Non-cosmetic Breast Surgery

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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:

Pre-operative recommendations for Non-cosmetic Breast Surgery

Intra-operative recommendations for Non-cosmetic Breast Surgery

Postoperative recommendations for Non-cosmetic Breast Surgery

Not recommended for Non-cosmetic Breast Surgery

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

  • 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

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

  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Intercostal nerve block plus other regional techniques versus placebo (GA in both groups)
  • Study details Fassoulaki et al 2001 Click here for more information
  • Minor and major breast surgery
  • Intercostal nerve block (no GA) versus GA
  • Study details Atanassoff et al 1994 Click here for more information
  • Minor breast surgery
  • Intercostal nerve block: LA versus other LA
  • Study details Atanassoff et al 1994 Click here for more information
  • Minor and 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 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

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