The review of this procedure is currently in progress and will be published by end of 2019
Knowledge Key:
Arguments against Arguments againste
Arguments for Arguments for
Prospect Recommendation Prospect Recommendation
Clinical Practice Clinical Practice
Transferable Evidence Transferable Evidence
Procedure Specific Evidence Procedure Specific Evidence

Postoperative

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Postoperative studies

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)

Systemic analgesia

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

Alternative analgesic interventions

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

Regional block

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

Local wound analgesia

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

Supplemental oxygen

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