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Intraperitoneal local anaesthetic instillation versus no intraperitoneal local anaesthetic instillation for laparoscopic cholecystectomy

  1. Kurinchi Selvan Gurusamy1,*,
  2. Myura Nagendran2,
  3. Gian Piero Guerrini3,
  4. Clare D Toon4,
  5. Murat Zinnuroglu5,
  6. Brian R Davidson1

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 13 MAR 2014

Assessed as up-to-date: 14 MAR 2013

DOI: 10.1002/14651858.CD007337.pub3


How to Cite

Gurusamy KS, Nagendran M, Guerrini GP, Toon CD, Zinnuroglu M, Davidson BR. Intraperitoneal local anaesthetic instillation versus no intraperitoneal local anaesthetic instillation for laparoscopic cholecystectomy. Cochrane Database of Systematic Reviews 2014, Issue 3. Art. No.: CD007337. DOI: 10.1002/14651858.CD007337.pub3.

Author Information

  1. 1

    Royal Free Campus, UCL Medical School, Department of Surgery, London, UK

  2. 2

    Department of Surgery, UCL Division of Surgery and Interventional Science, London, UK

  3. 3

    Ravenna Hospital, Department of Surgery, Ravenna, Italy

  4. 4

    West Sussex County Council, Public Health, Chichester, West Sussex, UK

  5. 5

    Physical Medicine and Rehabilitation/Algology and Clinical Neurophysiology, Gazi University Medical Faculty, Ankara, Turkey

*Kurinchi Selvan Gurusamy, Department of Surgery, Royal Free Campus, UCL Medical School, Royal Free Hospital, Rowland Hill Street, London, NW3 2PF, UK. k.gurusamy@ucl.ac.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 13 MAR 2014

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Characteristics of included studies [ordered by study ID]
Abdel-Raouf 2004

MethodsRandomised clinical trial.


ParticipantsCountry: Egypt.
Sample size: 40.
Post-randomisation drop-outs: not stated.
Revised sample size: 40.
Mean age: 39 years.
Females: 40 (100%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.
  3. Females.


Exclusion criteria

  1. Previous abdominal surgery.
  2. Magnesium therapy or on drugs containing magnesium.
  3. Central nervous system dysfunction.
  4. Psychotropic drugs.


(Note: magnesium was used in 1 of the arms not included in this review).


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.25% 50 mL (n = 20).
Group 2: normal saline (n = 20).


OutcomesNone of the outcomes of interest for this review were reported.


NotesAttempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Ahmad 1998

MethodsRandomised clinical trial.


ParticipantsCountry: UK.

Sample size: 40.

Post-randomisation drop-outs: not stated.

Revised sample size: 40.

Mean age: not stated.

Females: not stated.

Inclusion criteria

  1. People undergoing laparoscopic cholecystectomy.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.25% 40 mL (n = 10).

Group 2: normal saline (n = 10).

Group 3: same as group 1 with peri-portal local anaesthetic infiltration (n = 10).

Group 4: same as group 2 with peri-portal local anaesthetic infiltration (n =10).


OutcomesPain.


NotesPain scores were not reported. The authors stated that there were no significant differences in pain scores between people who received local anaesthetics versus normal saline.

Attempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Alagöl 2003

MethodsRandomised clinical trial.


ParticipantsCountry: Turkey.

Sample size: 82.

Post-randomisation drop-outs: not stated.

Revised sample size: 82.

Mean age: 49 years.

Females: 55 (67.1%).

Inclusion criteria

  1. Laparoscopic cholecystectomy.
  2. ASA I or II.


Exclusion criteria

  1. Drug allergy.
  2. Ischaemic heart disease.
  3. Arrhythmias.
  4. Elevation of liver enzymes.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 20 mL (n = 20).
Group 2: normal saline (n = 20).

Group 3: same as group 1 with intraperitoneal ondansetron (n = 22).

Group 4: same as group 2 with intraperitoneal ondansetron (n = 20).


OutcomesPain.


NotesAttempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "After the removal of the gallbladder, a sealed envelope was drawn...".

Comment: Unclear as to whether the random sequence was generated by drawing shuffled sealed envelopes or whether they were sequentially numbered.

Allocation concealment (selection bias)Unclear riskQuote: "After the removal of the gallbladder, a sealed envelope was drawn...".

Comment: Unclear as to whether the random sequence was generated by drawing shuffled sealed envelopes or whether they were sequentially numbered.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Alkhamesi 2007

MethodsRandomised clinical trial.


ParticipantsCountry: UK.

Sample size: 80.

Post-randomisation drop-outs: not stated.

Revised sample size: 80.

Mean age: 49 years.

Females: 69 (86.3%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.
  3. Aged ≥ 18 years.


Exclusion criteria

  1. Allergy to bupivacaine or other drugs used in the protocol.
  2. History of drug abuse.
  3. Regular NSAID intake.
  4. Diagnosed malignancy.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 10 mL aerosol (n = 20).

Group 2: bupivacaine 0.5% 10 mL liquid (n = 20).
Group 3: normal saline aerosol (n = 20).

Group 4: no intervention (n = 20).


OutcomesPain.


NotesAttempts were made to contact the authors in April 2008. Authors provided information on random sequence generation in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "The selection was based on computer program" (author replies).

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "All the patients, junior medical staff, and nursing staff in recovery and the wards were blinded to the study. The operating surgeons and the anesthetist were aware of the study protocol, but were blinded to the contents of the aerosol and the injected solutions".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "All the patients, junior medical staff, and nursing staff in recovery and the wards were blinded to the study. The operating surgeons and the anesthetist were aware of the study protocol, but were blinded to the contents of the aerosol and the injected solutions".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and serious adverse events were not reported.

For-profit biasHigh riskQuote: "We also acknowledge the help of Northgate Technologies, Chicago, USA, and Trudell Medical, Ontario, Canada, for their help in manufacturing the nebulizer machine and the intraperitoneal catheters".

Comment: Probably sponsored by industry.

Alper 2009

MethodsRandomised clinical trial.


ParticipantsCountry: Turkey.

Number randomised: 40.

Post-randomisation drop-outs: 0 (0%).

Revised sample size: 40.

Mean age: 44 years.

Females: 34 (85%).

Inclusion criteria

  1. ASA status I or II.
  2. Scheduled for laparoscopic cholecystectomy.


Exclusion criteria

  1. Acute cholecystitis.
  2. Hypersensitivity to local anaesthetics.
  3. Morbid obesity.


InterventionsThe participants were randomised to the following groups.
Group 1: levobupivacaine 0.25% 40 mL (n = 20).
Group 2: normal saline (n = 20).


OutcomesLocal anaesthetic-related complications.


NotesAttempts were made to contact the authors in July 2013.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "…patients were randomly assigned to one of two groups using a computer-generated random number table…".

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Solutions were prepared by another anesthesiologist so that neither the surgeon performing the intraperitoneal instillation nor the anesthesiologist following up the patient was aware of which drug was injected".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Solutions were prepared by another anesthesiologist so that neither the surgeon performing the intraperitoneal instillation nor the anesthesiologist following up the patient was aware of which drug was injected".

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Alptekin 2010

MethodsRandomised clinical trial.


ParticipantsCountry: Turkey.

Sample size: 30.

Post-randomisation drop-outs: not stated.

Revised sample size: 30.

Mean age: not stated.

Females: not stated.

Inclusion criteria

  1. Females with symptomatic cholelithiasis undergoing laparoscopic cholecystectomy.
  2. Aged < 45 years.


Exclusion criteria

  1. Acute cholecystitis.
  2. Choledocholithiasis.
  3. Previous cardiopulmonary disease.
  4. Smoking history.
  5. Previous upper abdominal operations.
  6. Iatrogenic gallbladder perforation.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 20 mL (n = 10).

Group 2: bupivacaine 0.5% 20 mL at the end of surgery + bupivacaine 0.5% 10 mL via catheter for 24-hour period (n = 10).
Group 2: no intervention (n = 10).


OutcomesIntraoperative complications.


NotesAttempts were made to contact the authors in August 2013.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Barczynski 2006

MethodsRandomised clinical trial.


ParticipantsCountry: Poland.

Sample size: 120.

Post-randomisation drop-outs: 0 (0%).

Revised sample size: 120.

Mean age: 49 years.

Females: 108 (90%).

Inclusion criteria

  1. Uncomplicated, symptomatic cholelithiasis.
  2. ASA I or II.
  3. Aged ≥ 18 years.


Exclusion criteria

  1. Allergy to local anaesthetics.
  2. Regular NSAID intake.
  3. Pregnancy and lactation.
  4. Previous extensive abdominal surgery.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 1 mg/kg diluted in 200 mL with saline before pneumoperitoneum (n = 30).

Group 2: bupivacaine 1 mg/kg diluted in 200 mL with saline just after pneumoperitoneum (n = 30).
Group 3: normal saline before pneumoperitoneum (n = 30).

Group 4: normal saline just after pneumoperitoneum (n = 30).


OutcomesIntraoperative complications and pain.


NotesAttempts were made to contact the authors in Augsut 2013.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "The randomization was based on each patient receiving a sealed envelope containing a random number selected from the table".

Allocation concealment (selection bias)Low riskQuote: "The randomization was based on each patient receiving a sealed envelope containing a random number selected from the table".

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskQuote: "Double-blinded".

Comment: The groups that were blinded were not stated.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskQuote: "Double-blinded"

Comment: The groups that were blinded were not stated.

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Authors report that there were no intra-operative complications. It was not clear whether there were any postoperative complications.

For-profit biasUnclear riskComment: This information was not available.

Bhardwaj 2002

MethodsRandomised clinical trial.


ParticipantsCountry: India.

Sample size: 40.

Post-randomisation drop-outs: not stated.

Revised sample size: 40.

Mean age: 34 years.

Females: 36 (90%).

Inclusion criteria

  1. Laparoscopic cholecystectomy.
  2. ASA I and II.
  3. Aged 20 to 40 years.


Exclusion criteria

  1. People with acute cholecystitis.
  2. Did not give consent.
  3. Did not understand VAS and verbal rating score.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 20 mL (n = 20).
Group 2: normal saline (n = 20).


OutcomesPain.


NotesAttempts were made to contact the authors in March 2009.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The observer was blinded to the solution instilled".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Castillo-Garza 2012

MethodsRandomised clinical trial.


ParticipantsCountry: Mexico.

Sample size: 60.

Post-randomisation drop-outs: 0 (0%).

Revised sample size: 60.

Mean age: 33 years.

Females: 55 (91.7%).

Inclusion criteria

  1. Aged 15 to 60 years.
  2. Elective laparoscopic cholecystectomy.


Exclusion criteria

  1. Pregnancy.
  2. Open cholecystectomy.
  3. Acute cholecystitis.
  4. Chronic treatment with analgesics or anti-inflammatories.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 20 mL (n = 30).
Group 2: normal saline (n = 30).


OutcomesMortality, morbidity, and pain.


NotesAttempts were made to contact the authors in July 2013.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "randomization was performed using a computer program (www.randomized.com)".

Allocation concealment (selection bias)Unclear riskQuote: "…with concealment of the random sequence…".
Comment: Further details were not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: A placebo was used but the groups blinded were not reported.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: A placebo was used but the groups blinded were not reported.

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)Low riskComment: Mortality and morbidity were reported.

For-profit biasUnclear riskComment: This information was not available.

Chundrigar 1993

MethodsRandomised clinical trial.


ParticipantsCountry: UK.

Sample size: 60.

Post-randomisation drop-outs: 2 (3.3%).

Revised sample size: 58.

Mean age: 48 years.

Females: 53 (91.4%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy for symptomatic gallstones


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.25% 20 mL (n = 28).
Group 2: normal saline (n = 30).


OutcomesPain.


NotesReasons for post-randomisation drop-out: conversion to open cholecystectomy.
Attempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "The solutions were given and the subsequent assessment were performed in a double blind manner".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The solutions were given and the subsequent assessment were performed in a double blind manner".

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

El-Labban 2011

MethodsRandomised clinical trial.


ParticipantsCountry: Egypt.

Sample size: 126.

Post-randomisation drop-outs: 0 (0%).

Revised sample size: 126.

Mean age: 41 years.

Females: 69 (54.8%).

Inclusion criteria

  1. Aged 25 to 64 years.
  2. ASA status I or II.


Exclusion criteria

  1. Known allergy to local anaesthetics.
  2. Acute cholecystitis.
  3. Conversion to open procedure.
  4. Intra-operative complications.
  5. Morbid obesity.
  6. Chronic medical diseases.
  7. Chronic opioid treatment.


InterventionsThe participants were randomised to the following groups.
Group 1: levobupivacaine 0.25% 20 mL (n = 63).
Group 2: no intervention (n = 63).


OutcomesNone of the outcomes of interest for this review were reported.


NotesAttempts were made to contact the authors in July 2013.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskQuote: "…using a blind envelope system".

Comment: Further details were not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The residents…were trained to obtain the VAS score…they were blinded to the patient's status concerning local analgesia".

Comment: The VAS score refers to abdominal pain and not overall pain.

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasLow riskQuote: "No grants or funds from any pharmaceutical industry were obtained for the study".

Elfberg 2000

MethodsRandomised clinical trial.


ParticipantsCountry: Sweden.

Sample size: 65.

Post-randomisation drop-outs: 1 (1.5%).

Revised sample size: 64.

Mean age: 49 years.

Females: 37 (57.8%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 2 mg/kg (n = 33).
Group 2: normal saline (n = 32).


OutcomesLocal anaesthetic-related complications and pain.


NotesReasons for post-randomisation drop-out: conversion to open cholecystectomy.
Attempts were made attempts to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "The solutions were administered, and subsequent assessment was performed in a double-blind manner".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Elhakim 2000a

MethodsRandomised clinical trial.


ParticipantsCountry: Egypt.

Sample size: 50.

Post-randomisation drop-outs: not stated.

Revised sample size: 50.

Mean age: 45 years.

Females: 38 (76%).

Inclusion criteria

  1. Laparoscopic cholecystectomy.
  2. ASA I or II.


InterventionsThe participants were randomised to the following groups.
Group 1: lignocaine 0.1% 200 mL (n = 25).
Group 2: normal saline (n = 25).


OutcomesNone of the outcomes of interest for this review were reported.


NotesAttempts were made attempts to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskQuote: "The surgeon was blinded to the nature of the solution used".

Comment: Not clear if participants and others caring for the participant were blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The investigator, who was blind to the group allocation of the patient and to any postoperative analgesia administered, assessed the patients postoperatively with reference to pain and respiratory function tests".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Feroci 2009

MethodsRandomised clinical trial.


ParticipantsCountry: Italy.

Sample size: 30.

Post-randomisation drop-outs: 0 (0%).

Revised sample size: 30.

Mean age: 54 years.

Females: 19 (63.3%).

Inclusion criteria

  1. Laparoscopic cholecystectomy for gallstones.
  2. Aged > 18 years.
  3. ASA 1 or 2.


Exclusion criteria

  1. Acute cholecystitis.
  2. Pregnant women.
  3. Upper abdominal surgery.
  4. Acute pancreatitis.
  5. Conversion to open surgery.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 2 mg/kg in absorbable cellulose strips (n = 15).
Group 2: no intervention (n = 15).


OutcomesMortality, morbidity, and pain.


NotesAttempts were made to contact the authors in August 2010. Authors provided further information in August 2010.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "The randomization was obtained through a computer-generated program" (author replies).

Allocation concealment (selection bias)Low riskQuote: "It consisted with an ordered series of numbers with a corresponding letter for each group. This series of numbers … in closed envelopes by a secretary not involved in patients' assistance. The envelopes were opaque and sealed" (author replies).

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "The surgeon who performed the intervention was not included in the follow-up. Neither the patients nor the investigating doctors were informed about the way in which bupivacaine was administered" (author replies).

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The surgeon who performed the intervention was not included in the follow-up. Neither the patients nor the investigating doctors were informed about the way in which bupivacaine was administered" (author replies).

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)Low riskComment: Mortality and morbidity were reported.

For-profit biasLow riskQuote: "For the study we didn't receive any fund from industry. All material used in the study (tabotamp and bupivacaine) was property of the hospital that authorized its use for the study" (author replies).

Fornari 1996

MethodsRandomised clinical trial.


ParticipantsCountry: Italy.
Sample size: 104.
Post-randomisation drop-outs: 4 (3.8%).
Revised sample size: 100.
Mean age: 46 years.
Females: 64 (64%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy for symptomatic cholelithiasis.
  2. ASA I or II.


Exclusion criteria

  1. Requiring drain insertion.
  2. Perforation of gallbladder during operation.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 20 mL (n = 50).
Group 2: normal saline (n = 50).


OutcomesMortality, morbidity, hospital stay, and pain.


NotesReasons for post-randomisation drop-out: perforation of gallbladder during surgery.
Attempts were made to contact the authors in April 2008. The authors replied in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "computer generated" (author replies).

Allocation concealment (selection bias)Low riskQuote: "sealed envelope" (author replies).

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskQuote: "This liquid, whose nature was recognized only by the anesthesiologist but not by the surgeon".

Comment: Further details were not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskQuote: "This liquid, whose nature was recognized only by the anesthesiologist but not by the surgeon".

Comment: Further details were not available.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)Low riskComment: Mortality and morbidity were reported.

For-profit biasUnclear riskComment: This information was not available.

Fu 2009

MethodsRandomised clinical trial.


ParticipantsCountry: China.

Sample size: 40.

Post-randomisation drop-outs: 0 (0%).

Revised sample size: 40.

Mean age: 42 years.

Females: 12 (30%).

Inclusion criteria

  1. Laparoscopic cholecystectomy.
  2. ASA I or II.
  3. Ability to understand VAS scores.


Exclusion criteria

  1. Previous upper abdominal surgeries.
  2. Choledocholithiasis.
  3. Acute cholecystitis.
  4. Conversion to open cholecystectomy.
  5. Body mass index > 35 kg/m2.
  6. Diminished kidney or liver function.


InterventionsThe participants were randomised to the following groups.
Group 1: ropivacaine 1 mg/kg mixed with 5-mL fibrin sealant (n = 20).
Group 2: no intervention (5 mL of fibrin sealant) (n = 20).


OutcomesPain.


NotesAttempts were made to contact the author in October 2010.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "The patients were randomly divided into 3 equal groups with the help of computer-generated randomization numbers".

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Fuhrer 1996

MethodsRandomised clinical trial.


ParticipantsCountry: France.

Sample size: 24.

Post-randomisation drop-outs: 2 (8.3%).

Revised sample size: 22.

Mean age: 60 years.

Females: 15 (68.2%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.


Exclusion criteria

  1. Drug addicts.
  2. People with epilepsy.
  3. Poor liver function.
  4. Cardiac dysfunction.
  5. Use of beta-blockers or H2 blockers.
  6. Allergy to anaesthetic agents.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.38% 0.6 mL/kg (n = 12).
Group 2: normal saline (n = 10).


OutcomesPain.


NotesReasons for post-randomisation drop-out: conversion to open cholecystectomy.

Pain scores were reported in a graph but it was not possible to identify the lines that indicated the intervention and those that indicated the control. The authors state that there were no significant differences in pain scores between people who received local anaesthetics versus normal saline.
Attempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Garcia 2007

MethodsRandomised clinical trial.


ParticipantsCountry: Brazil.

Sample size: 40.

Post-randomisation drop-outs: 8 (20%).

Revised sample size: 32.

Mean age: 46 years.

Females: 26 (81.3%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.


Exclusion criteria

  1. Allergy to drugs used in the protocol.
  2. Cardiac problems.
  3. Cognitive deficit.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine (S75-R25) 0.125% 80 mL (n = 19).
Group 2: normal saline (n = 13).


OutcomesLocal anaesthetic-related complications.


NotesReasons for post-randomisation drop-outs: impossibility of completing the protocol.

Attempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskQuote: "Both with 20 patients each, for a double-blind study, using sealed envelopes chosen immediately before the procedure".

Comment: Further details were not available.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "The investigator was unaware which group the patient belonged to until the end of the study....The solution for intraperitoneal instillation was prepared a member of the team who had no other role in the study".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The investigator was unaware which group the patient belonged to until the end of the study....The solution for intraperitoneal instillation was prepared a member of the team who had no other role in the study".

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Golubovic 2009

MethodsRandomised clinical trial.


ParticipantsCountry: Croatia.

Sample size: 60.

Post-randomisation drop-outs: 0 (0%).

Revised sample size: 60.

Mean age: 53 years.

Females: 38 (63.3%).

Inclusion criteria

  1. ASA status I or II.
  2. Elective laparoscopic cholecystectomy for cholelithiasis.


Exclusion criteria

  1. Contraindications to tramadol or bupivacaine.
  2. Intra-operative complications.
  3. Conversion to open procedure.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.25% 50 mL (n = 30).
Group 2: normal saline (n = 30).


OutcomesPain.


NotesAttempts were made to contact the authors in July 2013.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "The test solution were drawn into coded syringes and given to surgeons who did not know their content. The drugs were administered…by...recovery nurse with no knowledge of peri-operative analgesia administration".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "This was a prospective, randomized, double-blinded study.... The drugs were administrated on demand by an experienced recovery nurse with no knowledge of perioperative analgesia administration".

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Gvozdenovic 2011

MethodsRandomised clinical trial.


ParticipantsCountry: Serbia.

Sample size: 60.

Post-randomisation drop-outs: not stated.

Revised sample size: 60.

Mean age: not stated.

Females: not stated.

Inclusion criteria

  1. People undergoing elective laparoscopic cholecystectomy.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.25% 30 mL (n = 30).

Group 2: normal saline (n = 30).


OutcomesPain.


NotesPain scores were not reported. The authors state that there were no significant differences in pain scores between those who received local anaesthetics versus normal saline.

Attempts were made to contact the authors in August 2013.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Hasan 2007

MethodsRandomised clinical trial.


ParticipantsCountry: Belgium.

Sample size: 36.

Post-randomisation drop-outs: not stated.

Revised sample size: 36.

Mean age: not stated.

Females: not stated.

Inclusion criteria

  1. People undergoing laparoscopic cholecystectomy.


InterventionsThe participants were randomised to the following groups.
Group 1: ropivacaine 0.25% 20 mL (n = not stated).

Group 2: normal saline (n = not stated).

Group 3: same as group 1 with peri-portal local anaesthetic infiltration (n = not stated).

Group 4: same as group 2 with peri-portal local anaesthetic infiltration (n = not stated).


OutcomesNone of the outcomes of interest for this review were reported.


NotesAttempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Hazinedaroglu 2006

MethodsRandomised clinical trial.


ParticipantsCountry: Turkey.

Sample size: 50.

Post-randomisation drop-outs: 0 (0%).

Revised sample size: 50.

Mean age: not stated.

Females: not stated.

Inclusion criteria

  1. Adults undergoing elective laparoscopic cholecystectomy.
  2. Symptomatic gallstones.
  3. ASA I or II.


Exclusion criteria

  1. History of diabetes mellitus.
  2. Prior abdominal surgery.
  3. Allergy to bupivacaine.
  4. Chronic corticosteroid, NSAID, or immunosuppressive treatment.
  5. Gall bladder perforation.
  6. Bile contamination of the peritoneum.
  7. Surgical manipulation that necessitated the elongation of the incision at 1 of the trocar sites (eg, stone extraction, open laparoscopy, and haemostasis of the port sites).
  8. Repeated trocar entry attempts more than twice.
  9. Overt intra-abdominal adhesions.
  10. Conversion to open surgery.
  11. 1Surgical complication that required further medical or surgical intervention.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.25% 30 mL (n = 25).
Group 2: normal saline (n = 25).


OutcomesLocal anaesthetic-related complications and pain.


NotesAttempts were made attempts to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Low riskQuote: "50 adult elective LC [laparoscopic cholecystectomy] patients were randomly allocated into two groups by envelopes".

Comment: Further details were not available.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Surgical and anesthesiology teams were blind to the contents".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Surgical and anesthesiology teams were blind to the contents".

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Jabbour-Khoury 2005

MethodsRandomised clinical trial.


ParticipantsCountry: Lebanon.

Sample size: 80.

Post-randomisation drop-outs: not stated.

Revised sample size: 80.

Mean age: 47 years.

Females: 44 (55%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy without intra-operative cholangiography.
  2. ASA I or II.
  3. Aged between 20 and 60 years.


Exclusion criteria

  1. Chronic pain diseases other than gallstone disease.
  2. Chronic use of opioids, tranquillizers, steroids, NSAIDs.
  3. Alcohol.
  4. Amide local anaesthetic allergy.
  5. Contraindications to NSAIDs (allergy, peptic ulcer disease, gastro-oesophageal reflux disease, renal insufficiency, coagulopathy).
  6. Conversion to an open cholecystectomy.
  7. Postoperative complications that increased postoperative pain.
  8. Pain evaluation judged unreliable because of neurological disease.
  9. Intraoperative need for more than 2 μg/kg fentanyl.
  10. Heart rate not controlled by increasing sevoflurane concentration for 5 minutes.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.25% 40 mL (n = 20).
Group 2: normal saline (n = 20).

Group 3: same as group 1 but received intravenous ketoprofen (n = 20).
Group 4: same as group 2 but received intravenous ketoprofen (n = 20).


OutcomesNone of the outcomes of interest for this review were reported.


NotesAttempts were made attempts to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskQuote: "A surgical scrub nurse who had no further involvement in the study prepared the solutions administered intraperitoneally to the study patients".

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskQuote: "A surgical scrub nurse who had no further involvement in the study prepared the solutions administered intraperitoneally to the study patients".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Jiranantarat 2002

MethodsRandomised clinical trial.


ParticipantsCountry: Thailand.

Sample size: 80.

Post-randomisation drop-outs: not stated.

Revised sample size: 80.

Mean age: 52 years.

Females: 57 (71.3%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy for symptomatic gallstones.
  2. ASA I or II.


Exclusion criteria

  1. Arrhythmias


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 20 mL (n = 39).
Group 2: normal saline (n = 41).


OutcomesHospital stay and pain.


NotesAttempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Joris 1995

MethodsRandomised clinical trial.


ParticipantsCountry: Belgium.

Sample size: 43.

Post-randomisation drop-outs: 3 (7%).

Revised sample size: 40.

Mean age: 48 years.

Females: 29 (72.5%).

Inclusion criteria

  1. Laparoscopic cholecystectomy.
  2. ASA I or II.


Exclusion criteria

  1. Acute cholecystitis


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.13% 80 mL (n = 20).
Group 2: normal saline (n = 20).


OutcomesNone of the outcomes of interest for this review were reported.


NotesReasons for post-randomisation drop-out: conversion to open cholecystectomy.
Attempts were made to contact the authors in April 2008. Authors provided replies in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Computer generated" (author replies).

Allocation concealment (selection bias)Low riskQuote: "Held by a third party; syringes were prepared by the pharmacy" (author replies).

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Kallel 2011

MethodsRandomised clinical trial.


ParticipantsCountry: Tunisia.

Sample size: 40.

Post-randomisation drop-outs: not stated.

Revised sample size: 40.

Mean age: not stated.

Females: 40 (100%).

Inclusion criteria

  1. People undergoing laparoscopic cholecystectomy.
  2. Females aged between 20 and 60 years weighing > 50 kg with ASA physical status I or II.


InterventionsThe participants were randomised to the following groups.
Group 1: lignocaine 1% 40 mL (n = 20).

Group 2: normal saline (n = 20).


OutcomesLocal anaesthetic-related complications.


NotesAttempts were made to contact the authors in August 2013.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Karaaslan 2006

MethodsRandomised clinical trial.


ParticipantsCountry: Turkey.

Sample size: 80.

Post-randomisation drop-outs: 15 (18.8%).

Revised sample size: 65.

Mean age: 52 years.

Females: 41 (63.1%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.


Exclusion criteria

  1. Allergy to local anaesthetics.
  2. Requiring fentanyl in the last 30 minutes of operation.
  3. Requiring naloxone at the end of operation.
  4. Required pethidine after operation.


InterventionsThe participants were randomly assigned to the following groups.
Group 1: bupivacaine 0.5% 20 mL before pneumoperitoneum (n = 16).
Group 2: bupivacaine 0.5% 20 mL just after creation of pneumoperitoneum (n = 18).

Group 3: bupivacaine 0.5% 20 mL at the end of surgery (n = 16).

Group 4: no intervention (n = 15).


OutcomesLocal anaesthetic-related complications.


NotesReasons for post-randomisation drop-out: required opiates intraoperatively (n = 10) and post-operatively (n = 5).
Attempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Patients were blinded as to the analgesic regimen that they received intraoperatively… All assessments were performed by a single observer who was blinded to group allocations".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Patients were blinded as to the analgesic regimen that they received intraoperatively… All assessments were performed by a single observer who was blinded to group allocations".

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Karadeniz 2003

MethodsRandomised clinical trial.


ParticipantsCountry: Turkey.

Sample size: 67.

Post-randomisation drop-outs: 7 (10.4%).

Revised sample size: 60.

Mean age: 29 years.

Females: 47 (78.3%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. Aged 25 to 65 years.
  3. ASA I or II.


Exclusion criteria

  1. Allergy to local anaesthetics.
  2. Acute cholecystitis.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 20 mL just after creation of pneumoperitoneum (n = 15).

Group 2: bupivacaine 0.5% 20 mL end of surgery (n = 15).

Group 3: bupivacaine 0.5% 20 mL after end of surgery (n = 15).
Group 4: placebo (further details not available) (n = 15).


OutcomesMortality, morbidity, and pain.


NotesReasons for post-randomisation drop-out: conversion to open cholecystectomy (n = 3) and requirement for drain insertion (n = 4).
Attempts were made to contact the authors in April 2008. Authors provided replies in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "We used random number table".

Allocation concealment (selection bias)Low riskQuote: "It was held by third party".

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)Low riskComment: Mortality and morbidity were reported.

For-profit biasUnclear riskComment: This information was not available.

Kilic 1996

MethodsRandomised clinical trial.


ParticipantsCountry: Turkey.
Sample size: 40.
Post-randomisation drop-outs: not stated.
Revised sample size: 40.
Mean age: 49 years.
Females: 33 (82.5%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.125% 80 mL (n = 20).
Group 2: normal saline (n = 20).


OutcomesNone of the outcomes of interest for this review were reported.


NotesAttempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Kim 2010

MethodsRandomised clinical trial.


ParticipantsCountry: Korea.

Sample size: 40.

Post-randomisation drop-outs: not stated.

Revised sample size: 40.

Mean age: 50 years.

Females: 24 (60%).

Inclusion criteria

  1. Aged 18 to 65 years.
  2. Uncomplicated symptomatic cholecystitis with cholelithiasis.


Exclusion criteria

  1. Weigh < 45 kg or > 100 kg.
  2. Severe underlying cardiovascular, hepatic, or renal disease.
  3. Allergy to local anaesthetics.


InterventionsThe participants were randomised to the following groups.
Group 1: ropivacaine 2 mg/kg diluted in 100 mL saline (n = 20).
Group 2: normal saline (n = 20).


OutcomesIntraoperative complications and pain.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomization…were based on Excel random number generation".

Allocation concealment (selection bias)Low riskQuote: "The detail of series were unknown to investigators and contained in a set of sealed envelope, each bearing only the outside number".

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "The operator entered the room after instillation preparation and performed procedure without information".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The postoperative pain data was collected by blinded investigators".

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskQuote: "This research was supported by the Chung-Ang University Research Grants in 2009".

Kolsi 2000

MethodsRandomised clinical trial.


ParticipantsCountry: Tunisia.

Sample size: 42.

Post-randomisation drop-outs: 2 (4.8%).

Revised sample size: 40.

Mean age: 43 years.

Females: 40 (100%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.
  3. Aged between 20 and 60 years.


Exclusion criteria

  1. History of chronic pain.
  2. Regular intake of analgesic drugs (NSAIDs).
  3. Allergy to local anaesthetic agents.
  4. Psychiatric disease.


InterventionsThe participants were randomised to the following groups.
Group 1: lignocaine 1% 400 mg (n = 20).
Group 2: normal saline (n = 20).


OutcomesLocal anaesthetic-related complications and pain.


NotesReasons for post-randomisation drop-out: conversion to open cholecystectomy (n = 1) and lack of standardisation of anaesthetic technique (n = 1).
Attempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Patients were transferred to a post-anaesthesia care unit where they were monitored and questioned by an independent observer who was not involved in the patient randomisation or anaesthesia administration".

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Kucuk 2007

MethodsRandomised clinical trial.


ParticipantsCountry: Turkey.

Sample size: 80.

Post-randomisation drop-outs: not stated.

Revised sample size: 80.

Mean age: 50 years.

Females: 69 (86.3%).

Inclusion criteria

  1. Laparoscopic cholecystectomy.
  2. ASA I or II.


Exclusion criteria

  1. Morbid obesity.
  2. Severe chronic disease.
  3. Allergic reactions to NSAIDs or local anaesthetics.
  4. Chronic opioid treatment.
  5. Acute cholecystitis.
  6. Conversion to an open procedure.


InterventionsThe participants were randomised to the following groups.
Group 1: ropivacaine 1.5% 10 mL (n = 20).

Group 2: ropivacaine 0.5% 10 mL (n = 20).

Group 3: bupivacaine 0.5% 10 mL (n = 20).

Group 2: normal saline (n = 20).


OutcomesLocal anaesthetic-related complications and pain.


NotesAttempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This was a placebo-controlled trial. However, the groups that were blinded to the drug were not reported.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This was a placebo-controlled trial. However, the groups that were blinded to the drug were not reported.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Labaille 2002

MethodsRandomised clinical trial.


ParticipantsCountry: France.

Sample size: 42.

Post-randomisation drop-outs: 5 (11.9%).

Revised sample size: 37.

Mean age: 49 years.

Females: 24 (64.9%).

Inclusion criteria

  1. Laparoscopic cholecystectomy.
  2. ASA I or II.


Exclusion criteria

  1. Allergic to local anaesthetics.
  2. History of cardiac disease.
  3. Acute cholecystitis.
  4. Conversion to open procedure.
  5. Requiring rescue analgesia.


InterventionsThe participants were randomised to the following groups.
Group 1: ropivacaine 0.75% 40 mL (n = 11).

Group 1: ropivacaine 0.25% 40 mL (n = 14).
Group 2: normal saline (n = 12).


OutcomesLocal anaesthetic-related complications.


NotesReasons for post-randomisation drop-out: required rescue NSAIDs (n = 2); conversion to open cholecystectomy (n = 2); protocol violation (n = 1).
Attempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskQuote: "The surgeon was not informed of the contents of the solution".

Comment: It was not clear whether the participants and other healthcare professionals involved in patient care were blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Lee 2001

MethodsRandomised clinical trial.


ParticipantsCountry: South Korea.

Sample size: 88.

Post-randomisation drop-outs: 6 (6.8%).

Revised sample size: 82.

Mean age: 47 years.

Females: 36 (43.9%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.


Exclusion criteria

  1. Allergic to local anaesthetics.
  2. Severe systemic disease.
  3. Chronic pain diseases other than gallstone disease were excluded.
  4. Acute cholecystitis before the operation.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.25% 40 mL just after creation of pneumoperitoneum (n = 20).

Group 2: bupivacaine 0.25% 40 mL at end of surgery (n = 19).
Group 3: normal saline just after creation of pneumoperitoneum (n = 22).

Group 4: normal saline at end of surgery (n = 21).


OutcomesMortality and morbidity.


NotesReasons for post-randomisation drop-out: not stated.
Attempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "No patients or observers were informed of the treatment group (preoperative or postoperative)".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "No patients or observers were informed of the treatment group (preoperative or postoperative)".

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)Low riskComment: Mortality and morbidity were reported.

For-profit biasUnclear riskComment: This information was not available.

Lepner 2003

MethodsRandomised clinical trial.


ParticipantsCountry: Estonia.

Sample size: 40.

Post-randomisation drop-outs: 0 (0%).

Revised sample size: 40.

Mean age: 52 years.

Females: 35 (87.5%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy for gallstone disease.
  2. ASA I to III.


Exclusion criteria

  1. Acute cholecystitis.
  2. Inability to understand and use the VAS.
  3. History of allergy to NSAIDs, local anaesthetics, or both.


InterventionsThe participants were randomised to the following groups.
Group 1: lignocaine 0.15% 200 mL (n = 20).
Group 2: normal saline (n = 20).


OutcomesMortality and morbidity.


NotesAuthors provided information on post-randomisation drop-outs in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskQuote: "The patients were modernised prospectively, using a blind envelope system, into four groups of 20 persons each".

Comment: Further details were not available.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "The patients were blinded to the methods of analgesia used. The investigators, who were blinded to the patients' division into groups and to the method of postoperative analgesia, assessed the patients' postoperative abdominal pain and shoulder pain at rest".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The patients were blinded to the methods of analgesia used. The investigators, who were blinded to the patients' division into groups and to the method of postoperative analgesia, assessed the patients' postoperative abdominal pain and shoulder pain at rest".

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)Low riskComment: Mortality and morbidity were reported.

For-profit biasUnclear riskComment: This information was not available.

Louizos 2005

MethodsRandomised clinical trial.


ParticipantsCountry: Greece.

Sample size: 108.

Post-randomisation drop-outs: 4 (3.7%).

Revised sample size: 104.

Mean age: 49 years.

Females: 56 (53.8%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.
  3. Aged between 25 and 70 years.


Exclusion criteria

  1. Allergy to local anaesthetics.
  2. Acute cholecystitis.
  3. History of severe systemic disease.
  4. Chronic pain diseases other than gallstone disease.


InterventionsThe participants were randomised to the following groups.
Group 1: levobupivacaine 0.25% 20 mL (n = 26).
Group 2: normal saline (n = 25).

Group 3: same as group 1 with local anaesthetic wound infiltration (n = 28).

Group 4: same as group 2 with local anaesthetic wound infiltration (n = 25).


OutcomesLocal anaesthetic-related complications.


NotesReasons for post-randomisation drop-out: surgical complication (n = 2); protocol violation (n = 2).
Authors provided information on allocation sequence generation and allocation concealment in March 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "The random sequence was computer generated" (author replies).

Allocation concealment (selection bias)Unclear riskQuote: "We used sealed envelopes for the allocation" (author replies).

Comment: Further details were not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskQuote: "The surgeon performing both the preincisional local infiltration and the intraperitoneal instillation was not aware of the solution administered. Furthermore the anesthetist following up the pain score of the patients was not aware of the kind of solution administered to each patient".

Comment: Not clear whether the participants were blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The surgeon performing both the preincisional local infiltration and the intraperitoneal instillation was not aware of the solution administered. Furthermore the anesthetist following up the pain score of the patients was not aware of the kind of solution administered to each patient".

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Maestroni 2002

MethodsRandomised clinical trial.


ParticipantsCountry: Italy.

Sample size: 61.

Post-randomisation drop-outs: 1 (1.6%).

Revised sample size: 60.

Mean age: 54 years.

Females: 33 (55%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.


Exclusion criteria

  1. Allergy to local anaesthetic.
  2. Acute cholecystitis.
  3. Surgery time > 90 minutes.


InterventionsThe participants were randomised to the following groups.
Group 1: ropivacaine 5 mg/kg diluted in 200 mL saline (n = 30).
Group 2: normal saline (n = 30).


OutcomesLocal anaesthetic-related complications and pain.


NotesReasons for post-randomisation drop-out: duration of surgery > 90 minutes.
Attempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Mraovic 1997

MethodsRandomised clinical trial.


ParticipantsCountry: Croatia.

Sample size: 82.

Post-randomisation drop-outs: 2 (2.4%).

Revised sample size: 80.

Mean age: 54 years.

Females: 66 (82.5%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 30 mL (n = 40).
Group 2: normal saline (n = 40).


OutcomesLocal anaesthetic-related complications and pain.


NotesReasons for post-randomisation drop-out: conversion to open cholecystectomy (n = 1) and lost VAS (n = 1).
Attempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Solutions were prepared by a nurse using computer-generated randomised numbers".

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskQuote: "All clinical personnel were blinded to the treatment".

Comment: Not clear if the participants were blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "All clinical personnel were blinded to the treatment".

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Ng 2004

MethodsRandomised clinical trial.


ParticipantsCountry: UK.

Sample size: 48.

Post-randomisation drop-outs: 5 (10.4%).

Revised sample size: 43.

Mean age: 46 years.

Females: not stated.

Inclusion criteria

  1. Laparoscopic cholecystectomy.
  2. ASA I or II.


Exclusion criteria

  1. Chronic pain syndrome.
  2. Used analgesics regularly.


InterventionsThe participants were randomised to the following groups.
Group 1: levobupivacaine 0.25% 30 mL (n = 21).
Group 2: normal saline (n = 22).


OutcomesNone of the outcomes of interest for this review were reported.


NotesReasons for post-randomisation drop-out: intraperitoneal solution not administered (n = 1), protocol violation (n = 2), haemorrhage precluding standard laparoscopic technique (n = 1); declined to participate (n = 1).
The dose of adrenaline in the control group was half that of the intervention group. We do not consider that adrenaline in the absence of any local anaesthetic has any analgesic property on its own and included this trial.
Attempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Low riskQuote: "This allocation was done randomly by computer in blocks of six and from instructions in envelopes that were sealed and opaque so that they could not be viewed, e.g. by shining a light".

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "The treatment solution was prepared by the anaesthetist who was not involved further in the study".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The treatment solution was prepared by the anaesthetist who was not involved further in the study".

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Nicolau 2008

MethodsRandomised clinical trial.


ParticipantsCountry: Romania.

Sample size: 60.

Post-randomisation drop-outs: not stated.

Revised sample size: 60.

Mean age: 50 years.

Females: 53 (88.3%).

Inclusion criteria

  1. People scheduled for laparoscopic cholecystectomy


Exclusion criteria

  1. Acute cholecystitis.
  2. Conversion to open cholecystectomy.
  3. Post-operative complication.
  4. Allergy to local anaesthesia.


InterventionsThe participants were randomised to the following groups.
Group 1: ropivacaine 0.25% 20 mL (n = 15).
Group 2: normal saline (n = 15).

Group 3: same as group 1 with peri-portal local anaesthetic infiltration (n = 15).

Group 4: same as group 2 with peri-portal local anaesthetic infiltration (n = 15).


OutcomesLocal anaesthetic-related complications and pain.


NotesAttempts were made contact the author in October 2009.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Pasqualucci 1994

MethodsRandomised clinical trial.


ParticipantsCountry: Italy.

Sample size: 42.

Post-randomisation drop-outs: 5 (11.9%).

Revised sample size: 37.

Mean age: 47 years.

Females: 26 (70.3%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.


Exclusion criteria

  1. Allergy to local anaesthetics.
  2. History of severe pulmonary or hormonal diseases.
  3. Acute cholecystitis.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 20 mL just after creation of pneumoperitoneum (n = 12).

Group 2: bupivacaine 0.5% 20 mL each just after creation of pneumoperitoneum and end of surgery (n = 14).
Group 3: normal saline (n = 11).


OutcomesLocal anaesthetic-related complications and pain.


NotesReasons for post-randomisation drop-out: received glucose (n = 3), received opiates (n = 3), conversion to open cholecystectomy (n = 1).
Attempts were made to contact the author in April 2008. Although authors replied, no additional information was provided.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Pasqualucci 1996

MethodsRandomised clinical trial.


ParticipantsCountry: Italy.

Sample size: 120.

Post-randomisation drop-outs: 11 (9.2%).

Revised sample size: 109.

Mean age: 47 years.

Females: 61 (56%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.


Exclusion criteria

  1. Allergy to local anaesthetics.
  2. History of severe pulmonary or hormonal diseases.
  3. Acute cholecystitis.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 20 mL just after creation of pneumoperitoneum (n = 26).

Group 2: bupivacaine 0.5% 20 mL at end of surgery (n = 28).

Group 3: bupivacaine 0.5% 20 mL each just after creation of pneumoperitoneum and end of surgery (n = 28).
Group 4: normal saline (n = 27).


OutcomesLocal anaesthetic-related complications and pain.


NotesReasons for post-randomisation drop-out: received glucose (n = 1), received opiates (n = 3), intraoperative complications (n = 2), insufficient data (n = 5).
Attempts were made to contact the author in April 2008. Although authors replied, no additional information was provided.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Paulson 2003

MethodsRandomised clinical trial.


ParticipantsCountry: USA.

Sample size: 77.

Post-randomisation drop-outs: 11 (14.3%).

Revised sample size: 66.

Mean age: 42 years.

Females: 53 (80.3%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy starting before noon.
  2. ASA I or II.
  3. Aged > 18 years.


Exclusion criteria

  1. Allergy to study medications.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 15 mL just after creation of pneumoperitoneum (n = 18).

Group 2: bupivacaine 0.5% 15 mL at end of surgery (n = 15).

Group 3: bupivacaine 0.5% 15 mL each just after creation of pneumoperitoneum and end of surgery (n = 19).

Group 4: normal saline (n = 14).


OutcomesLocal anaesthetic-related complications and hospital stay.


NotesAttempts were made to contact the authors in April 2008.

Reasons for post-randomisation drop-outs: conversion to open procedure or drain use or liver pathology (n = 4), deviation from protocol (n = 2), loss of participants' chart (n = 1), intraoperative cancellation without documentation (n = 4).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Low riskQuote: "The pharmacy randomized the patients to one of four study groups" (only 2 groups were included for this review).

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "The pharmacy then sent two syringes (A and B) containing either 15 cc of 0.5% bupivacaine or 15 cc of normal saline with the patient to the operating room".

Comment: Syringe A was used just after creation of pneumoperitoneum and Syringe B was used towards the end of surgery. This ensured blinding.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The pharmacy then sent two syringes (A and B) containing either 15 cc of 0.5% bupivacaine or 15 cc of normal saline with the patient to the operating room".

Comment: Syringe A was used just after creation of pneumoperitoneum and Syringe B was used towards the end of surgery. This ensured blinding.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Rademaker 1994

MethodsRandomised clinical trial.


ParticipantsCountry: the Netherlands.

Sample size: 45.

Post-randomisation drop-outs: not stated.

Revised sample size: 45.

Mean age: 47 years.

Females: 35 (77.8%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.25% 20 mL (n = 15).

Group 2: lignocaine 0.5% 20 mL (n = 15).
Group 2: normal saline (n = 15).


OutcomesLocal anaesthetic-related complications and pain.


NotesAttempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Raetzell 1995a

MethodsRandomised clinical trial.


ParticipantsCountry: Germany.

Sample size: 30.

Post-randomisation drop-outs: not stated.

Revised sample size: 30.

Mean age: not stated.

Females: not stated.

Inclusion criteria

  1. Laparoscopic cholecystectomy.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.125% 50 mL (n = not stated).

Group 1: bupivacaine 0.25% 50 mL (n = not stated).
Group 2: normal saline (n = not stated).


OutcomesMortality, morbidity, and pain.


NotesAttempts were made to contact the authors in April 2008.

The number of participants in each group was not reported.

Bupivacaine 0.125% developed 1 complication (thrombophlebitis) and the control group developed 1 complication (umbilical abscess).

There was no significant differences in the pain scores between the groups.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Blinded solutions were prepared by our pharmacy department and were given intraperitoneally at the end of the operation through the trocars".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Blinded solutions were prepared by our pharmacy department and were given intraperitoneally at the end of the operation through the trocars".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)Low riskComment: Mortality and morbidity were reported.

For-profit biasUnclear riskComment: This information was not available.

Raetzell 1995b

MethodsRandomised clinical trial.


ParticipantsCountry: Germany.

Sample size: 24.

Post-randomisation drop-outs: not stated.

Revised sample size: 24.

Mean age: not stated.

Females: not stated.

Inclusion criteria

  1. Laparoscopic cholecystectomy.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.25% 50 mL (n = 12).
Group 2: normal saline (n = 12).


OutcomesMortality, morbidity, and pain.


NotesAttempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Blinded solutions were prepared by our pharmacy department and were given intraperitoneally at the end of the operation through the trocars".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Blinded solutions were prepared by our pharmacy department and were given intraperitoneally at the end of the operation through the trocars".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)Low riskComment: Mortality and morbidity were reported.

For-profit biasUnclear riskComment: This information was not available.

Razek 2003

MethodsRandomised clinical trial.


ParticipantsCountry: UK.

Sample size: 40.

Post-randomisation drop-outs: 0 (0%).

Revised sample size: 40.

Mean age: 43 years.

Females: 36 (90%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.
  3. Aged between 20 and 60 years.


Exclusion criteria

  1. History of chronic pain.
  2. Contraindication for analgesic drugs (NSAIDs).
  3. Allergy to local anaesthetic agents.
  4. History of psychiatric disease.


InterventionsThe participants were randomised to the following groups.
Group 1: levobupivacaine 0.25% 60 mL (n = 20).
Group 2: normal saline (n = 20).


OutcomesLocal anaesthetic-related complications and pain.


NotesAttempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Patients were transferred to the recovery room where they were monitored and questioned about their postoperative pain at rest by an independent observer who was not involved in patient randomisation or anaesthesia administration".

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were reported.

For-profit biasUnclear riskComment: This information was not available.

Razman 2010

MethodsRandomised clinical trial.


ParticipantsCountry: Malaysia.

Sample size: 60.

Post-randomisation drop-outs: not stated.

Revised sample size: 60.

Mean age: not stated.

Females: not stated.

Inclusion criteria

  1. People undergoing laparoscopic cholecystectomy.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 20 mL (n = 30).

Group 2: normal saline (n = 30).


OutcomesNone of the outcomes of interest for this review were reported in this trial.


NotesAttempts were made to contact the authors in August 2013.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Roberts 2011

MethodsRandomised clinical trial.


ParticipantsCountry: UK.

Sample size: 128.

Post-randomisation drop-outs: 2 (1.6%).

Revised sample size: 126.

Mean age: 52 years.

Females: 98 (77.8%).

Inclusion criteria

  1. Adults undergoing elective laparoscopic cholecystectomy.


Exclusion criteria

  1. Emergency laparoscopic cholecystectomy.
  2. Undergoing additional planned procedures intraoperatively.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.25% 20 mL in the subdiaphragmatic area (n = 42).

Group 2: bupivacaine 0.25% 20 mL in the gallbladder bed (n = 41).
Group 2: normal saline (n = 43).


OutcomesHospital stay and pain.


NotesReasons for post-randomisation drop-outs: converted to open procedure (n = 1); acidosis following anaesthesia (n = 1).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "The randomisation sequence (computer-generated) and sample size calculation were kindly provided by Dr. N. Parsons, medical statistician at the University of Warwick, UK".

Comment: This information was not available.

Allocation concealment (selection bias)Unclear riskQuote: "Randomisation was performed by opening sequentially numbered sealed envelopes in the operating theatre as part of the nursing staff’s preparation, with the operating surgeons outside of theatre".
Comment: Not clear whether envelopes were opaque.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Patients, anaesthetists, operating surgeons, recovery nursing, ward medical, and nursing staff were all blinded to the study".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Patients, anaesthetists, operating surgeons, recovery nursing, ward medical, and nursing staff were all blinded to the study".

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Rudra 2002

MethodsRandomised clinical trial.


ParticipantsCountry: India.

Sample size: 60.

Post-randomisation drop-outs: not stated.

Revised sample size: 60.

Mean age: 36 years.

Females: 60 (100%).

Inclusion criteria

  1. Laparoscopic cholecystectomy.
  2. ASA I.


Exclusion criteria

  1. Allergic to bupivacaine.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 20 mL (n = 30).
Group 2: normal saline (n = 30).


OutcomesLocal anaesthetic-related complications.


NotesAttempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "The test solutions were drawn into two coded syringes by a postgraduate to the investigators, who did not know their contents".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The test solutions were drawn into two coded syringes by a postgraduate to the investigators, who did not know their contents".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Scheinin 1995

MethodsRandomised clinical trial.


ParticipantsCountry: Finland.

Sample size: 60.

Post-randomisation drop-outs: not stated.

Revised sample size: 60.

Mean age: 49 years.

Females: 48 (80%).

Inclusion criteria

  1. Laparoscopic cholecystectomy.
  2. ASA I or II.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.15% 100 mL (n = 20).

Group 2: same as group 1 with adrenaline (n = 20).
Group 3: normal saline (n = 20).


OutcomesLocal anaesthetic-related complications and hospital stay.


NotesAttempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Szem 1996

MethodsRandomised clinical trial.


ParticipantsCountry: USA.

Sample size: 75.

Post-randomisation drop-outs: 20 (26.7%).

Revised sample size: 55.

Mean age: 45 years.

Females: not stated.

Inclusion criteria

  1. Elective laparoscopic cholecystectomy for chronic calculous cholecystitis.
  2. Aged between 18 and 80 years.


Exclusion criteria

  1. Acute cholecystitis.
  2. Planned exploration of the common bile duct.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.1% 100 mL (n = 26).
Group 2: normal saline (n = 29).


OutcomesPain.


NotesReasons for post-randomisation drop-out: conversion to open procedure (n = 17), stroke (n = 1), suspected intraoperative pulmonary embolism (n = 1), and did not receive the study drug (n = 1).
Attempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComment: This information was not available.

Allocation concealment (selection bias)Low riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskQuote: "Prior to the operation, only the scrub nurse was informed as to what substance would be used by the surgeon".

Comment: Not clear whether the participants and other healthcare personnel were blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Todorov 2009

MethodsRandomised clinical trial.


ParticipantsCountry: Bulgaria.

Number randomised: 40.

Post-randomisation drop-outs: 0 (0%).

Revised sample size: 40.

Mean age: 50 years.

Females: 33 (82.5%).

Inclusion criteria

  1. People undergoing laparoscopic cholecystectomy.


Exclusion criteria

  1. Lack of informed consent on behalf of the patient.
  2. Allergy to local anaesthetic.
  3. Conversion to open procedure.
  4. Unsuccessful application of local anaesthetic (there were no such cases).


InterventionsThe participants were randomised to the following groups.
Group 1: levobupivacaine 0.25% 20 mL (n = 20).
Group 2: normal saline (n = 20).


OutcomesHospital stay and pain.


NotesAttempts were made to contact the authors in December 2010. The authors provided replies.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskQuote: "Sequentially-numbered sealed envelopes" (author replies).

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "Only researchers were "unblinded", they did not participate in questionnaires' filling in" (author replies).

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Only researchers were "unblinded", they did not participate in questionnaires' filling in" (author replies).

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "There were no post-randomisation drop-outs" (author replies).

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasLow riskQuote: "There was no funding" (author replies)".

Tunca 2001

MethodsRandomised clinical trial.


ParticipantsCountry: Turkey.
Sample size: 32.
Post-randomisation drop-outs: 2 (6.3%).
Revised sample size: 30.
Mean age: 49 years.
Females: 26 (86.7%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.


Exclusion criteria

  1. Liver disease.
  2. Cardiovascular disease.
  3. Allergy to local anaesthetics.
  4. Sarcoidosis.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.25% 20 mL (n = 15).
Group 2: normal saline (n = 15).


OutcomesLocal anaesthetic-related complications and pain.


NotesReasons for post-randomisation drop-out: conversion to open cholecystectomy.
Attempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskQuote: "Double blind".

Comment: Further details were not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Verma 2006

MethodsRandomised clinical trial.


ParticipantsCountry: India.

Sample size: 30.

Post-randomisation drop-outs: 0 (0%).

Revised sample size: 30.

Mean age: not stated.

Females: not stated.

Inclusion criteria

  1. Elective laparoscopic cholecystectomy for chronic cholecystitis.
  2. ASA I or II.


Exclusion criteria

  1. History of major upper abdominal surgeries.
  2. Choledocholithiasis.
  3. Acute cholecystitis.
  4. Conversion to open cholecystectomy.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 2 mg/kg in absorbable cellulose strips (n = 15).
Group 2: normal saline soaked cellulose strips (n = 15).


OutcomesPain.


NotesAttempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "The patients were divided into four groups of 15 patients each with the help of computer-generated randomization numbers".

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Weber 1997

MethodsRandomised clinical trial.


ParticipantsCountry: Mexico.

Sample size: 150.

Post-randomisation drop-outs: not stated.

Revised sample size: 150.

Mean age: 47 years.

Females: 119 (79.3%).

Inclusion criteria

  1. People undergoing laparoscopic cholecystectomy.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.25% 40 mL (n = 50).

Group 2: normal saline (n = 50).

Group 3: no intervention (n = 50).


OutcomesLocal anaesthetic-related complications pain.


NotesAttempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.

Selective reporting (reporting bias)Unclear riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

Zimmer 2010

MethodsRandomised clinical trial.


ParticipantsCountry: USA.

Number randomised: 50.

Post-randomisation drop-outs: 0 (0%).

Revised sample size: 50.

Mean age: 43 years.

Females: 40 (80%).

Inclusion criteria

  1. Aged ≥ 18 years.


Exclusion criteria

  1. Pregnancy.
  2. Previous upper abdominal surgery.
  3. Known allergy to bupivacaine.
  4. Suspected common bile duct stones.
  5. Chronic pain syndrome or chronic narcotic use.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.5% 10 mL (n = 25).
Group 2: water (n = 25).


OutcomesMortality, morbidity, hospital stay, and pain.


NotesAttempts were made to contact the authors in July 2013.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Low riskQuote: "Fifty patients were randomized by the pharmacy...The agent was delivered to the operating room labeled as "study drug" for injection into the Insuflow device as routinely done".

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "All operative and perioperative team members were blinded to the contents of the study drug".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "All operative and perioperative team members were blinded to the contents of the study drug".

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation drop-outs.

Selective reporting (reporting bias)Low riskComment: Mortality and morbidity were reported.

For-profit biasLow riskQuote: "Appreciation is extended to the Penrose-St. Francis Health Foundation for their financial support of this study".

Zmora 2000

MethodsRandomised clinical trial.


ParticipantsCountry: USA.

Sample size: 60.

Post-randomisation drop-outs: 9 (15%).

Revised sample size: 51.

Mean age: 44 years.

Females: 35 (68.6%).

Inclusion criteria

  1. Elective laparoscopic cholecystectomy.


Exclusion criteria

  1. Conversion to an open procedure.
  2. Drain left in the peritoneal cavity.


InterventionsThe participants were randomised to the following groups.
Group 1: bupivacaine 0.2% 50 mL (n = 26).
Group 2: normal saline soaked cellulose strips (n = 25).


OutcomesPain.


NotesReasons for post-randomisation drop-out: requiring conversion to open cholecystectomy or requiring drain.
Attempts were made to contact the authors in April 2008.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskComment: This information was not available.

Allocation concealment (selection bias)Unclear riskComment: This information was not available.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "The patients, the surgeons, and the nursing staff were blinded to the randomization".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "The patients, the surgeons, and the nursing staff were blinded to the randomization".

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.

Selective reporting (reporting bias)High riskComment: Mortality and morbidity were not reported.

For-profit biasUnclear riskComment: This information was not available.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Ahmed 200830 (15%) people had to be excluded because of various reasons. These participants were replaced by other people. We consider that this will result in inadequate randomisation.

Alexander 1997Letter to editor containing no information of any trial suitable for inclusion in this review.

Bayar 1998Not a randomised clinical trial.

Beqiri 2012Not intraperitoneal local anaesthetic instillation.

Berven 1995Not a randomised clinical trial.

Bisgaard 1999Intraperitoneal and wound infiltration of local anaesthetic in 1 group and no local anaesthetic in 1 group.

Busley 1999Only the control group received systemic opioids.

Celik 2000No appropriate control group with normal saline or no intervention.

Cha 2012Excluded participants were replaced with other people. This might have introduced selection bias.

Cunniffe 1998No separate data available for people who underwent laparoscopic cholecystectomy.

Di Pace 2009No separate data available for laparoscopic cholecystectomy.

Elhakim 2000bLidocaine was combined with either intraperitoneal or intravenous tenoxicam and compared with control.

Gharaibeh 2000Quasi-randomised study (randomisation by alternation). This study did not report the adverse effects of the local anaesthetic.

Gupta 2002Intraperitoneal and wound infiltration of local anaesthetic in 1 group and no local anaesthetic in 1 group.

Hernández-Palazón 2003Only the local anaesthetic group received opiate analgesics.

Hilvering 2011The local anaesthetic intraperitoneal group alone received peri-portal local anaesthetic wound infiltration.

Inan 2004Not a randomised clinical trial.

Johnson 1999Comparison of intraperitoneal bupivacaine and bupivacaine by wound infiltration.

Lauwick 2008Apart from the difference in the groups related to the administration of local anaesthetic, the doses of pre-operative fentanyl was also different in the 2 groups.

Lindgren 1997Editorial about an included trial.

Mack 1995Letter to editor about an included trial.

Maharjan 2009The local anaesthetic intraperitoneal group alone received peri-portal local anaesthetic wound infiltration.

Memedov 2010Only the intervention group (local anaesthetic intraperitoneal instillation group) received local anaesthetic wound infiltration.

Michaloliakou 1996Assessment of multilayered local anaesthetic infiltration. However, only the treatment group received pethidine and ketorolac as pre-medication.

Moreira 2000Not a randomised clinical trial.

Newcomb 2007Assessment of multimodal analgesia compared with control.

Ng 2002Editorial; refers to identified trials.

Paech 2008No separate data available for people who underwent laparoscopic cholecystectomy.

Papadima 2009Open allocation schedule.

Pappas-Gogos 20087 people (5.8%) were excluded post-randomisation. These participants were replaced by new participants to "maintain homogeneity". This introduced selection bias.

Rizzotti 2002Not a randomised clinical trial.

Schulte-Steinberg 1995No appropriate control group with normal saline or no intervention.

Sozbilen 2007Comparison of different types of multimodal analgesia.

Stempin 2007There was no appropriate control to assess the effectiveness of intraperitoneal bupivacaine.

Tsimoyiannis 1998aIn this trial, participants who had to be excluded post-randomisation were replaced by selected participants.

Tsimoyiannis 1998bIn this trial, participants who had to be excluded post-randomisation were replaced by selected participants.

Tsimoyiannis 1998cIn this trial, participants who had to be excluded post-randomisation were replaced by selected participants.

Wallace 1996Compared intraperitoneal instillation with wound infiltration.

Özkoçak 2002No appropriate control group with normal saline or no intervention.

 
Comparison 1. Local anaesthetic versus no local anaesthetic

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mortality8446Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Serious adverse events8446Risk Ratio (M-H, Fixed, 95% CI)3.0 [0.13, 67.06]

 3 Proportion discharged as day surgery3242Risk Ratio (M-H, Fixed, 95% CI)1.25 [0.99, 1.58]

 4 Hospital stay5335Mean Difference (IV, Fixed, 95% CI)0.04 [-0.23, 0.32]

 5 Pain (4 to 8 hours)322020Mean Difference (IV, Fixed, 95% CI)-0.99 [-1.10, -0.88]

 6 Pain (9 to 24 hours)291787Mean Difference (IV, Fixed, 95% CI)-0.53 [-0.62, -0.44]

 
Comparison 2. Sensitivity analysis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Proportion discharged as day surgery3Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Best-best scenario
3244Risk Ratio (M-H, Fixed, 95% CI)1.25 [0.99, 1.58]

    1.2 Best-worst scenario
3244Risk Ratio (M-H, Fixed, 95% CI)1.21 [0.96, 1.53]

    1.3 Worst-best scenario
3244Risk Ratio (M-H, Fixed, 95% CI)1.26 [1.00, 1.60]

    1.4 Worst-worst scenario
3244Risk Ratio (M-H, Fixed, 95% CI)1.23 [0.97, 1.55]

 2 Hospital stay160Mean Difference (IV, Fixed, 95% CI)0.53 [-0.14, 1.21]

 3 Pain (4 to 8 hours) (studies with imputed values removed)10576Mean Difference (IV, Fixed, 95% CI)-1.04 [-1.17, -0.90]

 4 Pain (9 to 24 hours) (studies with imputed values removed)12676Mean Difference (IV, Fixed, 95% CI)-0.38 [-0.48, -0.28]

 
Comparison 3. Subgroup analysis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pain (4 to 8 hours) by local anaesthetic322020Mean Difference (IV, Random, 95% CI)-1.22 [-1.52, -0.91]

    1.1 Bupivacaine
251626Mean Difference (IV, Random, 95% CI)-1.38 [-1.77, -0.98]

    1.2 Levobupivacaine
280Mean Difference (IV, Random, 95% CI)-0.99 [-1.69, -0.28]

    1.3 Ropivacaine
5252Mean Difference (IV, Random, 95% CI)-0.71 [-1.03, -0.39]

    1.4 Lignocaine
262Mean Difference (IV, Random, 95% CI)-1.37 [-2.37, -0.37]

 2 Pain (4 to 8 hours) by dose322020Mean Difference (IV, Random, 95% CI)-1.22 [-1.52, -0.91]

    2.1 Weight-based
7385Mean Difference (IV, Random, 95% CI)-1.11 [-1.26, -0.96]

    2.2 Fixed dose
251635Mean Difference (IV, Random, 95% CI)-1.32 [-1.78, -0.87]

 3 Pain (4 to 8 hours) by form322020Mean Difference (IV, Random, 95% CI)-1.22 [-1.52, -0.91]

    3.1 Liquid
291880Mean Difference (IV, Random, 95% CI)-0.96 [-1.16, -0.75]

    3.2 Others
4140Mean Difference (IV, Random, 95% CI)-3.03 [-6.58, 0.51]

 4 Pain (4 to 8 hours) by time322020Mean Difference (IV, Random, 95% CI)-1.22 [-1.52, -0.91]

    4.1 Before pneumoperitoneum
2120Mean Difference (IV, Random, 95% CI)-1.01 [-1.23, -0.79]

    4.2 Just after creation of pneumoperitoneum
8382Mean Difference (IV, Random, 95% CI)-1.30 [-1.74, -0.86]

    4.3 End of surgery
241361Mean Difference (IV, Random, 95% CI)-1.17 [-1.70, -0.64]

    4.4 After end of surgery
120Mean Difference (IV, Random, 95% CI)-1.68 [-4.07, 0.71]

    4.5 Just after creation of pneumoperitoneum and end of surgery
3137Mean Difference (IV, Random, 95% CI)-1.49 [-2.87, -0.12]

 5 Pain (4 to 8 hours) by location322020Mean Difference (IV, Random, 95% CI)-1.22 [-1.52, -0.91]

    5.1 Gallbladder bed
9445Mean Difference (IV, Random, 95% CI)-0.87 [-1.23, -0.51]

    5.2 Subdiaphragmatic area
4358Mean Difference (IV, Random, 95% CI)-1.55 [-2.97, -0.14]

    5.3 Subdiaphragmatic area and gallbladder bed
18997Mean Difference (IV, Random, 95% CI)-0.92 [-1.21, -0.64]

    5.4 Diffuse
3220Mean Difference (IV, Random, 95% CI)-2.54 [-3.75, -1.33]

 6 Pain (4 to 8 hours) by norepinephrine use322020Mean Difference (IV, Random, 95% CI)-1.22 [-1.52, -0.91]

    6.1 Norepinephrine used
6395Mean Difference (IV, Random, 95% CI)-1.33 [-1.98, -0.68]

    6.2 Norepinephrine not used
261625Mean Difference (IV, Random, 95% CI)-1.19 [-1.54, -0.83]

 7 Pain (4 to 8 hours) by control322020Mean Difference (IV, Random, 95% CI)-1.22 [-1.52, -0.91]

    7.1 Normal saline
261619Mean Difference (IV, Random, 95% CI)-1.23 [-1.57, -0.89]

    7.2 No intervention
3145Mean Difference (IV, Random, 95% CI)-1.15 [-2.42, 0.11]

    7.3 Others
5256Mean Difference (IV, Random, 95% CI)-1.11 [-1.80, -0.43]

 8 Pain (4 to 8 hours) by wound infiltration8574Mean Difference (IV, Random, 95% CI)-1.22 [-1.79, -0.66]

    8.1 Wound infiltration used
5405Mean Difference (IV, Random, 95% CI)-1.81 [-2.66, -0.96]

    8.2 Wound infiltration not used
4169Mean Difference (IV, Random, 95% CI)-0.53 [-0.89, -0.18]

 9 Pain (4 to 8 hours) by routine supplemental analgesia281720Mean Difference (IV, Fixed, 95% CI)-0.99 [-1.10, -0.88]

    9.1 Routine supplemental analgesia
8495Mean Difference (IV, Fixed, 95% CI)-1.53 [-1.88, -1.19]

    9.2 No routine supplemental analgesia
201225Mean Difference (IV, Fixed, 95% CI)-0.93 [-1.05, -0.81]

 10 Pain (9 to 24 hours) by local anaesthetic291787Mean Difference (IV, Random, 95% CI)-0.81 [-1.11, -0.51]

    10.1 Bupivacaine
221415Mean Difference (IV, Random, 95% CI)-0.94 [-1.33, -0.55]

    10.2 Levobupivacaine
280Mean Difference (IV, Random, 95% CI)-0.47 [-1.48, 0.54]

    10.3 Ropivacaine
5252Mean Difference (IV, Random, 95% CI)-0.34 [-0.62, -0.06]

    10.4 Lignocaine
140Mean Difference (IV, Random, 95% CI)-1.1 [-2.12, -0.08]

 11 Pain (9 to 24 hours) by dose291787Mean Difference (IV, Random, 95% CI)-0.81 [-1.11, -0.51]

    11.1 Weight-based
7385Mean Difference (IV, Random, 95% CI)-0.41 [-0.53, -0.30]

    11.2 Fixed dose
221402Mean Difference (IV, Random, 95% CI)-0.91 [-1.36, -0.45]

 12 Pain (9 to 24 hours) by form291787Mean Difference (IV, Random, 95% CI)-0.81 [-1.11, -0.51]

    12.1 Liquid
251597Mean Difference (IV, Random, 95% CI)-0.63 [-0.89, -0.38]

    12.2 Others
5190Mean Difference (IV, Random, 95% CI)-1.93 [-4.10, 0.24]

 13 Pain (9 to 24 hours) by time291787Mean Difference (IV, Random, 95% CI)-0.81 [-1.11, -0.51]

    13.1 Before pneumoperitoneum
2120Mean Difference (IV, Random, 95% CI)-0.40 [-0.55, -0.25]

    13.2 Just after creation of pneumoperitoneum
7252Mean Difference (IV, Random, 95% CI)-1.08 [-1.95, -0.21]

    13.3 End of surgery
221258Mean Difference (IV, Random, 95% CI)-0.81 [-1.27, -0.35]

    13.4 After end of surgery
120Mean Difference (IV, Random, 95% CI)0.83 [-0.43, 2.09]

    13.5 Just after creation of pneumoperitoneum and end of surgery
3137Mean Difference (IV, Random, 95% CI)-1.19 [-2.17, -0.20]

 14 Pain (9 to 24 hours) by location291787Mean Difference (IV, Random, 95% CI)-0.81 [-1.11, -0.51]

    14.1 Gallbladder bed
17942Mean Difference (IV, Random, 95% CI)-0.58 [-0.99, -0.18]

    14.2 Subdiaphragmatic area
2250Mean Difference (IV, Random, 95% CI)-3.33 [-6.66, -0.00]

    14.3 Subdiaphragmatic area and gallbladder bed
7325Mean Difference (IV, Random, 95% CI)-0.57 [-0.90, -0.24]

    14.4 Diffuse
4270Mean Difference (IV, Random, 95% CI)-1.55 [-2.44, -0.66]

 15 Pain (9 to 24 hours) by norepinephrine use291787Mean Difference (IV, Random, 95% CI)-0.81 [-1.11, -0.51]

    15.1 Norepinephrine used
6395Mean Difference (IV, Random, 95% CI)-1.07 [-1.74, -0.41]

    15.2 Norepinephrine not used
231392Mean Difference (IV, Random, 95% CI)-0.69 [-1.03, -0.35]

 16 Pain (9 to 24 hours) by control291787Mean Difference (IV, Random, 95% CI)-0.81 [-1.11, -0.51]

    16.1 Normal saline
221336Mean Difference (IV, Random, 95% CI)-0.83 [-1.16, -0.50]

    16.2 No intervention
3145Mean Difference (IV, Random, 95% CI)-1.65 [-3.80, 0.51]

    16.3 Others
6306Mean Difference (IV, Random, 95% CI)-0.64 [-1.68, 0.39]

 17 Pain (9 to 24 hours) by wound infiltration8499Mean Difference (IV, Random, 95% CI)-0.81 [-1.24, -0.38]

    17.1 Wound infiltration used
5330Mean Difference (IV, Random, 95% CI)-1.27 [-1.98, -0.56]

    17.2 Wound infiltration not used
4169Mean Difference (IV, Random, 95% CI)-0.32 [-0.59, -0.05]

 18 Pain (9 to 24 hours) by routine supplemental analgesia261532Mean Difference (IV, Fixed, 95% CI)-0.54 [-0.63, -0.44]

    18.1 Routine supplemental analgesia
6315Mean Difference (IV, Fixed, 95% CI)-1.05 [-1.41, -0.69]

    18.2 No routine supplemental analgesia
201217Mean Difference (IV, Fixed, 95% CI)-0.50 [-0.60, -0.40]

 
Summary of findings for the main comparison. Intraperitoneal local anaesthetic instillation compared with control for people undergoing laparoscopic cholecystectomy

Intraperitoneal local anaesthetic instillation compared with control for people undergoing laparoscopic cholecystectomy

Patient or population: people undergoing laparoscopic cholecystectomy.
Settings: secondary or tertiary.
Intervention: intraperitoneal local anaesthetic instillation.
Comparison: control.

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)

Assumed riskCorresponding risk

ControlIntraperitoneallocal anaesthetic instillation

MortalityNo mortality in either groupNot estimable446
(8 studies)
⊕⊝⊝⊝
very low1,2





Serious adverse eventsModerateRR 3
(0.13 to 67.06)
446
(8 studies)
⊕⊝⊝⊝
very low1,2

20 per 100060 per 1000
(3 to 1000)

Proportion discharged as day surgery488 per 1000610 per 1000
(439 to 771)
RR 1.25

(0.99 to 1.58)
242
(3 studies)
⊕⊝⊝⊝
very low1,2,3

Hospital stayThe mean hospital stay in the control groups was
2.1 days
The mean hospital stay in the intervention groups was
0.04 higher
(0.23 lower to 0.32 higher)
-335
(5 studies)
⊕⊕⊝⊝
low1

Pain (4 to 8 hours)The mean pain (4 to 8 hours) in the control groups was
3.5 cm VAS
The mean pain (4 to 8 hours) in the intervention groups was
0.99 lower
(1.1 to 0.88 lower)
-2020
(32 studies)
⊕⊝⊝⊝
very low1,3

Pain (9 to 24 hours)The mean pain (9 to 24 hours) in the control groups was
2.05 cm VAS
The mean pain (9 to 24 hours) in the intervention groups was
0.53 lower
(0.62 to 0.44 lower)
-1787
(29 studies)
⊕⊝⊝⊝
very low1,3

*The basis for the assumed risk was the mean control group risk across studies for day-surgery proportion. Since there were no events in the control group in the trials included for serious adverse events, the control group proportion used was 2%. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 The trial(s) was (were) of high risk of bias.
2 The confidence intervals overlapped 1 and either 0.75 or 1.25 or both. The number of events in the intervention and control group was fewer than 300.
3 There was severe heterogeneity as noted by the I2 statistic and the lack of overlap of confidence intervals.
 
Table 1. Further details about intervention and co-interventions

Study nameLocal anaestheticTime§LocationNorepinephrinePeri-portal local anaesthetic infiltrationDrain useOther routine analgesia*

Abdel-Raouf 2004bupivacaineend of surgerysubdiaphragmatic areanoyesnonone

Ahmad 1998bupivacainenot statednot statednononot statednone

Ahmad 1998bupivacainenot statednot statednoyesnot statednone

Alagöl 2003bupivacaineend of surgerysubdiaphragmatic area and gallbladder bednonot statednot statednone

Alagöl 2003 (intraperitoneal ondansetron administered in both groups)bupivacaineend of surgerysubdiaphragmatic area and gallbladder bednonot statednot statednone

Alkhamesi 2007bupivacaineend of surgerydiffusenoyesnot statedroutine NSAID and opioid analgesics

Alkhamesi 2007bupivacaineend of surgerygallbladder bednoyesnot statedroutine NSAID and opioid analgesics

Alper 2009levobupivacainejust after creation of pneumoperitoneumsubdiaphragmatic area and gallbladder bednoyesnot statedno

Alptekin 2010bupivacaineend of surgerygallbladder bednonot statednot statednot stated

Alptekin 2010bupivacaineafter end of surgerygallbladder bednonot statedfor the continuous infusion groupnot stated

Barczynski 2006bupivacainebefore pneumoperitoneumdiffusenoyesnot statedno

Barczynski 2006bupivacainejust after creation of pneumoperitoneumdiffusenoyesnot statedno

Bhardwaj 2002bupivacaineend of surgerysubdiaphragmatic area and gallbladder bedyesnot statednot statedno

Castillo-Garza 2012bupivacaineend of surgerygallbladder bednonot statednono

Chundrigar 1993bupivacaineend of surgerygallbladder bednonot statednono

Elfberg 2000bupivacaineend of surgerygallbladder bednonot statednonot stated

Elhakim 2000lignocaineend of surgerysubdiaphragmatic areanoyesyesno

El-Labban 2011levobupivacaineend of surgerysubdiaphragmatic area and gallbladder bednononoroutine NSAID

Feroci 2009bupivacaineend of surgerygallbladder bednononot statedno

Fornari 1996bupivacaineend of surgerysubdiaphragmatic areayesnot statednono

Fu 2009ropivacaineend of surgerygallbladder bednonot statednot statedno

Fuhrer 1996bupivacaineend of surgerysubdiaphragmatic area and gallbladder bednonot statednot statedno

Garcia 2007bupivacaine (s75-r25)end of surgerysubdiaphragmatic areanonot statednot statedroutine NSAID

Golubovic 2009bupivacaineend of surgerysubdiaphragmatic area and gallbladder bednonot statednot statedno

Gvozdenovic 2011bupivacaineend of surgerynot statednonot statednot statednot stated

Hasan 2007bupivacainenot statednot statednononot statedroutine NSAID

Hasan 2007bupivacainenot statednot statednononot statedroutine NSAID

Hazinedaroglu 2006bupivacaineend of surgerysubdiaphragmatic area and gallbladder bednoyesnot statedno

Jabbour-Khoury 2005bupivacaineend of surgerynot statednonot statednot statedno

Jabbour-Khoury 2005 (intravenous ketoprofen administered in both groups)bupivacaineend of surgerynot statednonot statednot statedno

Jiranantarat 2002bupivacaineend of surgerysubdiaphragmatic area and gallbladder bednonot statednot statedno

Joris 1995bupivacaineend of surgerysubdiaphragmatic areayesnonot statedno

Kallel 2011lignocaineend of surgerysubdiaphragmatic area and gallbladder bednonot statednot statednot stated

Karaaslan 2006bupivacainebefore pneumoperitoneumgallbladder bednonot statednot statedno

Karaaslan 2006bupivacainejust after creation of pneumoperitoneumgallbladder bednonot statednot statedno

Karaaslan 2006bupivacaineend of surgerygallbladder bednonot statednot statedno

Karadeniz 2003bupivacainejust after creation of pneumoperitoneumsubdiaphragmatic area and gallbladder bednonot statednono

Karadeniz 2003bupivacaineend of surgerysubdiaphragmatic area and gallbladder bednonot statednono

Karadeniz 2003bupivacaineafter end of surgerysubdiaphragmatic area and gallbladder bed (by infusion pump)nonot statedpossibly for the continuous infusion groupno

Kilic 1996bupivacaineend of surgerysubdiaphragmatic areanonot statednot statednot stated

Kim 2010ropivacainejust after creation of pneumoperitoneumsubdiaphragmatic area and gallbladder bednonot statednot statedno

Kolsi 2000lignocaineend of surgerysubdiaphragmatic area and gallbladder bednonot statednot statedno

Kucuk 2007ropivacaineend of surgerysubdiaphragmatic area and gallbladder bedyesnonot statedno

Kucuk 2007ropivacaineend of surgerysubdiaphragmatic area and gallbladder bedyesnonot statedno

Kucuk 2007bupivacaineend of surgerysubdiaphragmatic area and gallbladder bedyesnonot statedno

Labaille 2002ropivacainejust after creation of pneumoperitoneum and end of surgerysubdiaphragmatic area and gallbladder bednononot statedno

Labaille 2002ropivacainejust after creation of pneumoperitoneum and end of surgerysubdiaphragmatic area and gallbladder bednononot statedno

Lee 2001bupivacainejust after creation of pneumoperitoneumsubdiaphragmatic area and gallbladder bedyesyesnot statedroutine NSAID

Lee 2001bupivacaineend of surgerysubdiaphragmatic area and gallbladder bedyesnonot statedroutine NSAID

Lepner 2003lignocaineend of surgerysubdiaphragmatic areanoyesnoroutine NSAID

Louizos 2005levobupivacaineend of surgerygallbladder bednononot statedno

Louizos 2005levobupivacaineend of surgerygallbladder bednoyesnot statedno

Maestroni 2002ropivacainebefore pneumoperitoneumdiffusenonot statednot statedroutine NSAID

Mraovic 1997bupivacainejust after creation of pneumoperitoneum and end of surgerysubdiaphragmatic area and gallbladder bednonot statednot statedno

Ng 2004levobupivacaineend of surgerysubdiaphragmatic area and gallbladder bedyesnot statedselectively (reasons not stated)not stated clearly

Nicolau 2008ropivacaineend of surgerygallbladder bednonoselectively (for patients with difficult haemostasis)routine NSAID

Nicolau 2008ropivacaineend of surgerygallbladder bednoyesselectively (for patients with difficult haemostasis)routine NSAID

Pasqualucci 1994bupivacainejust after creation of pneumoperitoneum and end of surgerysubdiaphragmatic area and gallbladder bedyesnot statednot statedno

Pasqualucci 1994bupivacainejust after creation of pneumoperitoneumsubdiaphragmatic area and gallbladder bedyesnot statednot statedno

Pasqualucci 1996bupivacainejust after creation of pneumoperitoneumsubdiaphragmatic area and gallbladder bedyesnot statednot statedno

Pasqualucci 1996bupivacaineend of surgerysubdiaphragmatic area and gallbladder bedyesnot statednot statedno

Pasqualucci 1996bupivacainejust after creation of pneumoperitoneum and end of surgerysubdiaphragmatic area and gallbladder bedyesnot statednot statedno

Paulson 2003bupivacainejust after creation of pneumoperitoneumsubdiaphragmatic area and gallbladder bednononono

Paulson 2003bupivacaineend of surgerysubdiaphragmatic area and gallbladder bednononono

Paulson 2003bupivacainejust after creation of pneumoperitoneum and end of surgerysubdiaphragmatic area and gallbladder bednononono

Rademaker 1994bupivacaineend of surgerysubdiaphragmatic areanonot statednot statednot stated

Rademaker 1994lignocaineend of surgerysubdiaphragmatic areanonot statednot statednot stated

Raetzell 1995abupivacaineend of surgerysubdiaphragmatic area and gallbladder bednonot statednot statedroutine NSAID

Raetzell 1995abupivacaineend of surgerysubdiaphragmatic area and gallbladder bednonot statednot statedroutine NSAID

Raetzell 1995bbupivacaineend of surgerysubdiaphragmatic area and gallbladder bednonot statednot statedroutine NSAID

Razek 2003levobupivacaineend of surgerysubdiaphragmatic area and gallbladder bednonot statednot statedroutine NSAID

Razman 2010bupivacainenot statednot statedyesyesnot statednot stated

Roberts 2011bupivacainejust after creation of pneumoperitoneumsubdiaphragmatic areanoyesselectively (reasons not stated)routine NSAID and opioid analgesics

Roberts 2011bupivacainejust after creation of pneumoperitoneumgallbladder bednoyesselectively (reasons not stated)routine NSAID and opioid analgesics

Rudra 2002bupivacaineend of surgerysubdiaphragmatic area and gallbladder bednonot statednot statedno

Scheinin 1995bupivacaineend of surgerysubdiaphragmatic areanonot statednono

Scheinin 1995bupivacaineend of surgerysubdiaphragmatic areayesnot statednono

Szem 1996bupivacainejust after creation of pneumoperitoneumsubdiaphragmatic area and gallbladder bednonot statednot statedroutine opioid analgesic

Todorov 2009levobupivacaineend of surgerysubdiaphragmatic area and gallbladder bednonot statednot statednot stated

Tunca 2001bupivacainejust after creation of pneumoperitoneumsubdiaphragmatic area and gallbladder bedyesnot statednot statedno

Verma 2006bupivacaineend of surgerygallbladder bednononot statedno

Weber 1997bupivacaineend of surgerysubdiaphragmatic areanonot statednot statednot stated

Weber 1997bupivacaineend of surgerysubdiaphragmatic areanonot statednot statednot stated

Zimmer 2010bupivacainejust after creation of pneumoperitoneumdiffusenoyesnot statedno

Zmora 2000bupivacaineend of surgerysubdiaphragmatic area and gallbladder bednonot statednoroutine NSAID and opioid analgesic

 NSAID: non-steroidal anti-inflammatory drug.
§ 'End of surgery' indicates instillation after removal of gallbladder usually before closure of the wounds but in all instances before the reversal of anaesthesia; 'after end of surgery' indicates that the participant received the local anaesthetic by an infusion pump after reversal of anaesthesia.
* refers to routine analgesia. Most trials allowed 'on-demand' analgesia or analgesia was administered if the pain was above a certain threshold.