Pre-operative

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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