Abstract: 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. 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.

Plain-language summary: We identified 19 randomised clinical trials in this review. Most participants in the trials were low anaesthetic risk people undergoing planned laparoscopic cholecystectomy. A total of 1095 participants were randomised to local anaesthetic wound infiltration (587 participants) or no local anaesthetic wound infiltration (508 participants) in 17 trials. The choice of whether the participants received local anaesthetic agents (or not) was determined by a method similar to the toss of a coin so that the treatments were compared in groups of patients who were as similar as possible. There were no deaths in either group in the seven trials (539 participants) that reported deaths. The difference in serious complications between the groups was imprecise. There were no local anaesthetic-related complications in nearly 450 participants who received local anaesthetic wound infiltration in the different trials that reported complications. None of the trials reported quality of life or the time taken to return to work. The proportion of participants who were discharged as day surgery patients was higher in the local anaesthetic group than in the control group in the only trial that reported this information. The difference in the length of hospital stay or the time taken to return to normal activity was imprecise. Pain was lower in the participants who received intra-abdominal local anaesthetic administration compared with those in the control groups at four to eight hours and at nine to 24 hours, as measured by the visual analogue scale (a chart which rates the amount of pain on a scale of 1 to 10). In the comparisons of different methods of local anaesthetic infiltration, there were differences between the groups in some outcomes but the changes were not consistent. There is, therefore, no evidence to prefer any particular drug or method of administering local anaesthetics. Serious adverse events were rare in studies evaluating local anaesthetic wound infiltration. 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. Most of the trials were at high risk of bias, that is there is a possibility of arriving at wrong conclusions by overestimating the benefits or underestimating the harms of one method over another because of the way a study was conducted. The overall quality of evidence was very low. Further trials are necessary. Such trials should include outcomes such as quality of life, hospital stay, the time taken to return to normal activity, and the time taken to return to work, which are important for the person undergoing laparoscopic cholecystectomy and the people who provide funds for the treatment.