoperative analgesia compared with intravenous PCA analgesia Wu et al 2005
  • A meta-analysis found that continuous epidural infusion provided superior analgesia and reduced the incidence of pruritis compared with PCEA analgesia, but was associated with a higher incidence of PONV and motor block Wu et al 2005
  • A meta-analysis of randomised controlled trials found that epidural analgesia significantly decreased the incidence of pulmonary morbidity compared with systemic opioids Ballantyne et al 1998 Click here for more information
  • Epidural administration of strong opioids is associated with side effects including pruritis, PONV, urinary retention, and respiratory depression Chaney 1995

Thoracotomy-specific Evidence

  • Intra-operative lumbar epidural morphine injection was superior to all concentrations of nalbuphine for reducing pain scores Baxter et al 1991 Click here for more information
  • Intra-operative lumbar epidural morphine injection was superior to all concentrations of nalbuphine for reducing PCA fentanyl use (p<0.01) (five treatment arms; n=52) Baxter et al 1991
  • One study showed that morphine 0.67 mg/ml and nalbuphine 0.5, 1, 1.5 and 2 mg/ml, for intra-operative lumbar epidural injection, were associated with a similar incidence of nausea (five treatment arms; n=52) Baxter et al 1991
  • Intra-operative lumbar epidural nalbuphine injection was superior to morphine for reducing the proportion of patients requiring naloxone, and nalbuphine was associated with a lower mean PaCO2 Baxter et al 1991 Click here for more information
  • Nalbuphine 1.5 mg/ml was superior to nalbuphine 0.5, 1 and 2 mg/ml lumbar epidural (p<0.01) for reducing total pain scores over the 24-h study period (four treatment arms; n=40) Baxter et al 1991
  • Nalbuphine 2 mg/ml was superior to nalbuphine 0.5, 1 and 1.5 mg/ml lumbar epidural (p<0.01) for reducing the 24-h dose of fentanyl Baxter et al 1991 Click here for more information
  • Intra-operative lumbar epidural nalbuphine 0.5, 1, 1.5 and 2 mg/ml were similar for blood gas levels (four treatment arms; n=40) Baxter et al 1991
  • Post-incisional administration of lumbar epidural fentanyl was inferior to pre-incisional administration for reducing pain scores Katz et al 1992 Click here for more information
  • Study details Baxter et al 1991 Click here for more information

PROSPECT recommendations

  • Thoracic epidural corticosteroid is not recommended because there are limited data (Grade D)
  • Epidural epinephrine is recommended if a low dose of epidural LA and/or opioid is used (Grade B)

Clinical Practice

  • None cited

Transferable Evidence from Other Procedures

  • Three studies in major thoracic or abdominal surgery showed that addition of epinephrine 1.5–2 µg/ml to thoracic epidural local anaesthetic plus strong opioid reduced pain intensity Niemi et al 1998 Click here for more information
  • Epinephrine 1.5–2 µg/ml was associated with reduced frequency of pruritis (p<0.002; n=36) Niemi et al 2003

Thoracotomy-specific Evidence

  • Addition of epinephrine to thoracic epidural strong opioid was superior to epidural strong opioid alone for reducing use of epidural fentanyl, and for extending the duration of analgesia Baron et al 1996 Click here for more information
  • Postoperative epidural methylprednisolone did not significantly reduce pain scores at rest and on mobilisation, or total morphine requirement over 48 h, compared with placebo (n=24) Blanloeil et al 2001
  • Postoperative epidural methylprednisolone did not significantly reduce the incidence of PONV compared with placebo (n=24) Blanloeil et al 2001
  • Addition of epinephrine to postoperative thoracic epidural strong opioid did not significantly reduce pain scores compared with epidural strong opioid alone Baron et al 1996 Click here for more information
  • Addition of epinephrine to postoperative thoracic epidural strong opioid did not significantly reduce the incidence of PONV compared with epidural strong opioid alone (n=34; n=23) Baron et al 1996
  • Addition of epinephrine to postoperative thoracic epidural strong opioid was associated with similar pulmonary function to epidural strong opioid alone: FEV1, FVC (n=34) PaCO2(n=23) Baron et al 1996
  • Study details Blanloeil et al 2001 Click here for more information

PROSPECT Recommendations

  • Paravertebral block with LA is recommended as an alternative to thoracic epidural LA plus strong opioid, based on evidence that the technique provides comparable postoperative analgesia and may be associated with fewer adverse effects (Grade A; see also Postoperative Paravertebral Block)

Clinical Practice

  • A paravertebral block can be used in combination with other analgesic techniques, as part of a multimodal analgesic regimen
  • Paravertebral LA may be administered as a bolus at the end of surgery
  • Paravertebral block is used less frequently than epidural analgesia in clinical practice

Transferable Evidence

  • Paravertebral block improved pain relief, reduced opioid use and was associated with improved pulmonary function compared with placebo in pleurectomy Mozell et al 1991
  • Four studies in breast surgery found that paravertebral block was associated with analgesic benefits compared with control Kairaluoma et al 2004 Click here for more information
  • Bilateral paravertebral block combined with general anaesthesia reduced pain scores, supplementary analgesic use, and the incidence of PONV, compared with general anaesthesia alone in laparoscopic cholecystectomy (n=60) Naja et al 2004

Thoracotomy-specific Evidence

  • Most studies of paravertebral block included postoperative administration, with or without an additional pre- or intra-operative bolus; all studies (with the exception of Richardson et al 1994

PROSPECT Recommendations

  • Intercostal nerve block with LA via a catheter is recommended, if epidural analgesia and paravertebral block are not possible (Grade D), based on evidence for a reduction in pain compared with systemic analgesia (Grade A) (see also Postoperative Intercostal Nerve Block)

Clinical Practice

  • Infusion techniques for intercostal nerve blocks are more convenient for use in clinical practice and adequate analgesia is more likely to be maintained than with intermittent bolus administration

Transferable Evidence

  • Two studies in open cholecystectomy and one study in upper abdominal surgery showed that intercostal nerve block did not significantly reduce pain scores compared with control (n=37, n=40, n=66) Maidatsi et al 1998
  • In open cholecystectomy, intercostal nerve block reduced supplementary opioid use compared with control in one study (n=37) Maidatsi et al 1998
  • A meta-analysis found that intercostal nerve block tended to reduce the incidence of pulmonary complications, but these differences did not achieve statistical significance. There were no significant differences in surrogate measures of pulmonary function (FEV1, FVC, and PEFR) Ballantyne et al 1998
  • The incidence of pneumothorax following intercostal nerve block in thoracic and upper abdominal surgery has been reported in the range of 0.073% to 19% Shanti et al 2001

Thoracotomy-specific Evidence

PROSPECT Recommendations

  • Addition of dextran to LA solution is not recommended because of lack of analgesic benefit (Grade A)
  • Intercostal phenol is not recommended because of limited evidence and the potential risk of neuropathic pain (Grade D)

Clinical Practice

  • Phenol may induce neuropathic pain

Transferable Evidence

  • None cited

Thoracotomy-specific Evidence

  • Intercostal bupivacaine plus dextran was superior to bupivacaine alone for extending the duration of skin anaesthesia as determined by pinprick (p<0.005) (n=12) Kaplan et al 1975
  • Intercostal nerve block with phenol reduced pain scores compared with control (no statistical analyses) (n=73) Roviaro et al 1986
  • Intercostal bupivacaine plus dextran was similar to bupivacaine alone for pain scores on days 1, 2 and 3 (n=12) Kaplan et al 1975
  • Intercostal bupivacaine plus dextran was similar to bupivacaine alone for the use of supplementary morphine on days 1, 2 and 3 (n=12) Kaplan et al 1975
  • Intercostal bupivacaine plus dextran was associated with similar pulmonary function to bupivacaine alone (FVC, FEFR, PaCO2, PaO2) (n=12) Kaplan et al 1975
  • Intercostal phenol was associated with similar pulmonary function to control in patients undergoing lobectomy, but was associated with superior pulmonary function in patients undergoing pneumonectomy Roviaro et al 1986 Click here for more information
  • Study details Kaplan et al 1975 Click here for more information

PROSPECT Recommendations

  • Interpleural strong opioid is not recommended due to limited evidence (Grade D)

Clinical Practice

  • None cited

Transferable Evidence

  • None cited

Thoracotomy-specific Evidence

PROSPECT Recommendations

  • Cryoanalgesia is not recommended due to the risk of neuropathic pain (Grade A), and inconsistent results for analgesia compared with control (Grade A)

Clinical Practice

  • Cryoanalgesia may increase the incidence of chronic pain and neuralgia

Transferable Evidence

  • Cryoanalgesia was of no benefit for reducing VAS pain scores compared with no treatment or sham treatment in two studies in herniorraphy (n=36) Khiroya et al 1986

Thoracotomy-specific Evidence

  • Cryoanalgesia was similar to postoperative indomethacin for pain scores at rest and on movement on days 1 and 2, and supplementary papaveretum use during 0–24 h (n=60) Keenan et al 1983
  • Cryoanalgesia plus intravenous morphine was associated with similar pulmonary function (FVC and FEV1) compared with postoperative interpleural bupivacaine (n=24) Miguel et al 1993
  • Cryoanalgesia was superior to postoperative interpleural LA for reducing the proportion of patients requiring supplementary papaveretum (no p-value) but not the dose of papaveretum or requirement for oral analgesia (n=31) Shafei et al 1990
  • Cryoanalgesia plus intravenous morphine was similar to postoperative interpleural bupivacaine for use of supplementary morphine (n=24) Miguel et al 1993
  • In two of three studies, intra-operative cryoanalgesia was superior to intercostal bupivacaine for reducing supplementary analgesic requirements Orr et al 1981 Click here for more information
  • Cryoanalgesia plus intravenous morphine was superior to postoperative interpleural bupivacaine for reducing pain scores on day 1 (p<0.05) but not on days 2 or 5, and for reducing persistent postthoracotomy pain at 12 weeks (p<0.007) (n=24) Miguel et al 1993
  • Cryoanalgesia was similar to postoperative interpleural LA for pain scores (n=31) Shafei et al 1990
  • Cryoanalgesia was similar to intra-operative intercostal bupivacaine plus postoperative intravenous morphine infusion for pain scores at rest, on movement or on physiotherapy on days 0, 1 or 8, and for supplementary morphine use (n=30) Orr et al 1981
  • In two of three studies, cryoanalgesia was superior to intercostal bupivacaine for reducing pain scores Orr et al 1981 Click here for more information
  • Cryoanalgesia plus intravenous morphine was associated with similar pulmonary function (FVC and FEV1) compared with lumbar epidural morphine (n=24) Miguel et al 1993
  • Cryoanalgesia plus intravenous morphine was superior to lumbar epidural analgesia for reducing the proportion of patients with persistent postthoracotomy pain at 12 weeks (p<0.007) (n=24) Miguel et al 1993
  • Cryoanalgesia was associated with superior PF values on days 1 and 2 (p<0.001) compared with postoperative indomethacin (n=60) Keenan et al 1983
  • In four of seven studies, cryoanalgesia was similar to control for reducing pain scores Brichon et al 1994 Click here for more information
  • In four of seven studies, cryoanalgesia was similar to control for reducing supplementary analgesic requirements Keenan et al 1983 Click here for more information
  • Cryoanalgesia was associated with more frequent long-term pain or neuralgia compared with control Muller et al 1989 Click here for more information
  • Cryoanalgesia was associated with similar pulmonary function compared with control Brichon et al 1994 Click here for more information
  • Cryoanalgesia was inferior to thoracic epidural analgesia for reducing pain scores: on days 1 and 2 (p<0.05) but not days 3–6 (n=87) Brichon et al 1994
  • Cryoanalgesia was inferior to postoperative thoracic epidural infusion of bupivacaine plus fentanyl for reducing supplementary oral analgesic use on days 1–6 (p<0.05) and intravenous analgesic use on days 0 and 1 (p<0.05) (n=87) Gough et al 1988 Click here for more information
  • One of two studies showed that cryoanalgesia was associated with inferior pulmonary function (FVC, but not FEV1) on day 7 (p<0.05) compared with thoracic epidural infusion of bupivacaine plus fentanyl (n=87) Gough et al 1988 Click here for more information
  • Cryoanalgesia plus intravenous morphine was inferior to lumbar epidural morphine for reducing pain scores on day 0 (p<0.05) but not on days 2 or 5 (n=24) Miguel et al 1993
  • Study details Brichon et al 1994 Click here for more information

PROSPECT Recommendations

  • Phrenic nerve block is not recommended to prevent post-thoracotomy shoulder pain due to limited evidence and the risk of impaired pulmonary function (Grade D)

Clinical Practice

  • Phrenic nerve block may interfere with diaphragmatic function and is associated with impaired respiratory function

Transferable Evidence

  • None cited

Thoracotomy-specific Evidence

  • Intra-operative phrenic nerve infiltration with lidocaine was superior to placebo for reducing the proportion of patients with shoulder pain immediately after surgery (p<0.008), total VAS pain scores during 0–2 h (p<0.05) and VRS scores at 30 min (p=0.0028), 1 h (p=0.016), and 2 h (p=0.0018), but not at 3–6 h (n=42) Scawn et al 2001
  • One study showed that intra-operative phrenic nerve infiltration with lidocaine was not significantly different from placebo for the amount of epidural solution used (n=42) Scawn et al 2001
  • Intra-operative phrenic nerve infiltration with lidocaine was associated with similar PaCO2 to placebo (n=42) Scawn et al 2001
  • Study details Scawn et al 2001 Click here for more information

PROSPECT Recommendations

  • Muscle-sparing thoracotomy reduced postoperative pain compared with conventional technique
  • Anterior thoracotomy may reduce postoperative pain compared with posterolateral thoracotomy
  • Intracostal sutures may reduce postoperative pain compared with pericostal sutures
  • Intercostal muscle flap may reduce postoperative pain compared with conventional technique
  • However, the operative technique used should also depend on factors other than postoperative pain (Grade D)

Clinical Practice

  • The recommendations apply to open thoracotomy, not video-assisted thoracotomy

Transferable Evidence

  • None cited

Thoracotomy-specific Evidence

  • Video-assisted thoracic surgery was superior to conventional axillary thoracotomy for reducing pain scores at 3 h (p<0.05), 15 h (p<0.01), 24 h (p<0.05), 48 h (p<0.01) and 72 h (p<0.01) (n=47) Tschernko et al 1996
  • Video-assisted thoracic surgery was superior to conventional axillary thoracotomy for reducing piritramide requirements at 3 h (p<0.01), 15 h (p<0.05), 24 h (p<0.01), 48 h (p<0.01) and 72 h (p<0.01) (n=47) Tschernko et al 1996
  • Video-assisted thoracic surgery was associated with increased PaO2 at 3, 15, 24, 48 and 72 h (p<0.05) compared with conventional axillary thoracotomy, but PaCO2 was not significantly different between groups (n=47) Tschernko et al 1996
  • Video-assisted thoracoscopy was superior to muscle-sparing lateral thoracotomy for reducing pain scores at day 6 (p<0.05), and for reducing ketorolac use (p<0.05) (n=44) Santambrogio et al 1995
  • Video-assisted thoracoscopy was superior to muscle-sparing lateral thoracotomy for reducing the duration of hospital stay (p<0.01) (n=44) Santambrogio et al 1995
  • In three of four studies, muscle-sparing thoracotomy was superior to standard posterolateral thoracotomy for reducing pain scores Akcali et al 2003 Click here for more information
  • In three of four studies, muscle-sparing thoracotomy was superior to standard posterolateral thoracotomy for reducing supplementary analgesic requirements Akcali et al 2003 Click here for more information
  • Intercostal muscle flap reduced pain scores on days 1–2 and at weeks 1–4, 8 and 12 (p<0.05), reduced analgesic requirements (p<0.05), and was associated with a smaller decrease in spirometric values (p<0.05), compared with control (n=114) Cerfolio et al 2005
  • A retrospective analysis found that non-serratus-sparing antero-axillary thoracotomy reduced chest pain on day 1 and from day 14 to 6 months after surgery (p<0.01 to p<0.001), compared with posterolateral thoracotomy; postoperative mortality, morbidity, and hospital stay were similar between groups (n=50) Nomori et al 1997
  • A cohort study found that intracostal sutures (stitches placed on top of the fifth and seventh ribs) for chest closure were less painful than pericostal sutures (stitches placed on top of the fifth rib and through small holes drilled in the bed of the sixth rib) at 2 weeks and 1–3 months after thoracotomy (n=280) Cerfolio et al 2003b
  • Video-assisted thoracoscopy and limited anterolateral thoracotomy were similar for pain scores during 1–72 h, at 2 weeks, 4 weeks and at 3 months, and for morphine use (n=42) Miller et al 2000
  • Video-assisted thoracoscopy and limited anterolateral thoracotomy were similar for the duration of hospital stay (n=42) (Miller 2000)
  • Video-assisted thoracoscopy and limited anterolateral thoracotomy were associated with similar pulmonary function (FEV1) on days 1, 2, 14 and 28 (n=42) Miller et al 2000
  • Three studies showed that muscle-sparing thoracotomy was similar to standard posterolateral thoracotomy for the duration of hospital stay (n=60; n=50; n=30) Akcali et al 2003
  • In three of four studies, muscle-sparing thoracotomy was similar to standard posterolateral thoracotomy for pulmonary function parameters Akcali et al 2003 Click here for more information
  • Study details Tschernko et al 1996 Click here for more information

PROSPECT Recommendations

  • Despite positive but limited procedure-specific evidence and positive transferable evidence, postoperative systemic dexmedetomidine is not recommended at this time because of potential side-effects (Grade D)

Clinical Practice

  • The risk/benefit ratio for dexmedetomidine is unclear. Potential side-effects include hypotension, sedation, dizziness and bradycardia

Transferable Evidence from other Procedures

Thoracotomy-specific Evidence

  • Postoperative intravenous dexmedetomidine, as an adjunct to thoracic epidural analgesia, reduced pain scores at 3 and 4 h (p=0.03), but there was no significant difference at 0, 1, 2, 8, 12, 16 and 24 h (n=28) Wahlander et al 2005
  • Postoperative intravenous dexmedetomidine reduced supplementary analgesic requirements compared with placebo Wahlander et al 2005 Click here for more information
  • Postoperative intravenous dexmedetomidine was associated with a reduction in PaCO2 compared with placebo from 8–24 h (p<0.05), but there was no significant difference from 0–4 h (n=28) Wahlander et al 2005
  • Postoperative intravenous dexmedetomidine decreased heart rates from 0–24 h (p<0.05), and increased the incidence of hypotension (p=0.04), compared with placebo (n=28) Wahlander et al 2005
  • Study details Wahlander et al 2005 Click here for more information

PROSPECT Recommendations

  • Postoperative conventional NSAIDs are recommended based on a reduction in pain scores and analgesic use (Grade A)
  • There is evidence that conventional NSAIDs do not provide additional pain relief in patients receiving epidural analgesia. Therefore it is recommended that conventional NSAIDs are used only if analgesia is inadequate in patients receiving epidural analgesia (Grade A), or paravertebral block (Grade D)
  • Conventional NSAIDs are not recommended in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (Grade B)
  • The use of conventional NSAIDs should depend upon assessment of individual patient risks (bleeding complications including epidural haematoma, cardiovascular morbidity, actual or recent gastroduodenal ulcer history, aspirin-sensitive asthma, renal function and hepatic function) (Grade B)

Clinical Practice

  • Caution is required when conventional NSAIDs are used in patients receiving epidural analgesia concomitantly with medications for thromboprophylaxis, due to the risk of spinal haematoma

Transferable Evidence from Other Procedures

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures Barden et al 2004
  • A meta-analysis of randomised controlled trials, which was performed to evaluate the risk of morphine side-effects in patients treated with NSAIDs, demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritis, urinary retention or respiratory depression Marret et al 2005
  • One study in major upper abdominal surgery showed that rectal piroxicam plus thoracic epidural bupivacaine plus morphine provided no significant benefit over epidural analgesia alone for reducing postoperative pain scores and supplementary analgesic use (n=44) Mogensen et al 1992b
  • Randomised trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with control Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
  • A large randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with impaired bone healing in various animal models and in vitro studies Gajraj 2003

Thoracotomy-specific Evidence

  • In seven of twelve studies, conventional NSAIDs were superior to placebo or control for reducing VAS pain scores Jain et al 1998 Click here for more information
  • Postoperative indomethacin was associated with greater PF values on days 1 and 2 compared with cryoanalgesia (p<0.001) (n=60) Keenan et al 1983
  • Postoperative indomethacin, but not cryoanalgesia, significantly reduced pain scores on movement compared with placebo (p<0.05); there was no significant difference for pain at rest; indomethacin also improved observer grading of pain compared with cryoanalgesia (p<0.05) (n=60) Keenan et al 1983
  • Postoperative metamizol was associated with better pain relief and reduced supplementary analgesic requirements compared with ketorolac Tulunay et al 1996 Click here for more information
  • Nimesulide was associated with less reduction in PEFR compared with ibuprofen (significance not stated), when spinal or epidural analgesia were used (four treatment arms; n=30) McCrory et al 2002
  • Nimesulide and ibuprofen were not significantly different for the incidence of PONV (four treatment arms; n=30) McCrory et al 2002
  • Nimesulide reduced spinal morphine use compared with ibuprofen, for patients receiving spinal analgesia (significance not stated), but bupivacaine/fentanyl use by patients receiving epidural analgesia was not reduced (four treatment arms; n=30) McCrory et al 2002
  • Nimesulide reduced VAS pain scores compared with ibuprofen, at rest and on coughing, for patients receiving spinal analgesia (significance not stated), but not for patients receiving epidural analgesia (four treatment arms; n=30) McCrory et al 2002
  • Conventional NSAIDs did not significantly decrease platelet counts (n=30) Perttunen et al 1992
  • Conventional NSAIDs plus epidural analgesia were superior to epidural analgesia alone for increasing the time between the first and second requests for analgesia (p=0.000001) (n=26) Jain et al 1998
  • Conventional NSAIDs were significantly superior to placebo for increasing the time between the first and second requests for analgesia (p=0.000001) (n=26) Jain et al 1998
  • Ketorolac 10 mg (p<0.05) or 30 mg (p<0.01) significantly reduced the proportion of patients withdrawn for lack of analgesia compared with placebo (n=75) Power et al 1994
  • In seven of eleven studies, conventional NSAIDs were superior to placebo or control for reducing supplementary analgesic use Carretta et al 1996 Click here for more information
  • In two of four studies, conventional NSAIDs plus epidural analgesia were similar to epidural analgesia alone for reducing pain scores Bigler et al 1992 Click here for more information
  • In three of four studies, conventional NSAIDs plus epidural analgesia were similar to epidural analgesia alone for reducing supplementary analgesic requirements Bigler et al 1992 Click here for more information
  • Conventional NSAIDs did not significantly reduce the incidence of PONV compared with placebo or control (n=45; n=19, n=41, n=30, n=42) McCrory et al 2002 Click here for more information
  • Results for pulmonary function parameters were mixed in studies of conventional NSAIDs versus placebo or control Bigler et al 1992 Click here for more information
  • Conventional NSAIDs plus epidural analgesia were associated with similar pulmonary function to epidural analgesia alone Bigler et al 1992 Click here for more information
  • Study details Bigler et al 1992 Click here for more information

PROSPECT Recommendations

  • Postoperative COX-2-selective inhibitors are recommended based on evidence that they provide similar postoperative analgesia to conventional NSAIDs (Grade B)
  • In patients receiving epidural analgesia or paravertebral block, it is recommended that COX-2-selective inhibitors are used only if analgesia is inadequate (Grade B, see Postoperative Conventional NSAIDs)
  • COX-2-selective inhibitors may be preferred to conventional NSAIDs in the peri-operative setting in patients who are at increased risk of bleeding or who are at risk of gastroduodenal ulcer/erosion (Grade B)
  • The use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (cardiovascular morbidity, actual or recent gastroduodenal ulcer history, renal function and hepatic function (Grade B) or aspirin-sensitive asthma (Grade D))

Clinical Practice

  • Thoracic surgery patients may frequently have coronary artery disease or cardiac contra-indications

Transferable Evidence from Other Procedures

  • COX-2-selective inhibitors provide similar postoperative analgesia to conventional NSAIDs Rømsing et al 2004
  • Peri-operative use of rofecoxib (50 mg at 24 hand at 1 to 2 h before total knee arthroplasty, followed by 50 mg daily for 5 days postoperatively, and 25 mg for another 8 days), as part of a multi-analgesic regimen, reduced pain, opioid use, vomiting, sleep disturbance and improved knee range of motion, compared with placebo (n=68) Buvanendran et al 2003
  • Randomised trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation Greenberg et al 2000
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) Nussmeier et al 2006
  • Two clinical trials showed that, in patients who had undergone CABG surgery, COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with impaired bone healing in various animal models and in vitro studies Gajraj 2003

Thoracotomy-specific Evidence

  • None cited

PROSPECT Recommendations

  • Low-dose ketamine cannot be recommended at this time due to a lack of procedure-specific evidence (Grade D), although analgesic data from other procedures are promising

Clinical Practice

  • Ketamine may be of benefit for prevention of chronic pain conditions following thoracotomy, where 40–60% patients may develop chronic pain and/or allodynia. Additionally, it may be of benefit in patients who have opioid tolerance. Ketamine is most often used after induction of GA, but before incision (pre-operatively)

Transferable Evidence

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genito-urinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine Bell et al 2005

Thoracotomy-specific Evidence

  • Postoperative ketamine and pethidine were similarly effective for reducing pain scores (n=30) Dich-Nielsen et al 1992
  • Postoperative ketamine and pethidine were similar for supplementary analgesic use during 0–5 h (n=30) Dich-Nielsen et al 1992
  • Postoperative ketamine and pethidine were similar for the proportion of patients requiring an extra analgesic injection within 2 h, but during 2–3 h ketamine was associated with a lower proportion of patients requiring supplementary analgesia than pethidine (p<0.05) (n=30) Dich-Nielsen et al 1992
  • Postoperative ketamine was associated with a lower PaCO2 than pethidine after 30 min and throughout the study (p<0.05), but there was no difference in PaO2 (n=30) Dich-Nielsen et al 1992
  • Postoperative ketamine and pethidine were not significantly different for the incidence of PONV (n=30) Dich-Nielsen et al 1992
  • Study details Dich-Nielsen et al 1992 Click here for more information

PROSPECT Recommendations

  • Gabapentin/pregabalin cannot be recommended at this time due to a lack of procedure-specific evidence (Grade D), although analgesic data from other procedures are promising

Clinical Practice

  • Gabapentin may be of benefit for prevention of chronic pain conditions following thoracotomy, where 40–60% of patients may develop chronic pain and/or allodynia

Transferable Evidence

  • Studies of gabapentin and pregabalin in mastectomy, abdominal surgery, laparoscopic cholecystectomy, spinal surgery, knee surgery, ear-nose-throat surgery, and nephrectomy showed reductions in postoperative pain and supplementary analgesic requirements for at least 24 h Dahl et al 2004
  • One study showed no significant benefit of gabapentin 800 mg for reducing pain or opioid use compared with placebo in spinal surgery (n=60) Radhakrishnan et al 2005

Thoracotomy-specific Evidence

  • None cited

PROSPECT Recommendations

  • Intravenous PCA strong opioid is recommended if regional analgesic techniques fail or are not possible (Grade A)
  • Even though intravenous PCA strong opioids showed no consistent analgesic benefit over intramuscular PRN opioids (grade B), they are recommended based on greater patient satisfaction compared with regular (fixed-interval) or PRN dosing (grade B); however, fixed-interval intravenous administration titrated to pain intensity is also recognised as an effective mode of administration (grade D)
  • Intramuscular strong opioids are not recommended due to the pain associated with these injections (grade D)
  • There is insufficient evidence to recommend any opioid in preference to another

Clinical Practice

  • Regular administration, titrated for pain intensity, is generally accepted as an effective method of administering strong opioids
  • Most clinical trials showing benefits of intramuscular strong opioids use nurse-administered regimens. In regular clinical practice, full adherence to nurse-administered regimens is not usually achievable, and the full analgesic benefits of intramuscular strong opioids are also not achieved
  • Intramuscular administration of strong opioids is considered to be more painful than intravenous administration; however, the dose and rapidity of intravenous administration should be assessed to minimise the risk of respiratory depression

Transferable Evidence

  • Bolus plus infusion IV PCA morphine conferred a significant benefit over bolus IV PCA morphine alone for reducing postoperative pain scores in abdominal hysterectomy, with no significant difference in overall analgesic consumption El-Falaki et al 2000 Click here for more information
  • Studies in abdominal surgery comparing IV PCA and IM regular/on-request administration of strong opioids showed inconsistent results for postoperative pain scores Choiniere et al 1998 Click here for more information
  • There is mixed evidence in abdominal surgery for a benefit of PCA compared with regular/on-request IM administration of strong opioids for reducing overall opioid consumption, although one study suggests that they produced different patterns of dosing Thomas et al 1995 Click here for more information
  • The incidence of PONV was not significantly different between PCA and IM morphine, in three studies in abdominal surgery (n=126, n=22, n=41) Choiniere et al 1998
  • A systematic review comparing intravenous PCA opioids with intravenous, intramuscular or subcutaneous opioids by injection showed that PCA opioids were associated with greater pain relief, reduced supplementary analgesic requirements (analysis of eleven studies, n=691), and more patients preferred PCA opioids (analysis of four trials, n=352) compared with traditional opioid analgesia Walder et al 2001
  • Strong opioids are associated with adverse effects, including nausea, vomiting, sedation, confusion, paralytic ileus and urinary retention Wheeler et al 2002

Thoracotomy-specific Evidence

  • Postoperative nalbuphine reduced supplementary fentanyl requirements compared with placebo Baxter et al 1989 Click here for more information
  • An intravenous morphine infusion and intramuscular morphine on demand were similar for the total dose of morphine used (n=30) Orr et al 1981
  • An intravenous morphine infusion reduced pain scores at rest compared with intramuscular morphine on demand, between 3 h and day 2 (p=0.001), but not at 1.5 h, or on day 8, or on movement or on physiotheraphy (n=30) Orr et al 1981
  • Intravenous PCA and intramuscular meperidine were similar for duration of hospital stay, but intravenous PCA meperidine increased the proportion of patients leaving hospital within the first week compared with intramuscular meperidine (p<0.05) (n=40) Boulanger et al 1993
  • Intravenous PCA meperidine reduced the proportion of patients requiring an increase in meperidine dose compared with intramuscular meperidine (p<0.05) (n=40) Boulanger et al 1993
  • Intravenous PCA meperidine reduced meperidine use in the recovery room compared with intramuscular meperidine (p<0.001), but not during 0–24 h or 24–48 h (n=40) Boulanger et al 1993
  • PCA-administered strong opioids were associated with better pain relief than intramuscularly administered strong opioids Lehmann et al 1991 Click here for more information
  • Postoperative PCA fentanyl was associated with a significantly higher PaO2 at 13 h, and a significantly lower PaCO2 at 7, 13 and 15 h, than PCA buprenorphine (no p-values reported) (two treatment arms, n=40) Lehmann et al 1991
  • Postoperative PCA buprenorphine was similar to PCA fentanyl for pain scores during 0–24 h, and for the number of analgesic requests (two treatment arms, n=40) Lehmann et al 1991
  • Postoperative nalbuphine 200 µg/kg bolus plus 50 µg/kg/h infusion reduced the incidence of therapeutic failures (defined as at least one measurement of PaCO2 >50 mmHg) compared with placebo or lower concentrations of nalbuphine (p<0.01) (three treatment arms; n=63) Baxter et al 1989
  • Postoperative nalbuphine did not significantly reduce pain scores compared with placebo (three treatment arms; n=63) Baxter et al 1989
  • Postoperative nalbuphine did not significantly reduce the incidence of PONV compared with placebo (three treatment arms; n=63) Baxter et al 1989
  • VAS pain scores and the incidence of PONV were similar for all concentrations of postoperative nalbuphine (three arms; n=63) Baxter et al 1989
  • PCA buprenorphine was similar to PCA fentanyl for the incidence of PONV (two treatment arms, n=40) Lehmann et al 1991
  • Intravenous PCA opioid showed no significant benefit compared with intramuscular opioid for reducing the incidence of PONV Boulanger et al 1993 Click here for more information
  • Intravenous PCA strong opioids were not associated with improved pulmonary function compared with intramuscular strong opioids: FEV1, FVC and arterial PaCO2 (n=40) arterial blood gas levels (two PCA arms, n=60) Boulanger et al 1993
  • Study details Baxter et al 1989 Click here for more information

PROSPECT Recommendations

  • Postoperative weak opioids are recommended to control moderate- (VAS>30<50) or low- (VAS £30) intensity pain in the late postoperative period, only if COX-2-selective inhibitors/conventional NSAIDs plus paracetamol are insufficient or are contra-indicated (grade D)

Clinical Practice

  • It cannot be concluded from procedure-specific evidence that intravenous tramadol is better or worse than intravenous morphine, as the study is under-powered Erolcay et al 2003
  • Opioid adverse effects, especially nausea and dizziness, limit the usefulness of tramadol, but many of the effects are less than for strong opioids

Transferable Evidence

  • None cited

Thoracotomy-specific Evidence

  • Intra-operative plus postoperative intravenous tramadol significantly reduced pain scores compared with placebo at rest at 2, 3, 4 and 8 h (p<0.05) but not at 1, 12, 16, 20 and 24 h, and reduced pain scores on coughing at 2, 3 and 4 h (p<0.05) (n=59) Bloch et al 2002
  • Intra-operative plus postoperative intravenous tramadol significantly reduced intravenous PCA morphine use compared with placebo up to 24 h Bloch et al 2002 Click here for more information
  • Intra-operative plus postoperative intravenous tramadol was associated with a greater vital capacity at 20 h (p<0.05) compared with placebo (n=59) Bloch et al 2002
  • In two studies, intravenous tramadol was similar to epidural morphine for reducing pain scores: at rest and on coughing during the first 24 h (n=59) Bloch et al 2002
  • In two studies, intravenous tramadol was similar to epidural morphine for morphine use Bloch et al 2002 Click here for more information
  • In two studies, intravenous tramadol was associated with a higher PaO2 compared with epidural morphine Bloch et al 2002 Click here for more information
  • Postoperative tramadol and morphine were similar for pain scores at rest and during deep inspiration at 2–24 h, and for measures of pulmonary function (PaCO2 and PaO2) (n=40) Erolcay et al 2003
  • Intra-operative plus postoperative intravenous tramadol did not significantly reduce the incidence of PONV compared with placebo (n=59) Bloch et al 2002
  • Intravenous tramadol was similar to epidural morphine for the incidence of PONV (n=59) Bloch et al 2002
  • Postoperative intravenous PCA tramadol and morphine were similar for the incidence of PONV (n=40) Erolcay et al 2003
  • Study details Bloch et al 2002 Click here for more information

PROSPECT Recommendations

  • Paracetamol alone is not recommended for high-intensity pain (VAS³50 mm) (grade B)
  • Paracetamol is recommended if analgesia is inadequate with regional techniques (Grade B)
  • Paracetamol is recommended as part of a multianalgesic regimen including intravenous PCA strong opioid (grade D)
  • The additional analgesic effect of paracetamol, when combined with conventional NSAIDs/COX-2-selective inhibitors, is limited in major surgery

Clinical Practice

  • None cited

Transferable Evidence

  • Paracetamol is an effective analgesic for the treatment of postoperative pain of moderate intensity Rømsing et al 2002
  • New formulations of intravenous paracetamol may aid accurate administration of paracetamol by producing more predictable plasma concentrations in the immediate postoperative period Holmer Pettersson et al 2004
  • There is evidence that concurrent use of paracetamol and conventional NSAIDs improves pain relief compared with paracetamol alone, but there is no evidence for a superior analgesic effect of the combination compared with conventional NSAIDs alone Altman 2004

Thoracotomy-specific Evidence

  • None cited

PROSPECT Recommendations

  • Thoracic epidural infusion of LA plus strong opioid, continued for 2–3 days after surgery, is recommended based on a reduction of pain compared with systemic analgesia (Grade A)
  • There are not enough data to recommend one specific combination of LA and opioid over another
  • There are not enough data to recommend a specific concentration or volume of LA and strong opioid
  • There are not enough data to recommend lipophilic opioids in preference to hydrophilic opioids or vice versa, in combination with LA

Clinical Practice

  • Postoperative thoracic epidural infusion of strong opioid alone may be used when a catheter is already in place, and hypotension is a problem (e.g. due to blood loss during the procedure)
  • If opiate side-effects are a problem then epidural LA alone may be used
  • PCEA is becoming a more commonly used technique for administering postoperative analgesics via the epidural route
  • Thoracic epidural bolus of strong opioids is a technique that is no longer used
  • Use of heparin or conventional NSAIDs may increase the risk of spinal haematoma due to epidural analgesia

Transferable Evidence

  • A meta-analysis of randomised controlled trials found that both continuous epidural infusion and PCEA analgesia provided superior postoperative analgesia compared with intravenous PCA analgesia Wu et al 2005
  • A meta-analysis found that continuous epidural infusion provided superior analgesia and reduced the incidence of pruritis compared with PCEA analgesia, but was associated with a higher incidence of PONV and motor block Wu et al 2005
  • A meta-analysis of randomised controlled trials found that epidural analgesia significantly decreased the incidence of pulmonary morbidity compared with systemic opioids Ballantyne et al 1998 Click here for more information
  • Epidural administration of strong opioids is associated with side effects including pruritis, PONV, urinary retention, and respiratory depression Chaney 1995

Thoracotomy-specific Evidence

  • Two studies showed a similar incidence of PONV for high volume/low concentration and low volume/high concentration bupivacaine plus sufentanil (n=30; n=60) Laveaux et al 1993 Click here for more information
  • Bupivacaine 0.06% and 0.125%, and 0.1% and 0.2% for peri-operative thoracic epidural infusion were similar for reducing pain scores up to 24 h Burgess et al 1994 Click here for more information
  • In one study, thoracic epidural bupivacaine 0.05% and 0.1% was superior to 0.01% for reducing pain scores on physiotherapy, but not at rest or on coughing, while another study showed thoracic epidural bupivacaine 0.1% and 0.01% were similar Etches et al 1996 Click here for more information
  • In two of four studies, thoracic epidural lipophilic strong opioid was superior to systemic lipophilic strong opioid for reducing the incidence of PONV Guinard et al 1992 Click here for more information
  • One study reported that postoperative thoracic epidural lipophilic strong opioid significantly reduced the duration of hospital stay compared with systemic strong opioid (p=0.02) (n=32) Guinard et al 1992
  • In two of four studies, thoracic epidural lipophilic strong opioid was associated with superior pulmonary function to systemic lipophilic strong opioid Salomaki et al 1991 Click here for more information
  • Thoracic epidural diamorphine provided analgesia of longer duration than intramuscular diamorphine (p<0.05) (n=18) Jacobson et al 1983
  • One of two studies showed that that thoracic epidural hydrophilic strong opioid was associated with superior pulmonary function to systemic hydrophilic strong opioid Hasenbos et al 1986 Click here for more information
  • Tetracaine, for thoracic epidural injection via PCEA, was similar to ropivacaine for pain scores on days 1 and 2, for the total use of LA solution, for the duration of the intervals between PCEA bolus injections, and for measures of pulmonary function (FEV1, FVC, PEFR) (n=40) Guo et al 2003
  • Ropivacaine, for thoracic epidural injection, was superior to bupivacaine for PaO2 (p<0.05) (n=30), but similar for PaCO2, FVC, PEFR and FEV1 (n=52; n=30) Shorrab et al 2003
  • Ropivacaine and bupivacaine, for thoracic epidural injection, were similar for the incidence of PONV (n=52; n=30) Shorrab et al 2003
  • Ropivacaine and bupivacaine, for thoracic epidural injection, were similar for the proportion of patients requesting supplementary analgesics (n=30) Shorrab et al 2003
  • Ropivacaine and bupivacaine, for thoracic epidural injection, were similar for pain scores: at rest at 4, 8, 12, and 24 h (n=30) (Shorrab 2003); at rest and on measurement of PEF during 2–48 h (n=52) Macias et al 2002
  • One study reported that high volume/low concentration and low volume/high concentration bupivacaine plus sufentanil were associated with similar PaCO2 (n=30) Laveaux et al 1993 Click here for more information
  • Two of three studies showed that thoracic epidural strong opioid plus LA was similar to LA alone for the incidence of PONV Bloch et al 2002 Click here for more information
  • High volume/low concentration bupivacaine plus sufentanil was superior to low volume/high for reducing supplementary analgesic requirements Snijdelaar, Hasenbos et al 1994 Click here for more information
  • For peri-operative thoracic epidural infusion of bupivacaine plus sufentanil, high volume/low concentration was similar to low volume/high concentration for reducing pain scores at rest and on exercise during days 0–3 (n=30; n=60) Laveaux et al 1993 Click here for more information
  • In three of four studies, thoracic epidural bupivacaine and thoracic epidural morphine were similar for pain scores El-Baz et al 1984 Click here for more information
  • Thoracic epidural morphine was superior to thoracic epidural bupivacaine for extending the duration of pain relief per injection during 0–72 h (p<0.01), 24–48 h (p<0.02) and 48–72 h (p<0.01), but not during 0–24 h (three treatment arms; n=60) El-Baz et al 1984
  • Thoracic epidural LA and thoracic epidural strong opioid were similar for supplementary analgesic use (n=22; n=30; n=18) Logas et al 1987
  • Thoracic epidural LA and thoracic epidural strong opioid were similar for the incidence of PONV (n=22; n=30) Logas et al 1987
  • Thoracic epidural bupivacaine was associated with similar pulmonary function measures to thoracic epidural morphine El-Baz et al 1984 Click here for more information
  • A continuous infusion of thoracic epidural morphine was superior to intermittent injections for reducing the mean dose of morphine/24-h period (p<0.01) (n=60) El-Baz et al 1984
  • Thoracic epidural bupivacaine plus fentanyl was similar to spinal morphine, or spinal morphine plus systemic ibuprofen, for pain scores (at rest or cough) (n=35) McCrory et al 2002
  • Peri-operative thoracic epidural bupivacaine plus fentanyl with or without systemic nimesulide or ibuprofen was associated with similar pain scores at rest or on coughing to spinal morphine (n=35) McCrory et al 2002
  • Thoracic epidural bupivacaine plus fentanyl was similar to spinal morphine for the use of rescue morphine (n=35) McCrory et al 2002
  • Thoracic epidural bupivacaine plus fentanyl and spinal morphine were associated with a similar incidence of PONV (n=35) McCrory et al 2002
  • Thoracic epidural bupivacaine plus fentanyl was associated with similar PEFR to spinal morphine (n=35) McCrory et al 2002
  • Thoracic epidural strong opioid plus LA was superior for reducing morphine use compared with epidural LA alone Bloch et al 2002 Click here for more information
  • Six of seven studies showed that thoracic epidural LA plus strong opioid was superior to systemic analgesia for reducing pain scores Azad et al 2000 Click here for more information
  • Thoracic epidural LA plus strong opioid reduced supplementary analgesic requirements compared with systemic analgesia Brichon et al 1994 Click here for more information
  • Thoracic epidural LA plus strong opioid was superior to systemic analgesia for reducing the incidence of nausea Azad et al 2000 Click here for more information
  • One of two studies showed that thoracic epidural LA plus strong opioid was superior to systemic analgesia for reducing the duration of hospital stay (p<0.05) (n=563) Boisseau et al 2001 Click here for more information
  • Thoracic epidural bupivacaine plus fentanyl, with or without systemic nimesulide or ibuprofen, was associated with similar PEFR compared with spinal morphine (n=35) McCrory et al 2002
  • For peri-operative thoracic epidural analgesia, fentanyl 2, 5 and 10 µg/ml were similar for the incidence of PONV (three treatment arms; n=89) Tan et al 2004
  • Two of three studies showed that thoracic epidural bupivacaine infusion was superior to systemic analgesia for reducing pain scores Bachmann-Mennenga et al 1993 Click here for more information
  • One of two studies showed that thoracic epidural LA infusion was superior to systemic analgesia for reducing the dose of strong opioid Bachmann-Mennenga et al 1993 Click here for more information
  • Thoracic epidural bupivacaine for anaesthesia and analgesia was superior to intravenous propofol plus fentanyl anaesthesia with postoperative piritramide, for maintaining intra-operative PaO2 and cardiac output (p<0.05) (n=50) Von Dossow et al 2001
  • Thoracic epidural bupivacaine for anaesthesia and analgesia was superior to intravenous propofol plus fentanyl anaesthesia with postoperative piritramide for reducing time to extubation and duration of intensive care unit stay (p<0.04) (n=50) Von Dossow et al 2001
  • For peri-operative thoracic epidural analgesia, fentanyl 5 or 10 µg/ml significantly reduced the proportion of patients with VAS pain score >30 mm (p<0.01) compared with 2 µg/ml (three treatment arms; n=89) Tan et al 2004
  • For peri-operative thoracic epidural analgesia, there was no significant difference between morphine 1 mg and 0.5 mg for PaCO2 (n=60) Geurts et al 1995
  • For peri-operative thoracic epidural analgesia, morphine 1 mg and 0.5 mg were similar for the incidence of PONV (n=60) Geurts et al 1995
  • Nine studies compared the effect of thoracic epidural LA plus strong opioid versus thoracic epidural strong opioid alone on postoperative pain scores Click here for more information
  • Thoracic epidural LA plus lipophilic strong opioid was superior to epidural lipophilic strong opioid alone for reducing pain George et al 1991 Click here for more information
  • Three of six studies showed that thoracic epidural LA plus lipophilic strong opioid reduced supplementary analgesic use compared with epidural lipophilic strong opioid alone Burgess et al 1994 Click here for more information
  • Peri-operative thoracic epidural LA plus lipophilic strong opioid was associated with better maintenance of pulmonary function compared with epidural lipophilic strong opioid alone Burgess et al 1994 Click here for more information
  • For peri-operative thoracic epidural analgesia, morphine 1 mg significantly reduced the proportion of patients who required additional bolus doses compared with morphine 0.5 mg on day 1 (p<0.001), day 2 (p<0.05), and day 3 (p<0.001) (n=60) Geurts et al 1995
  • For peri-operative thoracic epidural analgesia, morphine 1 mg significantly reduced pain scores compared with morphine 0.5 mg, and significantly reduced the proportion of patients experiencing pain on deep breathing, on coughing and on physiotherapy Geurts et al 1995 Click here for more information
  • Bupivacaine 0.06% and 0.125%, for peri-operative thoracic epidural infusion, were associated with similar blood gas levels (n=20) Burgess et al 1994
  • Three studies showed no significant difference between different concentrations of bupivacaine (0.1% and 0.01%; 0.01%, 0.05% and 0.1%; or 0.1% and 0.2%, respectively) for the incidence of PONV (n=18; n=44; n=62) Etches et al 1996
  • One study showed a significant benefit of thoracic epidural bupivacaine 0.05% and 0.1%, compared with 0.01% for reducing opioid use on day 1 (p<0.03) while another study showed no significant difference Liu et al 1995b Click here for more information
  • Bupivacaine 0.06% and 0.125% for peri-operative thoracic epidural infusion were similar for use of fentanyl and proportion of patients requiring fentayl or ketorolac; bupivacaine 0.1% and 0.2% were similar for the amount of epidural solution required Burgess et al 1994 Click here for more information
  • In two studies plus one arm of a third study, thoracic epidural strong opioid plus LA was superior to epidural LA alone for reducing pain scores Bloch et al 2002 Click here for more information
  • Thoracic epidural bupivacaine plus fentanyl was associated with a lower PEFR compared with spinal morphine plus systemic nimesulide (p<0.001) (n=35) McCrory et al 2002
  • Thoracic epidural morphine was similar to intravenous tramadol for the incidence of PONV (n=59) Bloch et al 2002
  • A continuous infusion of thoracic epidural morphine was similar to intermittent injections for reduction in pain scores up to 72 h (n=60) El-Baz et al 1984
  • A continuous infusion of thoracic epidural morphine was associated with similar outcomes of pulmonary function tests compared with intermittent injections: PaO2, PaCO2, FEV1/FVC and inspiratory flow rate (n=60)
  • In two of four studies, thoracic epidural lipophilic strong opioid was similar to systemic strong opioid for supplementary analgesic use Benzon et al 1993 Click here for more information
  • Two of three studies showed that epidural LA plus hydrophilic strong opioid was similar to epidural hydrophilic strong opioid alone for reducing VAS pain scores Burgess et al 1994 Click here for more information
  • Two of three studies showed that epidural LA plus hydrophilic strong opioid was similar to epidural hydrophilic strong opioid alone for supplementary analgesic requirements Etches et al 1996 Click here for more information
  • Thoracic epidural bupivacaine plus hydrophilic strong opioid showed no significant benefit for reducing the incidence of PONV compared with epidural hydrophilic strong opioid alone (n=66; n=20; n =43) Etches et al 1996
  • Thoracic epidural bupivacaine plus lipophilic strong opioid was of no significant benefit for reducing the incidence of PONV compared with epidural lipophilic strong opioid alone (n=21; n=37; n=24; n=40; n=65) George et al 1991
  • Thoracic epidural LA plus hydrophilic strong opioid was associated with similar pulmonary function (FVC, FEV1, FEF, and PEFR), on days 1 and 2, to epidural hydrophilic strong opioid alone (n=43) Singh et al 1997
  • Postoperative thoracic epidural bupivacaine was similar to intravenous buprenorphine for PaO2 and PaCO2 (n=20) Bachmann-Mennenga et al 1993
  • Studies of thoracic epidural strong opioid plus LA versus epidural LA alone showed inconsistent results for pulmonary function parameters Bloch et al 2002 Click here for more information
  • Thoracic epidural bupivacaine was similar to intramuscular morphine on request for the incidence of PONV (two systemic analgesia arms; n=30) Logas et al 1987
  • In three out of four studies, thoracic epidural lipophilic strong opioid and systemic lipophilic strong opioid were similar for pain scores Guinard et al 1992 Click here for more information
  • In three of four studies, thoracic epidural hydrophilic strong opioid and systemic hydrophilic strong opioid were similar for pain scores Hasenbos et al 1986 Click here for more information
  • Thoracic epidural hydrophilic strong opioid was similar to systemic hydrophilic strong opioid for supplementary analgesic use (n=20; n=22) Larsen et al 1986
  • Thoracic epidural hydrophilic strong opioid was similar to systemic hydrophilic strong opioid for the incidence of PONV (n=22) Logas et al 1987
  • Thoracic epidural morphine was of no significant benefit compared with intravenous tramadol for reducing pain scores at rest or on coughing during 0–24 h, or supplementary morphine use (n=59; n=39) Bloch et al 2002
  • Thoracic epidural morphine was associated with a greater PaCO2 at 2 and 6 h compared with intravenous tramadol (no p-value) (n=59) Bloch et al 2002
  • Four of six studies showed that thoracic epidural LA plus strong opioid was associated with similar pulmonary function to systemic analgesia Boisseau et al 2001 Click here for more information
  • Thoracic epidural bupivacaine plus fentanyl was inferior to spinal morphine plus systemic nimesulide for reducing pain scores on days 1 and 2 (p<0.001) (n=35) McCrory et al 2002
  • Study details Azad et al 2000 Click here for more information
  • Thoracic epidural LA + strong opioid versus systemic analgesia
  • Thoracic epidural LA versus systemic analgesia
  • Thoracic epidural LA + strong opioid versus thoracic epidural strong opioid alone
  • Thoracic epidural LA + strong opioid versus thoracic epidural LA alone
  • Thoracic epidural strong opioid versus systemic opioid
  • Thoracic epidural LA versus thoracic epidural strong opioid
  • Thoracic epidural analgesia versus other regional analgesic techniques
  • Thoracic epidural analgesia, miscellaneous studies

PROSPECT Recommendations

  • Lumbar epidural strong opioid is not recommended as the first choice of epidural technique, based on evidence that the thoracic epidural route is more effective for pain relief following thoracotomy (Grade A). However, there is procedure-specific evidence that lumbar epidural hydrophilic strong opioid reduces pain compared with systemic analgesia

Clinical Practice

  • Infusion techniques are more convenient for use in clinical practice and adequate analgesia is more likely to be maintained than with bolus administration of lumbar epidural strong opioid
  • Unlike morphine, there is a ceiling effect to the respiratory depressant effect of nalbuphine; however, less morphine is required for comparable analgesia
  • Use of heparin or conventional NSAIDs may increase the risk of spinal haematoma due to epidural analgesia

Transferable Evidence

  • A meta-analysis of randomised controlled trials found that both continuous epidural infusion and PCEA analgesia provided superior postoperative analgesia compared with intravenous PCA analgesia Wu et al 2005
  • A meta-analysis found that continuous epidural infusion provided superior analgesia and reduced the incidence of pruritis compared with PCEA analgesia, but was associated with a higher incidence of PONV and motor block Wu et al 2005
  • A meta-analysis of randomised controlled trials found that epidural analgesia significantly decreased the incidence of pulmonary morbidity compared with systemic opioids Ballantyne et al 1998 Click here for more information
  • Epidural administration of strong opioids is associated with side effects including pruritis, PONV, urinary retention, and respiratory depression Chaney 1995

Thoracotomy-specific Evidence

  • Lumbar and thoracic epidural bupivacaine plus fentanyl were similar for the incidence of PONV (n=82) Sahin et al 1994
  • One study showed that morphine and nalbuphine, for intra-operative lumbar epidural injection, were associated with a similar incidence of nausea (five treatment arms; n=52) Baxter et al 1991
  • One study showed that lumbar epidural morphine was superior to all concentrations of lumbar epidural nalbuphine for reducing PCA fentanyl use (p<0.01) (five treatment arms; n=52) Baxter et al 1991
  • Lumbar epidural morphine was superior to all concentrations of lumbar epidural nalbuphine for reducing pain Baxter et al 1991 Click here for more information
  • Lumbar epidural fentanyl plus morphine significantly reduced the proportion of patients with pains (other than lower back pain, i.e. incisional pain, radiculopathy) (p=0.034) compared with epidural morphine alone (n=60) Radpay et al 2003
  • Lumbar epidural nalbuphine was superior to lumbar epidural morphine for reducing the proportion of patients requiring naloxone for PaCO2>50 mmHg Baxter et al 1991 Click here for more information
  • One study showed that epidural infusion was associated with a higher PaCO2 compared with epidural boluses of diamorphine (p=0.005) (n=22) Patrick et al 1991
  • High volume fentanyl for postoperative lumbar epidural analgesia was superior to low volume fentanyl for overall VRS pain scores at certain time points, levels of activity and incision points Thomson et al 1995 Click here for more information
  • High volume and low volume fentanyl, for postoperative lumbar epidural analgesia, were associated with similar use of ketorolac and fentanyl (n=66) Thomson et al 1995
  • High volume and low volume fentanyl, for postoperative lumbar epidural analgesia, were associated with a similar incidence of PONV (n=66) Thomson et al 1995
  • Thoracic and lumbar epidural hydrophilic strong opioid were associated with similar pulmonary function parameters: FVC, FEV1 and PEFR (n=20) Grant et al 1993
  • In three of four studies, lumbar and thoracic epidural lipophilic strong opioid were associated with similar pulmonary function Guinard et al 1992 Click here for more information
  • Thoracic and lumbar epidural hydrophilic strong opioid were similar for the incidence of PONV (n=20) Grant et al 1993
  • Six studies showed that lumbar and thoracic epidural lipophilic strong opioid were similar for the incidence of PONV (n=29; n=52; n=32; n=23; n=30; n=22) Bouchard et al 1995 Click here for more information
  • Lumbar administration was superior to thoracic administration of epidural hydrophilic strong opioid for reducing epidural morphine use, but not epidural fentanyl use, during 0–24 h (p<0.05) (n=20) Grant et al 1993
  • In four of six studies, lumbar and thoracic epidural lipophilic strong opioid were similar for strong opioid use Bouchard et al 1995 Click here for more information
  • In five of six studies, lumbar epidural lipophilic strong opioid was similar to thoracic lipophilic epidural strong opioid for pain scores at rest Bouchard et al 1995 Click here for more information
  • For postoperative lumbar epidural injection, sufentanil 30, 50 and 75 µg were similar for pain scores 15 and 30 min after each dose, for the mean number of doses of sufentanil during 24 h, and for the mean duration of analgesia (three treatment arms; n=22) Whiting et al 1988
  • Two of three studies showed that lumbar epidural hydrophilic strong opioid was associated with superior pulmonary function to systemic hydrophilic strong opioid Shulman et al 1984 Click here for more information
  • Lumbar epidural hydrophilic strong opioid was superior to systemic hydrophilic strong opioid for reducing pain scores Miguel et al 1993 Click here for more information
  • In two of four studies, lumbar epidural lipophilic strong opioid was superior to systemic lipophilic strong opioid for reducing supplementary analgesic use Grant et al 1992 Click here for more information
  • In two of four studies, lumbar epidural lipophilic strong opioid was superior to systemic lipophilic strong opioid for reducing pain scores Baxter et al 1994 Click here for more information
  • Ten studies compared lumbar with thoracic epidural analgesia; scatter plots to illustrate the spread of average pain scores between studies show a trend towards increased pain scores with lumbar epidural analgesia Click here for more information
  • Epidural infusion of diamorphine did not significantly reduce pain scores during 0–18 h, or the total use of diamorphine, compared with epidural boluses of diamorphine (n=22) Patrick et al 1991
  • One study showed that epidural infusion and epidural boluses of diamorphine were similar for the incidence of PONV (n=22) Patrick et al 1991
  • Postoperative lumbar epidural fentanyl plus morphine was similar to lumbar epidural morphine alone for the incidence of PONV (n=60) Radpay et al 2003
  • Nalbuphine 10 mg and 20 mg lumbar epidural were not significantly different for pain scores at 1 and 2 h; 2/4 patients who received nalbuphine 10 mg, and 5/5 patients who received nalbuphine 20 mg were withdrawn from the study within 3 h due to inadequate analgesia (n=9) Etches et al 1991
  • For postoperative lumbar epidural injection, sufentanil 75 µg was associated with a greater PaCO2 than sufentanil 30 µg (p<0.05) (three treatment arms; n=22) Whiting et al 1988
  • One of two studies showed that lumbar was inferior to thoracic epidural hydrophilic strong opioid for reducing pain scores Yang et al 1993 Click here for more information
  • Lumbar was inferior to thoracic epidural bupivacaine plus fentanyl, for reducing the epidural infusion rate during 0–8 h (p=0.028) but not at 12 or 16 h (n=46) Hurford et al 1993
  • In one of two studies, lumbar was inferior to thoracic administration of epidural bupivacaine plus fentanyl for reducing pain scores and for reducing the epidural infusion rate Sahin et al 1994 Click here for more information
  • Two studies showed that lumbar epidural hydrophilic strong opioid was similar to systemic hydrophilic strong opioid for the duration of hospital stay (n=30; n=30) Slinger et al 1995
  • One study showed no significant benefit of lumbar epidural hydrophilic strong opioid for reducing the incidence of PONV compared with systemic hydrophilic strong opioid (n=30) Shulman et al 1984
  • In three of four studies, lumbar epidural lipophilic strong opioid was associated with similar pulmonary function to systemic lipophilic strong opioid Grant et al 1992 Click here for more information
  • Lumbar epidural lipophilic strong opioid did not reduce the incidence of PONV compared with systemic lipophilic strong opioid in three of four studies Baxter et al 1994 Click here for more information
  • Study details Baxter et al 1994 Click here for more information
  • Lumbar epidural analgesia, miscellaneous studies
  • Lumbar versus thoracic epidural analgesia
  • Lumbar strong opioid versus systemic strong opioid

PROSPECT Recommendations

  • Thoracic epidural corticosteroid is not recommended because there are limited data (Grade D)
  • Epidural epinephrine is recommended if a low dose of epidural LA and/or opioid is used (Grade B)

Clinical Practice

  • None cited

Transferable Evidence

  • Three studies in major thoracic or abdominal surgery showed that addition of epinephrine 1.5–2 µg/ml to thoracic epidural local anaesthetic plus strong opioid reduced pain intensity Niemi et al 1998 Click here for more information
  • Epinephrine 1.5–2 µg/ml was associated with reduced frequency of pruritis (p<0.002; n=36) Niemi et al 2003

Thoracotomy-specific Evidence

  • Addition of epinephrine to thoracic epidural strong opioid was superior to epidural strong opioid alone for reducing use of epidural fentanyl, and for extending the duration of analgesia Click here for more information
  • Postoperative epidural methylprednisolone did not significantly reduce pain scores at rest and on mobilisation, or total morphine requirement over 48 h, compared with placebo (n=24) Blanloeil et al 2001
  • Postoperative epidural methylprednisolone did not significantly reduce the incidence of PONV compared with placebo (n=24) Blanloeil et al 2001
  • Addition of epinephrine to postoperative thoracic epidural strong opioid did not significantly reduce pain scores compared with epidural strong opioid alone Baron et al 1996 Click here for more information
  • Addition of epinephrine to postoperative thoracic epidural strong opioid did not significantly reduce the incidence of PONV compared with epidural strong opioid alone (n=34; n=23) Baron et al 1996
  • Addition of epinephrine to postoperative thoracic epidural strong opioid was associated with similar pulmonary function to epidural strong opioid alone: FEV1, FVC (n=34) PaCO2 (n=23) Baron et al 1996
  • Study details Blanloeil et al 2001 Click here for more information

PROSPECT Recommendations

  • Spinal strong opioid should be administered only as a single pre-operative bolus dose for postoperative analgesia (grade A) (see Pre-operative Spinal Analgesia)
  • Repeated peri-operative doses by the spinal route are not recommended because they are not considered to be safe or practical (grade D)

Clinical Practice

  • Although one study shows that postoperative spinal fentanyl was superior to placebo or no treatment for VAS pain scores, the catheters used in the technique are no longer available
  • Spinal anaesthetics are generally administered as a single pre-operative bolus, and repeated peri-operative doses are not considered to be safe or practical

Transferable Evidence

  • Spinal administration of strong opioids is associated with side effects including pruritis, PONV, urinary retention, and respiratory depression Chaney 1995

Thoracotomy-specific Evidence

  • Postoperative spinal fentanyl was superior to placebo or no treatment for reducing VAS pain scores at 1 h (p<0.001) and during 2–10 h (p=0.03), and VRS pain scores at rest (p<0.001), on coughing (p<0.001) and on movement (p=0.025) (two control arms; n=30) Sudarshan et al 1995
  • Postoperative spinal fentanyl was superior to placebo or no treatment for reducing intravenous morphine use during 0–4 h (p=0.002), but not at 10 h (two control arms; n=30) Sudarshan et al 1995
  • Spinal morphine was similar to thoracic epidural bupivacaine plus fentanyl with or without systemic nimesulide or ibuprofen for reducing pain scores at rest or on coughing (n=35) McCrory et al 2002
  • Spinal morphine was similar to thoracic epidural bupivacaine plus fentanyl for reducing rescue morphine use (n=35) McCrory et al 2002
  • One study showed that spinal morphine was similar to thoracic epidural bupivacaine plus fentanyl for the incidence of PONV (n=35) McCrory et al 2002
  • Postoperative spinal fentanyl was associated with a greater PEFR than placebo or no treatment at 1 h (p<0.001) and 2–10 h (p=0.009) but there was no significant difference between groups for PaCO2 at 30 min or up to 180 min (two control arms; n=30) Sudarshan et al 1995
  • Spinal morphine was associated with a similar PEFR to thoracic epidural bupivacaine plus fentanyl (n=35) McCrory et al 2002
  • Spinal morphine plus systemic nimesulide (but not ibuprofen) was superior to epidural bupivacaine plus fentanyl for reducing pain scores McCrory et al 2002 Click here for more information
  • Spinal morphine plus systemic nimesulide (but not ibuprofen) was associated with a higher PEFR than epidural bupivacaine plus fentanyl (p<0.001) (n=35) McCrory et al 2002
  • Study details Sudarshan et al 1995 Click here for more information

PROSPECT Recommendations

  • Paravertebral block with LA, as a bolus followed by a continuous infusion for 2–3 days, is recommended, based on evidence that the technique provides comparable postoperative analgesia to thoracic epidural with LA (Grade A), and may be associated with fewer adverse effects (Grade A)
  • Paravertebral block cannot be recommended in preference to thoracic epidural with LA plus opioid, and vice versa, because of limited data
  • There is not enough evidence to recommend one LA in preference to another, or any particular concentration or volume of any LA

Clinical Practice

  • A paravertebral block can be used in combination with other analgesic techniques, as part of a multimodal analgesic regimen
  • Paravertebral LA may be administered as a bolus at the end of surgery
  • Paravertebral block is used less frequently than epidural analgesia in clinical practice

Transferable Evidence

  • Paravertebral block improved pain relief, reduced opioid use and was associated with improved pulmonary function compared with placebo in pleurectomy Mozell et al 1991
  • Four studies in breast surgery found that paravertebral block was associated with analgesic benefits compared with control Kairaluoma et al 2004 Click here for more information
  • Bilateral paravertebral block combined with general anaesthesia reduced pain scores, supplementary analgesic use, and the incidence of PONV, compared with general anaesthesia alone in laparoscopic cholecystectomy (n=60) Naja et al 2004

Thoracotomy-specific Evidence

  • Paravertebral bupivacaine was superior to interpleural bupivacaine plus wound infiltration for reducing pain scores on day 2 (p<0.05) but not on day 1 (n=40) Wedad et al 2004
  • Paravertebral bupivacaine plus fentanyl was associated with superior pulmonary function to thoracic epidural bupivacaine plus fentanyl for FEV1 and FVC during 0–72 h (n=50) Bimston et al 1999
  • Paravertebral LA was associated with reduced frequency of postoperative complications compared with thoracic epidural LA Dhole et al 2001 Click here for more information
  • Fewer patients receiving paravertebral LA compared with thoracic epidural LA + opioid suffered pruritis (0 and 2 patients, respectively) or urinary retention (0 and 3 patients, respectively) in one study De Cosmo et al 2002
  • A systematic review comparing paravertebral and epidural blockade for thoracotomy found no significant difference for postoperative pain scores or morphine use, but showed a significant benefit of paravertebral block for reducing postoperative pulmonary complications and side-effects Davies et al 2006 Click here for more information
  • Paravertebral bupivacaine was similar to intercostal bupivacaine for pain scores at rest and on coughing, or supplementary morphine use during 0–48 h (n=30) Perttunen et al 1995
  • Paravertebral bupivacaine was similar to intercostal bupivacaine for the incidence of PONV (n=30) Perttunen et al 1995
  • Paravertebral bupivacaine was similar to intercostal bupivacaine for PaO2, and FEV1 (n=30) Perttunen et al 1995
  • Paravertebral and interpleural bupivacaine were similar for pain scores and morphine use during 0–48 h (n=45; n=11) Richardson et al 1995
  • Paravertebral bupivacaine was associated with superior pulmonary function to interpleural bupivacaine during 0–48 h: FVC, FEV1 (p=0.001; n=45); FVC, FEV1 (p<0.05; n=11) Richardson et al 1995
  • One of two studies showed that paravertebral bupivacaine was associated with superior pulmonary function to thoracic epidural bupivacaine plus fentanyl Kaiser et al 1998 Click here for more information
  • Paravertebral bupivacaine was superior to interpleural bupivacaine plus wound infiltration for reducing pethidine use (p<0.05) (n=40) Wedad et al 2004
  • Paravertebral bupivacaine was associated with superior pulmonary function (FVC, FEV1, PEFR) to interpleural bupivacaine plus wound infiltration on days 1 and 2 (p<0.05) (n=40) Wedad et al 2004
  • One of two studies showed that paravertebral bupivacaine was superior to lumbar epidural morphine for reducing pain scores Richardson et al 1993 Click here for more information
  • Paravertebral bupivacaine was superior to lumbar epidural morphine for reducing the incidence of vomiting (p<0.05) but not the incidence of nausea (n=20) Richardson et al 1993
  • Paravertebral bupivacaine was associated with similar pulmonary function to lumbar epidural morphine (PEFR, FEV1 and FVC) (n=20) Richardson et al 1993
  • For paravertebral block, lidocaine and bupivacaine were associated with similar pulmonary function: PEFR, FVC and FEV1 (n=43) Barron et al 1999
  • For paravertebral block, lidocaine and bupivacaine were similar for pain scores and morphine use: during 0–72 h (n=43) Barron et al 1999
  • Continuous infusion and intermittent boluses of postoperative paravertebral bupivacaine were associated with similar PaO2 (n=30) Catala et al 1996
  • A postoperative infusion of paravertebral bupivacaine was superior to intermittent boluses for reducing pain scores at rest and on movement at 4, 10, 20 and 48 h (p=0.003), but not at 0 and 1 h (n=30) Catala et al 1996
  • Studies comparing paravertebral LA versus thoracic epidural LA plus strong opioid showed mixed results for postoperative pain scores Kaiser et al 1998 Click here for more information
  • For paravertebral block, ropivacaine 0.5% was associated with greater PEFR compared with ropivacaine 0.25% and 0.375% (p=0.004) (n=60) Gamal et al 2003
  • For paravertebral block, ropivacaine 0.5% was superior to 0.25% and 0.375% for reducing the incidence of PONV (p<0.05) (n=60) Gamal et al 2003
  • Six studies plus one arm of a study, out of eight studies, showed that paravertebral bupivacaine was superior to control for reducing pain scores (systemic analgesia available to all patients) Barron et al 1999 Click here for more information
  • Seven studies showed that paravertebral bupivacaine was superior to control for reducing supplementary analgesic use (systemic analgesia available to all patients) Barron et al 1999 Click here for more information
  • Five studies, plus two arms from a further two studies, showed that paravertebral bupivacaine was associated with superior pulmonary function to control (systemic analgesia available to all patients) Barron et al 1999 Click here for more information
  • For paravertebral block, ropivacaine 0.5% was superior to 0.25% and 0.375% for reducing the use of supplementary morphine during 0–24 h (p=0.008) and 24–48 h (p=0.005) (n=60) Gamal et al 2003
  • For paravertebral block, ropivacaine 0.5% was superior to 0.25% (p=0.001) and 0.375% (p=0.02) for reducing pain scores at rest and on coughing during 0–48 h (n=60) Gamal et al 2003
  • For paravertebral block, lidocaine and bupivacaine were associated with a similar duration of hospital stay (n=43) Barron et al 1999
  • Paravertebral LA and thoracic epidural LA were similar for reducing postoperative pain Dhole et al 2001 Click here for more information
  • Paravertebral and thoracic epidural administration of LA were not significantly different for the incidence of persistent chest pains at 6 months (n=95) Richardson et al 1999
  • Paravertebral bupivacaine was similar to thoracic epidural bupivacaine for supplementary analgesic requirements Dhole et al 2001 Click here for more information
  • Paravertebral LA was similar to thoracic epidural LA plus strong opioid for reducing supplementary analgesic use De Cosmo et al 2002 Click here for more information
  • Paravertebral bupivacaine plus fentanyl was similar to thoracic epidural bupivacaine plus fentanyl for the number of requests for analgesia (n=50) Bimston et al 1999
  • One of two studies showed that paravertebral bupivacaine reduced the incidence of PONV compared with thoracic epidural bupivacaine (no p-value) (n=95) Richardson et al 1999 Click here for more information
  • Paravertebral bupivacaine (± fentanyl) was similar to thoracic epidural bupivacaine plus fentanyl for the incidence of PONV (n=50, n=50) Bimston et al 1999
  • Paravertebral bupivacaine was similar to thoracic epidural bupivacaine for the duration of hospital stay (n=95) Richardson et al 1999
  • Paravertebral bupivacaine (± fentanyl) was similar to thoracic epidural bupivacaine plus fentanyl for the duration of intensive care unit or hospital stay (n=50; n=50; n=30) Bimston et al 1999
  • Two of four studies showed that paravertebral bupivacaine was associated with superior pulmonary function to thoracic epidural bupivacaine Richardson et al 1995 Click here for more information
  • Continuous infusion did not significantly reduce morphine use compared with intermittent boluses of postoperative paravertebral bupivacaine (n=30) Catala et al 1996
  • In one of two studies, paravertebral bupivacaine was inferior to peri-operative lumbar epidural morphine for reducing cumulative morphine use at 14–70 h (p<0.05) (n=72) Richardson et al 1993 Click here for more information
  • Paravertebral LA plus strong opioid increased pain scores compared with thoracic epidural LA plus strong opioid at 8 h (p=0.007), 16 h (p=0.023), 24 h (p=0.02), and 32 h (p=0.033), but not at 0 or 40–96 h (n=50) Bimston et al 1999
  • Paravertebral bupivacaine did not significantly reduce the duration of hospital stay compared with control (systemic analgesia available to all patients) (two treatment arms; n=63) Barron et al 1999
  • Paravertebral bupivacaine did not significantly reduce the incidence of PONV compared with control (systemic analgesia available to all patients) (n=20) Carabine et al 1995
  • Study detail Richardson et al 1994 Click here for more information
  • Paravertebral block, miscellaneous studies
  • Paravertebral block versus other regional analgesic techniques
  • Paravertebral block versus control
  • Most studies of paravertebral block included postoperative administration, with or without an additional pre- or intra-operative bolus; all results (with the exception of Richardson et al 1994

PROSPECT Recommendations

  • Intercostal nerve block with LA is recommended, if epidural analgesia and paravertebral block are not possible, as an infusion via a catheter, continued for 2–3 days postoperatively, which should be preceded by an intra-operative bolus dose (Grade D)
  • There is not enough evidence to recommend one LA in preference to another, or any particular concentration or volume of any LA

Clinical Practice

  • Infusion techniques for intercostal nerve block are more convenient for use in clinical practice and adequate analgesia is more likely to be maintained than with intermittent bolus administration

Transferable Evidence

  • Two studies in open cholecystectomy and one study in upper abdominal surgery showed that intercostal nerve block did not significantly reduce pain scores compared with control (n=37, n=40, n=66) Maidatsi et al 1998
  • In open cholecystectomy, intercostal nerve block reduced supplementary opioid use compared with control in one study (n=37) Maidatsi et al 1998
  • A meta-analysis found that intercostal nerve block tended to reduce the incidence of pulmonary complications compared with systemic opioids, but these differences did not achieve statistical significance. There were no significant differences in surrogate measures of pulmonary function (FEV1, FVC, and PEFR) Ballantyne et al 1998
  • The incidence of pneumothorax following intercostal nerve block in thoracic and upper abdominal surgery has been reported in the range of 0.073% to 19% Shanti et al 2001

Thoracotomy-specific Evidence

  • Two of three studies showed that repeat dose intercostal bupivacaine was superior to control for reducing pain scores Bachmann-Mennenga et al 1993 Click here for more information
  • Continuous infusion intercostal LA was superior to control for reducing pain scores during 0–24 h or during 24–48 h (p=0.03), whenever bupivacaine was administered (n=20) Dryden et al 1993
  • Two of three studies showed that repeat dose intercostal bupivacaine reduced supplementary analgesic requirements compared with control Bachmann-Mennenga et al 1993 Click here for more information
  • Continous infusion intercostal LA reduced morphine use compared with control, during 0–24 h or 24–48 h (p=0.04), whenever bupivacaine was administered (n=20) Dryden et al 1993
  • Repeat dose intercostal bupivacaine was associated with superior maintenance of pulmonary function compared with control Bachmann-Mennenga et al 1993 Click here for more information
  • Repeat dose intercostal LA was associated with similar postoperative pain scores to thoracic epidural analgesia Asantila et al 1986 Click here for more information
  • Three of three studies showed that repeat dose intercostal LA was similar to thoracic epidural analgesia for supplementary analgesic use (n=30; n=20; n=29) Asantila et al 1986 Click here for more information
  • Continuous infusion intercostal LA was similar to thoracic epidural analgesia for postoperative fentanyl use (n=47) Debreceni et al 2003
  • Repeat dose intercostal LA was associated with similar pulmonary function to thoracic epidural analgesia Asantila et al 1986 Click here for more information
  • Continuous infusion intercostal LA was associated with similar pulmonary function (PEFR, FVC, FEF, and FEV1/FVC) to thoracic epidural analgesia (n=47) Debreceni et al 2003
  • Continuous infusion intercostal bupivacaine was similar to thoracic epidural analgesia for the incidence of PONV (n=47) Debreceni et al 2003
  • Three studies showed that repeated intercostal bupivacaine injections were associated with similar pulmonary function to single intra-operative injections Asantila et al 1986 Click here for more information
  • Two of three studies showed that repeated intercostal bupivacaine injections were similar to single intra-operative injections for reducing supplementary analgesic use (n=20; n=22) Scheinin et al 1987b Click here for more information
  • Repeat intercostal bupivacaine injections, pre- or intra- plus postoperatively, were similar to single intra-operative injections for reducing pain scores (n=20; n=21; n=22) Asantila et al 1986 Click here for more information
  • Continuous infusion intercostal LA was inferior to thoracic epidural analgesia for reducing pain scores at 4, 8, and 12 h (p<0.05) but not at 16 and 20 h (n=47) Debreceni et al 2003
  • Limited data comparing intercostal LA with thoracic epidural analgesia could be meta-analysed; however, a scatter plot shows that both techniques were associated with similar postoperative pain scores at 1 h, although pain scores tended to be marginally higher at day 1/24 h following intercostal LA Click here for more information
  • Continuous infusion intercostal bupivacaine was similar to control for the incidence of nausea (n=20) Dryden et al 1993
  • Study detail Bachmann-Mennenga et al 1993 Click here for more information
  • Intercostal nerve block versus other regional techniques
  • Intercostal nerve block, repeat versus single injection
  • Intercostal nerve block versus control
  • Studies of intercostal LA included single dose, repeated dose, and continuous infusion regimens. Single dose, repeat dose, and continuous infusion regimens have been analysed separately; all results for repeat dose and continuous infusion studies are listed below

PROSPECT Recommendations

  • Interpleural LA is not recommended due to lack of efficacy (Grade A) as well as potential toxicity associated with high absorption of LA (Grade D)

Clinical Practice

  • Interpleural nerve blocks are associated with a high absorption of LA, because of the large surface area exposed to the drug

Transferable Evidence from other Procedures

  • None cited

Thoracotomy-specific Evidence

  • Postoperative interpleural bupivacaine was associated with similar spirometric test results (FVC, FEV1) during days 0–5 and at 12 weeks compared with intra-operative cryoanalgesia plus intravenous morphine (n=24) Miguel et al 1993
  • Postoperative interpleural bupivacaine was similar to intra-operative cryoanalgesia plus intravenous morphine for supplementary analgesic use (n=24) Miguel et al 1993
  • Postoperative interpleural bupivacaine was superior to intra-operative cryoanalgesia for reducing the proportion of patients who required papaveretum (no p value), but not the mean dose of papaveretum or the number of requests for oral analgesia (n=31) Shafei et al 1990
  • Postoperative interpleural bupivacaine was similar to intra-operative cryoanalgesia for average pain scores (n=31) Shafei et al 1990
  • Postoperative interpleural bupivacaine was associated with similar blood gas levels to postoperative intercostal bupivacaine (n=20) Bachmann-Mennenga et al 1993
  • Postoperative interpleural bupivacaine was superior to intra-operative intercostal bupivacaine for reducing papaveretum use (p=0.0012), the proportion of patients requiring papaveretum (no p value) and the number of requests for oral analgesia (p=0.0047) (n=32) Shafei et al 1990
  • Postoperative interpleural bupivacaine was similar to intra-operative intercostal bupivacaine for average pain scores (n=32) Shafei et al 1990
  • Interpleural bupivacaine was similar to paravertebral bupivacaine for pain scores and opioid use during 0–48 h (n=45; n=11) Richardson et al 1995
  • Postoperative interpleural bupivacaine and lumbar epidural morphine were associated with similar pulmonary function (FVC and FEV1) (n=20) Miguel et al 1993
  • Interpleural block plus wound infiltration was associated with superior pulmonary function compared with thoracic epidural bupivacaine on day 1 (p<0.05) but on day 2 thoracic epidural bupivacaine was superior to interpleural block plus wound infiltration (p<0.05) (n=40) Wedad et al 2004
  • Interpleural bupivacaine was associated with similar levels of blood gases compared with thoracic epidural bupivacaine (n=30) Bachmann-Mennenga et al 1993
  • Use of both paravertebral and lateral catheters for administration of postoperative interpleural bupivacaine was superior to use of a single paravertebral catheter for reducing supplementary opioid use Ferrante et al 1991 Click here for more information
  • Bupivacaine 0.25% and 0.5% for interpleural injection were similar for pain scores after each injection, and for supplementary analgesic use (n=18) Elman et al 1993
  • Postoperative interpleural bupivacaine was associated with superior pulmonary function compared with control Bachmann-Mennenga et al 1993 Click here for more information
  • Postoperative interpleural bupivacaine was superior to control for extending the duration of analgesia: after the 2nd injection (p<0.005), but not the 1st injection (n=15) Symreng et al 1989
  • In five of ten studies, postoperative interpleural LA was superior to control for reducing supplementary analgesic use Broome et al 1993 Click here for more information
  • Five of ten studies showed that postoperative interpleural LA was superior to control (systemic analgesia available to all patients) for reducing pain Broome et al 1993 Click here for more information
  • Interpleural bupivacaine was associated with inferior pulmonary function compared with paravertebral bupivacaine: FVC and FEV1 during days 0–2 (p<0.003) (n=45) FVC at 12 and 36 h (p<0.05), FEV1 at 12, 24, 36 and 48 h (p<0.05) (n=11) Richardson et al 1995
  • Interpleural bupivacaine was inferior to intercostal bupivacaine for reducing pain scores (no p-value) and supplementary buprenorphine use (p<0.01) (n=20) Bachmann-Mennenga et al 1993
  • Interpleural bupivacaine plus wound infiltration was associated with inferior pulmonary function compared with paravertebral bupivacaine (FVC, FEV1, PEFR) on days 1 and 2 (p<0.05) (n=40) Wedad et al 2004
  • Addition of epinephrine to the LA solution for interpleural nerve block was of no significant benefit over LA alone, for extending the duration of analgesia (n=24) Kambam et al 1989
  • Postoperative interpleural bupivacaine was inferior to intra-operative cryoanalgesia plus intravenous morphine for reducing pain scores and persistent postthoracotomy pain Miguel et al 1993 Click here for more information
  • For administration of postoperative interpleural bupivacaine, use of both paravertebral and lateral catheters was of no significant benefit over use of a single paravertebral catheter for reducing pain scores at 0–4 h (n=14) Ferrante et al 1991
  • Addition of epinephrine to the LA solution for interpleural nerve block was of no significant benefit over LA alone, for reducing pain scores (n=14; n=24) Ferrante et al 1991
  • Addition of epinephrine to the LA solution for interpleural nerve block was of no significant benefit over LA alone, for reducing opioid use or the frequency of interpleural injections during 24 h (n=14) Ferrante et al 1991
  • Interpleural bupivacaine plus wound infiltration was inferior to paravertebral bupivacaine for reducing pain scores on day 2 (p<0.05) but not on day 1, and for reducing pethidine use (p<0.05) (n=40) Wedad et al 2004
  • Two studies showed that interpleural LA was inferior to lumbar epidural strong opioid for reducing pain scores Miguel et al 1993 Click here for more information
  • Interpleural block plus wound infiltration was inferior to thoracic epidural bupivacaine for reducing pain scores on day 2 (p<0.05) but not on day 1, and for reducing pethidine use (p<0.05) (n=40) Wedad et al 2004
  • One of two studies showed that interpleural bupivacaine was inferior to thoracic epidural bupivacaine for reducing pain scores (no p value) and buprenorphine use (p<0.01) (n=30) Brockmeier et al 1994 Click here for more information
  • Interpleural bupivacaine increased persistent postthoracotomy pain at 12 weeks (p<0.007) compared with intravenous morphine (n=21) Miguel et al 1993
  • One study showed that postoperative interpleural morphine and intravenous morphine were associated with similar pulmonary function (FEV1) and blood gas levels (n=17) Welte et al 1992
  • Postoperative interpleural morphine and intravenous morphine were similar for pain scores and supplementary morphine use at 0–6 h, 22–24 h and at 1 week (n=17) Welte et al 1992
  • Postoperative interpleural bupivacaine did not significantly reduce the duration of hospital stay compared with control (n=16; n=19; n=40) Raffin et al 1994
  • Study detail Bachmann-Mennenga et al 1993 Click here for more information
  • Interpleural nerve block versus other regional analgesic techniques
  • Interpleural nerve block, miscellaneous studies
  • Interpleural nerve block versus control

PROSPECT Recommendations

  • Auricular acupuncture is not recommended due to limited evidence (Grade D)

Clinical Practice

  • None cited

Transferable Evidence from other Procedures

  • None cited

Thoracotomy-specific Evidence

  • Auricular acupuncture significantly reduced pain scores on coughing on days 1–5 (p<0.05), and supplementary analgesic requirements (no statistical analysis), compared with no acupuncture (n=36) Wang et al 1988
  • Auricular acupuncture was associated with superior pulmonary function to no acupuncture: the negative inspiratory force on days 1, 3, 4, and 5 (p<0.05), FVC and FEV1 on days 3 and 6 (p<0.05) (n=36) Wang et al 1988
  • Study details Wang et al 1988 Click here for more information

PROSPECT Recommendations

  • TENS is not recommended because of limited evidence (Grade D)

Clinical Practice

  • TENS could be considered as an adjuvant to pharmacological pain management, for those with sufficient expertise in the technique

Transferable Evidence from other Procedures

  • A metaanalysis of randomised, placebo-controlled trials, found that TENS, when administered with a strong, subnoxious intensity at an adequate frequency in the wound area, significantly reduced analgesic use after various types of surgery (including abdominal, gynaecological, and thoracic procedures) Bjordal et al 2003
  • TENS reduced pain scores after minor rib fracture on days 1 and 3 (p<0.05), but not day 0, compared with NSAID, or NSAID plus inactive TENS, or control (placebo tablet, no TENS) (n=100) Oncel et al 2002
  • TENS reduced pain scores during activity (p<0.05), but not at rest, compared with placebo TENS or no TENS, after abdominal surgery (n=30) Rakel et al 2003

Thoracotomy-specific Evidence

  • One of two studies showed that TENS significantly reduced pain scores compared with sham TENS on day 1 (p=0.014) but not on day 2 (n=24) Warfield et al 1985
  • TENS significantly increased tolerance of deep coughing and percussion on day 1 (p=0.018) and day 2 (p=0.0064) compared with sham TENS (n=24) Warfield et al 1985
  • One of two studies showed that TENS significantly reduced requirement for anti-emetics compared with no TENS (n=40) Stubbing et al 1988
  • One of two studies showed that TENS significantly reduced the duration of intensive care unit stay compared with sham TENS (p=0.013) (n=24) Warfield et al 1985
  • TENS did not significantly reduce supplementary analgesic requirements compared with no TENS: during 0–24 h (n=40) Stubbing et al 1988
  • TENS did not significantly extend the time to oral analgesia compared with no TENS (n=40) Stubbing et al 1988
  • One study showed that TENS was not associated with an increased PEFR compared with no TENS (n=40) Stubbing et al 1988
  • Study details Stubbing et al 1988 Click here for more information

PROSPECT Recommendations

  • Suprascapular nerve block is not recommended because of limited evidence (grade D)

Clinical Practice

  • Suprascapular nerve block is not associated with impaired respiratory function, in contrast to the phrenic nerve block

Transferable Evidence from other Procedures

  • None cited

Thoracotomy-specific Evidence

  • Postoperative suprascapular nerve block with bupivacaine was superior to placebo for reducing shoulder pain scores at 4 h (p<0.05) but not at any other time during 0–6 h (n=30) Tan et al 2002
  • Postoperative suprascapular nerve block with bupivacaine was not significantly different from placebo for the amount of epidural solution used (n=30) Tan et al 2002
  • Study details Tan et al 2002 Click here for more information

PROSPECT Recommendations

  • An ice pack is not recommended because of lack of analgesic benefit (Grade A)

Clinical Practice

  • None cited

Transferable Evidence from other Procedures

  • None cited

Thoracotomy-specific Evidence

PROSPECT Recommendations

  • Interpleural local anaesthestic is not recommended because of lack of analgesic benefit (Grade A)

Clinical Practice

  • None cited

Transferable Evidence from other Procedures

  • None cited

Thoracotomy-specific Evidence

PROSPECT Recommendations

  • Topical LA is not recommended, based on limited evidence (Grade D)

Clinical Practice

  • Topical LA should be applied 3 h before removal to achieve full analgesic benefit

Transferable Evidence from other Procedures

  • None cited

Thoracotomy-specific Evidence

Total Hip Arthroplasty 2004

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Summary Recommendations

The recommendations of the PROSPECT Working Group are graded A–D, based on the level of evidence from the studies, which is in accordance with the Oxford Centre for Evidence-Based Medicine (CEBM website accessed Dec 2003, Sackett 2000). In the context of PROSPECT, recommendations based on procedure-specific evidence are grade A, those based on transferable evidence are grade B, those based on evidence from case series are grade C, and those based on clinical practice are grade D (Click here to see the levels of evidence and grades of recommendation table). PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted. In summary, the PROSPECT recommendations for pre-, intra- and postoperative interventions for the management of postoperative pain in total hip arthroplasty are as follows:

Pre-operative

  • Analgesic medication should be initiated in time to ensure an adequate analgesic effect in the immediate postoperative period (grade D)

Intra-operative

  • The anaesthetic technique should be selected on the basis of minimum impact on the co-morbid state of the patient (grade D). The chosen anaesthetic technique can be continued, or may have a continued effect, for analgesia postoperatively (see Postoperative)
  • Analgesia, other than that required for adequate anaesthesia, is recommended only if the analgesic agent requires time to have maximum effect in the early postoperative recovery period (grade D)
  • For long-term analgesic benefits, cemented prostheses rather than non-cemented prostheses are recommended (grade B)
  • Surgical drains are not recommended because they are associated with an increase in discomfort (grade A), pain scores and risk of infection (grade B)

Postoperative

Systemic analgesia
The following are recommended:
  • COX-2-selective inhibitors (grade A) or conventional NSAIDs (grade B) (depending on patient risk factors) – in combination with strong or weak opioids, as required for pain intensity
  • Strong opioids (grade B) – in combination with non-opioid analgesia for high-intensity pain, preferably administered intravenously by patient-controlled analgesia (grade B) or fixed-interval injection (grade D)
  • Weak opioids for moderate- or low-intensity pain (grade A) if conventional NSAIDs or COX-2-selective inhibitors are not sufficient or are contraindicated
  • Paracetamol (grade A) – for all pain intensities in combination with conventional NSAIDs or COX-2-selective inhibitors (with or without weak opioids)
Regional analgesia
The following are recommended:
  • Peripheral neural block continued after surgery (grade A) in combination with systemic analgesia as required for pain intensity (as above)
  • Spinal LA and opioid as a ‘single shot’ given pre-operatively (grade A) (continuous infusion or repeat bolus spinal is not recommended, grade D), then systemic analgesia as required for pain intensity (as above)
  • Epidural analgesia continued after surgery, only in patients at high cardiopulmonary risk, and then systemic analgesia as required for pain intensity (as above)
See Overall PROSPECT Recommendations for the overall strategy for managing pain after total hip arthroplasty  

PROSPECT final recommendations

The PROSPECT final recommendations are based on short-term pain outcomes (e.g. pain scores and supplementary analgesic use), following total hip arthroplasty. The recommendations do not take into account rehabilitation related to long-term pain. This is because rehabilitation programmes for patients undergoing total hip arthroplasty vary greatly between countries, and there is a lack of data for the effects of different rehabilitation regimes on long-term pain outcomes. Indeed, most studies assessing postoperative pain in total hip arthroplasty do not continue beyond 48 h following surgery. It is considered that adequate postoperative pain control is a prerequisite for successful rehabilitation because it allows early mobilisation and permits a more rapid initiation of physiotherapy.

The PROSPECT final recommendations are presented in the table below and are categorised according to the different anaesthetic techniques used for total hip arthroplasty. The PROSPECT group recommends that the choice of anaesthetic technique should be primarily based on the disposition of the patient rather than the management of their postoperative pain. However, based on postoperative pain outcomes, the continuation of some form of regional analgesia following general anaesthesia is recommended over the use of general anaesthesia alone.

Following surgery, the PROSPECT recommendations for pain management encompass a step-down approach for managing high-intensity pain in the immediate postoperative period to moderate- and low-intensity pain later in the postoperative period. For this step-down approach, PROSPECT recommends opioids (strong opioids initially, followed by weak opioids) in combination with paracetamol and conventional NSAIDs or COX-2-selective inhibitors, administered as appropriate for the level of postoperative pain. 

 
GA alone Peripheral neural block + GA Spinal ± GA or IV sedation Epidural ± GA
Pre-operative Pre-operative analgesia is not recommended
Intra-operative Strong long-acting opioids to secure analgesia when the patient wakes Femoral nerve block or posterior lumbar plexus block Single shot spinal LA + morphine Epidural LA + opioid
Do not use clonidine
Surgical drains and wound infiltration are not recommended
Postop High-intensity pain* Paracetamol + COX-2-selective inhibitors or conventional NSAIDs + IV strong opioid by PCA or regular injection Continue nerve block (by continuous infusion or PCRA) + COX-2-selective inhibitors or conventional NSAIDs ± rescue strong opioids IV Establish systemic pain management as the nerve block regresses, using COX-2-selective inhibitors or conventional NSAIDs ± rescue strong opioids IV Establish epidural infusion as the nerve block regresses, ± PCEA, + COX-2-selective inhibitors or conventional NSAIDs ± rescue strong opioids IV
Postop

Low- and moderate-
intensity pain**


 Paracetamol + COX-2-selective inhibitors or conventional NSAIDs ± rescue weak opioid
 
*High-intensity pain, VAS ³ 50, on a scale of 1–100 mm 
**Moderate-intensity pain, VAS <50>30, on a scale of 1–100 mm 
**Low-intensity pain, VAS £ 30, on a scale of 1–100 mm 


IV, intravenous; LA, local anaesthetic; PCA, patient-controlled analgesia; PCEA, patient-controlled epidural analgesia; PCRA, patient-controlled regional analgesia
 


  

Description of studies

Literature search

Pre-operative analgesia

Data are available from studies that assessed pre-operative analgesia versus pre-operative placebo, as well as those that, to examine the concept of pre-emptive — or preventive — analgesia, assessed pre-operative analgesia versus the same analgesia given postoperatively. However, a previous systematic review of pre-emptive analgesia for acute or chronic postoperative pain relief in a variety of surgical procedures — such as orthopaedic, dental, gynaecological and abdominal — has concluded that there is no benefit of pre-emptive over postoperative administration (Møiniche 2002). Nevertheless, it is considered that analgesic medication needs to be initiated in time to ensure an adequate analgesic effect in the immediate postoperative period. This may necessitate administration prior to the postoperative period.

PROSPECT Recommendations

  • There is no procedure-specific evidence that pre-operative administration of COX-2-selective inhibitors is more effective than postoperative administration
  • As with all analgesics it is recommended that COX-2-selective inhibitors should be administered in enough time to provide sufficient analgesia when the patient wakes (grade D)
  • It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (cardiovascular morbidity, actual or recent gastroduodenal ulcer history, bone healing, renal function and hepatic function [grade B] or aspirin-sensitive asthma [grade D])
  • Although there is concern about impairment of bone-healing with COX-2-selective inhibitors, there are no conclusive clinical studies to show that they have detrimental effects

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • COX-2-selective inhibitors given pre-operatively significantly reduced postoperative pain scores compared with placebo following spinal fusion Reuben et al 2000 Click here for more information
  • COX-2-selective inhibitors given pre-operatively had a significant postoperative opioid-sparing effect compared with placebo following spinal fusion Reuben et al 2000 Click here for more information
  • Pre-operative administration of oral rofecoxib 25 mg once daily, oral rofecoxib 50 mg or oral celecoxib 200 mg, did not increase intra- or postoperative blood loss when compared with placebo, in patients undergoing total knee arthroplasty or spinal fusion Reuben et al 2000
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation Greenberg et al 2000
  • A randomised clinical trial showed that the COX-2-selective inhibitor rofecoxib was associated with significantly less intra-operative blood loss than the conventional NSAID diclofenac in patients undergoing abdominal or vaginal hysterectomy or breast surgery Hegi et al 2004
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following non-cardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) (in press, Anesthesiology)
  • Two clinical trials showed that in patients who had undergone CABG surgery, COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with impaired bone healing in various animal models and in vitro studies Gajraj 2003

Total Hip Arthroplasty-Specific Evidence

  • [No data found within the parameters of the systematic review]

PROSPECT Recommendations

  • Pre-operative conventional NSAIDs are not recommended, despite their analgesic efficacy, because they are associated with an increased risk of intra- and postoperative bleeding (grade A)
  • There is no procedure-specific evidence that pre-operative administration of conventional NSAIDs is more effective than postoperative administration

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Intravenous diclofenac 75 mg or ketorolac 60 mg given pre-operatively significantly reduced pain scores compared with pre-operative placebo in the immediate postoperative period and at 8 h after total hip or knee arthroplasty Alexander et al 2002
  • Intravenous diclofenac 75 mg or ketorolac 60 mg given pre-operatively had a significant opioid-sparing effect compared with pre-operative placebo after hip or knee arthroplasty (for both drugs versus placebo: time 0, p = 0.009 and 8 h, p = 0.026; n =1 02) Alexander et al 2002
  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Meta-analyses of randomised controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls Marret et al 2003
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • A randomised clinical trial showed that the conventional NSAID diclofenac was associated with significantly greater intra-operative blood loss than the COX-2-selective inhibitor rofecoxib in patients undergoing abdominal or vaginal hysterectomy or breast surgery Hegi et al 2004
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with impaired bone healing in various animal models and in vitro studies Gajraj 2003

Total Hip Arthroplasty-Specific Evidence

  • Pre-operative administration of ketorolac 60 mg intravenously was superior to administration of ketorolac at closure for pain scores in the immediate postoperative period (p=0.03 at rest, p=0.0002 on movement), but the effect was not significant at all other times (6–48 h) Fletcher et al 1995
  • Pre-operative administration of ketorolac was superior to administration of ketorolac at closure for reducing the requirement for supplementary analgesia up to 6 h postoperatively (p<0.01), but not from 6–48 h Fletcher et al 1995
  • Pre-operative ibuprofen, 600 mg orally three times per day two weeks before surgery, showed no significant benefit in reducing postoperative pain scores or morphine consumption and produced a similar incidence of PONV compared with placebo, for 0–24 h (n=50) Bugter et al 2003
  • Pre-operative ibuprofen, 600 mg orally three times per day two weeks before surgery, significantly increased the median total peri-operative blood loss compared with placebo (1161 ml versus 796 ml; p<0.01; n=50) Bugter et al 2003
  • Pre-operative conventional NSAIDs significantly increased peri-operative blood loss in patients undergoing total hip arthroplasty compared with other analgesic agents in four out of five studies An et al 1991 Click here for more information

 

PROSPECT Recommendations

  • Gabapentin cannot be recommended at this time due to a lack of procedure-specific evidence, although analgesic data from other procedures are promising.

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Studies of gabapentin and pregabalin in mastectomy, abdominal surgery, laparoscopic cholecystectomy and spinal surgery showed reductions in postoperative pain and supplementary analgesic requirements for at least 24 h Dahl et al 2004

 Total Hip Arthroplasty-Specific Evidence

  • [None cited]

PROSPECT Recommendations

  • Pre-operative ketamine cannot be recommended at this time (grade D) due to a lack of procedure-specific evidence, and due to associated side-effects that may hinder early ambulation, despite some evidence of analgesic efficacy in other procedures

Clinical Practice

  • Ketamine is associated with a risk of adverse effects on the central nervous system

Transferable Evidence from Other Procedures

  • Studies of ketamine in abdominal, orthopaedic, gastric, hepatic and renal surgery showed a reduction in postoperative pain and opioid use when used as an adjuvant to morphine, either epidurally or intravenously Subramaniam et al 2004

Total Hip Arthroplasty-Specific Evidence

  • [None cited]

PROSPECT Recommendations

  • Pre-operative strong opioids are not recommended because of inconsistent evidence of their postoperative analgesic efficacy (grade A)
  • As with all analgesia, strong opioids should be administered in time to provide sufficient analgesia in the early postoperative recovery period (grade D)

Clinical Practice

  • As with all types of analgesia for postoperative pain, strong opioids should be instituted in time to secure sufficient analgesia when the patient wakes

Transferable Evidence from Other Procedures

  • Pre-operative oral administration of morphine sulphate 20 mg reduced supplementary analgesia requirements compared with pre-operative placebo, in a group of patients undergoing total hip or knee arthroplasty (p<0.05; n=98) Reiter et al 2003
  • Pre-operative oral administration of morphine sulphate 20 mg did not reduce postoperative pain scores compared with pre-operative placebo, in a group of patients undergoing total hip or knee arthroplasty (n=98) Reiter et al 2003

Total Hip Arthroplasty-Specific Evidence

  • Pre-operative morphine or pre-operative buprenorphine were not significantly different from placebo for the incidence of nausea or vomiting O'Sullivan et al 1983
  • Pre-operative morphine or pre-operative buprenorphine were not significantly different from placebo for postoperative pain scores O'Sullivan et al 1983
  • Oral sustained-release morphine 20 mg every 12 h, starting at premedication, did not significantly decrease VAS scores compared with IM morphine 10 mg every 6 h postoperatively Bourke et al 2000
  • Study details O'Sullivan et al 1983 Click here for more information

PROSPECT Recommendations

  • The choice of anaesthetic should be based on the co-morbid state of the patient and the contraindications of the proposed anaesthetic technique (grades A and B) rather than on the management of postoperative pain
  • Depending on the pharmacokinetic profile of the analgesic drugs, it may be necessary to initiate analgesia intra-operatively to allow sufficient time for the analgesia to reach maximum effect in the early postoperative recovery period (grade D)
  • For recommendations on epidural, peripheral nerve block and spinal techniques, see Postoperative section

Clinical Practice

  • Spinal anaesthesia and postoperative analgesia using LA and strong opioid is widely used in clinical practice, although the effects on the incidence of postoperative nausea and vomiting, and on urine retention, should be carefully considered before administration
  • Long-acting opioids, such as morphine, are preferred to short-acting opioids for a long duration of analgesia postoperatively
  • Both the lumbar plexus block and the femoral nerve block can be used to inject a single bolus of local anaesthetic for short duration of analgesia; or by infusion or PCA via a nerve catheter for a prolonged effect
  • Epidural analgesia is associated with a risk of bladder complaints and neurological impairment, therefore patients should be assessed for this method of pain relief on an individual basis
  • Clonidine is not used routinely in postoperative epidural analgesia, despite its analgesic efficacy, because of the risk of hypotension, sedation and bradycardia
  • It is considered that analgesic drugs should be instituted in time to secure sufficient pain relief when the patient wakes

Transferable Evidence from Other Procedures

  • Combined spinal epidural block or spinal block were superior to epidural block (0.5% bupivacaine plus 0.2 or 0.4 mg morphine for spinal, or 0.5% bupivacaine plus 4 mg morphine for epidural) for surgical analgesia and for reducing consumption of perioperative sedatives and other analgesics in major orthopaedic surgery Holmstrom et al 1993
  • Epidural anaesthesia reduces the frequency of deep vein thrombosis and pulmonary embolism, and reduces intra-operative and postoperative blood loss, compared with general anaesthesia, particularly in total hip arthroplasty patients, as shown in a review Modig 1989
  • Epidural infusion of bupivacaine and meperidine (1 mg/ml) had a significantly slower regression of sensory anaesthesia and slower development of pain, in contrast to infusions of bupivacaine alone (control) or bupivacaine and fentanyl (3 µg/ml) following total knee arthroplasty (p<0.05; n=48) Ferrante et al 1993
  • A systematic review of different methods of anaesthesia for hip fracture surgery showed that regional anaesthesia was associated with reduced short-term mortality compared with general anaesthesia but there was no significant difference for other outcome measures Parker et al 2004 Click here for more information
  • Bolus spinal morphine (300 µg) was significantly more effective than saline placebo for reducing postoperative pain scores after total knee arthroplasty (p<0.05; n=60) Tan et al 2001
  • Peripheral neural blocks are associated with a lower risk of side-effects compared with neuraxial opioids Sinatra et al 2002
  • Femoral nerve block is associated with a lower risk of serious complications than spinal anaesthesia (using bupivacaine or lidocaine) Auroy et al 2002
  • In a systematic review of seven randomised trials in hip fracture, nerve blocks administered pre- or peri-operatively resulted in a reduction in pain score and supplementary analgesia requirement compared with control (n=269) Parker et al 2001a
  • 'Single shot' or continuous peripheral nerve block was significantly more effective than placebo for reducing the requirement for supplementary analgesia following total knee or hip arthroplasty (n=242) Allen JG et al 1998
  • 'Single shot' femoral nerve block reduced pain scores for up to 8 h and reduced morphine consumption following total knee arthroplasty Allen JG et al 1998
  • The posterior approach to the lumbar plexus (psoas sheath block) produces more reliable analgesia to the hip joint than the distal approach (femoral nerve or 3-in-1 blocks). However, the lumbar plexus block has the potential for more serious complications than the femoral nerve block Auroy et al 2002
  • Addition of epinephrine did not alter the duration of analgesia with a 'single shot' 3-in-1 femoral nerve block (20 ml ropivacaine 0.5% [~11–12 h] or 0.2% [~7 h]) following total knee arthroplasty (n=41) Weber et al 2001
  • In a systematic review, spinal morphine in patients undergoing caesarean section was shown to increase the relative risk of postoperative pruritis, nausea and vomiting compared with control; increasing the dose of morphine increased the relative risk of postoperative nausea and vomiting Dahl et al 1999
  • Spinal administration of bolus clonidine or morphine produced a high incidence of bladder distension in patients undergoing hip surgery, but there was a greater incidence with spinal morphine than clonidine (p<0.001) Gentili and Bonnet 1996

Total Hip Arthroplasty-Specific Evidence

  • Spinal morphine 0.1 mg was superior to a posterior lumbar plexus block using ropivacaine 0.475% for reducing postoperative pain scores for 6–18 h (p<0.05) and reducing supplementary analgesic consumption for 48 h, but there was no significant difference for the incidence of nausea, vomiting or pruritis (n=53) Souron et al 2003
  • Addition of a lumbar plexus block to general anaesthesia was associated with less intra-operative blood loss compared with general anaesthesia alone, in one study (n=30) Stevens et al 2000
  • Postoperative lumbar plexus block was superior to femoral nerve block for reducing postoperative pain scores at rest and supplementary analgesic consumption Biboulet et al 2004 Click here for more information
  • Femoral nerve block ('single shot' 40 ml bupivacaine 0.5% plus epinephrine after induction of general anaesthesia) increased the time to first analgesic request by approximately 4 h compared with placebo (p<0.05) (n=40) Fournier et al 1998
  • Posterior lumbar plexus block 'single shot' given pre- or postoperatively was superior to placebo for reducing postoperative pain scores and supplementary analgesic consumption Stevens et al 2000 Click here for more information
  • Epidural catheter insertion with the tip of the Tuohy needle rotated 45° toward the operative side was superior to catheter insertion with the tip of the Tuohy needle in the conventional position (90° cephalad) for reducing postoperative local anaesthetic consumption for 12–48 h (p=0.001), but there was no significant difference for pain scores (n=48) Borghi et al 2004
  • Epidural anaesthesia was associated with less intra-operative blood loss than neuroleptoanaesthesia, halothane, phenoperidine or general anaesthesia in four studies Chin et al 1982
  • Epidural ropivacaine produced a greater proportion of patients with recovered motor function (Bromage score <1) than epidural levobupivacaine and epidural bupivacaine groups immediately postoperatively (p<0.05). However, there were no differences at 6 h (n=45) Casati et al 2003 Click here for more information
  • Two studies showed that continuous epidural anaesthesia/analgesia was superior to general anaesthetic plus intravenous morphine analgesia for reducing postoperative pain scores Møiniche et al 1994 Click here for more information
  • A range of morphine doses (0.025, 0.05, 0.1 and 0.2 mg), administered with bupivacaine 20 mg for spinal anaesthesia, were similar for VAS pain scores Slappendel et al 1999
  • Spinal analgesia was superior to epidural analgesia in one study for pain scores Mollmann et al 1999 Click here for more information
  • Continuous spinal bupivacaine analgesia (and anaesthesia) was superior to IV PCA morphine analgesia (plus 'single shot' spinal anaesthesia) for reducing VAS scores for 3–24 h (p<0.05) and the incidence of PONV (n=68) Maurer et al 2003
  • Continuous spinal bupivacaine demonstrated a significant reduction in mean arterial pressure during anaesthetic induction compared with 'single shot' spinal bupivacaine (21 ± 11 mmHg versus 29 ± 14; p<0.05) (n=68) Maurer et al 2003
  • Femoral nerve block did not significantly reduce postoperative pain scores, and there was inconclusive evidence for the effect on supplementary analgesic consumption, compared with placebo Fournier et al 1998 Click here for more information
  • Posterior lumbar plexus block provided no significant benefit over femoral nerve block or control (no nerve block) for postoperative pain scores on movement, PONV or articular mobility during rehabilitation (n=45) Biboulet et al 2004
  • Posterior lumbar plexus block using ropivacaine 0.475% was less effective than spinal morphine 0.1 mg for reducing pain scores during 6–18 h (p<0.05) and supplementary analgesic consumption during 48 h, and there was no significant difference in the incidence of nausea, vomiting or pruritis (n=53) Souron et al 2003
  • There are no studies examining the effects of intra-operative wound infiltration on postoperative pain during total hip arthroplasty
  • Study details Chin et al 1982 Click here for more information

PROSPECT Recommendations

  • It is recommended that surgical requirement rather than pain management should be the main consideration in choosing the surgical procedure (grade D)
  • Cemented prostheses have not been shown to confer any short-term analgesic benefit over non-cemented prostheses, but they are associated with better long-term pain outcomes (>1 year) (grade B)
  • Drains are not recommended because they are associated with increased pain scores, do not confer a clinical benefit, and increase the risk of infection (grade B)

Clinical Practice

  • Surgical need rather than postoperative pain management should drive the choice of surgical approach

Transferable Evidence from Other Procedures

  • Cemented prostheses have been shown to be superior to non-cemented prostheses for long-term reduction of pain and for increasing mobility in patients with fractured neck of femur Parker et al 2001b Click here for more information
  • Wound drains without suction produced less postoperative pain intensity on removal compared with drains with suction in intra-articular procedures (n=126; p<0.05) Brandner et al 1991
  • No benefit of bipolar hemiarthroplasty over unipolar hemiarthroplasty (review of six trials, n=742) was demonstrated for postoperative pain in a range of arthroplasty procedures Parker et al 2001b
  • There was no significant benefit of drained compared with un-drained wounds for a range of postoperative pain outcomes, including postoperative pain scores Parker et al 2003 Click here for more information

Total Hip Arthroplasty-Specific Evidence

  • There was no difference between two surgical methods – the modified Hardinge approach and transtrochanteric lateral approach — in postoperative pain scores in one study (n=100) Horowitz et al 1993
  • Wound drains were associated with higher pain scores than no drains (no statistical analysis) in one study of patients undergoing total hip arthroplasty (n=23) Ravikumar et al 2001

PROSPECT Recommendations

  • COX-2-selective inhibitors are recommended for their analgesic and opioid-sparing effect (grade A). They should be given in combination with strong opioids for high-intensity pain (grade A), or with weak opioids for moderate- or low-intensity pain (grade D)
  • COX-2-selective inhibitors may be preferred to conventional NSAIDs in the peri-operative setting, in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (grade B)
  • The use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (cardiovascular morbidity, actual or recent gastroduodenal ulcer history, renal function and hepatic function [grade B] or aspirin-sensitive asthma [grade D])
  • Although there is concern about impairment of bone-healing with COX-2-selective inhibitors, there are no conclusive clinical studies to show that they have detrimental effects 

Clinical Practice

  • [None cited}

Transferable Evidence from Other Procedures

  • COX-2-selective inhibitors significantly reduced postoperative pain and the requirement for supplementary analgesia compared with placebo following knee arthroplasty Hubbard et al 2003 Click here for more information
  • Parecoxib (20 or 40 mg) was as effective as ketorolac (30 mg) administered intravenously for postoperative pain scores (for level, onset and duration of analgesia) following total knee arthroplasty (n=208) Rasmussen et al 2002
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation Greenberg et al 2000
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following non-cardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062) (in press, Anesthesiology)
  • Two clinical trials showed that in patients who had undergone CABG surgery, COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo Nussmeier et al 2005
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with impaired bone healing in various animal models and in vitro studies Gajraj 2005a

Total Hip Arthroplasty-Specific Evidence

  • Oral valdecoxib was effective in reducing postoperative pain scores at two doses (20 mg or 40 mg) compared with placebo when administered pre-operatively and then postoperatively (p<0.05 for 6, 12 and 18 h) Camu et al 2002
  • Oral valdecoxib was effective in reducing the requirement for supplementary analgesia compared with placebo (p<0.001) Camu et al 2002
  • Oral valdecoxib is not associated with a significant increase in the incidence of nausea or vomiting compared with placebo Camu et al 2002
  • Study details Camu et al 2002 Click here for more information

PROSPECT Recommendations

  • Conventional NSAIDs are recommended for their analgesic and opioid-sparing effect (grade A). They should be given in combination with strong opioids for high-intensity pain (grade A), or with weak opioids for moderate- or low-intensity pain (grade D)
  • Conventional NSAIDs are not recommended in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (grade B)
  • The use of conventional NSAIDs should depend upon assessment of individual patient risks (bleeding complications including epidural haematoma, cardiovascular morbidity, actual or recent gastroduodenal ulcer history, aspirin-sensitive asthma, renal function and hepatic function) (grade B)
  • Although there is concern about impairment of bone-healing with conventional NSAIDs, there are no conclusive clinical studies to show that they have detrimental effects

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • Ketoprofen 100 mg orally significantly reduced VAS scores compared with placebo following spinal fusion (p<0.001; n=50) Aubrun et al 2000
  • Oral keterolac 10 mg was as effective as intramuscular morphine 5 mg or 10 mg for reducing postoperative pain scores after orthopaedic procedures DeAndrade et al 1994
  • Intravenous ketorolac 30 mg was more effective than intravenous morphine 4 mg for reducing postoperative pain scores in one study of total knee replacement surgery (n=196) Rasmussen et al 2002
  • Ketoprofen significantly reduced supplementary analgesia requirements compared with placebo following spinal fusion (p=0.002; n=50) Aubrun et al 2000
  • Ketorolac (30 mg bolus, then 5 mg/h infusion for 24 h) reduced the duration of myocardial ischaemic episodes — compared with placebo — for 24 h following the operation in patients undergoing total hip or knee arthroplasty Beattie et al 1997
  • One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo Bricker et al 1987
  • Ketorolac (10 mg orally or 30 mg intravenously) was significantly more effective than placebo for reducing pain scores as shown in a number of studies of orthopaedic surgery (including knee, hip and spinal procedures) Kinsella et al 1992
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with impaired bone healing in various animal models and in vitro studies Gajraj 2005a
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication Cheng et al 2004
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease Stevenson 2004
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction Niemi et al 1997
  • Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls Marret et al 2003
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo Greer et al 1999
  • Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use Harris et al 2001

Total Hip Arthroplasty-Specific Evidence

PROSPECT Recommendations

  • Ketamine cannot be recommended at this time due to a lack of procedure-specific evidence, although analgesic data from other procedures are promising

Clinical Practice

  • Ketamine is associated with a risk of adverse effects on the central nervous system

Transferable Evidence from Other Procedures

  • Studies of ketamine in abdominal, orthopaedic, gastric, hepatic and renal surgery showed a reduction in postoperative pain and opioid use when used as an adjuvant to morphine, either epidurally or intravenously Subramaniam et al 2004

Total Hip Arthroplasty-Specific Evidence

  • [None cited]

PROSPECT Recommendations

  • Strong opioids are recommended in combination with non-opioid analgesia for managing high-intensity pain following total hip arthroplasty (grade B)
  • Intravenous patient-controlled analgesia (grade A) or fixed-interval intravenous administration titrated for pain intensity (grade D), is recommended over 'on-demand' administration
  • Intramuscular administration of strong opioids is not recommended because of injection-associated pain (grade D)

Clinical Practice

  • Strong opioids in equipotent doses are considered to give a similar level of analgesia
  • Intramuscular administration of strong opioids is considered to be more painful than intravenous administration. However, the size and speed of intravenous dose should be assessed to minimise the risk of respiratory depression

Transferable Evidence from Other Procedures

  • Meperidine significantly reduced postoperative pain scores compared with placebo following hip or knee arthroplasty Tarradell et al 1996 Click here for more information
  • Morphine 4 mg was superior for reducing pain scores and reducing the time to onset of analgesia compared with placebo following total knee arthroplasty Rasmussen et al 2002
  • Oral flupirtine maleate 100–200 mg and pentazocine 50–100 mg had similar effects on pain scores and on the requirement for supplementary analgesia after total hip or knee arthroplasty (n=66) Galasko et al 1985
  • Morphine administered by PCA device had a similar effect to continuous infusion on postoperative pain scores following total hip or knee arthroplasty (n=32) Smythe et al 1996
  • Opioids administered by PCA improved analgesia and decreased the risk of pulmonary complications, and patients preferred them compared with conventional intramuscular, intravenous or subcutaneous opioid treatment, as determined in a quantitative systematic review of randomised trials of postoperative pain management following various surgical procedures Walder et al 2001
  • Meperidine induced significantly higher sedation and respiratory depression compared with tramadol (both 100 mg intravenously) (n=48) Tarradell et al 1996

Total Hip Arthroplasty-Specific Evidence

  • Morphine (0.15 mg/kg intramuscularly) was superior to nalbuphine (0.3 mg/kg intramuscularly) for postoperative pain scores (p<0.02) and for the use of supplementary analgesia (p<0.05; n=80) Fee et al 1989
  • Morphine (2 mg bolus) was superior to meptazinol (20 mg bolus) — each given by PCA — for 8 h postoperative pain scores (p<0.05), and for the incidence of nausea and vomiting (p<0.05; n=49) Frater et al 1989
  • Morphine 2 mg and diamorphine 1 mg — given by PCA — were equally effective for reducing postoperative pain scores (n=40) Robinson et al 1991
  • IV PCA morphine 1 mg 8-min lockout was superior to 4-hourly intramuscular morphine 0.1 mg/kg for postoperative pain scores at rest (p<0.01) and on movement (p<0.05) at 24 and 48 h. There was no significant difference between groups for PONV (n=40) Keita et al 2003
  • Oral morphine (20 mg every 4 h) was superior to IM morphine (5–10 mg on demand) for postoperative pain scores (p<0.05; n=47) McCormack et al 1993
  • Oral sustained-release morphine 20 mg every 12 h, starting at premedication, and IM morphine 10 mg every 6 h postoperatively, were similar for VAS pain scores Bourke et al 2000
  • Study details Fee et al 1989 Click here for more information

PROSPECT Recommendations

  • Weak opioids are not recommended for controlling pain <6 h following total hip arthroplasty (grade A)
  • Weak opioids are recommended for moderate- or low-intensity pain after 6 h if conventional NSAIDs or COX-2-selective inhibitors, are insufficient or are contraindicated (grade D)

Clinical Practice

  • It is considered that weak opioids are ineffective as a single therapy for postoperative pain following total hip arthroplasty

Transferable Evidence from Other Procedures

  • Tramadol (100 mg bolus intravenously) provided no benefit over placebo for postoperative pain scores after total hip or knee arthroplasty (n=48) Tarradell et al 1996

 Total Hip Arthroplasty-Specific Evidence

  • Tramadol (50 or 100 mg orally) provided no benefit over placebo for postoperative pain scores up to 5 h after total hip arthroplasty (n=137) Stubhaug et al 1995
  • Codeine (60 mg orally) provided no benefit over placebo for postoperative pain scores up to 6 h after total hip arthroplasty (n=121) Dahl et al 1995

PROSPECT Recommendations

  • Paracetamol is recommended for all pain intensities because it reduces supplementary analgesic requirements immediately following total hip arthroplasty (grade A)
  • Paracetamol is recommended in combination with conventional NSAIDs or COX-2-selective inhibitors, with or without rescue opioids (grade D)

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

Total Hip Arthroplasty-Specific Evidence

  • Parenteral propacetamol 2 g (intravenous infusion) had a significant benefit over placebo in reducing postoperative morphine consumption (p<0.001; n=97) Peduto et al 1998
  • Oral paracetamol 1 g plus codeine 60 mg was superior to placebo and to tramadol (50 or 100 mg) for reducing postoperative pain scores at 2–6 h £ 0.01, all comparisons) and supplementary analgesic use (p<0.01, all comparisons) (n=137) Stubhaug et al 1995
  • Parenteral propacetamol 2 g (intravenous infusion) had no benefit over placebo for reducing postoperative pain scores after total hip arthroplasty (n=97) Peduto et al 1998

PROSPECT Recommendations

  • Epidural infusion with local anaesthetic plus opioid is recommended for cardiopulmonary risk patients (grade A) because of the reduction in cardiopulmonary morbidity associated with epidural analgesia
  • Despite the analgesic benefits of epidural clonidine, it is not recommended for the control of postoperative pain following total hip arthroplasty because of the risk of hypotension, sedation and bradycardia (grades A and D)

Clinical Practice

  • Epidural analgesia is associated with a risk of bladder complaints and neurological impairment, therefore patients are assessed for this method of pain relief on an individual basis
  • Clonidine is not used routinely in postoperative epidural analgesia, despite its analgesic efficacy, because of the risk of hypotension, sedation and bradycardia

Transferable Evidence from Other Procedures

  • Epidural analgesia was superior to systemic analgesia for postoperative pain outcomes Singelyn et al 1998 Click here for more information
  • Epidural analgesia was associated with a lower incidence of pulmonary complications, sedation, urinary retention, pruritis and hypotension compared with systemic analgesia Ballantyne et al 1998 Click here for more information
  • Ropivacaine epidural infusion was superior to placebo (no epidural infusion) for reducing postoperative pain scores (all groups received rescue IV morphine) Turner et al 1996 Click here for more information
  • A combination of epidural local anaesthetic plus opioid produced superior analgesic benefits compared with either drug administered alone Lorenzini et al 2002 Click here for more information
  • Epidural morphine (bolus 4 mg, infusion 12.5 mg/h over 13 h) was similar to epidural ketoprofen (200 mg over 30 min, 12.5 mg/h over 13 h) for postoperative pain scores following total hip or knee arthroplasty Hommeril et al 1994
  • The addition of epidural clonidine (bolus of 150 µg) to epidural bupivacaine (bolus of 50 mg) significantly prolonged the duration of analgesia in patients undergoing hip surgery for traumatic fracture (p<0.05; n=40) Klimscha et al 1995
  • Combined spinal epidural block or spinal block were superior to epidural block (0.5% bupivacaine plus 0.2 or 0.4 mg morphine for spinal, or 0.5% bupivacaine plus 4 mg morphine for epidural) for surgical analgesia and for reducing consumption of perioperative sedatives and analgesics in major orthopaedic surgery Holmstrom et al 1993
  • There was no significant difference between epidural fentanyl (3 µg/ml) plus bupivacaine and bupivacaine alone in the rate of regression of sensory anaesthesia or the development of postoperative pain (n=48) Ferrante et al 1993
  • Epidural infusion of ropivacaine (2 mg/ml) plus sufentanil (1 µg/ml) produced a significantly higher incidence of adverse events (pruritus, nausea and vomiting) than ropivacaine alone following major knee surgery (n=115) Lorenzini et al 2002
  • Neuraxial and parenteral opioids are associated with a greater risk of side-effects compared with continuous plexus and peripheral neural blockades after major orthopaedic surgery Sinatra et al 2002

Total Hip Arthroplasty-Specific Evidence

  • Two studies showed that continuous epidural anaesthesia/analgesia was superior to general anaesthetic plus intravenous morphine analgesia for reducing postoperative pain scores Møiniche et al 1994 Click here for more information
  • Epidural bolus (pethidine hydrochloride 60 mg) was superior to IM bolus (pethidine hydrochloride 1 mg/kg) administered postoperatively for pain scores at 0.5 and 1 h (p<0.05), but non-significant for 2–4 h pain scores and supplementary analgesic consumption (n=14) Gustafsson et al 1986
  • Postoperative epidural infusions of bupivacaine, ropivacaine or levobupivacaine were similar for postoperative pain scores, supplementary analgesia and PONV in two studies Bertini et al 2001 Click here for more information
  • Epidural infusion of bupivacaine (0.125 mg/ml) combined with morphine (0.05 mg/ml) was similar to combination with fentanyl (0.005 mg/ml) for postoperative pain scores after total hip arthroplasty (n=30) Berti et al 1998
  • Different epidural sufentanil doses (0.5 µg/ml, 0.75 µg/ml or 1.0 µg/ml) administered with ropivacaine 0.1% by continuous epidural infusion, were similar for VAS scores, supplementary analgesic consumption, pain-mobility-and-ability-to-walk scores and adverse events within 0–44 h (n=32) Kampe et al 2003
  • Epidural clonidine was superior to epidural local anaesthetic or morphine for a number of postoperative analgesia outcomes Carabine et al 1992a Click here for more information
  • Addition of clonidine to local anaesthetic or opioid was superior to local anaesthetic or opioid alone for a variety of postoperative analgesia outcomes Carabine et al 1992a Click here for more information
  • The addition of ropivacaine (1 mg/ml, 3 ml/h) to an infusion of fentanyl (10 µg/ml, 3 ml/h) conferred no benefit over fentanyl alone for postoperative pain scores (n=39) Kostamovaara et al 2001
  • Epidural clonidine reduced mean arterial pressure and heart rate compared with epidural morphine but did not increase the incidence of sedation and did not consistently reduce arterial pressure compared with epidural local anaesthetic Carabine et al 1992b Click here for more information

PROSPECT Recommendations

  • Femoral nerve blocks are recommended (grade B) based on their analgesic efficacy in hip fracture surgery and knee arthroplasty. They are recommended over neuraxial techniques and parenteral opioids based on a reduced risk of side-effects in major orthopaedic surgery (grade B). Supplementary obturator and lateral cutaneous nerve of thigh blocks may be required for analgesia in hip arthroplasty
  • Posterior lumbar plexus blocks (psoas sheath blocks) have a greater efficacy than distal lumbar plexus blocks (femoral nerve blocks) in total hip replacement, and are recommended (grade A). However, they have a potential for more serious complications than the femoral block and the risk/benefit balance should be determined for individual patients.
  • Continuous infusion, patient-controlled or 'on-demand' femoral nerve blocks are recommended over a 'single shot' approach as they provide an extended height of block and a greater duration of analgesia (grade D)  

Clinical Practice

  • 'On-demand', patient-controlled or continuous administration are preferred over a 'single-shot' peripheral neural block for longer-acting pain relief

Transferable Evidence from Other Procedures

  • In a systematic review of seven randomised trials in hip fracture, nerve blocks administered pre- or peri-operatively resulted in a reduction in pain score and supplementary analgesic requirement compared with control (n=269) Parker et al 2001a
  • 'Single shot' femoral nerve block reduced pain scores for up to 8 h and reduced morphine consumption following total knee arthroplasty Allen JG et al 1998
  • 'Single shot' or continuous peripheral nerve block was significantly more effective than placebo for reducing the requirement for supplementary analgesia following total knee or hip arthroplasty (n=242) Allen JG et al 1998
  • The posterior approach to the lumbar plexus block produces more reliable analgesia to the hip joint than the distal approach (femoral nerve or 3-in-1 blocks); however, the lumbar plexus block has the potential for more serious complications than the femoral nerve block Auroy et al 2002
  • Continuous plexus and peripheral neural blocks are associated with a reduced risk of side-effects compared with neuraxial and parenteral opioids, in pain management after major orthopaedic surgery Sinatra et al 2002
  • Femoral nerve block is associated with a lower risk of serious complications than spinal anaesthesia (using bupivacaine or lidocaine) Auroy et al 2002
  • Addition of epinephrine did not alter the duration of analgesia with a 'single shot' 3-in-1 femoral nerve block (20 ml ropivacaine 0.5% or 0.2%) following total knee arthroplasty (n=41) Weber et al 2001
  • Continuous 3-in-1 femoral block 10 ml/h (0.125% bupivacaine plus sufentanil 0.1 µg/ml and clonidine 1 µg/ml) provided no benefit over IV PCA morphine for the incidence of nausea and vomiting although a reduction in catheter problems was noted Singelyn et al 1998
  • As with all regional anaesthetic techniques, peripheral neural blockade has a failure rate and can cause neural injury and local anaesthetic toxicity Cox et al 2003

Total Hip Arthroplasty-Specific Evidence

  • Posterior lumbar plexus block 'single shot' given pre- or postoperatively was superior to placebo for reducing postoperative pain scores and supplementary analgesic consumption Stevens et al 2000 Click here for more information
  • Femoral nerve block ('single shot' 40 ml bupivacaine 0.5% plus epinephrine after induction of general anaesthesia) increased the time to first analgesic request by approximately 4 h compared with placebo (p<0.05) (n=40) Fournier et al 1998
  • Postoperative lumbar plexus block was superior to femoral nerve block for reducing postoperative pain scores at rest and supplementary analgesic consumption Biboulet et al 2004 Click here for more information
  • Femoral nerve block did not significantly reduce postoperative pain scores, and there was inconclusive evidence for the effect on supplementary analgesic consumption, compared with placebo Fournier et al 1998 Click here for more information
  • Posterior lumbar plexus block provided no significant benefit over femoral nerve block or control (no nerve block) for postoperative pain scores on movement, PONV or articular mobility during rehabilitation (n=45) Biboulet et al 2004
  • Posterior lumbar plexus block using ropivacaine 0.475% was less effective than spinal morphine 0.1 mg for reducing pain scores during 6–18 h (p<0.05) and supplementary analgesic consumption during 48 h, and there was no significant difference in the incidence of nausea, vomiting or pruritis (n=53) Souron et al 2003
  • Femoral nerve block delivered by PCA provided no benefit over delivery by continuous infusion for postoperative pain scores (n=45) Singelyn et al 2001

PROSPECT Recommendations

  • Where appropriate, single bolus spinal morphine (0.1–0.2 mg) plus local anaesthetic is recommended, administered before surgery, as it provides pain relief for up to 24 h (grade A). The decision to use a spinal technique should be based on the overall benefits of spinal anaesthesia/analgesia to each individual patient
  • Spinal clonidine is not recommended because it is less effective than spinal morphine for analgesia (grade A)
  • Short-acting opioids are not recommended because of their shorter duration of effect compared with morphine at appropriate doses (grade D)
  • Continuous spinal administration of morphine following total hip arthroplasty is not recommended due to safety concerns (grade D)

Clinical Practice

  • Spinal local anaesthetics combined with morphine are widely used for postoperative analgesia in clinical practice, although their effects on the incidence of postoperative nausea and vomiting, and on the bladder, should be carefully considered before administration
  • Long-acting opioids, such as morphine, are preferred to short-acting opioids for a long duration of analgesia postoperatively

Transferable Evidence from Other Procedures

  • Bolus spinal morphine (300 µg) was significantly more effective than saline placebo for reducing postoperative pain scores after total knee arthroplasty (p<0.05; n=60) Tan et al 2001
  • Combined spinal epidural block or spinal block were superior to epidural block (0.5% bupivacaine plus 0.2 or 0.4 mg morphine for spinal, or 0.5% bupivacaine plus 4 mg morphine for epidural) for surgical analgesia and for reducing consumption of perioperative sedatives and other analgesics in major orthopaedic surgery Holmstrom et al 1993
  • In a systematic review, spinal morphine in patients undergoing caesarean section was shown to increase the relative risk of postoperative pruritis, nausea and vomiting compared with control; increasing the dose of morphine increased the relative risk of postoperative nausea and vomiting Dahl et al 1999
  • Spinal administration of bolus clonidine or morphine produced a high incidence of bladder distension in patients undergoing hip surgery, but there was a greater incidence with spinal morphine than clonidine (p<0.001) Gentili and Bonnet 1996
  • Neuraxial opioids are associated with a higher risk of side-effects compared with peripheral neural blocks Sinatra et al 2002
  • Spinal anaesthesia (using bupivacaine or lidocaine) is associated with a higher risk of serious complications than femoral nerve block Auroy et al 2002

Total Hip Arthroplasty-Specific Evidence

  • Spinal morphine 0.1 mg was superior to a posterior lumbar plexus block using ropivacaine 0.475% for reducing postoperative pain scores for 6–18 h (p<0.05) and reducing supplementary analgesic consumption for 48 h, but there was no significant difference for the incidence of nausea, vomiting or pruritis (n=53) Souron et al 2003
  • Continuous spinal bupivacaine analgesia (and anaesthesia) was superior to IV PCA morphine analgesia (plus 'single shot' spinal anaesthesia) for reducing VAS scores for 3–24 h (p<0.05) and the incidence of PONV (n=68) Maurer et al 2003
  • Spinal analgesia was superior to epidural analgesia in one study for pain scores Mollmann et al 1999 Click here for more information
  • Strong opioid plus local anaesthetic was superior to local anaesthetic alone for postoperative pain scores, requirement for supplementary analgesia and time to first analgesia request, when administered by the spinal route Fernandez-Galinski et al 1996 Click here for more information
  • Different spinal strong opioids or local anaesthetics were similar for postoperative pain scores  Fournier et al 2000a Click here for more information
  • Spinal morphine 1 mg was superior to clonidine 75–100 µg in combination with isobaric bupivacaine 2.75 ml 0.5% for pain scores up to and including 10 h after the operation (p<0.01), time to first analgesia request and use of supplementary analgesia (p<0.05; n=90) Fogarty et al 1993
  • Patient-controlled spinal analgesia was superior to spinal bolus doses on demand in one study for pain Rundshagen et al 1997 Click here for more information
  • A combination of bupivacaine and morphine may cause a greater incidence of vomiting compared with bupivacaine alone Grace et al 1995 Click here for more information
  • Continuous spinal bupivacaine demonstrated a significant reduction in mean arterial pressure during anaesthetic induction compared with 'single shot' spinal bupivacaine (21 ± 11 mmHg versus 29 ± 14; p<0.05) (n=68) Maurer et al 2003
  • Spinal clonidine provided no significant benefit over placebo in two of three studies Grace et al 1995 Click here for more information

PROSPECT Recommendations

  • Postoperative continuous wound infusion with local anaesthetic cannot be recommended at this time (grade D) due to lack of procedure-specific evidence, although analgesic data from other procedures are promising
  • Wound infiltration at the drain site is not recommended (grade D) because drains are not recommended

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

Total Hip Arthroplasty-Specific Evidence

Total Knee Arthroplasty 2005

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PROSPECT Total Knee Arthroplasty Subgroup

For each review, a Subgroup of the prospect Working Group performs an initial evaluation of the evidence and also drafts clinical practice statements and recommendations, which are then discussed by the whole Working Group before a final consensus is reached. The Subgroup may sometimes include a non-Working Group member, to provide additional expertise in the procedure being reviewed.   For the total knee arthroplasty review, the Subgroup members were:
  • Dr Christian Simanski
  • Dr Barrie Fischer

Grades of Recommendation

Recommendations are graded according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence: (Levels of evidence and grades of recommendation in PROSPECT reviews (from 2006)) PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted.

Summary Recommendations

Pre-, intra- and postoperative interventions have been evaluated for the management of postoperative pain following total knee arthroplasty. Unless otherwise stated, ‘pre-operative’ refers to interventions applied before surgical incision, ‘intra-operative’ refers to interventions applied after incision and before wound closure, ‘postoperative’ refers to interventions applied at or after wound closure. The following peri-operative interventions for total knee arthroplasty have been reviewed: See Overall Recommendations for the overall strategy for managing pain after total knee arthroplasty.

PROSPECT overall recommendations for postoperative pain management following total knee arthroplasty:

Description of studies

Literature search

Study quality assessments, levels of evidence and grades of recommendation Recommendations are graded according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence: (Levels of evidence and grades of recommendation in PROSPECT reviews (from 2006)

Quantitative analyses

Overall, few meta-analyses could be performed that used data from more than two studies. This is because there are a limited number of studies of homogeneous design that report similar outcome measures. Therefore, the majority of the procedure-specific evidence was assessed only qualitatively.

Transferable evidence

Transferable evidence of analgesic efficacy from comparable procedures or evidence of other outcomes, such as adverse effects, has been included to support the procedure-specific evidence where this is insufficient to formulate the recommendations.

Many studies that were identified in the literature search included patients undergoing total knee or hip replacement and reported data pooled from all these patients. Such studies are excluded from the procedure-specific systematic review but have been used as additional transferable evidence where required. Data from other types of orthopaedic surgery (e.g. ACL reconstruction, spinal surgery, hip surgery) were not used for transferable evidence of analgesic efficacy in most instances because it was considered that the pain profile of these procedures was too different from that of TKA. However, data from studies in a variety of procedures have been used for evidence of adverse-effects, which can occur regardless of the procedure.

Topics for future research:

  • Pre-operative corticosteroids
  • Alpha-2-delta subunit ligands (gabapentinoids)
  • Peri-operative ketamine
  • Single injection versus continuous infusion peripheral nerve block
  • Combination femoral and sciatic/obturator nerve block
  • Intra-articular/incisional techniques
  • Pre- versus post-incisional administration of various agents
  • Dose- and duration-dependent effects of conventional NSAIDs and COX-2-selective inhibitors on bone healing
  • Combination of conventional NSAIDs with regional analgesic techniques
  • Combination of COX-2-selective inhibitors with regional analgesic techniques

 

Abbreviations

bd

twice per day

GA

general anaesthetic

IM

intramuscular

Intra-op

intra-operatively

IV

intravenous

LA

local anaesthetic

NRS

numerical rating scale

PACU

post-anaesthesia care unit

PCA

patient-controlled analgesia

PCEA

patient-controlled epidural analgesia

POD

postoperative day

PONV

postoperative nausea and vomiting

Pre-op

pre-operatively

Postop

postoperatively

RCT

randomised controlled trial

ROM

range of motion

SpO2

median oxygen saturation

TKA

total knee arthroplasty

VAS

visual analogue scale

VRS

verbal rating scale

PROSPECT Recommendations

  • Peripheral nerve blocks are not recommended to be performed intra-operatively (Grade D, LoE 4). PROSPECT definition of pre-operative, intra-operative and postoperative administration Click here for more information

Clinical practice

  • None cited

Transferable evidence

  • None cited

Total knee arthroplasty-specific evidence

  • Evidence suggests that the time of administration of femoral nerve blocks has no effect on postoperative pain outcomes after TKA. Therefore, included studies of such techniques have been pooled for analysis irrespective of the timing of administration. All of the procedure-specific evidence is presented in the Postoperative section

PROSPECT Recommendations

  • GA + femoral nerve block, or spinal anaesthesia (with LA) + femoral nerve block are recommended as first choices for anaesthesia/analgesia (Grade D, LoE 4) (see also Pre-operative Peripheral nerve block techniques for evidence and recommendations about femoral nerve block)
  • Spinal LA + morphine is recommended but not as the first choice of anaesthetic/analgesic technique (Grade D, LoE 4), because of a greater potential for adverse events compared with femoral nerve block (transferable evidence, LoE 3) (see also Pre-operative Spinal techniques)
  • GA or spinal anaesthesia without any local or regional analgesic technique is not recommended (Grade D, LoE 4)
  • Epidural anaesthesia is not recommended (Grade D, LoE 4) because postoperative epidural analgesia is not recommended

Clinical practice

  • It is considered that analgesic drugs should be administered in time to secure sufficient pain relief when the patient wakes
  • Spinal anaesthesia provides a more complete surgical block than epidural anaesthesia
  • Epidural analgesia is associated with a relatively high degree of patient monitoring and serious (although rare) major complications
  • Epidural analgesia is a relatively complicated and invasive technique compared with peripheral nerve blocks

Transferable evidence

  • Epidural analgesia was superior to systemic analgesia for postoperative pain outcomes following hip or knee replacement Choi et al 2003 Click here for more information
  • A combination of epidural local anaesthetic plus opioid produced superior analgesic benefits compared with either drug administered alone in three studies of hip or knee surgery Lorenzini et al 2002 Click here for more information
  • Epidural analgesia was associated with a lower incidence of sedation compared with systemic analgesia Choi et al 2003 Click here for more information
  • Epidural anaesthesia reduces the frequency of deep vein thrombosis and pulmonary embolism, and reduces intra-operative and postoperative blood loss, compared with general anaesthesia, particularly in total hip arthroplasty patients, as shown in a review
  • Two studies showed superior analgesic effects of spinal LA plus opioid compared with LA alone, following total hip or knee arthroplasty Drakeford et al 1991 Click here for more information
  • Bupivacaine administered via spinal infusion (0.5% at 0.4 ml/h or 0.2 ml/h) resulted in an increase in the incidence of sensory and motor block compared with saline infusion
  • Diamorphine administered spinally in combination with bupivacaine showed a significantly higher incidence of nausea and vomiting compared with the bupivacaine alone group (p<0.05) following knee or hip replacement surgery
  • Epidural infusion of ropivacaine (2 mg/ml) plus sufentanil (1 µg/ml) produced a significantly higher incidence of adverse events (pruritus, nausea and vomiting) than ropivacaine alone following major knee surgery (p<0.01; n=115)
  • Epidural administration of strong opioids is associated with side-effects including pruritus, PONV, urinary retention, and respiratory depression
  • Epidural analgesia was associated with more frequent urinary retention, pruritus and low blood pressure compared with systemic analgesia in hip or knee replacement Choi et al 2003 Click here for more information
  • Neuraxial opioids are associated with a greater risk of side-effects compared with continuous plexus and peripheral neural blockades after major orthopaedic surgery

Total knee arthroplasty-specific evidence

  • Pain scores during ROM were significantly lower in the epidural group compared with the spinal anaesthesia + IV PCA morphine group on postoperative days 1–10 (p<0.001, in all cases)
  • Pain scores at rest were significantly lower in the epidural group compared with the spinal anaesthesia + IV PCA morphine group on postoperative day 1 (p<0.001), but not on days 2–10
  • There was significantly less sedation in the epidural group compared with the spinal anaesthesia + IV PCA morphine group on postoperative day 1 (p=0.04), but not on day 2
  • VAS pain scores were significantly lower in the IV propofol + spinal anaesthesia group compared with the IV propofol + fentanyl group at 3–4 days postoperatively (p<0.05), but not at 8 h or 1–2 days following surgery (
  • IV propofol + spinal anaesthesia was associated with significantly reduced time to extubation, emergence, response to command, and orientation (p<0.001, in all cases) compared with IV propofol + fentanyl anaesthesia (
  • IV propofol + spinal anaesthesia was associated with significantly reduced requirement for antihypertensive therapy compared with IV propofol + fentanyl anaesthesia (p<0.01) (
  • The incidence of sore throat (p=0.002), hoarseness (p=0.009), and nausea (p=0.049) was significantly lower in the IV propofol + spinal anaesthesia group compared with the IV propofol + fentanyl group; the incidence of vomiting, dizziness and back pain was similar in both groups (
  • Significantly more patients reported feeling comfortable (p=0.01) and having good dreams (p<0.0001) in the IV propofol + spinal anaesthesia group than in the IV propofol + fentanyl group (
  • Postoperative pentazocine consumption was significantly higher in the IV propofol + spinal anaesthesia group compared with the IV propofol + fentanyl group in the first 8 h postoperatively (p<0.05); there were no significant differences between the two groups in the consumption of diclofenac sodium at 8 h postoperatively (postoperative analgesia was diclofenac sodium [50 mg] administered rectally every 6 h, and pentazocine, as required) (
  • Study Details Farag et al 2005 Click here for more information
  • Study Details Kudoh et al 2004 Click here for more information
  • Lumbar epidural versus spinal anaesthesia
  • Spinal versus IV anaesthesia

PROSPECT Recommendations

  • Intra-articular LA and/or morphine is not recommended at this time (Grade D, LoE 4) because of inconsistent analgesic efficacy in procedure-specific and transferable evidence (see Postoperative Intra-articular Analgesia)
  • Intra-articular NSAIDs, neostigmine, or clonidine are not recommended (Grade D, LoE 4) because there is no procedure-specific and inconsistent transferable evidence
  • Intra-articular corticosteroid is not recommended at this time (Grade D, LoE 4) because there is no procedure-specific evidence, despite positive transferable evidence from minor orthopaedic procedures (LoE 1)
  • After the cut-off date of the systematic literature search, additional studies of combined intra-articular and incisional LA have shown an analgesic benefit (procedure-specific evidence, LoE 1) (see Postoperative Intra-articular Analgesia)

Clinical practice

  • Doses of IA morphine in some studies (5–10 mg) represent systemic, not IA doses

Transferable evidence

  • A systematic review of knee joint surgery RCTs looked at the effects of IA morphine, compared with saline Kalso E et al 2002 Click here for more information
  • Several randomised studies in arthroscopic knee or ankle surgery have shown that intra-articular corticosteroid reduced pain after surgery
  • A second systematic review of RCTs examining the effects of IA morphine following knee joint surgery suggested that there were no significant analgesic effects of morphine compared with saline Rosseland LA 2005 Click here for more information

Total knee arthroplasty-specific evidence

  • There is no evidence that the timing of administration of intra-articular analgesia has a significant effect on postoperative pain outcomes. All studies of intra-articular analgesia are presented in the Postoperative Intra-articular section, except for studies comparing different times of administration.

PROSPECT Recommendations

  • After the cut-off date of the systematic literature search, additional studies of combined intra-articular and incisional LA have shown an analgesic benefit (procedure-specific evidence, LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • None cited

Total knee arthroplasty-specific evidence

PROSPECT Recommendations

  • Drains are not recommended (Grade A), as they do not provide analgesic or other recovery benefits (procedure-specific evidence, LoE 1) and are associated with pain on removal (LoE 4)

Clinical practice

  • Drains are associated with pain on removal

Transferable evidence

  • Wound drains without suction produced less postoperative pain intensity on removal compared with drains with suction in intra-articular procedures (n=126; p<0.05)
  • Several studies showed no significant benefit of drained compared with un-drained wounds for a range of postoperative pain outcomes, including postoperative pain scores, in orthopaedic surgery Parker et al 2003 Click here for more information
  • Wound drains were associated with higher pain scores than no drains (no statistical analysis) in one study of patients undergoing total hip arthroplasty (n=23)
  • A meta-analysis evaluating the effectiveness of closed suction drainage systems during orthopaedic surgery found no difference in the incidence of wound infection, haematoma or dehiscence between patients with drains and those with un-drained wounds, and concluded that the evidence was insufficient to support or refute the use of drains

Total knee arthroplasty-specific evidence

  • Three studies out of three showed that drainage was not associated with any significant difference compared with no drainage for VAS pain scores, see Table 5 for details ( Click here for more information
  • Only one study out of three reported analgesic use following the use of drainage or no drainage and showed no significant difference for the number of requests for analgesia (
  • Three studies out of three showed no significant difference between drainage and no drainage for knee flexion; see Table 5 for details Click here for more information
  • One of three studies showed that drainage significantly increased the circumference of the knee on day 3 (p<0.0096) compared with no drainage, but there was no significant difference at 1 week, 1 month or 4 months postoperatively, or for the circumference of the thigh or the calf ( Click here for more information
  • One out of one study showed that drainage significantly increased the time to regain active straight-leg raising (p=0.02) compared with no drainage (
  • Two studies comparing drainage with no drainage reported hospital stay and showed no significant difference between groups (
  • Two studies comparing drainage with no drainage reported blood loss and transfusion requirements, with mixed results: one study reported no significant difference for blood loss or incidence of blood transfusion, but drainage was associated with a significant increase in units of transfused blood (p=0.03) (
  • One study reported no significant difference between drainage and no drainage for postoperative complications ( Click here for more information
  • Study details and Table 5 Click here for more information

PROSPECT Recommendations

  • No recommendation can be made for tourniquet use, as this depends on surgical/anatomical requirements, rather than pain

Clinical practice

  • Tourniquet use provides a better intra-operative surgical overview of the anatomy and avoids nerve damage (med vastus approach). Decision to use rests with the surgeon, depending on the individual patient’s anatomy and the surgeon’s experience
  • Results are difficult to interpret, due to insufficient description of anaesthetic techniques

Transferable evidence

  • None cited

Total knee arthroplasty-specific evidence

  • Release of a pneumatic tourniquet around the thigh before suturing and bandaging was significantly superior to release after suturing and bandaging for reducing VAS pain scores at 4 h postoperatively (p<0.001) (
  • Use of tourniquet was not found to be associated with any significant effect on postoperative complications, except for a significant reduction in overall blood loss in one of the two studies ( Click here for more information
  • Release of a pneumatic tourniquet around the thigh before suturing and bandaging was significantly superior to release after suturing and bandaging for the time to achieve a straight leg (p<0.00001) (
  • Release of a pneumatic tourniquet around the thigh before suturing and bandaging was significantly superior to release after suturing and bandaging for reducing the incidence of minor wound complications (p=0.04) and excessive swelling (p=0.02) (
  • Two out of three studies found that surgery with tourniquet was associated with increased pain scores compared with no tourniquet; see Table 6 for details ( Click here for more information
  • Two out of three studies reported no differences between treatment groups in terms of supplemental analgesic use; see Table 6 for details ( Click here for more information
  • Three out of three studies reported that short-term functional outcomes were superior among patients who had not had a tourniquet (see Table 6 for details), although longer-term (>3 months) joint flexibility was not found to differ significantly according to tourniquet use ( Click here for more information
  • Release of a pneumatic tourniquet around the thigh after suturing and bandaging was not significantly different from release before suturing and bandaging for the mean range of flexion at 5 or 10 days or 6 weeks (
  • Two out of two studies reported no significant difference between use of tourniquet and no tourniquet for length of hospital stay (
  • Release of a pneumatic tourniquet around the thigh after suturing and bandaging was similar to release before suturing and bandaging for hospital stay (
  • Study details and Table 6 Barwell et al 1997 Click here for more information

PROSPECT Recommendations

  • No recommendation can be made for one type of approach over another, as use depends on individual patient factors and surgical requirements, rather than pain

Clinical practice

  • Type of approach depends on individual patient factors and surgical requirements, rather than pain

Transferable evidence

  • None cited

Total knee arthroplasty-specific evidence

  • The medial trivector approach and the parapatellar approach were associated with similar Knee Society pain scores at 6 weeks and 6 months postoperatively (
  • The subvastus and medial parapatellar approaches were not significantly different for postoperative VAS pain scores (
  • Patients in the posterior cruciate ligament (PCL) excised, PCL retained, posterior stabilised and valgus groups had significantly better Knee Society mean pain scores than those in the PCL released group (p=0.03); no significant differences were observed between the PCL excised, PCL retained and posterior stabilised groups (
  • The medial trivector approach was associated with a significant decrease in the number of days to achieve straight leg raising (p<0.05) compared with the parapatellar approach (
  • The subvastus approach was significantly superior to the medial parapatellar approach for the time to attainment of 90-degree flexion (p<0.01), but there was no significant difference for the time to attainment of full extension or active straight leg raising (
  • Patients in the PCL excised, PCL retained, posterior stabilised and valgus groups had significantly better knee scores than those in the PCL released group (p=0.002) (
  • No significant differences were observed between the PCL excised, PCL retained and posterior stabilised groups with regards to ROM, knee scores or function scores (
  • The medial trivector approach and the parapatellar approach were associated with similar quadriceps strength at 6 months, Knee Society function scores at 6 weeks and 6 months, and ROM at discharge, 6 weeks and 6 months (
  • The subvastus and medial parapatellar approaches were not significantly different for walking ability with full weight-bearing (
  • A meta-analysis evaluating the effects of retention and sacrifice of the posterior cruciate ligament (PCL) in total knee arthroplasty concluded that there was no basis for a decision regarding the benefits of either retaining or sacrificing the PCL, with or without posterior stabilisation, due to heterogeneity in study quality
  • Study details Fisher et al 1998 Click here for more information

PROSPECT Recommendations

  • No recommendation can be made for choice of prosthesis, as this depends on individual patient factors and surgical requirements, rather than pain

Clinical practice

  • The choice of prosthesis depends on factors such as patient’s age, activity level, bone quality and osteoporosis (leg position/axis, ligamentous knee stability), rather than pain

Transferable evidence

Total knee arthroplasty-specific evidence

  • A mobile-bearing knee replacement was significantly superior to a fixed-bearing prosthesis for reducing Oxford knee pain scores at 1 year postoperatively (p=0.009), and also American Knee Society pain score (p=0.015) (
  • Patient preference was not significantly different between a mobile-bearing knee replacement and a fixed-bearing prosthesis (
  • Different designs of prosthesis (Tricon-M, Tricon stem, and PCA resurfacing) were similar for activity at 2 and 4 years postoperatively (
  • A meta-analysis of patellar replacement during total knee replacement showed that the resurfaced patella performed better than the non-resurfaced patella (which had a higher risk for re-operation, significant anterior knee pain, and pain during stair climbing), although there were no differences observed between groups for knee scores or patient satisfaction, and the authors concluded that many confounding factors could influence the outcome (
  • Different designs of prosthesis (Tricon-M, Tricon stem, and PCA resurfacing) were similar for Nottingham Health Profile scores e.g. sleep, pain, mobility, house work, hobbies (
  • A meta-analysis of two studies evaluating mobile bearing versus fixed bearing prostheses for total knee arthroplasty found that ROM and functional performance were similar with both types of prosthesis
  • A mobile-bearing knee replacement was similar to a fixed-bearing prosthesis for range of flexion postoperatively (
  • A meta-analysis evaluating patellar resurfacing in total knee arthroplasty showed a reduced risk of anterior knee pain and reoperation with patellar resurfacing compared with knees without patellar resurfacing
  • A meta-analysis of patellar resurfacing during total knee arthroplasty demonstrated that the incidence of anterior knee pain was significantly less in knees with resurfaced patellas compared with non-resurfaced patellas (p=0.00001), although functional outcomes improved regardless of whether or not the patella was resurfaced. Patients in the resurfaced patella group reported better satisfaction (p=0.00001) and a reduced risk of reoperation compared with those in the non-resurfaced patella group
  • Resurfacing of the patella was associated with superior pain control, for measures of pain other than Knee Society Pain Scores, and especially for anterior knee pain, compared with non-resurfacing ( Click here for more information
  • Different designs of prosthesis (Tricon-M, Tricon stem, and PCA resurfacing) were similar for pain at rest or "first-step pain" at 6 months, and 1, 2 and 4 years; the Tricon stem design was significantly superior to the other designs for pain during activity at 4 years (p=0.04) (
  • Six out of six studies that used the Knee Society Pain Score to evaluate pain at follow-up after knee surgery (months to years) reported no significant difference in pain between patients with resurfaced patella versus retained patella Barrack et al 2001 Click here for more information
  • Different designs of prosthesis (Tricon-M, Tricon stem, and PCA resurfacing) were similar for Hospital for Special Surgery (HSS) clinical scores, except at 4 years postoperatively when HSS scores had deteriorated significantly with the Tricon stem compared with the other two designs (p=0.02) (
  • Pain scores (frequency, severity and pain at night, measured using the Nottingham scale) were not significantly different in the cemented and cementless groups at 5 years postoperatively (
  • Six studies out of six Click here for more information
  • Six studies out of six ( Click here for more information
  • One study out of one reported a significantly better Knee Society Clinical Rating Score 2 years postoperatively with the non-resurfaced patella group compared with the resurfaced group; however, the scores were not significantly different between groups at 1, 4, 6, 8 or 9 years postoperatively (
  • The degrees of flexion contracture and the total range of movement at 5 years after surgery were not significantly different beween the cemented and cementless groups (
  • Study details and Table 7 Barrack et al 2001 Click here for more information

Data are available from studies that assessed intra-operative analgesia versus intra-operative placebo, as well as those that assessed intra-operative analgesia versus the same analgesia given pre- or postoperatively. It is considered that analgesic medication needs to be initiated in time to ensure an adequate analgesic effect in the immediate postoperative period. This may necessitate administration prior to the postoperative period.

Where there is evidence that the time of administration of analgesics has no significant effect on postoperative pain outcomes, studies are presented in the Postoperative section only, except for those studies specifically comparing different times of administration.

Studies of analgesics that are given peri-operatively (pre-/intra- and postoperatively) are also presented in the Postoperative section only.

PROSPECT Recommendations

  • Intra-operative dextromethorphan is not recommended (Grade D, LoE 4) because of inconsistent analgesic effects in procedure-specific and transferable evidence
  • Intra-operative ketamine cannot be recommended at this time (Grade D, LoE 4) because there is limited procedure-specific evidence (LoE 1; see Postoperative NMDA receptor antagonists), despite analgesic efficacy in other procedures (transferable evidence, LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine
  • A quantitative systematic review found that dextromethorphan does not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases

Total knee arthroplasty-specific evidence

  • VAS scores at rest were significantly lower in the dextromethorphan + chlorpheniramine maleate (CPM) after skin incision group compared with the CPM alone before skin incision group at 8 (p<0.05) and 24 h (p<0.001) postoperatively only; there was no effect at 1, 2, 4, 48 and 72 h (
  • The time to first postoperative PCA analgesia was significantly increased in the dextromethorphan + CPM after skin incision group compared with the CPM alone before skin incision group (p<0.05) (
  • Total morphine consumption over days 1–3 and mean morphine consumption on each day was reduced in the dextromethorphan + CPM after skin incision group compared with the CPM alone before skin incision group (p<0.05) (
  • There were no significant differences in morphine-related side-effects between the dextromethorphan + CPM after skin incision and CPM alone before skin incision groups (
  • Study details Yeh et al 2000 Click here for more information

PROSPECT Recommendations

  • Intra-operative weak opioids are not recommended (Grade D, LoE 4) because there is no evidence that intra-operative administration is of greater analgesic benefit than postoperative administration

Clinical practice

  • It is considered that weak opioids are ineffective as a single therapy for postoperative pain following total knee arthroplasty, and are ineffective for treatment of high-intensity pain (VAS >/=50 mm)

Transferable evidence

  • Tramadol was more effective than placebo for pain relief in a meta-analysis of post-surgical patients
  • The combination of tramadol and paracetamol enhances analgesic efficacy compared with either agent alone (
  • Tramadol (50 or 100 mg orally) provided no benefit over placebo for postoperative pain scores up to 5 h after total hip arthroplasty (n=137)
  • Codeine (60 mg orally) provided no benefit over placebo for postoperative pain scores up to 6 h after total hip arthroplasty (n=121)
  • Tramadol (100 mg bolus IV) provided no benefit over placebo for postoperative pain scores after total hip or knee arthroplasty (n=48)
  • Two studies found that codeine 30 mg + paracetamol 300 mg was associated with a higher incidence of constipation and vomiting than tramadol 37.5 mg + paracetamol 325 mg following arthroscopy

Total knee arthroplasty-specific evidence

  • The VAS pain scores of the lowest dose tramadol group (1.25 mg/kg) were significantly higher than those of all the other groups (2.5 mg/kg, 3.75 mg/kg and 5 mg/kg) at 0 and 10 min (p<0.05, in both cases) after arrival in PACU, but there were no significant differences between groups at later time points (recorded every 10 min until 60 min post-PACU) (
  • The total number of patients requiring supplemental analgesic in PACU to achieve a VAS pain score </=3 was significantly higher in the low dose tramadol group compared with all the other groups (2.5 mg/kg, 3.75 mg/kg and 5 mg/kg) (p<0.05, in all cases) (
  • The frequency of PCA use was significantly higher in the low dose tramadol group compared with all other groups (2.5 mg/kg, 3.75 mg/kg and 5 mg/kg) (p<0.05, in all cases) (postoperative analgesia was tramadol 20 mg/ml PCA bolus doses, 5-min lockout) (
  • Study details Pang et al 2003 Click here for more information

PROSPECT Recommendations

  • Femoral nerve block is recommended (Grade A) based on evidence for a reduction in pain scores and supplemental analgesia (procedure-specific evidence, LoE 1)
  • No recommendation can be made concerning continuous femoral infusion techniques versus a single bolus because of heterogeneity in study design and inconsistency of procedure-specific data (LoE 4). Only one study, published after the cut-off date for the literature search, directly compared continuous and single bolus techniques. This study shows a benefit of continuous femoral nerve block for reducing pain scores and analgesic use compared with single injection femoral nerve block, although no d
  • A combination of femoral and sciatic nerve blocks cannot be recommended (Grade D, LoE 4) at this time because of limited and inconsistent procedure-specific evidence
  • A combination of femoral and obturator nerve blocks cannot be recommended (Grade D, LoE 4) because of limited procedure-specific evidence (LoE 1) (see Postoperative Peripheral Nerve Blocks)
  • Pre-operative lumbar plexus block (posterior approach) is not recommended (Grade C, LoE 3) because femoral nerve block is equally effective (transferable evidence, LoE 1) and is associated with fewer complications (transferable evidence, LoE 3)
  • Alpha-2-adrenoceptor agonists (clonidine, epinephrine) are not recommended as part of the LA solution in peripheral nerve blocks (Grade A) because of lack of efficacy in procedure-specific studies (LoE 1; see Postoperative Peripheral Nerve Blocks)

Clinical practice

  • The evidence shows important effects of peripheral nerve blocks on reducing pain scores and improving functional recovery after TKA
  • Peripheral nerve blocks require appropriate training
  • Performance of continuous infusion peripheral nerve blocks is associated with greater technical difficulty, and may be associated with a higher failure rate, than performance of single injection peripheral nerve blocks
  • Continuous infusion peripheral nerve blocks require a greater intensity of nursing care than single injection peripheral nerve blocks
  • Continuous infusion peripheral nerve blocks may delay early mobilisation
  • Although the combination of femoral and sciatic nerve blocks may provide more effective analgesia than femoral nerve block alone, the combination may increase the density and duration of motor blockade, delay mobilisation and increase the risk of nerve damage

Transferable evidence

  • Continuous plexus and peripheral neural blocks are associated with a reduced risk of side-effects compared with neuraxial opioids, in pain management after major orthopaedic surgery
  • The posterior approach to the lumbar plexus (psoas sheath block) produces more reliable analgesia to the hip joint than the distal approach (femoral nerve or 3-in-1 blocks), whereas both techniques produced equivalent analgesia distally
  • Femoral nerve block is associated with a lower risk of serious complications than spinal anaesthesia (using bupivacaine or lidocaine)
  • Posterior lumbar plexus block provided no significant benefit over femoral nerve block or control (no nerve block) for postoperative pain scores on movement, PONV or articular mobility during rehabilitation in total hip arthroplasty (n=45)
  • As with all regional anaesthetic techniques, peripheral neural blockade has a failure rate and can cause neural injury and local anaesthetic toxicity

Total knee arthroplasty-specific evidence

  • Evidence suggests that the time of administration of femoral nerve blocks has no effect on postoperative pain outcomes after TKA. Therefore, included studies of such techniques have been pooled for analysis irrespective of the time of administration. All of the procedure-specific evidence is presented in the Postoperative section

PROSPECT Recommendations

  • Pre-operative epidural analgesia (LA and/or opioid) is not recommended (Grade B); see Intra-operative Anaesthetic techniques and Postoperative Epidural sections
  • Epidural ketamine is not recommended (Grade B) because of sedative side-effects and inconclusive analgesic effects (procedure-specific evidence, LoE 1; see Postoperative Epidural section)
  • Epidural tramadol is not recommended (Grade B) because it does not provide sufficient analgesia (procedure-specific evidence, LoE 1; see Postoperative Epidural section)

Clinical practice

  • It is considered that analgesic drugs should be administered in time to secure sufficient pain relief when the patient wakes
  • Epidural analgesia is associated with a relatively high degree of patient monitoring and serious (although rare) major complications
  • Epidural analgesia is a relatively complicated and invasive technique compared with peripheral nerve blocks

Transferable evidence

  • Epidural analgesia was superior to systemic analgesia for postoperative pain outcomes following hip or knee replacement Choi et al 2003 Click here for more information
  • A combination of epidural local anaesthetic plus opioid produced superior analgesic benefits compared with either drug administered alone in three studies of hip or knee surgery Lorenzini et al 2002 Click here for more information
  • Epidural analgesia was associated with a lower incidence of sedation compared with systemic analgesia Choi et al 2003 Click here for more information
  • Epidural anaesthesia reduces the frequency of deep vein thrombosis and pulmonary embolism, and reduces intra-operative and postoperative blood loss, compared with general anaesthesia, particularly in total hip arthroplasty patients, as shown in a review
  • Epidural infusion of ropivacaine (2 mg/ml) plus sufentanil (1 µg/ml) produced a significantly higher incidence of adverse events (pruritus, nausea and vomiting) than ropivacaine alone following major knee surgery (p<0.01; n=115)
  • Epidural administration of strong opioids is associated with side-effects including pruritus, PONV, urinary retention, and respiratory depression
  • Epidural analgesia was associated with more frequent urinary retention, pruritus and low blood pressure compared with systemic analgesia in hip or knee replacement Choi et al 2003 Click here for more information
  • Neuraxial opioids are associated with a greater risk of side-effects compared with continuous plexus and peripheral neural blockades after major orthopaedic surgery

Total knee arthroplasty-specific evidence

  • VAS pain scores were significantly lower in the pre-operative epidural combination (lidocaine + morphine + ketamine) group compared with the intra-operative epidural combination group at 6, 12 and 72 h postoperatively (p<0.05, in all cases), but not at 24 or 48 h (
  • IV PCA-morphine consumption was significantly lower in the pre-operative epidural combination (lidocaine + morphine + ketamine) group compared with the intra-operative epidural combination group on postoperative day 1 (p<0.05), but not on days 2 or 3 (
  • Time to first PCA use was longer in the pre-operative epidural combination (lidocaine + morphine + ketamine) group compared with the intra-operative epidural combination group (p<0.05) (
  • VAS pain scores at rest or on movement were not significantly different between pre- + postoperative and the postoperative lumbar epidural bupivacaine plus morphine groups at postoperative days 0.3–7 and 1–7, respectively ( Dahl et al 1994 Click here for more information
  • Consumption of IM and IV morphine during the first 24 h postoperatively was not significantly different between the pre- + postoperative and the postoperative lumbar epidural bupivacaine plus morphine groups; no significant differences were observed in the requirement for morphine/ketobemidone, orally or rectally, between the two groups after 2–7 days postoperatively ( Click here for more information
  • The incidence of nausea, vomiting, drowsiness and pruritus one day after surgery was similar in the pre-operative epidural combination (lidocaine + morphine + ketamine) group compared with the intra-operative epidural combination group (
  • Study details Dahl et al 1994 Click here for more information

PROSPECT Recommendations

  • Spinal LA + opioid is recommended (Grade A, LoE 1), but not as the first choice of analgesic technique because of a greater potential for adverse events compared with femoral nerve block (transferable evidence, LoE 3)
  • Morphine is recommended as the opioid in the spinal LA + opioid combination (Grade A) based on evidence for a longer duration of analgesic effect than other opioids (procedure-specific evidence, LoE 1)
  • Spinal clonidine is not recommended (Grade D, LoE 4) because there is limited and inconsistent procedure-specific evidence
  • Spinal neostigmine is not recommended (Grade D, LoE 4) because procedure-specific evidence of analgesic efficacy (LoE 1) is limited, and because of side-effects (transferable evidence, LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • Two studies showed superior analgesic effects of spinal LA plus opioid compared with LA alone, following total hip or knee arthroplasty Drakeford et al Click here for more information
  • Bupivacaine plus fentanyl plus clonidine showed superior analgesic efficacy compared with bupivacaine plus fentanyl following hip or knee replacement Fernandez-Galinski D et al 2005 Click here for more information
  • Patients receiving bupivacaine (0.5%) via spinal infusion at a rate of 0.4 ml/h for 24 h following knee or hip replacement required significantly less post-operative oxycodone than those receiving spinal bupivacaine at 0.2 ml/h or saline infusion (p<0.05) (n=35 patients;
  • Bupivacaine administered via spinal infusion (0.5% at 0.4 ml/h or 0.2 ml/h) resulted in an increase in the incidence of sensory and motor block compared with saline infusion
  • Diamorphine administered spinally in combination with bupivacaine showed a significantly higher incidence of nausea and vomiting compared with the bupivacaine alone group (p<0.05) following knee or hip replacement surgery
  • Neostigmine added to spinal anaesthesia in a randomised, double-blinded study in healthy volunteers produced a dose-dependent increase in nausea and vomiting
  • Two studies out of two showed that spinal neostigmine increased the incidence of nausea and vomiting following knee or below-the-knee surgery Lauretti GR et al 1997 Click here for more information

Total knee arthroplasty-specific evidence

  • The incidence of patients having >/=1 hypotensive or desaturation events was not significantly different between the morphine (250 µg) + low-dose (25 µg) and high-dose (75 µg) spinal clonidine groups and the saline group (all patients received spinal LA anaesthesia) (
  • VAS scores at rest or on movement were not significantly different between the pre-operative spinal morphine + bupivacaine group and the single injection femoral nerve block + spinal anaesthesia group at 1, 2, 4, 6, 12 or 24 h postoperatively
  • The cumulative morphine dose was not significantly different between the pre-operative spinal morphine + bupivacaine group and single injection femoral nerve block + spinal anaesthesia group at 1, 2, 4, 6, 12 or 24 h postoperatively (while in PACU patients received postoperative IV PCA-morphine [1 mg, 6-min lockout], if needed) (
  • The time to first PCA demand was not significantly different between the spinal morphine and spinal diamorphine groups (
  • Supplemental analgesic requirements were reduced in the high-dose (0.5 mg) spinal morphine group compared with the low-dose (0.2 mg) spinal morphine group Bowrey et al 2005 Click here for more information
  • The time to first request for supplemental analgesic (tramadol) was significantly longer in the high-dose (0.5 mg) spinal morphine group compared with the low-dose (0.2 mg) group (p=0.003) (
  • Time to first diclofenac request was significantly longer in the spinal morphine group compared with the spinal neostigmine group (p<0.05) (
  • Postoperative morphine consumption was significantly lower in the spinal morphine group compared with the spinal diamorphine group at 4 (p=0.001), 8 (p<0.007) and 12 h postoperatively (p<0.043), but not at 16 or 24 h (IV PCA-morphine (1 mg, 5-min lockout) (
  • Spinal morphine and diamorphine were similar for the proportion of patients rating pain relief as good or excellent (
  • NRS pain scores (scale 0–10) on movement were significantly lower in the spinal morphine group compared with the spinal diamorphine group at 4 (p=0.0046) and 8 h (p=0.0083) postoperatively, but not at 12, 16 or 24 h (
  • Sedation scores were similar in the morphine (250 µg) + low-dose (25 µg) and high-dose (75 µg) spinal clonidine groups compared with the saline group (
  • The incidence of patients having >/=1 episodes of moderate-to-severe vomiting and incidence of patients requiring >/= 1 dose anti-emetics was not significantly different between the morphine (250 µg) + low-dose (25 µg) and high-dose (75 µg) spinal clonidine groups and the saline group (all patients received spinal LA anaesthesia) (
  • The time to first diclofenac request was significantly longer in the spinal neostigmine group compared with the saline group (p<0.05) (
  • Two ( Click here for more information
  • Postoperative IV morphine consumption was significantly lower in both low-dose (25 µg) and high-dose (75 µg) spinal clonidine groups compared with the saline group (all patients received spinal LA anaesthesia) ( Sites et al 2003 Click here for more information
  • Two studies Click here for more information
  • VAS pain scores were significantly lower in the spinal neostigmine group compared with the saline group over the first 24 h postoperatively (p<0.05) (all patients received spinal LA anaesthesia) (
  • VAS pain scores were significantly lower in the spinal morphine (250 µg) + clonidine (25 µg) group compared with the saline group at 1 h (p<0.01), and 2, 4, 6 h (p<0.0001, in all cases), and 12 h (p<0.05) postoperatively, but not at 24 h (all patients received spinal LA anaesthesia) (
  • VAS pain scores were significantly lower in the spinal morphine (250 µg) + clonidine (75 µg) group compared with the saline group at 1 h (p<0.01) and 2, 4 and 6 h (p<0.0001, in all cases) postoperatively, but not at 12 or 24 h (all patients received spinal LA anaesthesia) (
  • Four out of five studies Cole et al 2000 Click here for more information
  • VAS pain scores were significantly lower in the spinal morphine group compared with the spinal neostigmine group at 8 h postoperatively (p<0.05), but not at 4, 12, 16, 20 or 24 h (
  • There were no significant differences between the spinal morphine and diamorphine groups in the incidence of nausea and/or vomiting, itching, urinary retention or catheterisation, or in the NRS for itching and vomiting; there was no incidence of respiratory depression (
  • VAS pain scores were not significantly different between the high (0.5 mg) and low-dose (0.2 mg) morphine groups at 2 h intervals for the first 24 h postoperatively (
  • VAS pain scores, as assessed by an investigator, were not significantly different between the diamorphine dose groups (0.25 mg, 0.75mg, 1.5 mg and 2.5 mg) every hour in the first 2–8 h, and every 2 h from 10–22 h postoperatively (
  • Requirement for IM diclofenac was not significantly different between the spinal morphine and spinal neostigmine groups at 24 h postoperatively (postoperative analgesia was IM diclofenac [75 mg] if VAS >4 and every 12 h as required) (
  • Supplemental postoperative morphine consumption was not significantly different between the diamorphine groups (0.25 mg, 0.75mg, 1.5 mg and 2.5 mg) at 24 h postoperatively (postoperative analgesia was IV morphine until adequate analgesia was achieved, followed by IM morphine as required)
  • The incidence of nausea/vomiting, dizziness and anxiety was not significantly different between the spinal morphine and spinal neostigmine groups; the incidence of pruritus was significantly lower in the neostigmine group compared with the morphine group (p<0.05); no respiratory depression was recorded (
  • VAS pain scores were significantly higher in the spinal block group compared with the combined sciatic-femoral block group at 0–12 (p<0.05) and 0–24 h postoperatively (p<0.01), but not at 24–36 or 36–48 h (scores were taken every 4 h for 48 h and averaged to give one pain score for each 12 h) (
  • There were no significant differences between the low-dose (0.2 mg) spinal morphine group and the high-dose (0.5 mg) spinal morphine group for the incidence of nausea, vomiting, urinary retention, sedation, respiratory depression or pruritus (
  • The incidence of nausea/vomiting, pruritus and urinary retention was similar in all diamorphine dose (0.25 mg, 0.75mg, 1.5 mg and 2.5 mg) groups (
  • The ability to straight-leg-raise was not significantly different between spinal morphine and diamorphine groups at 24 or 48 h postoperatively (
  • A significantly greater proportion of patients were unsatisfied with their anaesthetic experience in the spinal morphine group compared with the femoral block group (p=0.035) (
  • Spinal morphine and femoral block were associated with a similar incidence of hypotension and desaturation events, and sedation scores (
  • The incidence of nausea, vomiting and pruritus was significantly higher in the spinal morphine group compared with the femoral block group (p<0.05, in all cases), as was the proportion of patients requiring anti-emetic or anti-pruritus medication (p<0.05, in both cases) (
  • Postoperative morphine consumption was significantly higher in the spinal block group compared with the combined sciatic-femoral block group at 0–12 (p<0.01) and 0–24 h postoperatively (p<0.05), but cumulative morphine consumption over 0–36 and 0–48 h postoperatively was not significantly different between the two groups (PCA-morphine [1 mg, 3-min lockout]) (
  • The incidence of patients having >/=1 episodes of moderate-to-severe itching was significantly higher in the morphine (250 µg) + clonidine (75 µg) group compared with the saline group (p<0.05) (
  • One study (
  • The incidence of nausea/vomiting was significantly higher in the spinal neostigmine group compared with the saline group (p<0.05), but there was no significant difference between groups for the incidence of pruritus, dizziness, or anxiety and no respiratory depression was recorded (
  • Two studies ( Click here for more information
  • Four studies that reported the incidence of PONV, found no significant differences between spinal opioids and control, but quantitative analysis of the pooled data show an increased incidence with spinal opioids; see Table 4 for details Click here for more information
  • Requirement for IM diclofenac was not significantly different between the spinal neostigmine and saline groups at 24 h postoperatively (postoperative analgesia was IM diclofenac [75 mg] if VAS >4 and every 12 h, as required) (all patients received spinal LA anaesthesia) (
  • Study details Tan et al 2001 Click here for more information
  • Study details Sites et al 2004 Click here for more information
  • Study details and Table 4 Cole et al 2000 Click here for more information
  • Spinal anaesthesia/analgesia miscellaneous
  • Spinal analgesia versus control
  • Spinal anaesthesia/analgesia versus peripheral nerve block

PROSPECT Recommendations

  • Pre-operative intra-articular techniques are not recommended at this time (Grade D, LoE 4) because of inconsistent analgesic efficacy in procedure-specific and transferable evidence (see Postoperative intra-articular section)

Clinical practice

  • Doses of IA morphine in some studies (5–10 mg) represent systemic, not IA doses

Transferable evidence

  • A systematic review of knee joint surgery RCTs looked at the effects of IA morphine, compared with saline Kalso E et al 2002 Click here for more information
  • Several randomised studies in arthroscopic knee or ankle surgery have shown that intra-articular corticosteroid reduced pain after surgery
  • A second systematic review of RCTs examining the effects of IA morphine following knee joint surgery suggested that there were no significant analgesic effects of morphine compared with saline Rosseland LA 2005 Click here for more information

Total knee arthroplasty-specific evidence

  • There were no significant differences in VAS pain scores between the pre-operative and postoperative intra-articular bupivacaine groups at 1, 2, 4 or 24 h after arrival in PACU; there were also no significant differences in VRS pain scores (scale 0–4) between the two treatment groups (
  • ROM at discharge was significantly greater in the postoperative intra-articular bupivacaine group compared with the pre-operative intra-articular bupivacaine group (p=0.02) (
  • The incidence of nausea and vomiting, urinary retention and pruritus was similar in both pre-operative and postoperative intra-articular bupivacaine groups (
  • Study details Badner et al 1996 Click here for more information

PROSPECT Recommendations

  • Pre-operative physical therapy cannot be recommended (Grade D, LoE 4) based on postoperative analgesic effects alone (procedure-specific evidence, LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • None cited

Total knee arthroplasty-specific evidence

  • Two out of two studies showed that pre-operative physical therapies were not associated with any significant reduction in pain scores compared with standard treatment ( D'Lima et al 1996 Click here for more information
  • Two out of two studies showed pre-operative physical therapies were not associated with any significant improvement in postoperative function compared with standard treatment ( D'Lima et al 1996 Click here for more information
  • Pre-operative physical therapies were not associated with any significant reduction in length of hospital stay or rate of complications compared with standard treatments (
  • There were no significant differences between home visit and outpatient physiotherapy treatment for WOMAC dimension scores for pain or SF-36 dimension scores for bodily pain (
  • There were no significant differences between home visit and outpatient physiotherapy treatment for WOMAC dimension scores for physical function or SF-36 dimension scores for physical function (
  • There was no significant difference between home visit and outpatient physiotherapy treatment for mean total costs, but home visit physiotherapy costs were significantly higher than outpatient physiotherapy costs (p=0.001) (
  • Study details Beaupre et al 2004 Click here for more information

Pre-operative analgesia

Data are available from studies that assessed pre-operative analgesia versus pre-operative placebo, as well as those that, to examine the concept of pre-emptive — or preventive — analgesia, assessed pre-operative analgesia versus the same analgesia given postoperatively.

A meta-analysis of studies comparing pre-operative interventions with similar postoperative interventions in various procedures found that pre-operative epidural analgesia resulted in improvements in pain scores, analgesic consumption and time to first rescue analgesic request, whereas pre-operative NSAIDs and local anaesthetic wound infiltration improved analgesic consumption and time to first rescue analgesic request, but not pain scores. Evidence did not support an improvement in postoperative analgesia following administration of pre-operative NMDA antagonists and opioids (Ong 2005).

A previous systematic review of pre-emptive analgesia for acute or chronic postoperative pain relief in a variety of surgical procedures — such as orthopaedic, dental, gynaecological and abdominal — has concluded that there is no benefit of pre-emptive over postoperative administration (Møiniche 2002; LoE 1). 

It is considered that analgesic medication needs to be initiated in time to ensure an adequate analgesic effect in the immediate postoperative period. This may necessitate administration prior to the postoperative period.

Where there is evidence that the time of administration of analgesics has no significant effect on postoperative pain outcomes, studies are presented in the Postoperative section only, except for those studies specifically comparing different times of administration. This is to simplify interpretation of the overall evidence for efficacy of each analgesic agent or intervention.

Studies of analgesics that are given peri-operatively (administration pre-/intra- and postoperatively) are also presented in the Postoperative section only.

PROSPECT Recommendations

  • Pre-operative conventional NSAIDs are not recommended (Grade B) because there is limited evidence (procedure-specific, LoE 1), and because they are associated with an increased risk of intra- and postoperative bleeding (transferable evidence, LoE 1)
  • There is no evidence that pre-operative administration of conventional NSAIDs is more effective than postoperative administration for reducing pain scores

Clinical practice

  • Conventional NSAIDs should not be given pre- or intra-operatively in TKA due to potential for bleeding complications.

Transferable evidence

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures
  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression
  • Two meta-analyses comparing pre-incisional and post-incisional NSAIDs/COX-2-selective inhibitors have found no significant benefit of pre-incisional administration for reducing pain scores
  • Randomised endoscopic trials in healthy elderly volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo (
  • Meta-analyses of randomised controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls (
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery
  • A randomised clinical trial showed that the conventional NSAID diclofenac was associated with significantly greater intra-operative blood loss than the COX-2-selective inhibitor rofecoxib in patients undergoing abdominal or vaginal hysterectomy or breast surgery
  • Pre-operative ibuprofen, 600 mg orally three times per day two weeks before total hip arthroplasty, significantly increased the median total peri-operative blood loss compared with placebo (1161 ml versus 796 ml; p<0.01; n=50)
  • Pre-operative conventional NSAIDs significantly increased peri-operative blood loss in patients undergoing total hip arthroplasty compared with other analgesic agents in four out of five studies An et al 1991 Click here for more information
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible (
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients (
  • Chronic administration of conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication (
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with impaired bone healing in various animal models and in vitro studies (

Total knee arthroplasty-specific evidence

  • There was no significant difference between the pre-operative oral + postoperative IV/oral tenoxicam group and the postoperative IV/oral tenoxicam group for reducing VAS pain scores at rest at any time point (i.e. 0–48 h following surgery or days 3–9); and for reducing VAS pain scores on movement on days 3–9
  • Total morphine use over the initial 24-h period was similar in both the pre-operative oral + postoperative IV/oral tenoxicam group and the postoperative IV/oral tenoxicam group (1 mg IV PCA bolus doses, 5-min lockout, were given up to 48 h postoperatively; further IV boluses were given if rescue analgesia was required)
  • There was no significant difference in total co-dydramol use between the pre-operative oral + postoperative IV/oral tenoxicam group and the postoperative IV/oral tenoxicam group over 3–9 days postoperatively (dihydrocodeine tartrate 10 mg/paracetamol 500 mg was taken as required from the 48-h postoperatively to day 9)
  • There was no significant difference in the incidence of postoperative nausea or vomiting between pre-operative oral + postoperative oral/IV tenoxicam group and the postoperative IV/oral tenoxicam group
  • Study Details Eggers et al 1999 Click here for more information

PROSPECT Recommendations

  • Pre-operative corticosteroids are not recommended (Grade D, LoE 4) for analgesia, as there is no procedure-specific evidence, despite positive transferable evidence in minor orthopaedic procedures (LoE 1). However pre-operative corticosteroids may be used for reasons other than analgesia

Clinical practice

  • None cited

Transferable evidence

  • Intravenous methylprednisolone (125 mg) given one day after orthopaedic surgery reduced pain and opioid consumption compared with placebo (n=50)
  • A single prophylactic dose of corticosteroid is effective for preventing PONV in surgery associated with high emetic effects
  • A meta-analysis evaluated the effects of a single prophylactic dose of corticosteroid, and reported results from two orthopaedic surgery trials where both pulmonary and cardiac function were increased

Total knee arthroplasty-specific evidence

  • None cited

PROSPECT Recommendation

  • There is no procedure-specific evidence that pre-operative administration of COX-2-selective inhibitors is more effective than postoperative administration. As with all analgesics, it is recommended that COX-2-selective inhibitors should be administered at the appropriate time to provide sufficient analgesia in the early recovery period (Grade D, LoE 4)
  • No recommendations can be made at this time about combining pre-operative COX-2-selective inhibitors with regional analgesic techniques because of lack of data
  • It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B) (cardiovascular morbidity (transferable evidence, LoE 1), renal function and hepatic function (transferable evidence, LoE 3) or actual or recent gastroduodenal ulcer history (LoE 4))
  • Although there is concern about impairment of bone-healing with COX-2-selective inhibitors, there are no clinical studies on which to base a recommendation regarding whether or not these agents influence bone-healing

Clinical practice

  • COX-2-selective inhibitors should be administered at the appropriate time to provide sufficient analgesia when the patient wakes
  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries
  • No recommendations can be made at this time about combining postoperative COX-2-selective inhibitors with regional analgesic techniques because of lack of data

Transferable evidence

  • Rofecoxib 50 mg and parecoxib 40 mg have an equipotent analgesic efficacy relative to traditional NSAIDs in postoperative pain after minor and major surgical procedures
  • Randomised endoscopic trials in healthy elderly volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use (
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation or bleeding time compared with placebo Greenberg et al 2000 Click here for more information
  • A randomised clinical trial showed that the COX-2-selective inhibitor rofecoxib was associated with significantly less intra-operative blood loss than the conventional NSAID diclofenac in patients undergoing abdominal or vaginal hysterectomy or breast surgery
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function (
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following non-cardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062)
  • Two meta-analyses comparing pre-incisional and post-incisional NSAIDs/COX-2-selective inhibitors have found no significant benefit of pre-incisional administration for reducing pain scores
  • Two clinical trials showed that in patients who had undergone CABG surgery, COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo (
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents (
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible (
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients (
  • Chronic administration of COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication (
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting (
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with impaired bone healing in various animal models and in vitro studies (

Total knee arthroplasty-specific evidence

  • None cited

PROSPECT Recommendations

  • Pre-operative dextromethorphan is not recommended (Grade D, LoE 4) because of inconsistent analgesic effects in procedure-specific and transferable evidence
  • Pre-operative ketamine cannot be recommended at this time (Grade D, LoE 4) because there is limited procedure-specific evidence (LoE 1; see Postoperative NMDA receptor antagonists), despite analgesic efficacy in other procedures (transferable evidence, LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine
  • A quantitative systematic review found that dextromethorphan does not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases
  • Two meta-analyses comparing pre-incisional and postincisional treatments found no significant analgesic benefit of pre-incisional administration of NMDA receptor antagonists

Total knee arthroplasty-specific evidence

  • VAS scores at rest were significantly lower in the dextromethorphan + chlorpheniramine maleate (CPM) before skin incision group compared with the CPM alone before skin incision group at 8 (p<0.05) and 24 h (p<0.001) only; there was no effect at 1, 2, 4, 48 and 72 h (
  • VAS scores at rest were significantly lower in the dextromethorphan + CPM after skin incision group compared with the CPM alone before skin incision group at 8 (p<0.05) and 24 h (p<0.001) postoperatively only; there was no effect at 1, 2, 4, 48 and 72 h (
  • The time to first postoperative PCA analgesia was significantly increased in the dextromethorphan + CPM before skin incision group compared with the CPM alone before skin incision group (p<0.05) (
  • The time to first postoperative PCA analgesia was significantly increased in the dextromethorphan + CPM after skin incision group compared with the CPM alone before skin incision group (p<0.05) (
  • Total morphine consumption over days 1–3 was significantly reduced in the dextromethorphan + CPM before skin incision group compared with the CPM alone before skin incision group (p<0.05). Mean morphine consumption was significantly reduced in the dextromethorphan + CPM before skin incision group compared with the CPM alone before skin incision group on day 1 (p<0.05), but not on days 2 or 3 (
  • Total morphine consumption over days 1–3 and mean morphine consumption on each day was reduced in the dextromethorphan + CPM after skin incision group compared with the CPM alone before skin incision group (p<0.05) (
  • There were no significant differences in morphine-related side-effects between the dextromethorphan + CPM before skin incision and CPM alone before skin incision groups (
  • There were no significant differences in morphine-related side-effects between the dextromethorphan + CPM after skin incision and CPM alone before skin incision groups (
  • Study Details Yeh et al 2000 Click here for more information
  • Dextromethorphan

PROSPECT Recommendations

  • Pre-operative strong opioids are not recommended (Grade D, LoE 4) because there is no evidence that pre-operative administration is of any greater analgesic benefit than postoperative administration
  • As with all analgesia, strong opioids should be administered at the appropriate time to provide sufficient analgesia in the early postoperative recovery period (Grade D, LoE 4)

Clinical practice

  • As with all types of analgesia for postoperative pain, strong opioids should be administered at the appropriate time to secure sufficient analgesia when the patient wakes

Transferable evidence

  • Two studies showed that pre-operative administration of morphine reduced supplemental analgesia requirements compared with placebo in patients undergoing total hip or knee arthroplasty Reiter et al 2003 Click here for more information
  • Pre-operative oral administration of morphine sulphate 20 mg did not reduce postoperative pain scores compared with pre-operative placebo, in a group of patients undergoing total hip or knee arthroplasty (n=98)

Total knee arthroplasty-specific evidence

  • VAS pain scores were significantly reduced in the morphine group compared with the placebo group at 1–6 h (p<0.001), but not at 7–20 h; at 16 h the VAS scores of the morphine group were significantly higher than those of the placebo group (p<0.05) (
  • There were no significant differences in VAS pain scores between IV morphine in the exsanguinated operative leg + IM saline in the opposite leg versus IV saline in the exsanguinated operative leg + IM morphine in the opposite leg at the two time points assessed (i.e. at 6 and 24 h postoperatively) (
  • There was no significant difference between IV morphine in the exsanguinated operative leg + IM saline in the opposite leg versus IV saline in the exsanguinated operative leg + IM morphine in the opposite leg for supplemental analgesic requirement (postoperative analgesia was 1 mg PCA morphine, 5-min lockout) (
  • There were no significant differences between pre-operative morphine and placebo groups for the mean supplemental analgesic required (postoperative analgesia was PCA IV fentanyl 50 µg, 5-min lockout) (
  • There were no significant differences for the incidence of nausea, vomiting, pruritus, urinary retention or respiratory depression between the pre-operative morphine and placebo groups (
  • Study details Hendolin et al 1996 Click here for more information

PROSPECT Recommendations

  • Pre-operative alpha-2-delta agonists (gabapentin/pregabalin) cannot be recommended at this time (Grade D, LoE 4) because there is no procedure-specific evidence, despite analgesic efficacy in other procedures (transferable evidence, LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • Two systematic reviews and a meta-analysis evaluated the use of gabapentin for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls
  • One systematic review
  • One systematic review

Total knee arthroplasty-specific evidence

  • None cited

PROSPECT Recommendations

  • Peri-operative clonidine is not recommended (Grade D, LoE 4), because of limited procedure-specific evidence (LoE 1)

Clinical practice

  • Clonidine has not been used extensively as an analgesic agent by itself.

Transferable Evidence

  • None cited

Total knee arthroplasty-specific evidence

  • Peri-operative clonidine was associated with a significantly reduced cumulative morphine dose at 36 h postoperatively (p=0.031) compared with placebo ( Park et al 1996 Click here for more information
  • Peri-operative clonidine significantly reduced the incidence of postoperative nausea and vomiting (p<0.01, in both cases) compared with placebo; antiemetics consumption was not significantly different between the two groups (
  • Peri-operative clonidine did not reduce VAS pain scores compared with placebo at any time point (i.e. 0–36 h after surgery) (
  • Study details Park et al 1996 Click here for more information

PROSPECT Recommendations

  • Postoperative alpha-2-delta agonists (gabapentin/pregabalin) cannot be recommended at this time (Grade D, LoE 4) because there is no procedure-specific evidence, despite analgesic efficacy in other procedures (transferable evidence, LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • Two systematic reviews and a meta-analysis evaluated the use of gabapentin for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls (
  • One systematic review
  • One systematic review (

Total knee arthroplasty-specific evidence

  • None cited

PROSPECT Recommendations

  • Postoperative conventional NSAIDs are recommended (Grade A) for their analgesic and opioid-sparing effect (procedure-specific, LoE 1, and transferable evidence, LoE 1)
  • Postoperative conventional NSAIDs are recommended in combination with strong opioids for high-intensity pain (Grade D, LoE 4), or with weak opioids for moderate- or low-intensity pain (Grade D, LoE 4), or with paracetamol (Grade D, LoE 4)
  • No recommendations can be made at this time about combining postoperative conventional NSAIDs with regional analgesic techniques because of lack of data
  • The use of conventional NSAIDs should depend upon assessment of individual patient risks (Grade B), including bleeding complications, actual or recent gastroduodenal ulcer history (transferable evidence, LoE 1), cardiovascular morbidity (LoE 4), aspirin-sensitive asthma, renal function and hepatic function (transferable evidence, LoE 3)
  • Although there is concern about impairment of bone-healing with conventional NSAIDs and COX-2-selective inhibitors, there are no clinical studies on which to base a recommendation regarding whether or not these agents influence bone-healing

Clinical practice

  • No recommendations can be made at this time about combining postoperative conventional NSAIDs with regional analgesic techniques because of lack of data

Transferable evidence

  • Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures
  • Conventional NSAIDs reduced pain and analgesic use following total hip and knee replacement in five studies Anderson SK et al 1991 Click here for more information
  • Ketorolac (30 mg bolus, then 5 mg/h infusion for 24 h) reduced the duration of myocardial ischaemic episodes — compared with placebo — for 24 h following the operation in patients undergoing total hip or knee arthroplasty
  • A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression
  • Patients receiving IV ketorolac experienced significantly less sedation at 6 and 24 h (p=0.007 and 0.034, respectively) following total hip or knee arthroplasty compared with those receiving placebo
  • Patients receiving IV ketorolac received anti-emetic therapy less frequently compared with those receiving placebo (p=0.03)
  • Randomised endoscopic trials in healthy volunteers have shown that conventional NSAIDs are associated with a higher incidence of upper gastrointestinal ulceration compared with COX-2-selective inhibitors for short-term use (
  • Randomised trials in healthy volunteers showed that conventional NSAIDs (ketorolac, naproxen or diclofenac) reduced the platelet aggregation response compared with placebo; ketorolac and naproxen also prolonged bleeding time compared with placebo (
  • Meta-analyses of randomised controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls (
  • A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction
  • A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery
  • Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease (
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible (
  • Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients (
  • Conventional NSAIDs and COX-2-selective inhibitors may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication (
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with impaired bone healing in various animal models and in vitro studies (

Total knee arthroplasty-specific evidence

  • Three studies out of three showed a benefit of postoperative conventional NSAIDs compared with placebo for reducing supplemental analgesic use; see Table 8 for details Click here for more information
  • Irritation at the infusion site in the recovery room at 4 h after spinal anaesthesia was significantly reduced in the diclofenac group compared with the ketoprofen group (p<0.01) (
  • Diclofenac significantly reduced the incidence of postoperative nausea and/or vomiting on day 3 (p<0.01) compared with ketoprofen, but not on days 0 or 1; on day 2, the incidence was identical between groups (
  • One study (
  • Diclofenac significantly decreased the mean number of boluses of oxycodone at 49–60 h compared with ketoprofen (p<0.05), but not at any other study period (i.e. 0–12, 13–24, 25–36, 37–48 and 61–72 h) (postoperative analgesia was PCA IV 30 µg/kg oxycodone, 12-min lockout; if this was insufficient for pain relief, an extra dose of 30 µg/kg was given IV) (
  • Time to first analgesic request was similar following postoperative IV ketorolac (single injection, 30 mg) and parecoxib (40 mg) (
  • Postoperative IV ketorolac showed similar analgesic efficacy to postoperative IV parecoxib ( Rasmussen et al 2002 Click here for more information
  • Total co-dydramol requirement, but not total morphine consumption, was significantly lower with peri-operative tenoxicam compared with placebo ( Eggers et al 1999 Click here for more information
  • Only one study out of three showed a significant benefit of postoperative conventional NSAIDs over placebo for reducing VAS pain scores, see Table 8 for details ( Click here for more information
  • There was no significant difference between the peri-operative tenoxicam and placebo groups for reducing VAS pain scores at rest at any time point (i.e. 0–48 h following surgery or between days 3–9) and for reducing VAS pain scores on movement on days 3–9 (
  • There was no significant difference between the pre-operative oral tenoxicam group and the postoperative IV tenoxicam group for reducing VAS pain scores at rest at any time point (i.e. 0–48 h following surgery or between days 3–9); similarly, there was no significant difference between the two groups for reducing VAS pain scores on movement on days 3–9 (
  • There were no significant differences in mean VAS pain scores between the postoperative diclofenac and ketoprofen groups at any time point (i.e. between days 1–3) (
  • Total morphine use over the initial 24 h period was similar in both pre-operative oral tenoxicam group and the postoperative IV tenoxicam group; similarly, there was no significant difference in total co-dydramol use between the two groups over 3–9 days postoperatively Eggers et al 1999 Click here for more information
  • One study out of one ( Click here for more information
  • One study out of one found that placebo was significantly superior to conventional NSAIDs for the incidence of irritation at infusion site on day 0 (p<0.01, in both cases); there were no significant differences between conventional NSAIDs and placebo groups for the incidence of dizziness or drowsiness (
  • There was no significant difference in the incidence of postoperative nausea or vomiting between the pre-operative oral tenoxicam group and the postoperative IV tenoxicam groups (
  • Study details and Table 8 Boeckstyns et al 1992 Click here for more information

PROSPECT Recommendations

  • Postoperative COX-2 selective inhibitors are recommended (Grade A) based on evidence for a reduction in pain scores and supplemental analgesic requirements (procedure-specific evidence, LoE 1)
  • Postoperative COX-2 selective inhibitors are recommended in combination with strong opioids for high-intensity pain (Grade D, LoE 4), or with weak opioids for moderate- or low-intensity pain (Grade D, LoE 4), or with paracetamol (Grade D, LoE 4)
  • No recommendations can be made at this time about combining postoperative COX-2-selective inhibitors with regional analgesic techniques because of lack of data
  • It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B) (cardiovascular morbidity (transferable evidence, LoE 1), renal function and hepatic function (transferable evidence, LoE 3) or actual or recent gastroduodenal ulcer history (LoE 4)
  • Although there is concern about impairment of bone-healing with conventional NSAIDs and COX-2-selective inhibitors, there are no clinical studies on which to base a recommendation regarding whether or not these agents influence bone-healing

Clinical practice

  • Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries
  • No recommendations can be made at this time about combining postoperative COX-2-selective inhibitors with regional analgesic techniques because of lack of data

Transferable evidence

  • Etoricoxib provided superior analgesic efficacy compared with placebo, and similar analgesic efficacy to naproxen, when administered orally following knee or hip replacement (n=186 patients; Rasmussen et al 2002 Click here for more information
  • Rofecoxib 50 mg and parecoxib 40 mg have an equipotent analgesic efficacy relative to traditional NSAIDs in post-operative pain after minor and major surgical procedures
  • Randomised endoscopic trials in healthy elderly volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use (
  • Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation or bleeding time compared with placebo Greenberg et al 2000 Click here for more information
  • Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function (
  • A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following non-cardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062)
  • IV paracetamol (1000 mg), IV parecoxib (40 mg) and placebo (saline IV) were similar for reducing NRS pain scores following orthopaedic surgery (2, 4 and 6 h after surgery, and on postoperative days 1–3). Rescue analgesia consumption (IV tramadol or piritramide) was significantly lower in the paracetamol compared with placebo groups on POD1 (p<0.05), but there were no other significant differences observed between the paracetamol, parecoxib and placebo groups at any other time point (on the da
  • Two clinical trials showed that in patients who had undergone CABG surgery, COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo (
  • Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents (
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible (
  • Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients (
  • Chronic administration of COX-2-selective inhibitors and conventional NSAIDs may elevate blood pressure, particularly in hypertensive patients receiving antihypertensive medication (
  • Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting (
  • Conventional NSAIDs and COX-2-selective inhibitors have been associated with impaired bone healing in various animal models and in vitro studies (

Total knee arthroplasty-specific evidence

  • Four studies out of four showed that COX-2-selective inhibitors were associated with reduced pain compared with placebo ( Buvanendran et al 2003 Click here for more information
  • Postoperative IV parecoxib showed similar analgesic efficacy to postoperative IV ketorolac ( Rasmussen et al 2002 Click here for more information
  • Postoperative IV parecoxib showed superior analgesic efficacy to postoperative IV morphine ( Rasmussen et al 2002 Click here for more information
  • Postoperative IV parecoxib at 40 mg showed superior analgesic efficacy to postoperative IV parecoxib at 20 mg ( Rasmussen et al 2002 Click here for more information
  • Three studies out of three showed that COX-2-selective inhibitors reduced supplemental analgesic requirements compared with placebo ( Buvanendran et al 2003 Click here for more information
  • A significantly higher number of patients rated their analgesic treatment as good or excellent following postoperative IV parecoxib (single injection, 40 mg) compared with placebo (no p values given) (
  • Time to first analgesic request was significantly longer following postoperative IV parecoxib (single injection, 20 and 40 mg) administration compared with placebo (no p value given) (
  • There was significantly improved ROM with rofecoxib compared with placebo at hospital discharge for both active (p=0.03) and passive flexion (p=0.05) and also at one month postoperatively for active flexion (p=0.01) (
  • Peri-operative rofecoxib significantly reduced the incidence of postoperative vomiting, but not nausea, compared with placebo (p=0.047) (
  • Incidence of fever was significantly lower in the low-dose and high-dose valdecoxib groups compared with the placebo group (p<0.001) (
  • Patient's global evaluation of study medication was significantly higher in the high-dose valdecoxib group compared with the placebo group (p<0.01)
  • Time to onset of analgesia was similar following postoperative IV parecoxib (single injection, 20 mg) and placebo (
  • There was no significant difference in the incidence of nausea and vomiting between the low-dose and high-dose valdecoxib groups and the placebo group (
  • Study details Buvanendran et al 2003 Click here for more information

PROSPECT Recommendations

  • Postoperative ketamine infusion cannot be recommended at this time (Grade D, LoE 4), because there is limited procedure-specific evidence (LoE 1), despite analgesic efficacy in other procedures (transferable evidence, LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, renal and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine (

Total knee arthroplasty-specific evidence

  • Morphine use was significantly reduced in the ketamine group compared with the placebo group ( Adam et al 2005 Click here for more information
  • Maximal knee flexion was greater in the ketamine group compared with the placebo group on days 6 and 7 (p<0.02, in both cases) postoperatively, but not on days 1–5 (
  • The time to reach active knee flexion was significantly shorter in the ketamine infusion group than in the placebo group (p<0.03) (
  • There were no significant differences between the ketamine infusion and placebo groups in VAS pain scores at rest or on mobilisation at any time point during the first 48 h or at any time thereafter until discharge (
  • There was no significant difference between the ketamine infusion and placebo groups in the delay before the first request for analgesics while in PACU (
  • There were no significant differences in active knee flexion after 6 weeks nor after 3 months between the ketamine infusion and placebo groups (
  • There were no significant differences in the incidence of nausea and/or vomiting between the ketamine infusion and placebo groups (
  • Study details Adam et al 2005 Click here for more information
  • Ketamine

PROSPECT Recommendations

  • Postoperative strong opioids are recommended (Grade A), in combination with non-opioid analgesia (Grade D, LoE 4) for managing high-intensity pain (procedure-specific evidence, LoE 1)
  • IV PCA is recommended in preference to other analgesic administration regimens (Grade B) because of improved pain control and higher patient satisfaction (transferable evidence, LoE 1)
  • IM administration is not recommended (Grade B) because of unfavourable pharmacokinetics, injection-associated pain (LoE 4) and patient dissatisfaction (transferable evidence, LoE 1)

Clinical practice

  • Regular administration, titrated for pain intensity, is generally accepted as an effective method of administering strong opioids
  • Strong opioids can provide similar levels of analgesia when equipotent doses are used
  • Most clinical trials showing benefits of intramuscular strong opioids use nurse-administered regimens. In regular clinical practice, full adherence to nurse-administered regimens is not usually achievable, and the full analgesic benefits of intramuscular strong opioids are also not achieved
  • Intramuscular administration of strong opioids is considered to be more painful than intravenous administration. However, the size and speed of intravenous dose should be assessed to minimise the risk of respiratory depression

Transferable evidence

  • Pethidine significantly reduced postoperative pain scores compared with placebo following hip or knee arthroplasty Tarradell et al 1996 Click here for more information
  • A quantitative systematic review showed that opioid by PCA provided better pain control and greater patient satisfaction than conventional opioid parenteral analgesia in a variety of surgical procedures (37/56 trials used IM analgesia in the control group) 
  • Oral flupirtine maleate 100–200 mg and pentazocine 50–100 mg had similar effects on pain scores and on the requirement for supplemental analgesia after total hip or knee arthroplasty (n=66)
  • Morphine administered by PCA device had a similar effect to continuous infusion on postoperative pain scores following total hip or knee arthroplasty (n=32)
  • Strong opioids are effective for reducing high- and moderate-intensity postoperative pain
  • Opioids administered by PCA improved analgesia and decreased the risk of pulmonary complications, and patients preferred them compared with conventional intramuscular, intravenous or subcutaneous opioid treatment, as determined in a quantitative systematic review of randomised trials of postoperative pain management following various surgical procedures
  • A systematic review comparing intravenous PCA opioids with intravenous, intramuscular or subcutaneous opioids by injection showed that PCA opioids were associated with greater pain relief, reduced supplemental analgesic requirements (analysis of eleven studies, total n=691), and more patients preferred PCA opioids (analysis of four trials, total n=352) compared with traditional opioid analgesia
  • Patients using PCA consumed a greater quantity of opioids than those treated using conventional opioid parenteral analgesia, and had a higher incidence of pruritus, but a similar incidence of other side-effects, in a variety of surgical procedures. There was no difference between groups in the length of hospital stay
  • Pethidine induced significantly higher sedation and respiratory depression compared with tramadol (both 100 mg intravenously) (n=48)
  • Strong opioids are associated with adverse effects, including nausea, vomiting, sedation, confusion, paralytic ileus and urinary retention
  • One study found no significant differences in PCA usage or adverse side-effects between the variable dose PCA and the fixed dose PCA groups following knee or hip replacement (n=32 patients; Love DR et al 1996 Click here for more information
  • One study comparing PCA with conventional pain therapy (CPT; IV piritramide or oral/IM tramadol) demonstrated an increased consumption of postoperative analgesic in the PCA group compared with the CPT group (p<0.01), although the PCA group reported a significantly greater satisfaction with pain therapy compared with the CPT group (p<0.01) (n=42 patients;

Total knee arthroplasty-specific evidence

  • Two out of two studies showed that extended-release opioid resulted in significantly lower VAS pain scores compared with placebo at all recorded time points (i.e. at 2 and 12 h postoperatively, p=0.0058; p=0.0324, respectively (
  • VRS pain scores, measured hourly for 40 h postoperatively, indicated that the frequency of moderate pain was significantly reduced in the IM morphine group compared with the IV morphine PCA group (p<0.05); however, there was no significant difference in the frequency of mild pain nor the frequency of severe pain between groups (
  • Two out of two studies showed a significant reduction in supplemental analgesic use in the extended-release opioid group compared with the placebo group Ahdieh et al 2004 Click here for more information
  • Time to onset of analgesia was similar following postoperative IV morphine (single injection, 4 mg) and parecoxib (40 mg) (
  • One study showed that the extended-release opioid group had significant improvements in functional outcomes parameters compared with the placebo group Cheville et al 2001 Click here for more information
  • Total pain relief (computed from pain relief scores with time-weighted methods) was significantly greater in the extended-release opioid group compared with the placebo group over 0 to 12 h (p=0.0056) (
  • The incidence of actual sleep over 40 h postoperatively was significantly higher in the IM group compared with the IV morphine PCA group (p<0.01) (
  • Hospital discharge occurred significantly earlier in the extended-release opioid group than in the placebo group (p=0.013) (
  • Following postoperative IV morphine (single injection, 4 mg), pain intensity reduction (relative to baseline) was significantly smaller at 1–24 h, and pain relief scores were significantly lower at 1.5–24 h, compared with postoperative IV parecoxib (single injection, 40 mg) (no p value given) (
  • The summed pain intensity difference (relative to baseline) was significantly lower in the postoperative IV morphine (single injection, 4 mg) group compared with the postoperative IV parecoxib (single injection, 40 mg) groups at 8–24 h after drug administration (p<0.001), and similar in the morphine group compared with the IV parecoxib 20 mg group (
  • Significantly fewer patients rated their analgesic treatment as good or excellent following postoperative IV morphine (single injection, 4 mg) administration compared with postoperative IV parecoxib (single injection, 40 mg) (no p value given) (
  • Time to first analgesic request was significantly shorter following postoperative IV morphine (single injection, 4 mg) administration compared with postoperative IV parecoxib (single injection, 20 or 40 mg) (no p value given) (
  • There was no significant difference between the incidence of nausea and/or vomiting in the extended-release opioid and placebo groups (
  • There was no significant difference between IM morphine group and IV morphine PCA group in opioid use in the recovery room (
  • Study details Cheville et al 2001 Click here for more information

PROSPECT Recommendations

  • Weak opioids are not recommended for controlling high-intensity pain (Grade D, LoE 4)
  • Weak opioids are recommended to be used (Grade B) for moderate- or low-intensity pain if non-opioid analgesia is insufficient or is contraindicated (transferable evidence, LoE 1)
  • Weak opioids are recommended (Grade B) to be used in combination with non-opioid analgesics (transferable evidence, LoE 1)

Clinical practice

  • It is considered that weak opioids are ineffective as a single therapy for postoperative pain following total knee arthroplasty, and are ineffective for treatment of high-intensity pain (VAS >/=50 mm)

Transferable evidence

  • Tramadol was more effective than placebo for pain relief in a meta-analysis of post-surgical patients
  • The combination of tramadol and paracetamol enhances analgesic efficacy compared with either agent alone (
  • Tramadol delivered via PCA was not significantly different from PCA morphine for VAS pain scores, although the mean frequency of PCA delivery was significantly less in the tramadol group at 24 and 48 h (both p<0.05) following knee or hip arthroplasty (n=80)
  • A systematic review found that the combination of dextropropoxyphene 65 mg with paracetamol 650 mg showed similar efficacy to tramadol 100 mg but with a lower incidence of adverse effects
  • A systematic review found that the combination of codeine with paracetamol provided additional pain relief compared with paracetamol alone
  • Tramadol (100 mg bolus intravenously) provided no benefit over placebo for postoperative pain scores after total hip or knee arthroplasty (n=48)
  • Tramadol (50 or 100 mg orally) provided no benefit over placebo for postoperative pain scores up to 5 h after total hip arthroplasty (n=137)
  • Codeine (60 mg orally) provided no benefit over placebo for postoperative pain scores up to 6 h after total hip arthroplasty (n=121)
  • Tramadol delivered via PCA showed a significant increase in the incidence of nausea and vomiting (p<0.05) compared with PCA morphine, although sleepiness occurred more often in the PCA morphine group (p<0.05) following knee or hip arthroplasty
  • Two studies found that codeine 30mg + paracetamol 300 mg was associated with a higher incidence of constipation and vomiting than tramadol 37.5 mg + paracetamol 325 mg following arthroscopy
  • Adverse effects associated with tramadol include headache, nausea, vomiting, dizziness, somnolence. A meta-analysis of individual patient data from randomised controlled trials found a dose-response of adverse effects with tramadol; postsurgical patients had fewer side-effects than dental patients
  • A systematic review found that the combination of codeine with paracetamol was associated with an increase in drowsiness and dizziness compared with paracetamol alone
  • A systematic review found an increased incidence of central nervous system adverse effects with paracetamol plus dextropropoxyphene compared with placebo

Total knee arthroplasty-specific evidence

  • None cited

PROSPECT Recommendations

  • Paracetamol alone is not recommended for high-intensity pain (Grade D, LoE 4)
  • Paracetamol is recommended to be used in combination with other analgesics (Grade B), based on evidence that it reduces supplemental analgesic use in orthopaedic surgeries (transferable evidence, LoE 1)

Clinical practice

  • It is considered that paracetamol is ineffective as a single therapy for treatment of high-intensity postoperative pain (VAS >/=50 mm) following total knee arthroplasty

Transferable evidence

  • Paracetamol is an effective analgesic for the treatment of postoperative pain of moderate intensity
  • In a qualitative review of 28 paracetamol studies, five out of seven studies of orthopaedic procedures reported a significant reduction in analgesic consumption with paracetamol compared with placebo
  • Propacetamol (an injectable prodrug of paracetamol) showed equivalent analgesic efficacy to ketorolac when given IV following knee or hip replacement (n=164 patients; Zhou TJ et al 2001 Click here for more information
  • Analgesic efficacy of paracetamol combined with weak opioids (codeine, tramadol) was superior to weak opioids alone in a review of dental, gynaecological and orthopaedic surgery (
  • In a randomised study, patients undergoing orthopaedic surgery had transiently impaired kidney function, but there were no significant differences between patients receiving IV paracetamol (1000 mg), IV parecoxib (40 mg) and placebo (saline IV) (
  • IV paracetamol (1000 mg), IV parecoxib (40 mg) and placebo (saline IV) were similar for reducing NRS pain scores following orthopaedic surgery (2, 4 and 6 h after surgery, and on postoperative days 1–3). Rescue analgesia consumption (IV tramadol or piritramide) was significantly lower in the paracetamol group compared with the placebo group on POD1 (p<0.05), but there were no other significant differences observed between the paracetamol, parecoxib and placebo groups at any other time point (
  • Although there is evidence that concurrent use of paracetamol and conventional NSAIDs improves pain relief compared with paracetamol alone, there is no evidence for a superior analgesic effect of the combination compared with conventional NSAIDs alone (

Total knee arthroplasty-specific evidence

  • None cited

PROSPECT Recommendations

  • Femoral nerve block is recommended (Grade A) based on evidence for a reduction in pain scores and supplemental analgesia (procedure-specific evidence, LoE 1)
  • No recommendation can be made concerning continuous femoral infusion techniques versus a single bolus because of heterogeneity in study design and inconsistency of procedure-specific data (LoE 4). Only one study, published after the cut-off date for the literature search, directly compared continuous and single bolus techniques. This study shows a benefit of continuous femoral nerve block for reducing pain scores and analgesic use compared with single injection femoral nerve block, although no d
  • A combination of femoral and sciatic nerve blocks cannot be recommended (Grade D, LoE 4) at this time because of limited and inconsistent procedure-specific evidence
  • A combination of femoral and obturator nerve blocks cannot be recommended (Grade D, LoE 4), because of limited procedure-specific evidence (LoE 1)
  • Postoperative lumbar plexus block (posterior approach) is not recommended (Grade C, LoE 3), because femoral nerve block is equally effective (transferable evidence, LoE 1) and is associated with fewer complications (transferable evidence, LoE 3)
  • Alpha-2-adrenoceptor agonists (clonidine, epinephrine) are not recommended as part of the LA solution in peripheral nerve block (Grade A) because of lack of efficacy in procedure-specific studies (LoE 1)

Clinical practice

  • The evidence shows important effects of peripheral nerve blocks on reducing pain scores and improving functional recovery after TKA
  • Peripheral nerve block may be administered by means of a patient-controlled infusion pump
  • Peripheral nerve blocks require appropriate training
  • Performance of continuous infusion peripheral nerve blocks is associated with greater technical difficulty, and may be associated with a higher failure rate, than performance of single injection peripheral nerve blocks
  • Continuous infusion peripheral nerve blocks require a greater intensity of nursing care than single injection peripheral nerve blocks
  • Although the combination of femoral and sciatic nerve blocks may provide more effective analgesia than femoral nerve block alone, the combination may increase the density and duration of motor blockade, delay mobilisation and increase the risk of nerve damage

Transferable evidence

  • A randomised trial in patients undergoing TKA or arthrolysis found that continuous epidural infusion and continuous femoral block (both with 1% lidocaine, 0.03 mg/ml morphine and 2 µg/ml clonidine at 0.1 ml/kg/h) groups had reduced pain scores at rest and on continuous passive motion compared with a PCA morphine group (p<0.01)
  • A randomised trial in patients undergoing TKA or arthrolysis found that pain scores during continuous passive motion, and supplemental morphine consumption, were similar in the continuous femoral block and continuous epidural infusion groups
  • A randomised trial in patients undergoing TKA or arthrolysis found that continuous epidural infusion and continuous femoral block groups had improved early postoperative knee mobilisation compared with the PCA morphine group (p<0.05), although no significant differences were observed between the epidural and femoral block groups
  • A randomised trial in patients undergoing TKA or arthrolysis found that continuous femoral block was associated with reduced frequency of urinary retention and dysesthesia compared with continuous epidural analgesia, and reduced frequency of urinary retention and nausea compared with PCA morphine (in each case, p<0.05)
  • Continuous plexus and peripheral neural blocks are associated with a reduced risk of side-effects compared with neuraxial opioids, in pain management after major orthopaedic surgery
  • The posterior approach to the lumbar plexus (psoas sheath block) produces more reliable analgesia to the hip joint than the distal approach (femoral nerve or 3-in-1 blocks), whereas both techniques produced equivalent analgesia distally
  • Femoral nerve block is associated with a lower risk of serious complications than spinal anaesthesia (using bupivacaine or lidocaine)
  • Posterior lumbar plexus block provided no significant benefit over femoral nerve block or control (no nerve block) for postoperative pain scores on movement, PONV or articular mobility during rehabilitation in total hip arthroplasty (n=45)
  • A randomised trial in patients undergoing TKA or arthrolysis found that continuous femoral block was associated with higher pain scores at rest compared with continuous epidural infusion (no p value given)
  • As with all regional anaesthetic techniques, peripheral neural blockade has a failure rate and can cause neural injury and local anaesthetic toxicity

Total knee arthroplasty-specific evidence

  • Verbal pain scores (at rest and during movement) were not significantly different between the ropivacaine (low and high dose) and bupivacaine groups at 1, 4, 8, 24 or 48 h postoperatively (
  • Total morphine consumption in the first 6 h postoperatively was significantly lower in the pre-operative combined obturator and femoral block group compared with the femoral block group (p<0.001), as was the number of morphine boluses received via PCA (p<0.0001); the number of requests for morphine via PCA was similar between groups (
  • Total morphine consumption was significantly lower in the pre-operative femoral-sciatic and obturator block group compared with the femoral-sciatic block group at 20–48 h (p<0.05), but not in the early postoperative period (i.e. at 0–16 h) (postoperative analgesia comprised IV PCA-morphine [1 mg, 5-min lockout]) (
  • The time to first request for morphine was significantly longer in the pre-operative femoral-sciatic and obturator block group compared with the femoral-sciatic block group (p<0.05) (
  • The time to first request for morphine was significantly prolonged following pre-operative combined femoral and sciatic nerve block with bupivacaine or ropivacaine compared with no block (p<0.001) (all patients received spinal anaesthesia) (
  • Total morphine consumption in the continuous combined femoral and sciatic block group was significantly lower compared with the femoral block group (p<0.003) ( Dang et al 2005 Click here for more information
  • Emesis scores were significantly lower in the pre-operative combined femoral and sciatic block with bupivacaine group compared with the no block group at 8 h (p<0.05), but there was no significant difference between the pre-operative femoral-sciatic block with ropivacaine and no block groups (all patients received spinal anaesthesia) (
  • The incidence of nausea, but not vomiting, was significantly lower in the pre-operative combined obturator and femoral block group compared with the femoral block group (p=0.0117) (
  • The incidence of nausea and vomiting was significantly lower in the continuous combined femoral and sciatic block group compared with the femoral block group (p=0.014; p=0.042, respectively) (
  • The continuous infusion femoral nerve block group had significantly lower VAS pain scores and consumed significantly less rescue analgesia compared with the single injection group Salinas et al 2006 Click here for more information
  • Length of hospital stay was similar in the ropivacaine (low and high dose) and bupivacaine group (
  • Cumulative morphine consumption was not significantly different between the ropivacaine (low and high dose) and bupivacaine groups at 1, 4, 8, 24 or 48 h postoperatively Click here for more information
  • 24-h consumption of ropivacaine was significantly lower in the 20 ml group compared with the 15 (p=0.009) and 25 ml (p=0.027) groups, but not the 30 ml group; the number of patients receiving rescue morphine, paracetamol and/or ibuprofen was not significantly different between the groups (
  • The incidence of nausea, but not vomiting, was significantly lower in the pre-operative combined obturator and femoral block group compared with the sham femoral block group (p=0.0117) (
  • Pre-operative combined femoral and sciatic block with bupivacaine was associated with significantly lower VAS pain scores than the same block with ropivacaine at 24 and 28 h (p<0.05), but not at 4, 8, 12, 16, 20, 32, 36, 40, 44 and 48 h (all patients received spinal anaesthesia) (
  • There were no significant differences in the degree of knee flexion or the time to achieve 90-degree flexion and the duration of hospital stay between the femoral nerve block and epidural analgesia groups (LA + opioid + clonidine in both groups) (
  • VAS pain scores on movement were significantly lower in the pre-operative combined femoral and sciatic block group compared with the epidural group at 24 h postoperatively (p=0.004), but not at discharge from the recovery room or at 6 or 48 h (
  • VAS pain scores were not significantly different between the postoperative single injection femoral nerve block and the epidural group at any time point assessed (i.e. at 15, 30, 60, 120 and 180 min after start of postoperative pain management) (
  • VAS pain scores at rest and on movement were not significantly different between the pre-operative femoral nerve block and the spinal morphine groups at 1, 2, 4, 6, 12 or 24 h postoperatively (
  • Morphine consumption was significantly lower in the pre-operative combined femoral and sciatic block group compared with the epidural group at discharge from the recovery room (p=0.02), but not at any other time point assessed (6, 24 or 48 h) (1 mg PCA-parenteral morphine sulphate, 5-min lockout) (
  • Supplemental analgesic use was similar in the continuous infusion femoral nerve block group and epidural analgesia group (LA + opioid + clonidine in both groups) over 48 h postoperatively ( Singelyn et al 1998 Click here for more information
  • The cumulative morphine dose was not significantly different between pre-operative femoral nerve block and the spinal morphine groups at 1, 2, 4, 6, 12 or 24 h postoperatively (while in PACU, patients received postoperative IV PCA-morphine [1 mg, 6-min lockout]) (
  • The frequency of urinary retention (p=0.05) and catheter-related problems (p<0.001) was reduced in the continuous infusion femoral nerve block group compared with the epidural analgesia group (
  • The incidence of nausea, vomiting and pruritus was significantly lower in the pre-operative femoral nerve block group compared with the spinal morphine group (p<0.05, in all cases) (
  • Time to straighten the knee and time to discharge, as well as 85-degree active knee flexion, were not significantly different between the pre-operative combined femoral and sciatic block group and the epidural group (
  • Morphine consumption was significantly lower in the pre-operative combined femoral and sciatic block groups compared with the no block groups (from 8–48 h in the bupivacaine group, p<0.05; 4–24 h in the ropivacaine group, p<0.05) (all patients received spinal anaesthesia) (
  • One study out of one found that the length of hospital stay was significantly shorter in the continuous infusion femoral nerve block group compared with the no treatment group (p<0.001) (
  • Two studies out of two reported significant improvements in some functional outcomes parameters in the continuous infusion femoral nerve block group compared with the placebo/no treatment group ( Click here for more information
  • In two out of three studies, single injection femoral nerve block was associated with significant improvements in some functional outcomes parameters compared with placebo or no treatment ( Click here for more information
  • A femoral nerve block performed on the first postoperative day was associated with significantly reduced supplemental analgesia requirements compared with no such treatment both for number of IM oxycodone injections and total oxycodone dose (p=0.017; p=0.021, respectively) (
  • Four out of six studies showed that the use of supplemental analgesia was significantly reduced in the continuous infusion femoral or lumbar plexus nerve block group compared with the placebo/no treatment group Hirst et al 1996 Click here for more information
  • Four out of seven studies showed that single injection femoral nerve block was associated with significantly lower supplemental analgesic use compared with placebo, no treatment or systemic analgesia Szczukowski et al 2004 Click here for more information
  • A femoral nerve block performed on the first postoperative day was associated with significantly reduced VAS pain scores compared with no such treatment at 1 and 3 h post-block (p=0.045; p=0.035, respectively), but not at 5, 7, 9 or 11 h post-block, or on the 2nd or 5th postoperative day (
  • Five studies out of six reported significantly reduced postoperative VAS pain scores with continuous infusion femoral or lumbar plexus nerve block compared with placebo/no treatment ( Serpell et al 1991 Click here for more information
  • Six out of eight studies showed that single injection femoral nerve block was associated with significantly lower postoperative pain scores compared with placebo, no treatment or systemic analgesia ( Hirst et al 1996 Click here for more information
  • VAS pain scores at rest were significantly lower in the pre-operative combined obturator and femoral block group compared with the sham femoral block group at 0, 0.5, 1 and 2 h (p<0.01, in all cases) and at 4 and 6 h postoperatively (p<0.03, in both cases), but not at 3 or 5 h (
  • VAS pain scores at rest were significantly lower in the pre-operative combined femoral and sciatic nerve block groups compared with the no block groups (at 8 h for bupivacaine and at 4 h for ropivacaine [p<0.05 in both cases], but not at 12, 16, 20, 24, 28, 32, 36, 40, 44 or 48 h) (all patients received spinal anaesthesia) (
  • Morphine consumption was significantly lower in the postoperative combined femoral and sciatic block injection group compared with the combined sham block group on the day of surgery and on postoperative day 1 (p<0.02, in both cases), but not on postoperative days 2 or 3 (while in PACU patients received IV PCA-morphine [1 mg bolus, 10-min lockout]) (
  • VAS pain scores at rest were significantly lower in the postoperative combined femoral and sciatic block injection group compared with the combined sham block group for the first 8 h postoperatively (p<0.05), but there were no significant differences on postoperative days 1 or 2 ( Allen et al 1998 Click here for more information
  • VAS pain scores at rest were significantly lower in the pre-operative combined obturator and femoral block group compared with the femoral nerve block group at 0, 0.5, 1 and 2 h (p<0.01, in all cases) and at 4 and 6 h postoperatively (p<0.03, in both cases), but not at 3 or 5 h (
  • VAS pain scores at rest were significantly lower in the continuous combined femoral and sciatic block group compared with the femoral block group up to 36 h postoperatively (p<0.0001), but not at 42, 48 or 54 h; VAS pain scores on ambulation were not significantly different between the two groups (
  • Total morphine consumption in the first 6 h postoperatively was significantly lower in the pre-operative combined obturator and femoral block group compared with the sham femoral block group (p<0.001), as were the number of morphine boluses received via PCA (p<0.0001) and the number of requests for morphine via PCA (p=0.0058) ( Macalou et al 2004 Click here for more information
  • Motor blockade was significantly greater following pre-operative femoral and sciatic nerve block with ropivacaine compared with bupivacaine at 12 h (p<0.05), but this did not prevent mobilisation of any patient on the day following surgery (all patients received spinal anaesthesia) (
  • VAS pain scores at rest and on movement were significantly higher in the continuous infusion femoral nerve block group compared with the epidural analgesia group at 4 h postoperatively (p<0.001, in both cases), but not at 24 or 48 h (LA + opioid + clonidine in both groups) ( Singelyn et al 1998 Click here for more information
  • The incidence of postoperative complications (nausea, vomiting, confusion, hypotension, pruritus) was similar in the pre-operative combined femoral and sciatic block group and the epidural group (
  • The incidence of nausea and/or vomiting was not significantly different between the postoperative single injection femoral nerve block and the epidural group (
  • There were no significant differences in the incidence of nausea and/or vomiting between the femoral nerve block and epidural analgesia groups (LA + opioid + clonidine in both groups) (
  • Intra-operative and postoperative blood loss was not significantly different between the pre-operative combined femoral and sciatic block group and the epidural group (
  • The incidence of nausea and vomiting was not significantly different between the clonidine bolus, clonidine infusion and control groups (
  • The incidence of nausea and vomiting was similar in the low and high- dose bupivacaine femoral nerve block groups (
  • The incidence of nausea, vomiting, pruritus and sedation was not significantly different between the ropivacaine (low and high dose) and bupivacaine groups (
  • Emesis and sedation scores were similar between bupivacaine and ropivacaine groups for pre-operative combined femoral and sciatic block (all patients received spinal anaesthesia) (
  • A larger proportion of patients receiving clonidine infusion showed motor function impairment (i.e. the persistence of motor block) from 16–48 h of infusion, compared with the clonidine bolus and control groups (p<0.05, in both cases) (
  • VAS pain scores were significantly higher in the 15 ml ropivacaine group compared with the 20 (p=0.02), 25 (p=0.031) and 30 ml (p=0.013) groups at 4 h after the initial injection, but not at 8, 12, 16, 20 or 24 h; there were no other significant differences in pain scores between groups (
  • VAS pain scores during activity were similar following femoral nerve block in both low-dose and high-dose bupivacaine groups (0.1% and 0.2% bupivacaine at 10 ml/hr) at all time points assessed (i.e. on the day of surgery, on postoperative days 1 and 2 and on the day of discharge) (
  • The incidence of inadequate analgesia (VAS >30 mm) was not significantly different between ropivacaine and bupivacaine in a pre-operative femoral and sciatic block (all patients received spinal anaesthesia) (
  • Adding alpha-2-adrenoceptor agonist to continuous infusion femoral nerve block was not associated with significantly different VAS pain scores compared with continuous infusion femoral nerve block without alpha-2-adrenoceptor agonist Casati et al 2005 Click here for more information
  • Morphine consumption was not significantly different between the low- and high-dose bupivacaine femoral nerve block groups (PCA-morphine [1.5 mg, 6-min lockout] increased to 2 mg if VAS >50 mm) (
  • Morphine consumption and the time to first request for morphine were not significantly different between ropivacaine and bupivacaine groups for pre-operative combined femoral and sciatic block (all patients received spinal anaesthesia) (
  • ROM was similar in the low and high- dose bupivacaine femoral nerve block groups (
  • Adding alpha-2-adrenoceptor agonist to continuous infusion femoral nerve block did not significantly alter supplemental analgesia use compared with continuous infusion femoral nerve block without alpha-2-adrenoceptor agonist Weber et al 2001 Click here for more information
  • There were no significant differences in the incidence of nausea or pruritus between the postoperative combined femoral and sciatic block injection group and combined sham block group (
  • Three studies out of four found that continuous infusion femoral nerve block had no significant effect on the incidence of postoperative nausea and/or vomiting compared with placebo/no treatment ( Click here for more information
  • Three out of four studies found that there was no significant difference between the single injection femoral nerve block and placebo/no treatment groups for the length of hospital stay ( Click here for more information
  • The incidence of complications, such as respiratory depression, pruritus, dizziness and urinary retention, was found to be similar in the single injection femoral nerve block and control groups in four studies out of four, see Table 9 for details Szczukowski et al 2004 Click here for more information
  • VAS pain scores were not significantly different between the pre-operative femoral-sciatic and obturator block group compared with the femoral-sciatic block group (p<0.05) during 0–48 h (
  • VAS pain scores at rest and on physical therapy were not significantly different between the postoperative combined femoral and sciatic nerve block injection group and the femoral nerve block alone group on postoperative days 1 or 2 (
  • There were no significant differences between the continuous lumbar plexus block group and the continuous femoral nerve block group for reducing VAS pain scores at rest at 6, 24 or 48 h; also there were no significant differences between the two treatment groups for reducing VAS pain scores during physiotherapy (
  • VAS pain scores at rest and on movement were not significantly different between the continuous infusion femoral nerve block group, continuous infusion femoral nerve block plus PCA boluses group and the PCA boluses alone group at 4, 24 or 48 h postoperatively (
  • Morphine consumption was not significantly different between the postoperative combined femoral and sciatic nerve block injection group and the femoral nerve block alone group on the day of surgery or on postoperative days 1, 2 or 3 (while in PACU patients received IV PCA-morphine [1 mg bolus, 10-min lockout]) (
  • Supplemental morphine consumption (IV PCA-morphine [1 mg, 5-min lockout]) during 48 h postoperatively was similar in the lumbar plexus block and the femoral nerve block groups (
  • Requirements for supplemental analgesic were not significantly different between the continuous infusion femoral nerve block group, continuous infusion femoral nerve block plus PCA boluses group and the PCA boluses alone group over 48 h postoperatively ( Singelyn and Gouverneur 2000 Click here for more information
  • Knee flexion was not significantly different between the continuous combined femoral and sciatic block group and the femoral block group, on postoperative day 2 or after 1 month following hospital discharge (
  • The incidence of postoperative complications (sedation, hypotension, respiratory depression, and bradycardia) was similar in both the pre-operative combined obturator and femoral block group and the sham femoral block group (
  • The incidence of other postoperative complications (sedation, hypotension, respiratory depression and bradycardia) was similar in both the pre-operative combined obturator and femoral block group and the femoral block group (
  • Postoperative VAS nausea scores were similar in the femoral nerve block performed on the first postoperative day and no treatment groups at all time points (i.e. at 9, 10, 12, 14, 16, 18 and 20 h and on the 2nd and 5th postoperative days)
  • Seven out of eight studies found that the incidence of PONV was not significantly different in the single injection femoral nerve block and placebo, no treatment or systemic analgesia groups, see Table 9 for details Hirst et al 1996 Click here for more information
  • Sedation scores were not significantly different between the pre-operative combined femoral and sciatic block (with bupivacaine or ropivacaine) and the no block groups (all patients received spinal anaesthesia) (
  • The incidence of nausea and pruritus was similar in postoperative combined femoral and sciatic nerve block injection group and the femoral nerve block alone group (
  • The incidence of nausea and/or vomiting was not significantly different between the continuous infusion femoral nerve block group, continuous infusion femoral nerve block plus PCA boluses group and the PCA boluses alone group (
  • Motor blockade was greater in the pre-operative combined femoral and sciatic block with ropivacaine group (but not the bupivacaine group) compared with the no block group at 12, 16 and 20 h (p<0.05), but this did not prevent mobilisation of any patient on the day following surgery (all patients received spinal anaesthesia) (
  • Study details and Tables 9 & 10 Niskanen and Strandberg 2005 Click here for more information
  • Study details Sites et al 2004 Click here for more information
  • Study details Macalou et al 2004 Click here for more information
  • Study details Weber et al 2005 Click here for more information
  • Alternative nerve block techniques
  • Femoral nerve block versus placebo/no treatment/systemic analgesia
  • Peripheral nerve block, miscellaneous
  • Peripheral nerve block versus other analgesic techniques

PROSPECT Recommendations

  • Epidural analgesia (LA and/or opioid) is not recommended (Grade B) because of an increased risk of adverse events (procedure-specific evidence and transferable evidence, LoE 1) and no improvement in analgesia (procedure-specific evidence, LoE 1) compared with femoral nerve block
  • Epidural ketamine is not recommended (Grade B) because of sedative side-effects and inconclusive analgesic effects (procedure-specific evidence, LoE 1)
  • Epidural tramadol is not recommended (Grade B) because it does not provide sufficient analgesia (procedure-specific evidence, LoE 1)

Clinical practice

  • Epidural analgesia is associated with a relatively high degree of patient monitoring and serious (although rare) major complications
  • Epidural analgesia is a relatively complicated and invasive technique compared with peripheral nerve blocks

Transferable evidence

  • Epidural analgesia was superior to systemic analgesia for postoperative pain outcomes following hip or knee replacement Choi et al 2003 Click here for more information
  • Epidural anaesthesia reduces the frequency of deep vein thrombosis and pulmonary embolism, and reduces intra-operative and postoperative blood loss, compared with general anaesthesia, particularly in total hip arthroplasty patients, as shown in a review
  • Epidural analgesia was associated with a lower incidence of sedation compared with systemic analgesia Choi et al 2003 Click here for more information
  • A meta-analysis found that continuous epidural infusion provided superior analgesia and reduced the incidence of pruritus compared with PCEA analgesia, but was associated with a higher incidence of PONV and motor block
  • A combination of epidural local anaesthetic plus opioid produced superior analgesic benefits compared with either drug administered alone in three studies of hip or knee surgery Lorenzini et al 2002 Click here for more information
  • A meta-analysis of randomised controlled trials found that both continuous epidural infusion and PCEA analgesia provided superior postoperative analgesia compared with intravenous PCA analgesia
  • A randomised trial in patients undergoing TKA or arthrolysis found that continuous epidural infusion and continuous femoral block groups had improved early postoperative knee mobilisation compared with the PCA morphine group (p<0.05), although no significant differences were observed between the epidural and femoral block groups
  • A randomised trial in patients undergoing TKA or arthrolysis found that pain scores during continuous passive motion, and supplemental morphine consumption, were similar in the continuous epidural infusion and continuous femoral block groups
  • A randomised trial in patients undergoing TKA or arthrolysis found that continuous epidural infusion and continuous femoral block (both with 1% lidocaine, 0.03 mg/ml morphine and 2 µg/ml clonidine at 0.1 ml/kg/h) groups had reduced pain scores at rest and on continuous passive motion compared with the PCA morphine group (p<0.01). Continuous epidural infusion was associated with lower pain scores at rest compared with continuous femoral block (no p value given)
  • Ropivacaine epidural infusion was superior to no epidural infusion for reducing postoperative pain scores in a group of patients undergoing total hip or knee arthroplasty (all groups received rescue IV morphine) Turner et al 1996 Click here for more information
  • Epidural morphine (bolus 4 mg, infusion 12.5 mg/h over 13 h) was similar to epidural ketoprofen (200 mg over 30 min, 12.5 mg/h over 13 h) for postoperative pain scores following total hip or knee arthroplasty
  • VAS pain scores at rest and during movement were significantly decreased at all time points (3, 6, 12, 24 and 48 h) following knee or hip replacement in the pre-operative epidural morphine group compared with the pre-operative IV morphine and IV saline groups (p<0.001) (n=60 patients)
  • Postoperative morphine consumption was significantly increased in the pre-operative epidural morphine group (75 µg/kg) compared with the pre-operative IV morphine group (0.15 mg/kg), following knee or hip replacement (p<0.0003)
  • A randomised trial in patients undergoing TKA or arthrolysis found that continuous epidural analgesia was associated with increased frequency of urinary retention and dysesthesia compared with continuous femoral block (in each case, p<0.05)
  • Epidural infusion of ropivacaine (2 mg/ml) plus sufentanil (1 µg/ml) produced a significantly higher incidence of adverse events (pruritus, nausea and vomiting) than ropivacaine alone following major knee surgery (p<0.01; n=115)
  • Epidural administration of strong opioids is associated with side-effects including pruritus, PONV, urinary retention, and respiratory depression
  • Epidural analgesia was associated with more frequent urinary retention, pruritus and low blood pressure compared with systemic analgesia in hip or knee replacement Choi et al 2003 Click here for more information
  • Neuraxial and parenteral opioids are associated with a greater risk of side-effects compared with continuous plexus and peripheral neural blockades after major orthopaedic surgery

Total knee arthroplasty-specific evidence

  • The time taken for the verbal pain score (reported by patient, scale 1–10) to reach 5 (moderate) or the cephalad level of pinprick anaesthesia to regress five dermatomal segments was significantly longer in the epidural LA + pethidine group compared with the epidural LA + fentanyl group (p<0.05) (
  • There was significantly less sedation in the epidural group compared with the spinal anaesthesia + IV opioid PCA group on postoperative day 1 (p=0.04), but not on day 2 (
  • Pain scores during ROM were significantly lower in the epidural group compared with the spinal anaesthesia + IV opioid PCA group on postoperative days 1–10 (p<0.001, in all cases); pain scores at rest were significantly lower in the epidural group compared with the spinal anaesthesia group on postoperative day 1 (p<0.001), but not days 2–10 (
  • VAS pain scores were not significantly different between the epidural analgesia group and single injection femoral block group at any time point assessed (i.e. at 15, 30, 60, 120 and 180 min after application of LA or analgesics) (
  • Mean levels of supplemental analgesic were not significantly different between the epidural and continuous infusion femoral blockade groups over 48 h postoperatively ( Singelyn et al 1998 Click here for more information
  • There was significantly less sedation in the epidural group compared with the spinal anaesthesia plus IV opioid PCA group on postoperative day 1 (p=0.04), but not on day 2 (
  • Time to straighten the knee, intra-operative and postoperative blood loss, and time to discharge were not significantly different between the single injection femoral and sciatic block group and the epidural group (
  • The time for cephalad level of pinprick anaesthesia to regress five dermatomal segments or for the verbal pain score (reported by patient, scale 1–10) to reach 5 (moderate) was significantly longer in the bupivacaine + pethidine group compared with the epidural bupivacaine alone group (p<0.05) (
  • Area under the curve measures of motor block were significantly lower for the epidural ropivacaine infusion group compared with the epidural bupivacaine infusion group at 0–4 (p=0.041), 4–8 (p=0.032) and 8–24 h postoperatively (p=0.012) (
  • Postoperative 20 h consumption of bupivacaine (1.1 mg/ml) and fentanyl (5 µg/ml) solution was significantly lower in the PCEA group compared with the epidural group (p<0.001); there were no significant differences between the two groups in the consumption of oxycodone (IM oxycodone [0.15 mg/kg] was available as rescue medication) (
  • The number of patients requiring morphine in the first 48 h postoperatively was significantly lower in the high-dose ropivacaine plus morphine group compared with the low-dose ropivacaine plus morphine group (p=0.01) ( Axelsson et al 2005 Click here for more information
  • The incidence of postoperative side-effects (nausea, vomiting, drowsiness and pruritus) was reduced in the pre-operative epidural combination (lidocaine + morphine + ketamine) group and the intra-operative epidural combination group compared with the epidural saline + morphine + ketamine group (no p values given) (
  • VAS pain scores on movement were significantly lower in the high-dose ropivacaine plus morphine group compared with the low-dose ropivacaine plus morphine group at 4–9 h postoperatively (p<0.05), but not at 0–3 or 12–48 h; there were no significant differences between the two groups in pain while sitting or walking (
  • VAS pain scores at rest were significantly lower in the high-dose ropivacaine plus morphine group compared with the low-dose ropivacaine plus morphine group at 4–6 h postoperatively (p<0.05), but not at 0–3 or 9–48 h (
  • VAS pain scores on movement were significantly lower in the morphine group compared with both tramadol groups at all times recorded (i.e. at 0.5, 2, 10 and 12 h postoperatively) (p<0.05, in all cases) but the trial was stopped due to inadequate analgesia
  • VAS pain scores at rest were significantly lower in the morphine group compared with both low-dose and high-dose tramadol groups at 0.5 and 2 h postoperatively (p<0.05, in all cases) but the trial was stopped due to inadequate analgesia ( Grace et al 1995 Click here for more information
  • There were no significant differences in the degree of knee flexion or the time taken to achieve 90-degree flexion between the epidural and continuous infusion femoral blockade groups (
  • There were no significant differences in the incidence of nausea or vomiting between the epidural and continuous infusion femoral blockade groups (
  • The incidence of postoperative complications (nausea, vomiting, confusion, hypotension, pruritus) was similar in the single injection femoral and sciatic block group and the epidural group (
  • The incidence of nausea and/or vomiting was not significantly different between the epidural analgesia group and single injection femoral block group (
  • There was no significant difference in the duration of hospital stay between the epidural and continuous infusion femoral blockade groups (
  • Total postoperative morphine use was significantly lower in the intra-operative combination (lidocaine + morphine + ketamine) group compared with epidural saline + morphine + ketamine on postoperative days 1 and 2 (p<0.001) and 3 (p<0.05) (
  • VAS pain scores at rest and on movement were significantly lower in the epidural group compared with the femoral blockade group at 4 h postoperatively (p<0.05), but not at 24 or 48 h ( Singelyn et al 1998 Click here for more information
  • One of two studies showed that VAS pain scores at rest and on movement were significantly lower in the pre-operative lumbar epidural LA plus ketamine group compared with placebo at 24 and 48 h postoperatively (p<0.05, in all cases), but not at 2, 4, 6 or 8 h ( Weir and Fee 1998 Click here for more information
  • VAS pain scores at rest and during movement were significantly lower in the clonidine group compared with the no clonidine group at 24:00 on the day of surgery (both p<0.025), although there were no significant differences between groups at 18:00 on the day of surgery or at 06:00 or 12:00 on postoperative day 1 (
  • Pain scores during ROM were significantly lower in the epidural group compared with the spinal anaesthesia + IV opioid PCA group on postoperative days 1–10 (p<0.001, in all cases) (
  • Pain scores at rest were significantly lower in the epidural group compared with the spinal anaesthesia + IV opioid PCA group on postoperative day 1 (p<0.001), but not days 2–10 (
  • PCEA-ropivacaine consumption was significantly lower in the pre-operative lumbar epidural LA plus ketamine group compared with the placebo group (p<0.01) ( Himmelseher et al 2001 Click here for more information
  • VAS pain scores were significantly lower in the pre-/intra-operative epidural LA groups compared with saline control (epidural morphine + ketamine in all groups) Wong et al 1997 Click here for more information
  • In three out of four studies, epidural LA plus opioid was associated with reduced postoperative VAS pain scores compared with systemic opioid, at different time points ( Møiniche et al 1994 Click here for more information
  • Consumption of IM oxycodone was significantly lower in the clonidine group compared with the group receiving no clonidine (p=0.027) (
  • Total morphine consumption in the pre-operative epidural combination group (lidocaine + morphine + ketamine) was significantly lower compared with epidural saline + morphine + ketamine on postoperative day 1 (p<0.001), but not on days 2 or 3 ( Wong et al 1997 Click here for more information
  • Two studies ( Nielsen et al 1989 Click here for more information
  • In three out of four studies epidural LA plus opioid significantly reduced supplemental analgesic use (including opioid use) ( Møiniche et al 1994 Click here for more information
  • Two studies ( Klasen et al 1999 Click here for more information
  • In two studies out of two ( Click here for more information
  • Supplemental analgesic requirement was reduced in the systemic morphine pre-medication plus epidural morphine group compared with the systemic morphine pre-medication group at 1–7 h and at 14, 16 and 20 h after surgery (p<0.01, in all cases) (postoperative analgesia was PCA IV fentanyl 50 µg, 5 min lockout) (
  • Total cumulative fentanyl consumption over 20 h was reduced in the systemic morphine pre-medication plus epidural morphine group compared with the systemic morphine pre-medication group (p<0.01) (
  • Time to first request for PCA-morphine was significantly longer in the pre-operative epidural combination (lidocaine + morphine + ketamine) group compared with the epidural saline + morphine + ketamine group (p<0.05), but there was no significant difference between the intra-operative epidural combination group and the epidural saline + morphine + ketamine group (
  • The incidence of hypotension was similar in both lumbar epidural LA plus ketamine and placebo/no treatment groups (
  • The incidence of pruritus was significantly reduced in the clonidine group at 24:00 on the day of surgery compared with the group receiving no clonidine (p<0.04), although this difference was not significant between groups at 18:00 on the day of surgery or at 06:00 or 12:00 on postoperative day 1 (
  • Comparison of ropivacaine and bupivacaine for epidural infusion showed that ropivacaine was associated with higher pain scores, but only at certain time points ( Muldoon et al 1998 Click here for more information
  • VAS pain scores on movement were significantly lower in the single injection femoral and sciatic block group compared with the epidural group at 24 h postoperatively (p=0.004), but not at discharge from the recovery room or at 6 or 48 h (
  • Postoperative PCA morphine consumption was significantly higher in the epidural group compared with the single injection femoral and sciatic block group at 24 h postoperatively (p=0.004), but not at 6 or 48 h (
  • The frequency of urinary retention (p=0.05) and catheter-related problems (p<0.001) was increased in the continuous epidural analgesia group compared with the continuous infusion femoral nerve block group (
  • Time to first PCA pethidine demand was not significantly different between the two epidural tramadol groups and the morphine group (
  • Postoperative piritramide consumption (postoperative analgesia was IV PCA-piritramide) was similar in low-dose and high-dose epidural ropivacaine plus sufentanil groups (
  • There were no significant differences between the PCEA-LA group and the continuous epidural infusion group in VAS or VRS pain scores at rest or on movement at any time point recorded (i.e. 3, 9 and 20 h after the start of treatment) (
  • The incidence of pruritus was significantly higher in patients receiving epidural LA plus opioid (high- and low-dose) compared with patients receiving saline control (p<0.05) (
  • VAS pain scores at rest or on movement were not significantly different between the low-dose and high-dose epidural ropivacaine plus sufentanil groups at any time point recorded (4, 8, 20, 32 and 44 h after start of infusion) (
  • VAS pain scores were not significantly different between three epidural ketamine dose groups (0.3 mg/kg, 0.5 mg/kg and 0.67 mg/kg) (
  • There were no significant differences between ketamine dose groups (0.3 mg/kg, 0.5 mg/kg and 0.67 mg/kg) in the time taken from epidural injection to threshold (VAS >30 mm) at which supplemental analgesia was administered (
  • Pethidine consumption was significantly greater in both low-dose and high-dose tramadol groups compared with the morphine group ( Grace et al 1995 Click here for more information
  • Morphine consumption was not significantly different between the epidural ropivacaine and bupivacaine infusion groups (postoperative analgesia was ropivacaine or bupivacaine (0.2%) at 8 ml/h postoperatively for 24 h; PCA-morphine [1 mg, 5-min lockout]) (
  • The incidence of urinary retention was higher in the epidural LA plus opioid group versus the systemic opioid group (p=0.05) (
  • There were no significant differences between the 0.3 mg/kg, 0.5 mg/kg and 0.67 mg/kg epidural ketamine groups in the number of patients who developed hypotension within 20 min of epidural injection (
  • VAS pain scores were significantly higher in the systemic morphine pre-medication plus epidural morphine group compared with the systemic morphine pre-medication group at 5 h postoperatively (p<0.05), but at 16 h, the opposite was evident (p<0.05)
  • Two studies out of three found no significant differences in postoperative VAS pain scores between epidural bupivacaine and PCA IV analgesia ( Click here for more information
  • There was no significant difference between the pre-operative lumbar epidural ketamine and placebo groups in the time to first analgesic request (
  • The number of separate painful episodes at rest (categorised as VAS 4–6 and VAS 7–10) was not significantly different in the clonidine and no clonidine groups (
  • There was no significant difference in the overall patient satisfaction with the pain management regimen between the clonidine and no clonidine groups (
  • Two of three studies showed no improvement in functional outcomes in the lumbar epidural LA plus opioid group compared with the systemic opioid group ( Møiniche et al 1994 Click here for more information
  • The incidence of postoperative side-effects (nausea, vomiting, and sedation) was similar in the clonidine and no clonidine groups (
  • The incidence of nausea and/or vomiting was not significantly different between the epidural LA + opioid and systemic opioid groups in any of the four studies (
  • There were no significant differences between patients receiving postoperative epidural bupivacaine versus IV PCA analgesia for the incidence of PONV in one study out of one (
  • In four out of four studies, the incidence of PONV was similar in both lumbar epidural morphine group and the placebo or systemic analgesia group ( Click here for more information
  • The incidences of nausea, vomiting, pruritus, urinary retention and respiratory depression were similar in the IM morphine pre-medication + epidural morphine group compared with the IM morphine pre-medication + epidural saline group (
  • More patients in the pre-operative lumbar epidural ketamine groups compared with the no treatment group exhibited sedation (p<0.0001, in all cases)
  • VAS fatigue scores were not significantly different between the epidural LA plus opioid and the GA plus systemic opioid groups (
  • Three of four studies (
  • The incidence of PONV and urinary retention was not significantly different between the PCEA-LA group and the continuous epidural infusion group (
  • Catheter-related problems were significantly more common in the epidural LA plus opioid group versus the systemic opioid group (p<0.001) (
  • One study (
  • In two out of two studies ( Click here for more information
  • In one out of one study, there was no significant difference in ROM between the lumbar epidural morphine and IM ketobemidone groups (
  • Blood loss in the recovery room was similar in the clonidine and no clonidine groups (
  • Two of two studies showed that the length of hospital stay was not significantly different between the epidural LA plus opioid and systemic opioid groups (
  • The incidence of nausea was significantly higher in the high-dose epidural ropivacaine plus sufentanil group compared with the low-dose ropivacaine plus sufentanil group (p=0.042); there was no significant difference between the two dose groups for the incidence of vomiting, pruritus, sedation or hypotension (
  • The incidence of nausea, vomiting and pruritus was not significantly different between the low-dose and high-dose epidural ropivacaine plus morphine groups (
  • VAS pain scores were not significantly different between the epidural LA plus opioid compared with lumbar epidural infusion with opioid alone at any time point recorded (i.e. at discharge from the recovery room and postoperative days 0 [pm], 1 [am and pm] and 2 [am]) (
  • There was no significant difference between epidural bupivacaine plus fentanyl (3 µg/ml) and bupivacaine alone in the rate of regression of sensory anaesthesia or the development of postoperative pain (n=48) (
  • Epidural infusion rates were not significantly different between lumbar epidural infusion with LA plus opioid compared with lumbar epidural infusion with opioid alone (postoperative analgesia comprised an additional epidural bolus of 3 ml and an increase in the infusion rate of 2 ml/h if VAS pain scores >33) (
  • The incidence of nausea, vomiting and pruritus was not significantly different between lumbar epidural infusion with LA plus opioid compared with lumbar epidural infusion with opioid alone (
  • There was no significant difference in the incidence of PONV and pruritus between the two tramadol groups and the morphine group; respiratory depression was absent in all three groups (
  • Study details Badner et al 1991 Click here for more information
  • Study details Silvasti and Pitkanen 2001 Click here for more information
  • Study details Singelyn et al 1998 Click here for more information
  • Study details and Tables 11 & 12 Weir and Fee 1998 Click here for more information
  • Lumbar epidural, miscellaneous studies
  • Lumbar epidural versus other regional techniques
  • Lumbar epidural analgesia versus placebo or systemic analgesia
  • Lumbar epidural LA plus opioid versus epidural LA/opioid alone

PROSPECT Recommendations

  • Intra-articular LA and/or morphine is not recommended at this time (Grade D, LoE 4) because of inconsistent analgesic efficacy in procedure-specific and transferable evidence
  • Intra-articular NSAIDs, neostigmine, or clonidine are not recommended (Grade D, LoE 4) because there is no procedure-specific and inconsistent transferable evidence
  • Intra-articular corticosteroid is not recommended at this time (Grade D, LoE 4), because there is no procedure-specific evidence, despite positive transferable evidence from minor orthopaedic procedures (LoE 1)
  • After the cut-off date of the systematic literature search, additional studies of combined intra-articular and incisional LA have shown an analgesic benefit (procedure-specific evidence, LoE 1)

Clinical practice

  • Doses of IA morphine in some studies (5–10 mg) represent systemic, not IA doses

Transferable evidence

  • A systematic review of knee joint surgery RCTs looked at the effects of IA morphine, compared with saline Kalso E et al 2002 Click here for more information
  • Several randomised studies in arthroscopic knee or ankle surgery have shown that intra-articular corticosteroid reduced pain after surgery
  • A second systematic review of RCTs examining the effects of IA morphine following knee joint surgery suggested that there were no significant analgesic effects of morphine compared with saline Rosseland LA 2005 Click here for more information

Total knee arthroplasty-specific evidence

  • Two out of three studies ( Mauerhan et al 1997 Click here for more information
  • After the cut-off date of the systematic literature search, additional randomised studies of combined intra-articular and incisional LA versus placebo have shown a reduction in pain scores and analgesic use in the LA group
  • In one study out of one, the time to first analgesic use was significantly lengthened by postoperative intra-articular LA plus morphine compared with placebo (p<0.01) (
  • The length of time in PACU was significantly lower in the intra-operative intra-articular bupivacaine group compared with the placebo group (p=0.02) (
  • One study out of one (
  • In one study out of one, the length of hospital stay was similar in intra-articular morphine group and intra-articular LA group (
  • In one study out of one, the length of hospital stay was similar in both postoperative intra-articular LA plus morphine and placebo groups (
  • In one study out of one, the length of hospital stay was similar in both postoperative intra-articular bolus LA group and placebo group (
  • The length of hospital stay was similar in the continuous intra-articular bupivacaine group and the placebo group (
  • Three of three studies reported no significant differences between intra-articular LA + morphine compared with intra-articular LA alone for reducing postoperative VAS or McGill-Melzack pain scores at any time point during 0–48 h after surgery, ( Click here for more information
  • Three of three studies reported no significant difference between intra-articular injection of morphine versus LA in terms of postoperative VAS or McGill-Melzack pain scores at any time point during 0–48 h after surgery; ( Click here for more information
  • Three of three studies found no significant difference in VAS or McGill-Melzack pain scores between intra-articular LA plus morphine group and intra-articular morphine alone group ( Click here for more information
  • Two of three studies ( Click here for more information
  • Two of three studies ( Click here for more information
  • Three out of three studies found that intra-articular LA plus morphine and intra-articular morphine alone did not differ significantly in terms of their effect on supplemental analgesic requirements in the first 24 h after surgery, ( Click here for more information
  • In one study out of one, there were no significant differences between intra-articular LA plus morphine and intra-articular LA alone for the incidence of PONV or postoperative complications ( Click here for more information
  • In one study out of one, there were no significant differences between intra-articular morphine and intra-articular LA for the incidence of PONV or postoperative complications ( Click here for more information
  • One study out of one ( Click here for more information
  • In one study out of one, the length of hospital stay was similar in both intra-articular LA plus morphine group and intra-articular LA alone group (
  • There were no significant differences between the intra-operative intra-articular bupivacaine group and the placebo group in ROM or in distance ambulated on postoperative day 1 or at discharge
  • In one study out of one, there were no significant differences between the intra-articular LA plus morphine group and intra-articular morphine alone group for length of hospital stay (
  • In one study out of one, ROM was similar in both intra-articular LA plus morphine group and intra-articular LA alone group ( Click here for more information
  • In one study out of one, ROM was similar in both intra-articular morphine group and intra-articular LA group ( Click here for more information
  • In one study out of one, there were no significant differences between intra-articular LA plus morphine group and intra-articular morphine alone group for ROM (
  • There were no significant differences in VAS pain scores between the pre-operative versus postoperative intra-articular bupivacaine groups at 1, 2, 4 or 24 h after arrival in PACU; there were also no significant differences in VRS pain scores (scale 0–4) between the two treatment groups (
  • One study noted that patients receiving intra-articular bupivacaine pre-incision had significantly superior ROM at discharge compared with the postoperative intra-articular bupivacaine group (p=0.02) and placebo (p=0.009) (
  • The incidence of nausea and vomiting, urinary retention and pruritus was similar in pre-operative intra-articular bupivacaine versus postoperative intra-articular bupivacaine groups (
  • There were no significant differences between the continuous intra-articular bupivacaine and placebo groups for passive ROM or ambulation distance (
  • VAS pain scores in PACU, post-PACU and for the first 24 h postoperatively were not significantly different between the intra-operative intra-articular bupivacaine group and the placebo group (
  • Two studies out of three reported no significant difference in VAS pain scores for intra-/postoperative intra-articular morphine compared with placebo, see Table 13b for details Click here for more information
  • Two out of three studies reported no significant effect of postoperative intra-articular LA bolus compared with placebo on postoperative VAS or McGill-Melzack pain scores ( Click here for more information
  • VAS pain scores were not significantly different between the continuous intra-articular bupivacaine versus placebo groups on the day of surgery or on postoperative days 1 or 2 (
  • Postoperative morphine consumption was not significantly different between the pre-operative intra-articular bupivacaine and placebo groups (postoperative analgesia was IV morphine [0.02 mg/kg at 5-min intervals] until comfortable, then PCA-morphine [0.02 mg/kg, 8-min lockout]) (
  • Narcotic dose equivalents consumption was not significantly different between the intra-operative intra-articular bupivacaine group and the placebo group in PACU, post-PACU or at 24 h postoperatively (postoperative analgesia was PCA-morphine or IM narcotics, supplemented by oral narcotics as needed) (
  • There were no consistent findings between studies comparing postoperative intra-articular LA plus morphine versus placebo for supplemental analgesic use ( Mauerhan et al 1997 Click here for more information
  • Two studies out of three reported no significant differences between intra-/postoperative intra-articular morphine group and control group for supplemental morphine use ( Klasen et al 1999 Click here for more information
  • Two out of three studies ( Click here for more information
  • The number of requests for narcotics (postoperative analgesia was PCA-morphine or hydromorphone) and the mean dose of narcotic were not significantly different between the continuous intra-articular bupivacaine and placebo groups; cumulative use of NSAIDs and oxycodone-based analgesia was also similar in both groups (
  • The incidence of nausea and vomiting, urinary retention and pruritus was similar in pre-operative intra-articular bupivacaine and placebo groups (
  • The incidence of nausea was similar in intra-operative intra-articular bupivacaine group compared with the placebo group
  • One study out of one reported that there were no significant differences between postoperative intra-articular LA plus morphine and placebo for the incidence of complications such as pruritus, respiratory depression, rash or urinary retention (
  • One study out of one reported no significant differences between postoperative intra-articular bolus bupivacaine and placebo in terms of nausea and vomiting, urinary retention and pruritus (
  • One study out of one ( Click here for more information
  • VAS pain relief scores (scale 0–10) were significantly lower in the intra-operative intra-articular bupivacaine group compared with the placebo group in post-PACU (p=0.05), but not in PACU or at 24 h postoperatively (
  • There were no significant differences in VAS pain scores between the pre-operative intra-articular bupivacaine and placebo treatment groups at 1, 2, 4 or 24 h after arrival in PACU; there were also no significant differences in VRS pain scores (scale 0–4) between the two treatment groups (
  • Requirement for anti-emetics was not significantly different between the continuous intra-articular bupivacaine and placebo groups (
  • ROM at discharge was similar in the pre-operative intra-articular bupivacaine and placebo groups (
  • Study details and Tables 13a, 13b & 13c Badner et al 1996 Click here for more information
  • Study details Badner et al 1996 Click here for more information
  • Study details and Tables 14a, 14b & 14c Click here for more information
  • Intra-articular, miscellaneous
  • Intra-articular LA and/or morphine versus intra-articular LA/morphine alone
  • Intra-articular LA and/or morphine versus control

PROSPECT Recommendations

  • After the cut-off date of the systematic literature search, additional studies of combined intra-articular and incisional LA have shown an analgesic benefit (procedure-specific evidence, LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • None cited

Total knee arthroplasty-specific evidence

  • After the cut-off date of the systematic literature search, additional randomised studies of combined intra-articular and incisional LA versus placebo have shown a reduction in pain scores and analgesic use in the LA group

PROSPECT Recommendations

  • Cooling and compression techniques are recommended (Grade B) for postoperative analgesia, based on limited procedure-specific evidence for a reduction in pain scores (LoE 2) and analgesic use (LoE 1)

Clinical practice

  • None cited

Transferable evidence

  • None cited

Total knee arthroplasty-specific evidence

  • A cold compressive dressing was significantly superior to a standard compressive dressing for reducing postoperative VAS pain scores on day 2 (p<0.01) and 3 (p<0.05), but there was no significant difference on day 1 (
  • Cryo/Cuff ® was significantly superior to control for reducing the mean volume of suction drainage (p<0.05) (
  • Cryo/Cuff ® and epidural bupivacaine groups were not significantly different for blood loss or swelling (
  • Cryotherapy was significantly superior to a modified Robert Jones bandage for reducing blood loss (p<0.05), but there was no significant difference for transfusion requirements (
  • A cold compressive dressing was significantly superior to a standard compressive dressing for reducing blood loss (into the drain and into soft tissue, and total body blood loss) (p<0.001) (
  • Cryo/Cuff ® and epidural bupivacaine groups were not significantly different for passive or active ROM (
  • A cold compressive dressing was significantly superior to a standard compressive dressing for increasing the total arc ROM on day 7 (p<0.05) and 14 (p<0.01) (
  • A cold compressive dressing was significantly superior to a standard compressive dressing for reducing total use of injectable morphine in mg/kg/48 h (p<0.05) (
  • Two out of two studies showed a reduction in supplemental analgesia consumption with Cryo/Cuff ® compared with control Holmstrom and Hardin 2005 Click here for more information
  • One of two studies found that pain scores (assessed using the visual analogue method of Huskisson) were significantly lower in the Cryo/Cuff ® group compared with the control group, in patients undergoing both unilateral (p<0.05) and bilateral (p<0.02) total knee replacement ( Holmstrom and Hardin 2005 Click here for more information
  • Cryo/Cuff ® use and epidural bupivacaine use were not significantly different for reducing postoperative VAS pain scores at rest or on motion during the first 7 days postoperatively or at 6 weeks (
  • Cryo/Cuff ® and epidural bupivacaine groups were not significantly different for morphine consumption during days 1–7 postoperatively (
  • Cryotherapy was associated with increased length of hospital stay (13 days) compared with a modified Robert Jones bandage (11 days) (no p value given) (
  • A compression bandage and cold therapy were similar for total length of hospital stay (
  • A compression bandage and cold therapy were similar for knee swelling, wound drainage, transfusions, and haemoglobin, but cold therapy was associated with significantly higher INR (international normalised ratio for prothrombin time) compared with compression bandaging (p=0.03) (
  • Cryo/Cuff ® use was of no significant benefit for reducing blood loss compared with control (
  • Two out of two studies demonstrated no difference in knee swelling with Cryo/Cuff ® compared with control (
  • Cryotherapy and a modified Robert Jones bandage were similar for ROM (
  • A compression bandage and cold therapy were similar for flexion at 24 and 48 h postoperatively (
  • Two out of two studies showed no differences in ROM between the Cryo/Cuff ® and control groups Holmstrom and Hardin 2005 Click here for more information
  • Cryotherapy and a modified Robert Jones bandage were similar for morphine consumption (standardised to patient's weight) and co-dydramol doses
  • Cryotherapy and a modified Robert Jones bandage were similar for postoperative VAS pain scores (
  • A compression bandage and cold therapy were similar for postoperative VAS pain scores on days 1–3 and opiate use in 48 h (
  • Study details Holmstrom and Hardin 2005 Click here for more information

PROSPECT Recommendations

  • TENS is not recommended (Grade B) because limited procedure-specific evidence suggests a lack of benefit (LoE 1)

Clinical practice

  • TENS may be used as a co-analgesic without detriment. Effect may depend on intensity and many studies may not use adequate intensity

Transferable evidence

  • A meta-analysis of randomised, placebo-controlled trials, found that TENS, when administered with a strong, subnoxious intensity at an adequate frequency in the wound area, significantly reduced analgesic use after various types of surgery (including abdominal, gynaecological, and thoracic procedures)
  • TENS reduced pain scores after minor rib fracture on days 1 and 3 (p<0.05), but not day 0, compared with NSAID, or NSAID plus inactive TENS, or control (placebo tablet, no TENS) (n=100)
  • TENS reduced pain scores during activity (p<0.05), but not at rest, compared with placebo TENS or no TENS, after abdominal surgery (n=30)

Total knee arthroplasty-specific evidence

  • Different levels of TENS (40 mA and 14 mA) were associated with similar decreases in postoperative VAS pain scores during days 1–3 (
  • Different levels of TENS (40 mA and 14 mA) were associated with similar doses of postoperative narcotics during days 1–3 (
  • Different levels of TENS (40 mA and 14 mA) were associated with similar knee flexion arc on postoperative day 3 or day of discharge (
  • Different levels of TENS (40 mA and 14 mA) were associated with similar lengths of hospital stay (
  • Study Details Angulo and Colwell 1990 Click here for more information

PROSPECT Recommendations

  • Continuous passive motion (Grade A) and intensive rehabilitation (Grade D) are recommended for reasons other than analgesia (procedure-specific evidence, LoE 1 and 2 respectively)

Clinical practice

  • None cited

Transferable evidence

  • None cited

Total knee arthroplasty-specific evidence

  • Two out of two studies of intensive rehabilitation protocols used measurements other than VAS pain score for knee pain, and one of the two showed that supervised intensive rehabilitation of 2–4 months duration was superior to standard care for reducing WOMAC pain scoring ( Click here for more information
  • One study comparing continuous passive motion (CPM) treatment with control found CPM was associated with increased ROM, and the CPM group found it easier to regain movement postoperatively compared with control ( Harms and Engstrom 1991 Click here for more information
  • One study out of two describing inter-group differences in functional outcome, showed that patients given intensive/accelerated rehabilitation had significantly better walking abilities postoperatively compared with control ( Click here for more information
  • One study out of one demonstrated superior active flexion in the continuous passive motion group compared with the control group (p=0.004), although there were no significant differences in postoperative active extension or passive extension between groups (
  • One study out of one showed that the number of days taken to achieve 70º ROM was significantly fewer with continuous passive motion compared with control, although knee flexion at discharge was not significantly different between the two groups
  • Two studies out of two reported a significant reduction in knee swelling with continuous passive motion compared with control (
  • A meta-analysis evaluating the effectiveness of continuous passive motion following total knee arthroplasty showed that continuous passive motion with physical therapy was more effective than physical therapy alone for significantly increasing active knee flexion, decreasing the length of hospital stay, and decreasing the need for post-operative manipulation. Continuous passive motion did not significantly improve passive knee flexion and passive or active knee extension
  • There was no significant difference between home visit and outpatient physiotherapy treatment for mean total costs, but home visit physiotherapy costs were significantly higher than outpatient physiotherapy costs (p=0.001) (
  • One study comparing continuous passive motion treatment with control reported no significant difference between groups for wound drainage (
  • Duration of hospital stay was not significantly different between the continuous passive motion and lower limb mobility board groups (
  • Three out of three studies comparing continuous passive motion treatment with control reported no significant difference between groups for length of hospital stay (
  • Knee function was not significantly different between the continuous passive motion and lower limb mobility board groups May 1999 Click here for more information
  • One study out of one reported no significant differences in 6 week ROM or function assessed by HAQ (Health Assessment Questionnaire) between the continuous passive motion and control groups (
  • There were no significant differences between home visit and outpatient physiotherapy treatment for WOMAC dimension scores for physical function or SF-36 dimension scores for physical function (
  • Two out of two studies showed no significant difference between continuous passive motion treatment group versus control group for postoperative rescue analgesic requirements Harms and Engstrom 1991 Click here for more information
  • There were no significant differences between home visit and outpatient physiotherapy treatment for WOMAC dimension scores for pain or SF-36 dimension scores for bodily pain (
  • There were no significant differences in VAS pain scores at discharge between groups in a study comparing continuous passive motion with the use of a lower limb mobility board (
  • Three studies out of four showed no significant difference between continuous passive motion treatment and control for pain scores Can and Alpaslan 2003 Click here for more information
  • Study details and Table 15 Can and Alpaslan 2003 Click here for more information

Testing the   Paragraphs

Testing the Paragraphs    

A Detailed Methodology 2006 [archived]

prospect provides recommendations for procedure-specific postoperative pain management based on expert interpretation of procedure-specific and transferable evidence in the context of current clinical practice

The process by which the prospect Working Group formulates its recommendations has been refined to take greater account of the quality of available evidence and to reduce the potential for bias in the formulation of recommendations (Neugebauer 2007). The refined methodology will be implemented in full for procedure reviews performed from 2006

Working Group

  • The Working Group is an international collaboration of surgeons and anaesthesiologists, chaired by Professor Francis Bonnet
  • The Working Group review in detail the evidence from the procedure-specific systematic review, as well as the transferable evidence, the clinical practice information and the draft recommendations agreed at the Subgroup meeting. For each analgesic, anaesthetic or surgical intervention, the group first comes to a consensus about the applicability and relevance of transferable evidence and clinical practice information. The group then refines each recommendation according to consensus, considering all of the evidence and information. The process is described in more detail in subsequent folders

Subgroup

  • Consists of at least two members of the Working Group, and occasionally a clinician external to the prospect group, who have particular expertise in the operative technique to be reviewed. May also include an expert member of the data analysis team
  • Advises on literature searches, assesses the level of evidence of each study, performs a detailed review of the summary ‘Outcomes Document", identifies relevant transferable evidence, and agrees a draft of the clinical practice information and recommendations for procedure-specific postoperative pain management

Data Analysis and Medical Writing Team

  • Work closely with the Subgroup and Working Group to coordinate literature searches, review abstracts and papers, assess quality and level of evidence of each study, create data tables, carry out qualitative and quantitative analyses, draft the summary Outcomes and Review documents for review by the Subgroup and Working Group, collate comments of Subgroup and Working Group, prepare the final version of the Review document which is subsequently presented on the prospect website

Information Specialist

  • Provides advice on literature search terms and performs literature searches

Recommendations

  • Best practice recommendations, which are graded based on the source and level of evidence Click here for more information
  • Consensus of the prospect Working Group, based on the evidence, with expert interpretation in the context of clinical practice
  • Formulating the recommendations – the process Click here for more information

Clinical practice

Transferable evidence

  • Transferable evidence is identified by the Subgroup and may include evidence of analgesic efficacy from other surgical procedures with a similar pain profile, or evidence regarding adverse effects from a variety of other surgical procedures Neugebauer et al 2007

Procedure-specific evidence

  • Procedure-specific evidence is derived from systematic literature reviews, performed using a process based on the protocol of the Cochrane Collaboration. prospect systematic reviews incorporate the following key characteristics Click here for more information

Prospect flowchart

Literature search

Comprehensive search strategy to identify relevant studies

Literature search terms are clearly defined and agreed by the prospect Subgroup, Data Analysis and Medical Writing Team and Information Specialist (see Review Team section), and include words or phrases related to pain and possible interventions, as well as procedure-specific terms. MEDLINE and EMBASE are searched by an Information Specialist to identify studies published within a defined time period; secondary literature searches are also performed and relevant systematic reviews are identified in the Cochrane library

Review abstracts: decision to select

Studies that appear relevant to the systematic review are selected for closer inspection by the Data Analysis and Medical Writing Team

Inclusion criteria:

  • Randomised controlled clinical trials of analgesic, anaesthetic and operative interventions in adults, relating to surgical procedure being reviewed
  • Pain scores from a linear pain scale, e.g. visual analogue scale (VAS) or verbal or numerical rating scale (VRS or NRS)
  • While there is evidence that studies published in English are more likely to report beneficial effects for a particular treatment or intervention than studies published in other languages (Moher 1996, Egger 1997, Juni 2002, Song 2000), only English language studies are included, due to time and resource constraints

Review selected papers: include/exclude (performed by Data Analysis and Medical Writing Team)

Inclusion criteria:

  • Randomised controlled clinical trials of analgesic, anaesthetic and operative interventions in adults, relating to surgical procedure being reviewed
  • Pain scores from a linear pain scale, e.g. visual analogue scale (VAS) or verbal or numerical rating scale (VRS, NRS)

Data summary and table

The Data Analysis and Medical Writing Team record information from each included study, in tables, with similar comparisons grouped together for ease of analysis.

Information is collected according to the list of outcome measures for assessment, as agreed at the outset of the review. The following information is always recorded if included in the published study:

  • Interventions compared and patient numbers in each group
  • Analgesia administered to all patients
  • Qualitative outcomes for pain scores, supplementary analgesic use, time to first request for rescue analgesia, postoperative nausea and vomiting
  • Additional outcomes that are considered to be important in the procedure under review

Assess quality and level of evidence of each study

Quality assessment is performed by the Data Analysis and Medical Writing Team, and the Subgroup

Levels of evidence and grades of recommendation in PROSPECT reviews (from 2006)

Qualitative analysis

Qualitative analyses are performed for each group of studies reporting similar treatment comparisons (for example, all studies comparing incisional local anaesthetics versus placebo). All analyses are reported in a summary Outcomes Document. Qualitative results are reported for all specified outcomes, and details of the assigned levels of evidence are recorded in the text of the document

Meta-analysis of pooled data

Quantitative analyses are performed where possible, where study designs are homogenous and data are reported in a suitable manner, using Review Manager 4.2.2 software (RevManAnalyses), which has been developed for Cochrane Collaboration systematic reviews. Quantitative analyses are reported in the summary Outcomes Document

  • Meta-analysis of continuous data provides a weighted mean difference (WMD) and a probability of overall treatment effect, based on means and standard deviations
  • Meta-analysis of dichotomous data provides an odds ratio (OR) and a probability of overall treatment effect, based on the proportion of patients affected
  • Studies that do not report mean and standard deviation (SD) data (for continuous variables) or proportion of patients affected (for dichotomous variables), are not included in the meta-analyses

Review by Subgroup

The Subgroup consists of at least two members of the Working Group and, in some cases, one additional, external expert with special interest in the procedure in question; the Subgroup reviews the Outcomes Document, evaluating the strength of evidence for each surgical, anaesthetic or analgesic intervention

Subgroup meeting

The Subgroup members and the Data Analysis and Medical Writing Team discuss the Outcomes Document; the Subgroup drafts the transferable evidence, clinical practice information and recommendations. The recommendations are formulated after a discussion of the relative benefits and harms of each intervention, taking into account:

  • Strength of results and consistency of evidence
  • Important safety considerations related to the analgesic intervention
  • Ethical constraints
  • Clinical expertise
  • Patient preferences
  • Clinical relevance
  • Pathophysiology and clinical plausibility
  • Applicability to patient group
  • Practicality
  • Side-effects

Review document

The Data Analysis and Medical Writing Team prepares the ‘Review’ document. All statements of evidence, including procedure-specific, transferable and clinical practice information, are presented with a tick or cross, indicating whether or not they support the use of that particular intervention. Recommendations drafted at the Subgroup meeting are included

Review by Working Group

The Review document is circulated to each member of the prospect Working Group for review

Comments of Working Group collated by Delphi method

Following evaluation of the Review document, Working Group members comment on the evidence and draft recommendations. The Working Group does not discuss individual comments until the Data Analysis and Medical Writing Team has received all the comments, according to the Delphi method (Dalkey 1963):

  • Comments are forwarded only to the Data Analysis and Medical Writing Team, and not to the whole Working Group (this method avoids the potential for one Working Group member’s views to be accepted by the rest of the Group without full consideration of the data)
  • Individual comments are then collated for discussion at a round-table meeting

Working Group meeting

Collated comments are discussed and the recommendations are finalised. Where consensus is not reached by group discussion, a modified Nominal Group Process is used. This is a method whereby:

1. Each Working Group member expresses his or her comments/concerns about each recommendation, one after the other; at this stage, there is no discussion, agreement or disagreement from the other members

2. Comments are discussed

3. Each Working Group member votes to accept or reject individual comments

4. Further rounds of comments, discussion and voting are included until consensus is reached

5. Where full consensus of the Working Group is not achieved, a majority decision is taken based on a vote, and this is noted alongside the recommendation

6. Recommendations are presented with a brief explanation of the evidence on which they are based (including details of the balance of benefits and harms, where relevant). Recommendations are graded to indicate the strength of the recommendation, which reflects the level and source of evidence (also specified)

Levels of evidence and grades of recommendation in PROSPECT reviews (from 2006)

Revision of Review document and final consideration by Working Group

The Review document is updated according to the consensus agreements from the Working Group meeting and circulated to the Working Group for a final round of comments by the Delphi method; any final comments are incorporated according to the consensus of the Working Group

Procedure review available at www.postoppain.org

The final version of the Review Document is presented on the prospect website.

Evidence and graded recommendations for peri-operative interventions are contained within folders, in which procedure-specific evidence, transferable evidence, clinical practice information and prospect recommendations are clearly separated.

A summary of the recommendations and details of the procedure-specific systematic literature review are also presented, including criteria for study inclusion as well as lists of included and excluded studies.

The web-based format offers a user-friendly way to present the large amount of information contained within each review, and encourages users to submit feedback to the Working Group via the website.

PROSPECT Methodology

Optimal recovery after surgery depends upon effective perioperative pain management. The PROSPECT (PROcedure-SPECific postoperative pain managemenT) initiative, a collaboration of anaesthesiologists and surgeons with broad international representation, provides healthcare professionals with practical, procedure-specific pain management recommendations, formulated in a way that facilitates clinical decision-making across all stages of the perioperative period. Recommendations are based on a systematic review and critical analysis of available procedure-specific evidence. With rapid changes in perioperative care and implementation of multidisciplinary, early rehabilitation programs (fast track or enhanced recovery programs), which are becoming standard of care, the PROSPECT methodology has been modified to critically analyse the design of each study with regards to its relevance in current perioperative care practice. The process by which the recommendations are formulated has been refined to take account of not only the quality of the available procedure-specific evidence, but also critical expert interpretation of the study design. The refined methodology has been implemented for all procedure reviews performed from 2016 onwards. A detailed description of the methodology has been published and is freely accessible: Joshi et al 2019.

Once the procedure to be reviewed has been identified, a subgroup is selected which consists of at least two members of the PWG (including the subgroup lead). External members (i.e. non-PWG members) are invited to join a subgroup, if they have specific expertise in the surgical procedure to be reviewed. In addition, specialists in literature searches and/or data analysis, and research fellows may also be invited to assist with a particular project. The subgroup performs the initial literature search, and reviews all the manuscripts to identify relevant studies for inclusion, assesses the quality and level of evidence of included studies, creates data tables, carries out qualitative and quantitative analyses, critically analyses the design of the included studies with regards to their relevance in current perioperative care practice, and drafts the summary documents for presentation to the full PWG. The PWG subsequently examines, in detail, each analgesic, anaesthetic or surgical intervention recommended and not recommended by the subgroup. The PWG refines the recommendations, as necessary, and comes to a consensus agreement on all the recommendations, which are subsequently presented on the website. The processes of performing the systematic review and formulating the recommendations are outlined below. For full details, please access the PROSPECT methodology publication: Joshi et al 2019.

  • A systematic search for literature specific to perioperative pain management for the selected procedure is performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) recommendations.
  • Several electronic databases are searched, including EMBASE, MEDLINE, PubMed and Cochrane Databases (Cochrane Central Register of Controlled Trials, Cochrane Database of Abstracts or Reviews of Effects, Cochrane Database of Systematic Reviews).
  • Broad search terms are used to reduce the risk of missing relevant publications. Search terms include words or phrases associated with specific procedures, possible interventions and pain-related outcomes.
  • Reference lists of the relevant articles are manually screened to identify additional eligible studies that may have been missed in the initial literature search.
  • The time period for the literature search for a new review is determined by the PWG, generally the preceding 10 years; for updates the period is usually 3–5 years from the end-date of the previous review.

  • Inclusion criteria are randomised controlled clinical trials (RCTs) and systematic reviews or meta-analyses of analgesic, anaesthetic or surgical interventions, published in the English language, and addressing pain management relating to the surgical procedure being reviewed.
  • Included RCTs should report pain scores using a linear pain scale, such as the visual analogue scale or verbal or numerical rating scale.
  • Studies reporting data pooled from patients undergoing mixed surgical procedures are excluded if data tables specifically related to the surgical procedure being reviewed cannot be obtained.

  • Two reviewers independently screen the titles and abstracts.
  • Included studies then undergo full-text review and irrelevant papers are excluded.
  • At any stage, in the event of disagreement between the two reviewers, the opinion of a third reviewer is obtained.
  • A PRISMA flow chart is used to present the results of the search data, records screened, records excluded with reasons for exclusion, and studies included in the qualitative analyses.

  • The studies undergo quality assessments which are used to assign the level of evidence.
  • Criteria employed for quality assessments include:
    • Allocation concealment of treatment assignment by those involved in recruitment (A, adequate; B, unclear; C, inadequate; D, not used)
    • Quality scoring using the Jadad score (1–5) to assess randomisation, blinding, and reporting of the flow of patients
    • Participant follow-up of greater or less than 80%.
  • Relationship between quality and source of evidence, levels of evidence and recommendation grade:
    Study type Study quality assessments Grade of recommendation
    Allocation concealment (A–D) Jadad score Statistical analyses and patient follow-up Level of evidence
    Systematic review with homogeneous results NA NA NA 1 A
    Randomised controlled trial A or B 1–5 Statistics reported and >80% follow-up 1 A
    Randomised controlled trial C or D 1–5 Statistics not reported or questionable, or <80% follow-up 2 B
    Non-systematic review, cohort study, case study (e.g. some adverse effect guidance) NA NA NA 3 C
    Clinical practice information (expert opinion), inconsistent evidence NA NA NA 4 D
    Allocation concealment is rated as: A, adequate; B, unclear; C, inadequate; D, not used. The grade of recommendation is based on the overall level of evidence, considering the balance of clinical practice information and evidence. NA: not applicable

  • Included studies are stratified by timing of the intervention (pre-operative, intra-operative or postoperative), and further categorised into the type of intervention: analgesic (systemic analgesics, analgesic adjuncts or regional analgesia techniques), anaesthetic or surgical.
  • Summary information from the included studies is extracted and tabulated using a predefined data extraction form.
  • Extracted information includes: study design (including interventions); population characteristics; outcomes assessed (e.g. pain scores, supplementary analgesic use, adverse events); and critical evaluation (e.g. relevance to current clinical practice, and use of paracetamol and non-steroidal anti-inflammatory drugs or COX-2 specific inhibitors [termed as ‘basic analgesic regimen’] in the study groups).
  • Primary outcomes are: postoperative pain intensity scores at rest and/or pain intensity during activity (when available). A change of more than 10 mm in pain scores is considered clinically relevant.
  • Secondary outcomes include: time to first request for rescue analgesia; cumulative 24-h opioid requirements; other supplementary analgesic use; opioid-related adverse events; and patient-related outcome measures.

  • The effectiveness of each intervention for each outcome is evaluated qualitatively by assessing the number of studies showing a significant difference between treatment arms (p<0.05 as reported in the study publication).

  • Meta-analyses are performed if the studies are homogenous in the analgesic technique(s) utilised, with similar outcome measures that are reported or can be estimated as mean (SD) for continuous variables and proportions for dichotomous variables.

  • The subgroup determines whether each intervention should be recommended or not.
  • To be recommended, an intervention must be shown to be beneficial in at least two RCTs.
  • The subgroup assesses the relevance of each intervention to current perioperative practice.
  • Additionally, an assessment is made of whether the intervention would improve postoperative pain relief and/or outcomes when added to the ‘basic analgesic regimen’ or would be beneficial if this regimen is not possible or is contra-indicated.
  • The balance between the invasiveness of the analgesic technique and the consequences of postoperative pain, as well as the balance between the analgesic efficacy and the adverse event profile of the analgesic technique, are also considered.
  • Finally, a draft table or algorithm of the recommendations of analgesic, anaesthetic or surgical interventions is prepared, with each recommendation assigned a grade based on the overall level of evidence and balance of clinical practice information and evidence.
  • Relationship between quality and source of evidence, levels of evidence and recommendation grade:
Study type Study quality assessments Grade of recommendation
Allocation concealment (A–D) Jadad score Statistical analyses and patient follow-up Level of evidence
Systematic review with homogeneous results NA NA NA 1 A
Randomised controlled trial A or B 1–5 Statistics reported and >80% follow-up 1 A
Randomised controlled trial C or D 1–5 Statistics not reported or questionable, or <80% follow-up 2 B
Non-systematic review, cohort study, case study (e.g. some adverse effect guidance) NA NA NA 3 C
Clinical practice information (expert opinion), inconsistent evidence NA NA NA 4 D
Allocation concealment is rated as: A, adequate; B, unclear; C, inadequate; D, not used. The grade of recommendation is based on the overall level of evidence, considering the balance of clinical practice information and evidence. NA: not applicable

  • The proposed recommendations are circulated to all members of the PWG, along with data extraction files, included studies and excluded studies with reasons for exclusion, level of evidence of the included studies and reasons for recommending or not recommending interventions.
  • Five questions are asked of the Working Group about each recommendation:
  1. Is the recommended intervention clinically relevant?
  2. Does it add to the ‘basic analgesic’ technique?
  3. Does the balance between efficacy and adverse effects allow recommendation?
  4. Does the balance between invasiveness of the analgesic intervention and degree of pain after surgery allow recommendation?
  5. Are the reasons for not recommending an analgesic intervention appropriate?
  • To formulate consensus recommendations, a modified Delphi approach is used, which includes several rounds of individual comments followed by round-table discussions.
  • A final review document, including the consensus recommendations agreed during discussions at the face-to-face meeting, is circulated to the PWG for review and approval. No major changes are incorporated during this final review stage.
  • Finally, the sub-group prepares a manuscript for publication in a peer-reviewed journal, if appropriate.

  • A web copy is prepared, with the help of a medical writer, to present the large amount of evidence and the recommendations from each procedure review on the PROSPECT website in a user-friendly manner.
  • The PROSPECT website also includes the overall recommendations in several languages.

Despite the rigour of the PROSPECT methodology, there are some limitations, including:
    • The strength of the systematic review is based on the quality of published studies
    • Most RCTs assess a single-analgesic intervention with a placebo group commonly receiving opioid monotherapy and opioids as a rescue
    • There is a lack of evidence on analgesic interventions for some specific surgical procedures, and a lack of accurate dosing and duration data
    • Some interventions, doses or routes of administration in published studies are no longer appropriate in current practice
    • Some analgesic techniques are introduced into current clinical practice without being subjected to a rigorous comparative study
    • Published literature may lag behind clinical practice, thus decreasing the clinical relevance of the review
    • Most studies of analgesic interventions do not assess their effects on clinically-relevant outcomes, such as movement-related pain scores or surgery-related physical function.

  • PROSPECT is supported by an unrestricted grant from the European Society of Regional Anaesthesia and Pain Therapy (ESRA).
  • In the past, PROSPECT has received unrestricted grants from Pfizer Inc. (New York, NY, USA) and Grunenthal (Aachen, Germany).