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Methods of intraperitoneal local anaesthetic instillation for laparoscopic cholecystectomy

  1. Kurinchi Selvan Gurusamy1,*,
  2. Myura Nagendran2,
  3. Clare D Toon3,
  4. Gian Piero Guerrini4,
  5. Murat Zinnuroglu5,
  6. Brian R Davidson1

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 25 MAR 2014

Assessed as up-to-date: 14 MAR 2013

DOI: 10.1002/14651858.CD009060.pub2


How to Cite

Gurusamy KS, Nagendran M, Toon CD, Guerrini GP, Zinnuroglu M, Davidson BR. Methods of intraperitoneal local anaesthetic instillation for laparoscopic cholecystectomy. Cochrane Database of Systematic Reviews 2014, Issue 3. Art. No.: CD009060. DOI: 10.1002/14651858.CD009060.pub2.

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

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

  4. 4

    Ravenna Hospital, Department of Surgery, Ravenna, Italy

  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: 25 MAR 2014

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Characteristics of included studies [ordered by study ID]
Alkhamesi 2007

MethodsRandomised clinical trial.


ParticipantsCountry: UK.

Sample size: 80.

Post-randomisation drop-out: not stated.

Revised sample size: 40.

Females: 35 (87.5%).

Mean age: 50 years.

Inclusion criteria:

  1. Elective laparoscopic cholecystectomy.
  2. ASA I or II.
  3. Age ≥ 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 randomly assigned to 1 of the following groups.
Group 1: bupivacaine; 0.5%; 10 mL; aerosol ; end of surgery; diffuse; bolus administration (n = 20).
Group 2: bupivacaine; 0.5%; 10 mL; liquid ; end of surgery; gallbladder bed; bolus administration (n = 20).


OutcomesPain.


NotesAuthors provided information on random sequence generation in April 2008.

The main difference between the intervention and control are shown in bold and italics.


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 (performance bias and 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.

Barczynski 2006

MethodsRandomised clinical trial.


ParticipantsCountry: Poland.

Sample size: 60.

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

Revised sample size: 60.

Females: 53 (88.3%).

Mean age: 49 years.

Inclusion criteria:

  1. Uncomplicated, symptomatic cholelithiasis.
  2. ASA I or II.
  3. Age ≥ 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 randomly assigned to 1 of the following groups.
Group 1: bupivacaine; 1 mg/kg; diluted in 200 mL with saline; liquid; before pneumoperitoneum ; diffuse; bolus administration (n = 30).
Group 2: bupivacaine; 1 mg/kg; diluted in 200 mL with saline; liquid; just after creation of pneumoperitoneum ; diffuse; bolus administration (n = 30).


OutcomesIntra-operative complications and pain.


NotesAttempts were made to contact the authors in August 2013.

The main difference between the intervention and control are shown in bold and italics.


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 (performance bias and detection bias)
All outcomes
Unclear riskQuote: "Double-blinded".

Comment: The groups that were blinded was 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 reported that there were no intra-operative complications. It was not clear whether there were any post-operative complications.

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

Bucciero 2011

MethodsRandomised clinical trial.


ParticipantsCountry: Italy.

Number randomised: 60.

Post-randomisation drop-outs: 3 (5%).

Revised sample size: 57.

Mean age: 48 years.

Females: 32 (56.1%).

Inclusion criteria:

  1. Age 18 to 70 years.
  2. ASA status I to III.
  3. Scheduled to undergo elective laparoscopic cholecystectomy.


Exclusion criteria:

  1. Clinical diagnosis of acute pancreatitis.
  2. Acute preoperative pain other than biliary colic.
  3. Required chronic pain treatment or antiepileptic drugs.
  4. History of alcohol or drug addiction.
  5. Severe hepatic or renal impairment.
  6. Allergy to the study drugs.
  7. Pregnant or lactating.
  8. Predictable possibility of requiring open cholecystectomy.
  9. Cognitive impairment or communication problems.


InterventionsThe participants were randomly assigned to 1 of the following groups.
Group 1: ropivacaine; 0.5%; 3 mL twice; aerosol ; just after creation of pneumoperitoneum and end of surgery; diffuse; bolus administration (n = 27).
Group 2: ropivacaine; 0.5%; 20 mL twice; liquid ; just after creation of pneumoperitoneum and end of surgery; gallbladder bed; bolus administration (n = 30).


OutcomesLocal anaesthetic-related complications, pain, and hospital stay.


NotesReasons for post-randomisation drop-outs: converted to open procedure (n = 3 in aerosol group).

The main difference between the intervention and control are shown in bold and italics.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Patients were randomized to 1 of 2 groups using a computer-generated randomization sequence".

Allocation concealment (selection bias)Low riskQuote: "A research assistant not involved in patient care confirmed patient eligibility, obtained written consent, and gave the sealed white envelope containing patient allocation and instructions for the solution preparation to a previously trained anesthesia nurse who was not involved in the study".

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "The solutions were prepared in one 20-mL transparent syringe containing ropivacaine 0.5% or normal saline and two 5-mL transparent syringes containing 3 mL of ropivacaine 1% or 3 mL of normal saline according to the randomization sequence. To maintain blinding, the re- search assistant was not allowed to enter the operating room when the study solutions were being prepared. In case of an emergency related to or possibly related to the study or study drugs, the nurse was authorized to disclose the contents of the syringe to the anesthesiologist in charge of the case who was not involved in the study and to the research assistant".

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 biasLow riskQuote: "Financial support from departmental and institutional funding of the Department of Experimental Medicine Milan Bicocca University, Italy, and from the Service d’Anesthesiologie - Reanimation Chirurgicale, CHU de Hautepierre, Strasbourg, France".

Karaaslan 2006

MethodsRandomised clinical trial.


ParticipantsCountry: Turkey.

Sample size: 62.

Post-randomisation drop-out: 12 (19.4%).

Revised sample size: 50.

Females: 31 (62.0%).

Mean age: 51 years.

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 1 of the following groups.
Group 1: bupivacaine; 0.5%; 20 mL; liquid; before pneumoperitoneum ; gallbladder bed; bolus administration (n = 16).
Group 2: bupivacaine; 0.5%; 20 mL; liquid; just after creation of pneumoperitoneum ; gallbladder bed; bolus administration (n = 18).

Group 3: bupivacaine; 0.5%; 20 mL; liquid; end of surgery ; gallbladder bed; bolus administration (n = 16).


OutcomesLocal anaesthetic-related complications.


NotesReasons for post-randomisation drop-out: Required opiates intraoperatively (n = 9) and postoperatively (n = 3).
Attempts were made to contact the authors in April 2008.

The main difference between the intervention and control are shown in bold and italics.


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 (performance bias and 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: 51.

Post-randomisation drop-out: 6 (11.8%).

Revised sample size: 45.

Females: 34 (75.6%).

Mean age: 29 years.

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 randomly assigned to 1 of the following groups.

Group 1: bupivacaine; 0.5%; 20 mL; liquid; just after creation of pneumoperitoneum ; subdiaphragmatic and gallbladder bed; bolus administration (n = 15).
Group 2: bupivacaine; 0.5%; 20 mL; liquid; end of surgery ; subdiaphragmatic and gallbladder bed; bolus administration (n = 15).

Group 3: bupivacaine; 0.5%; 20 mL; liquid; after end of surgery ; subdiaphragmatic and gallbladder bed; continuous infusion (n = 15).


OutcomesMortality, morbidity, and pain.


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

The main difference between the intervention and control are shown in bold and italics.


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 (performance bias and 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.

Khan 2012

MethodsRandomised clinical trial.


ParticipantsCountry: Pakistan.

Number randomised: 224.

Post-randomisation drop-outs: 18 (8%).

Revised sample size: 206.

Mean age: 44 years.

Females: 136 (66.0%).

Inclusion criteria:

  1. Adults undergoing elective laparoscopic cholecystectomy.
  2. ASA status I or II.


Exclusion criteria:

  1. Refused consent.
  2. Acute cholecystitis.
  3. History of long-term analgesic use.
  4. Allergy to local anaesthetic agents.
  5. Pre-operative cholangiogram or common bile duct exploration.
  6. People with stone spillage during the procedure.
  7. Conversion to open procedure or re-exploration.


InterventionsThe participants were randomly assigned to 1 of the following groups.
Group 1: b upivacaine; 0.5%; 10 mL; liquid; just after creation of pneumoperitoneum and end of surgery; subdiaphragmatic and gallbladder bed; bolus administration (n = 100).
Group 2: l ignocaine; 2%; 10 mL; liquid; just after creation of pneumoperitoneum and end of surgery; subdiaphragmatic and gallbladder bed; bolus administration (n = 106).


OutcomesMortality, morbidity, and hospital stay.


NotesReasons for post-randomisation drop-outs: converted to open procedure (n = 3); additional procedure performed (n = 2); gallbladder perforation and stone spillage during procedure (n = 13).

Attempts were made to contact the authors in August 2013. Authors provided replies.

The main difference between the intervention and control are shown in bold and italics.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomization was performed by computer-generated envelopes".

Allocation concealment (selection bias)Low riskQuote: "The sequence were generated randomly and each sequence was separately printed. The printed papers were sequentially placed in opaque envelopes and numbered accordingly. A new envelope was sequentially opened and used for the patients" (author replies).

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "The patient, surgeon, and data collectors were unaware of the medication given to the patient".

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 biasLow riskQuote: "This project was funded by Grant 091026SUR from the University Research Council of the Aga Khan University".

Kucuk 2007

MethodsRandomised clinical trial.


ParticipantsCountry: Turkey.

Sample size: 60.

Post-randomisation drop-out: not stated.

Revised sample size: 60.

Females: 52 (86.7%).

Mean age: 49 years.

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 randomly assigned to 1 of the following groups.
Group 1: ropivacaine ; 1.5%; 10 mL; liquid; end of surgery; subdiaphragmatic and gallbladder bed; bolus administration (n = 20).
Group 2: ropivacaine ; 1%; 10 mL; liquid; end of surgery; subdiaphragmatic and gallbladder bed; bolus administration (n = 20).
Group 3: bupivacaine ; 0.5%; 10 mL; liquid; end of surgery; subdiaphragmatic and gallbladder bed; bolus administration (n = 20).
All 3 groups had 1 mL of 1:200,000 adrenaline (epinephrine) added.


OutcomesLocal anaesthetic-related complications and pain.


NotesAttempts were made to contact the authors in April 2008.

The main difference between the intervention and control are shown in bold and italics.


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 (performance bias and 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.

Lee 2001

MethodsRandomised clinical trial.


ParticipantsCountry: South Korea.

Sample size: 88.

Post-randomisation drop-out: 8 (9.1%).

Revised sample size: 80.

Females: 37 (46.3%).

Mean age: 47 years.

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 randomly assigned to 1 of the following groups.
Group 1: bupivacaine; 0.25%; 40 ml; liquid; just after creation of pneumoperitoneum ; subdiaphragmatic and gallbladder bed; bolus administration (n = 20).
Group 2: bupivacaine; 0.25%; 40 ml; liquid; end of surgery ; subdiaphragmatic and gallbladder bed; bolus administration (n = 19).
Group 3: same as group 1 but without wound infiltration with local anaesthetic (n = 20).
Group 4: same as group 2 but without wound infiltration with local anaesthetic (n = 21).

All 4 groups had 1:200,000 epinephrine (adrenaline).


OutcomesMortality and morbidity.


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

The main difference between the intervention and control are shown in bold and italics.


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 (performance bias and 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.

Pasqualucci 1996

MethodsRandomised clinical trial.


ParticipantsCountry: Italy.

Sample size: 60.

Post-randomisation drop-out: 6 (10.0%).

Revised sample size: 54.

Females: 31 (57.4%).

Mean age: 45 years.

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 randomly assigned to 1 of the following groups.
Group 1: bupivacaine; 0.5%; 20 mL; liquid; just after creation of pneumoperitoneum ; subdiaphragmatic and gallbladder bed; bolus administration (n = 26).
Group 2: bupivacaine; 0.5%; 20 mL; liquid; end of surgery ; subdiaphragmatic and gallbladder bed; bolus administration (n = 28).
Both groups received 1:200,000 epinephrine (adrenaline).


OutcomesLocal anaesthetic-related complications and pain.


NotesReasons for post-randomisation drop-out: not stated
Attempts were made to contact the author in April 2008. Although authors replied, no additional information was provided.

The main difference between the intervention and control are shown in bold and italics.


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 (performance bias and 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: 33.

Post-randomisation drop-out: not stated.

Revised sample size: 33.

Females: 26 (78.8%).

Mean age: 40 years.

Inclusion criteria:

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


Exclusion criteria:

  1. Allergy to study medications.


InterventionsThe participants were randomly assigned to 1 of the following groups.
Group 1: bupivacaine; 0.5%; 15 mL; liquid; just after creation of pneumoperitoneum ; subdiaphragmatic and gallbladder bed; bolus administration (n = 18).
Group 2: bupivacaine; 0.5%; 15 mL; liquid; end of surgery ; subdiaphragmatic and gallbladder bed; bolus administration (n = 15).


OutcomesLocal anaesthetic-related complications and discharge as day-surgery.


NotesAttempts were made to contact the authors in April 2008.

The main difference between the intervention and control are shown in bold and italics.


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 (performance bias and 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: Netherlands.

Sample size: 30.

Post-randomisation drop-out: not stated.

Revised sample size: 30.

Females: 24 (80.0%).

Mean age: 46 years.

Inclusion criteria:

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


InterventionsThe participants were randomly assigned to 1 of the following groups.
Group 1: b upivacaine ; 0.25%; 20 mL; liquid; end of surgery; subdiaphragmatic area; bolus administration (n = 15).
Group 2: l ignocaine ; 0.5%; 20 mL; liquid; end of surgery; subdiaphragmatic area; bolus administration (n = 15).


OutcomesLocal anaesthetic-related complications and pain.


NotesAttempts were made to contact the authors in April 2008.

The main difference between the intervention and control are shown in bold and italics.


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 (performance bias and 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.

Number randomised: 84.

Post-randomisation drop-outs: 1 (1.2%).

Revised sample size: 83.

Mean age: 52 years.

Females: 66 (79.5%).

Inclusion criteria:

  1. Adults undergoing elective laparoscopic cholecystectomy.


Exclusion criteria:

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


InterventionsParticipants were randomly assigned to 1 of the following groups.
Group 1: bupivacaine; 0.25%; 20 mL; liquid; just after creation of pneumoperitoneum; subdiaphragmatic area ; bolus administration (n = 42).
Group 2: bupivacaine; 0.25%; 20 mL; liquid; just after creation of pneumoperitoneum; gallbladder bed ; bolus administration (n = 41).


OutcomesHospital stay and pain.


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

The main difference between the intervention and control are shown in bold and italics.


Risk of bias

BiasAuthors' judgementSupport for judgement

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

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

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 (performance bias and 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)Unclear 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%) participants were excluded because of various reasons and were replaced by other participants. We consider that this will result in inadequate randomisation.

Alptekin 2010The doses in the 2 groups were different.

Bayar 1998Not a randomised clinical trial. This trial did not report treatment-related complications.

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

Pasqualucci 1994In this trial, the dose of local anaesthetic varied in addition to the timing of local anaesthetic instillation.

 
Comparison 1. Intervention versus control

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

 1 Proportion discharged as day-surgery2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Just after creation of pneumoperitoneum versus end of surgery
133Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.65, 1.50]

    1.2 Subdiaphragmatic instillation versus gallbladder bed instillation
182Risk Ratio (M-H, Fixed, 95% CI)1.56 [0.76, 3.19]

 2 Hospital stay2Mean Difference (IV, Fixed, 95% CI)Subtotals only

    2.1 Aerosol versus liquid
160Mean Difference (IV, Fixed, 95% CI)0.0 [-0.13, 0.13]

    2.2 Bupivacaine versus lignocaine
1206Mean Difference (IV, Fixed, 95% CI)0.10 [-0.16, 0.36]

 3 Pain 4 to 8 hours8Mean Difference (IV, Fixed, 95% CI)Subtotals only

    3.1 Bupivacaine versus lignocaine
130Mean Difference (IV, Fixed, 95% CI)-2.0 [-6.53, 2.53]

    3.2 Ropivacaine versus bupivacaine
160Mean Difference (IV, Fixed, 95% CI)-0.22 [-0.79, 0.35]

    3.3 Before pneumoperitoneum versus just after creation of pneumoperitoneum
160Mean Difference (IV, Fixed, 95% CI)-0.30 [-0.53, -0.07]

    3.4 Just after creation of pneumoperitoneum versus end of surgery
284Mean Difference (IV, Fixed, 95% CI)-0.60 [-1.41, 0.20]

    3.5 Just after creation of pneumoperitoneum versus after end of surgery
130Mean Difference (IV, Fixed, 95% CI)1.28 [0.08, 2.48]

    3.6 End of surgery versus after end of surgery
130Mean Difference (IV, Fixed, 95% CI)0.95 [-0.41, 2.31]

    3.7 Aerosol versus liquid
2100Mean Difference (IV, Fixed, 95% CI)-2.20 [-2.89, -1.50]

    3.8 Subdiaphragmatic versus gallbladder bed instillation
182Mean Difference (IV, Fixed, 95% CI)-0.30 [-1.01, 0.41]

 4 Pain 9 to 24 hours6Mean Difference (IV, Fixed, 95% CI)Subtotals only

    4.1 Ropivacaine versus bupivacaine
160Mean Difference (IV, Fixed, 95% CI)-0.05 [-0.25, 0.16]

    4.2 Before pneumoperitoneum versus just after creation of pneumoperitoneum
160Mean Difference (IV, Fixed, 95% CI)0.0 [-0.18, 0.18]

    4.3 Just after creation of pneumoperitoneum versus end of surgery
284Mean Difference (IV, Fixed, 95% CI)-0.28 [-0.95, 0.38]

    4.4 Just after creation of pneumoperitoneum versus after end of surgery
130Mean Difference (IV, Fixed, 95% CI)0.06 [-0.70, 0.82]

    4.5 End of surgery versus after end of surgery
130Mean Difference (IV, Fixed, 95% CI)-0.30 [-1.32, 0.72]

    4.6 Aerosol versus liquid
2100Mean Difference (IV, Fixed, 95% CI)-1.27 [-1.80, -0.74]

 
Summary of findings for the main comparison. Methods of intraperitoneal local anaesthetic instillation for laparoscopic cholecystectomy

Methods of intraperitoneal local anaesthetic instillation for laparoscopic cholecystectomy

Patient or population: people undergoing laparoscopic cholecystectomy
Settings: secondary or tertiary
Comparison: various comparisons

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

Assumed riskCorresponding risk

ControlIntervention

MortalityNot estimable (as there was no mortality in either group in this comparison)Not estimable
  • Bupivacaine versus lignocaine: 206 participants (1 trial).
  • Just after creation of pneumoperitoneum versus end of surgery: 110 participants (2 trials).
  • Just after creation of pneumoperitoneum versus after the end of surgery: 30 participants (1 trial).
  • End of surgery versus after the end of surgery: 30 participants (1 trial).
⊕⊝⊝⊝
very low1,2





MorbidityNot estimable (as there was no morbidity in either group in this comparison)Not estimable
  • Bupivacaine versus lignocaine: 206 participants (1 trial).
  • Just after creation of pneumoperitoneum versus end of surgery: 110 participants (2 trials).
  • Just after creation of pneumoperitoneum versus after the end of surgery: 30 participants (1 trial).
  • End of surgery versus after the end of surgery: 30 participants (1 trial).
⊕⊝⊝⊝
very low1,2





Proportion discharged as day-surgery

Just after creation of pneumoperitoneum versus end of surgery733 per 1000719 per 1000
(477 to 1000)
RR 0.98
(0.65 to 1.5)
33
(1 study)
⊕⊝⊝⊝
very low1,2

Subdiaphragmatic instillation versus gallbladder bed instillation220 per 1000342 per 1000
(167 to 700)
RR 1.56
(0.76 to 3.19)
82
(1 study)
⊕⊝⊝⊝
very low1,2

Hospital stay

Bupivacaine versus lignocaineThe mean hospital stay - bupivacaine versus lignocaine in the control groups was
1 day
The mean hospital stay - bupivacaine versus lignocaine in the intervention groups was
0.1 higher
(0.16 lower to 0.36 higher)
-206
(1 study)
⊕⊝⊝⊝
very low1,3

Aerosol versus liquidThe mean hospital stay - aerosol versus liquid in the control groups was
1 day
The mean hospital stay - aerosol versus liquid in the intervention groups was
0 higher
(0.13 lower to 0.13 higher)
-60
(1 study)
⊕⊝⊝⊝
very low1,3

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. 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 points).
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 (2 points).
3 Fewer than 400 participants were included in this comparison (1 point).
 
Table 1. Summary characteristics table

Study nameNumber randomisedPost-randomisation drop-outs (%)Revised sample sizeInterventionControlComparisonWound local anaesthetic infiltrationDrain useOutcomes reported


Number randomisedLocal anaestheticNumber randomisedLocal anaesthetic

Alkhamesi 200740Not stated4020Bupivacaine20BupivacaineFormYesNot statedPain

Barczynski 2006600 (0%)6030Bupivacaine30BupivacaineTimingYesNot statedIntra-operative complications and pain

Bucciero 2011603 (5%)5730Ropivacaine30RopivacaineFormNot statedNot statedLocal anaesthetic-related complications, hospital stay, and pain

Karaaslan 20066212 (19.4%)5016Bupivacaine18BupivacaineTimingNot statedNot statedLocal anaesthetic-related complications

Karaaslan 2006§Not applicable16Bupivacaine18BupivacaineTimingNot statedNot statedLocal anaesthetic-related complications










Karadeniz 2003527 (13.5%)4515Bupivacaine15BupivacaineTimingNot statedNoMortality, morbidity, and pain

Karadeniz 2003§Not applicable15Bupivacaine15BupivacaineTimingNot statedPossibly for the continuous infusion groupMortality, morbidity, and pain










Karadeniz 2003§Not applicable15Bupivacaine15BupivacaineTimingNot statedPossibly for the continuous infusion groupMortality, morbidity, and pain










Khan 201222418 (8%)206100Bupivacaine106LignocaineDifferent local anaestheticYesNot statedMortality, morbidity, and hospital stay

Kucuk 200760Not stated6020Ropivacaine10*BupivacaineDifferent local anaestheticNoNot statedLocal anaesthetic-related complications and pain

Kucuk 2007§Not applicable20Ropivacaine10*BupivacaineDifferent local anaestheticNoNot statedLocal anaesthetic related complications and pain










Lee 2001888 (9.1%)8020Bupivacaine19BupivacaineTimingYesNot statedMortality and morbidity

Lee 2001§not applicable20Bupivacaine21BupivacaineTimingNoNot statedMortality and morbidity










Pasqualucci 1996606 (10%)5426Bupivacaine28BupivacaineTimingNot statedNot statedLocal anaesthetic-related complications and pain

Paulson 200333Not stated3318Bupivacaine15BupivacaineTimingNot statedNoLocal anaesthetic-related complications and discharge as day-surgery

Rademaker 199430Not stated3015Bupivacaine15LignocaineDifferent local anaestheticNot statedNot statedLocal anaesthetic-related complications and pain

Roberts 2011841 (1.2%)8341Bupivacaine41BupivacaineLocationYesSelectively (reasons not stated)Hospital stay and pain

 § Multiple groups from the same trial.
* Sample size divided by 2 as otherwise the same participants would be included twice in the meta-analysis.