Laparoscopic Cholecystectomy Update

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SUMMARY RECOMMENDATIONS
PROSPECT laparoscopic cholecystectomy update 2006 Subgroup
For each review, a Subgroup of the PROSPECT Working Group performs an initial evaluation of the evidence and also drafts clinical practice statements and recommendations, which are then discussed by the whole Working Group before a final consensus is reached. The Subgroup may sometimes include a non-Working Group member, to provide additional expertise in the procedure being reviewed.

For the laparoscopic cholecystectomy update 2006 review, the Subgroup members were:

Mr Rory McCloy
Professor Edmund Neugebauer
Professor Stephan Schug

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

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

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

Pre-operative Recommendations for Laparoscopic Cholecystectomy
Intra-operative Recommendations for Laparoscopic Cholecystectomy
Postoperative Recommendations for Laparoscopic Cholecystectomy

See Overall PROSPECT recommendations for the overall strategy for managing pain after laparoscopic cholecystectomy.

PROSPECT OVERALL RECOMMENDATIONS

PROSPECT overall recommendations for postoperative pain management following laparoscopic cholecystectomy:

DESCRIPTION OF STUDIES
Literature search

Study quality assessments, levels of evidence and grades of recommendation

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

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

Transferable evidence

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


 

TOPICS FOR FUTURE RESEARCH

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

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

ABBREVIATIONS

FVC

forced vital capacity

FEV1

forced expiratory volume in 1 sec

PEF

peak expiratory flow

PEFR

peak expiratory flow rate

FEF

forced expiratory flow

FEFR

forced expiratory flow rate

FEFR25­–75

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

PCA

patient-controlled analgesia

PaO2

partial pressure of arterial oxygen

PaCO2

partial pressure of arterial carbon dioxide

IM

intramuscular

IV

intravenous

IP

intraperitoneal

Pre-op

pre-operatively

Intra-op

intra-operatively

Postop

postoperatively

VAS

visual analogue scale

VRS

verbal rating scale

LA

local anaesthetic

NRS

numerical rating scale

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

Laparoscopic Cholecystectomy-specific evidence

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • Paracetamol is not effective for severe pain

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

  • [None cited]

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

  • [None cited]

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • Paracetamol is not effective for severe pain

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

  • [None cited]

Transferable Evidence from Other Procedures

  • [None cited]

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable Evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

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

PROSPECT Recommendations

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

Clinical Practice

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

Transferable evidence from Other Procedures

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

Laparoscopic Cholecystectomy-specific evidence

  • Three out of three studies showed no significant differences between outpatient and inpatient management groups for reducing VAS pain scores Curet et al 2002 Click here for more information
  • In one study, VRS pain/discomfort at 1 week and 6 weeks follow-up was similar in the daycare and clinical observation groups Keulemans et al 1998
  • The outpatient management group consumed significantly more oral analgesic (oxycodone + paracetamol) compared with the inpatient management group prior to PACU discharge (p<0.05), but there were no significant differences between groups for total analgesia used (fentanyl, narcotics, oxycodone + paracetamol; details not given) Curet et al 2002
  • There were no significant differences in outpatient and inpatient management groups for analgesic consumption (a single dose of 5–10 mg IM morphine was given on request; 500 mg paracetamol + 20 mg codeine was given up to 6 times/day; 500 mg naproxen was also given, up to 3 times/day) during the first 48 h postoperatively Keulemans et al 1998
  • In two out of two studies, the incidence of PONV (assessed at 4 h and 24 h) Curet et al 2002
  • In one study out of one, there were no significant differences between inpatient and outpatient management groups for bowel movement Young and O'Connell 2001
  • Study details Curet et al 2002 Click here for more information