Pre-operative

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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

  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Rescue morphine requirements in the PACU were significantly lower with PVB compared with PCA IV opioid (p=0.04) Buggy 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
  • The time to first request for rescue analgesic was significantly longer with bupivacaine PVB compared with placebo (p<0.02) 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
  • 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
  • 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
  • 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
  • One study out of one reported that patient satisfaction scores were significantly higher following PVB versus GA (p=0.008) Terheggen et al 2002
  • 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
  • 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
  • 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
  • There was no significant difference in blood loss between groups receiving bupivacaine PVB versus placebo Kairaluoma et al 2004
  • 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
  • Study details Kairaluoma 2004 Click here for more information
  • Minor and major breast surgery

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