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Meta-Analysis
. 2014 Mar 12;2014(3):CD007049.
doi: 10.1002/14651858.CD007049.pub2.

Wound infiltration with local anaesthetic agents for laparoscopic cholecystectomy

Sofronis Loizides  1 , Kurinchi Selvan Gurusamy, Myura Nagendran, Michele Rossi, Gian Piero Guerrini, Brian R Davidson
Affiliations
Meta-Analysis

Wound infiltration with local anaesthetic agents for laparoscopic cholecystectomy

Sofronis Loizides et al. Cochrane Database Syst Rev. .

Abstract

Background: While laparoscopic cholecystectomy is generally considered to be less painful than open surgery, pain is one of the important reasons for delayed discharge after day surgery resulting in overnight stay following laparoscopic cholecystectomy. The safety and effectiveness of local anaesthetic wound infiltration in people undergoing laparoscopic cholecystectomy is not known.

Objectives: To assess the benefits and harms of local anaesthetic wound infiltration in patients undergoing laparoscopic cholecystectomy and to identify the best method of local anaesthetic wound infiltration with regards to the type of local anaesthetic, dosage, and time of administration of the local anaesthetic.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded until February 2013 to identify studies of relevance to this review. We included randomised clinical trials for benefit and quasi-randomised and comparative non-randomised studies for treatment-related harms.

Selection criteria: Only randomised clinical trials (irrespective of language, blinding, or publication status) comparing local anaesthetic wound infiltration versus placebo, no intervention, or inactive control during laparoscopic cholecystectomy, trials comparing different local anaesthetic agents for local anaesthetic wound infiltration, and trials comparing the different times of local anaesthetic wound infiltration were considered for the review.

Data collection and analysis: Two review authors collected the data independently. We analysed the data with both fixed-effect and random-effects meta-analysis models using RevMan. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI).

Main results: Twenty-six trials fulfilled the inclusion criteria of the review. All the 26 trials except one trial of 30 participants were at high risk of bias. Nineteen of the trials with 1263 randomised participants provided data for this review. Ten of the 19 trials compared local anaesthetic wound infiltration versus inactive control. One of the 19 trials compared local anaesthetic wound infiltration with two inactive controls, normal saline and no intervention. Two of the 19 trials had four arms comparing local anaesthetic wound infiltration with inactive controls in the presence and absence of co-interventions to decrease pain after laparoscopic cholecystectomy. Four of the 19 trials had three or more arms that could be included for the comparison of local anaesthetic wound infiltration versus inactive control and different methods of local anaesthetic wound infiltration. The remaining two trials compared different methods of local anaesthetic wound infiltration.Most trials included only low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. Seventeen trials randomised a total of 1095 participants to local anaesthetic wound infiltration (587 participants) versus no local anaesthetic wound infiltration (508 participants). Various anaesthetic agents were used but bupivacaine was the commonest local anaesthetic used. There was no mortality in either group in the seven trials that reported mortality (0/280 (0%) in local anaesthetic infiltration group versus 0/259 (0%) in control group). The effect of local anaesthetic on the proportion of people who developed serious adverse events was imprecise and compatible with increase or no difference in serious adverse events (seven trials; 539 participants; 2/280 (0.8%) in local anaesthetic group versus 1/259 (0.4%) in control; RR 2.00; 95% CI 0.19 to 21.59; very low quality evidence). None of the serious adverse events were related to local anaesthetic wound infiltration. None of the trials reported patient quality of life. The proportion of participants who were discharged as day surgery patients was higher in the local anaesthetic infiltration group than in the no local anaesthetic infiltration group (one trial; 97 participants; 33/50 (66.0%) in the local anaesthetic group versus 20/47 (42.6%) in the control group; RR 1.55; 95% CI 1.05 to 2.28; very low quality evidence). The effect of local anaesthetic on the length of hospital stay was compatible with a decrease, increase, or no difference in the length of hospital stay between the two groups (four trials; 327 participants; MD -0.26 days; 95% CI -0.67 to 0.16; very low quality evidence). The pain scores as measured by the visual analogue scale (0 to 10 cm) were lower in the local anaesthetic infiltration group than the control group at 4 to 8 hours (13 trials; 806 participants; MD -1.33 cm on the VAS; 95% CI -1.54 to -1.12; very low quality evidence) and 9 to 24 hours (12 trials; 756 participants; MD -0.36 cm on the VAS; 95% CI -0.53 to -0.20; very low quality evidence). The effect of local anaesthetic on the time taken to return to normal activity between the two groups was imprecise and compatible with a decrease, increase, or no difference in the time taken to return to normal activity (two trials; 195 participants; MD 0.14 days; 95% CI -0.59 to 0.87; very low quality evidence). None of the trials reported on return to work.Four trials randomised a total of 149 participants to local anaesthetic wound infiltration prior to skin incision (74 participants) versus local anaesthetic wound infiltration at the end of surgery (75 participants). Two trials randomised a total of 176 participants to four different local anaesthetics (bupivacaine, levobupivacaine, ropivacaine, neosaxitoxin). Although there were differences between the groups in some outcomes the changes were not consistent. There was no evidence to support the preference of one local anaesthetic over another or to prefer administration of local anaesthetic at a specific time compared with another.

Authors' conclusions: Serious adverse events were rare in studies evaluating local anaesthetic wound infiltration (very low quality evidence). There is very low quality evidence that infiltration reduces pain in low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. However, the clinical importance of this reduction in pain is likely to be small. Further randomised clinical trials at low risk of systematic and random errors are necessary. Such trials should include important clinical outcomes such as quality of life and time to return to work in their assessment.

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Conflict of interest statement

None known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Trial sequential analysis of mortality (local anaesthetic versus no local anaesthetic) 
 The diversity‐adjusted required information size (DARIS) was calculated to 352,564 patients, based on the proportion of patients in the control group with the outcome of 0.2%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z‐curve (blue line). After accruing a total of 539 participants in seven trials, only 0.15% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, the cumulative Z‐curve do not even cross the conventional statistical boundaries (dotted red lines).
5
5
Trial sequential analysis of morbidity (local anaesthetic versus no local anaesthetic) 
 The diversity‐adjusted required information size (DARIS) was calculated to 185,703 participants, based on the proportion of patients in the control group with the outcome of 0.42%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z‐curve (blue line). After accruing a total of 539 participants in seven trials, only 0.29% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, cumulative Z‐curve do not even cross the conventional statistical boundaries (dotted red lines).
6
6
Trial sequential analysis of length of hospital stay (local anaesthetic versus no local anaesthetic) 
 The diversity‐adjusted required information size (DARIS) was 931 participants based on a minimal relevant difference (MIRD) of 1 day, a variance (VAR) of 7.40, an alpha (a) of 5%, a beta (b) of 20%, and a diversity (D2) of 79.99%. After accruing a total of 327 participants in three trials, only 35.12% of the DARIS has been reached. Accordingly, the futility area has not been drawn. The cumulative Z‐curve (blue line) has not crossed the trial sequential monitoring boundaries (red line) or the conventional statistical boundaries (dotted red line). This suggests that further trials are required to identify benefits or harms of local anaesthetic wound infiltration compared to no local anaesthetic wound infiltration with regards to the length of hospital stay.
7
7
Trial sequential analysis of pain (4 to 8 hours) (local anaesthetic versus no local anaesthetic) 
 The diversity‐adjusted required information size (DARIS) was 789 participants based on a minimal relevant difference (MIRD) of 1 cm on the visual analogue scale, a variance (VAR) of 4.68, an alpha (a) of 5%, a beta (b) of 20%, and a diversity (D2) of 81.38%. The conventional statistical boundary for benefit (dotted red line) is crossed by the cumulative Z‐curve (blue line) after the fifth trial. The trial sequential monitoring boundaries (red line) are crossed by cumulative Z‐curve after the sixth trial. The findings are consistent with local anaesthetic infiltration decreasing pain between 4 and 8 hours compared to no local anaesthetic infiltration with no risk of random errors.
8
8
Trial sequential analysis of pain (9 to 24 hours) (local anaesthetic versus no local anaesthetic) 
 The diversity‐adjusted required information size (DARIS) was 168 participants based on a minimal relevant difference (MIRD) of 1 cm on the visual analogue scale, a variance (VAR) of 2.66, an alpha (a) of 5%, a beta (b) of 20%, and a diversity (D2) of 50.3%. The conventional statistical boundary for benefit (dotted red line) is crossed by the cumulative Z‐curve (blue line) after the fifth trial. The findings are consistent with local anaesthetic infiltration decreasing pain between 9 and 24 hours compared with no local anaesthetic infiltration without the risk of random errors.
9
9
Trial sequential analysis of return to normal activity (local anaesthetic versus no local anaesthetic) 
 The diversity‐adjusted required information size (DARIS) was 562 participants based on a minimal relevant difference (MIRD) of 1 day, a variance (VAR) of 13.59, an alpha (a) of 5%, a beta (b) of 20%, and a diversity (D2) of 24.03%. After accruing a total of 195 participants in two trials, only 34.70% of the DARIS has been reached. Accordingly, the futility area has not been drawn. The cumulative Z‐curve (blue line) has not crossed the trial sequential monitoring boundaries (red lines) or the conventional statistical boundaries (dotted red lines). This suggests that further trials are required to identify benefits or harms of local anaesthetic wound infiltration compared with no local anaesthetic wound infiltration with regards to the time taken to return to normal activity.
10
10
Trial sequential analysis of pain (4 to 8 hours) (before incision versus after surgery) 
 The diversity‐adjusted required information size (DARIS) was 1344 participants based on a minimal relevant difference (MIRD) of 1 cm on the visual analogue scale, a variance (VAR) of 42.78, an alpha (a) of 5%, a beta (b) of 20%, and a diversity (D2) of 0%. After accrual of 76 participants in two trials, only 5.65% of DARIS has been reached. Accordingly, the futility area was not drawn. The trial sequential boundaries (red lines) or the conventional statistical boundaries (dotted red lines) were not crossed by the cumulative Z‐curve (blue line). This suggests that further trials are necessary to show significant benefits or harms of local anaesthetic infiltration before incision versus local anaesthetic infiltration towards the end of surgery.
1.1
1.1. Analysis
Comparison 1 Local anaesthetic versus no local anaesthetic, Outcome 1 Serious adverse events.
1.2
1.2. Analysis
Comparison 1 Local anaesthetic versus no local anaesthetic, Outcome 2 Proportion discharged as day surgery.
1.3
1.3. Analysis
Comparison 1 Local anaesthetic versus no local anaesthetic, Outcome 3 Length of hospital stay.
1.4
1.4. Analysis
Comparison 1 Local anaesthetic versus no local anaesthetic, Outcome 4 Pain 4 to 8 hours.
1.5
1.5. Analysis
Comparison 1 Local anaesthetic versus no local anaesthetic, Outcome 5 Pain 9 to 24 hours.
1.6
1.6. Analysis
Comparison 1 Local anaesthetic versus no local anaesthetic, Outcome 6 Return to normal activity.
1.7
1.7. Analysis
Comparison 1 Local anaesthetic versus no local anaesthetic, Outcome 7 Length of hospital stay (sensitivity analysis).
1.8
1.8. Analysis
Comparison 1 Local anaesthetic versus no local anaesthetic, Outcome 8 Pain 4 to 8 hours (sensitivity analysis).
1.9
1.9. Analysis
Comparison 1 Local anaesthetic versus no local anaesthetic, Outcome 9 Pain 9 to 24 hours (sensitivity analysis).
1.10
1.10. Analysis
Comparison 1 Local anaesthetic versus no local anaesthetic, Outcome 10 Return to normal activity (sensitivity analysis).
1.11
1.11. Analysis
Comparison 1 Local anaesthetic versus no local anaesthetic, Outcome 11 Pain 4 to 8 hours (stratified by local anaesthetic agent).
1.12
1.12. Analysis
Comparison 1 Local anaesthetic versus no local anaesthetic, Outcome 12 Pain 9 to 24 hours (stratified by local anaesthetic agent).
1.13
1.13. Analysis
Comparison 1 Local anaesthetic versus no local anaesthetic, Outcome 13 Pain 4 to 8 hours (stratified by time of administration).
1.14
1.14. Analysis
Comparison 1 Local anaesthetic versus no local anaesthetic, Outcome 14 Pain 9 to 24 hours (stratified by time of administration).
2.1
2.1. Analysis
Comparison 2 Comparison of different local anaesthetics, Outcome 1 Length of hospital stay.
2.2
2.2. Analysis
Comparison 2 Comparison of different local anaesthetics, Outcome 2 Pain 4 to 8 hours.
2.3
2.3. Analysis
Comparison 2 Comparison of different local anaesthetics, Outcome 3 Pain 9 to 24 hours.
2.4
2.4. Analysis
Comparison 2 Comparison of different local anaesthetics, Outcome 4 Return to normal activity.
3.1
3.1. Analysis
Comparison 3 Before incision versus end of surgery, Outcome 1 Pain 4 to 8 hours.
3.2
3.2. Analysis
Comparison 3 Before incision versus end of surgery, Outcome 2 Pain 9 to 24 hours.
3.3
3.3. Analysis
Comparison 3 Before incision versus end of surgery, Outcome 3 Return to normal activity.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD007049

References

References to studies included in this review

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