Background
Between 10% and 20% of the Western population are affected by gallstones. Annually, 1% to 4% of those will develop symptoms. Removal of the gallbladder (cholecystectomy) is the main treatment of patients who develop symptomatic gallstones. Laparoscopic cholecystectomy (keyhole surgery to remove of the gallbladder) is the preferred method of surgery. Laparoscopic cholecystectomy is considered less painful than open surgery.
Previous systematic reviews have demonstrated that administration of local anaesthetic (drug that numbs part of the body) into the abdomen (tummy) is possibly effective and associated with low rates of serious adverse events. However, the evidence to support this is of very low quality. We carried out this review to update the evidence with recently published trials.
Searching for studies and Study characteristics
We searched medical literature databases to 19 January 2021. We searched reference lists of studies retrieved. We also searched other resources to identify unpublished or ongoing trials to 10 September 2021.
We identified 85 completed trials, with 76 trials (4957 patients undergoing laparoscopic cholecystectomy) contributing data to at least one of the outcomes. The majority of participants were fit and healthy and undergoing laparoscopic cholecystectomy on a planned basis. Participants were randomly assigned to receiving local anaesthetic (or not) to ensure the groups being compared were as similar as possible.
Funding
Seven trials received funding for their research from external bodies, of these three trials were assessed to be at risk of conflicts of interest. A further 17 trials declared no funding.
Key results
There were no deaths noted in the eight trials that reported deaths. Thirteen trials reported on serious side effects (for example low heart rate or blood pressure) and did not demonstrate a difference in rates of side effects between those receiving local anaesthetic and those receiving the control. None of the trials reported health-related quality of life. Twelve trials reported the length of hospital stay after surgery and demonstrated small difference in length of stay in the intraperitoneal group. Three trials reported on same day of surgery discharge and demonstrated no difference between local anaesthetic and control. Pain scores were lower in the group receiving intraperitoneal anaesthetic compared to those receiving controls at four to eight hours (57 trials; 4046 participants) and nine to 24 hours (52 trials; 3588 participants) as measured by a visual analogue score (a chart from 1cm to 10cm to indicate the level of pain). None of the trials reported return to activity or return to work.
In addition, we found two trials that are still ongoing, and one trial that was completed but with no published results. The three trials are registered on the WHO trial register.
Certainty of evidence
The majority of the trials were at high risk of bias, this means that there was a chance that the wrong conclusions were reached because of the way the study was conducted. For the majority of outcomes a high degree of concern regarding the imprecision of our results contributed to a reduction in certainty in our conclusions. This means we are uncertain about where the value of true effect lies. Overall, the strength of the evidence was assessed to be of very low or low certainty, which means the benefits or harms of local anaesthetic for laparoscopic cholecystectomy could be greater or smaller.
Conclusions
Serious adverse events were rare (very low-certainty evidence). We found moderate-certainty evidence that intraperitoneal local anaesthetic probably results in a reduction in length of hospital stay. We did not find any clear evidence that intraperitoneal local anaesthetic instillation affects the proportion of patients that are discharged the same day of surgery. We found that intra-peritoneal local anaesthetic administration reduces pain scores after laparoscopic cholecystectomy in a randomised trial setting, but this evidence was of low certainty.
Further research
Further trials are necessary. Such trials should include outcomes such as quality of life, 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.
We are very uncertain about the effect estimate of intraperitoneal local anaesthetic for laparoscopic cholecystectomy on all-cause mortality, serious adverse events, and proportion of patients discharged on the same day of surgery because the certainty of evidence was very low. Due to inadequate reporting, we cannot exclude an increase in adverse events. We found that intraperitoneal local anaesthetic probably results in a small reduction in length of stay in hospital after surgery. We found that intraperitoneal local anaesthetic may reduce pain at up to 24 hours for low-risk patients undergoing laparoscopic cholecystectomy. Future randomised clinical trials should be at low risk of systematic and random errors, should fully report mortality and side effects, and should focus on clinical outcomes such as quality of life.
Pain is one of the important reasons for delayed discharge after laparoscopic cholecystectomy. Use of intraperitoneal local anaesthetic for laparoscopic cholecystectomy may be a way of reducing pain. A previous version of this Cochrane Review found very low-certainty evidence on the benefits and harms of the intervention.
To assess the benefits and harms of intraperitoneal instillation of local anaesthetic agents in people undergoing laparoscopic cholecystectomy.
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and three other databases to 19 January 2021 together with reference checking of studies retrieved. We also searched five online clinical trials registries to identify unpublished or ongoing trials to 10 September 2021. We contacted study authors to identify additional studies.
We only considered randomised clinical trials (irrespective of language, blinding, publication status, or relevance of outcome measure) comparing local anaesthetic intraperitoneal instillation versus placebo, no intervention, or inactive control during laparoscopic cholecystectomy, for the review. We excluded non-randomised studies, and studies where the method of allocating participants to a treatment was not strictly random (e.g. date of birth, hospital record number, or alternation).
Two review authors collected the data independently. Primary outcomes included all-cause mortality, serious adverse events, and quality of life. Secondary outcomes included length of stay, pain, return to activity and work, and non-serious adverse events. The analysis included both fixed-effect and random-effects models using RevManWeb. We performed subgroup, sensitivity, and meta-regression analyses. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs). We assessed risk of bias using predefined domains, graded the certainty of the evidence using GRADE, and presented outcome results in a summary of findings table.
Eighty-five completed trials were included, of which 76 trials contributed data to one or more of the outcomes. This included a total of 4957 participants randomised to intraperitoneal local anaesthetic instillation (2803 participants) and control (2154 participants). Most trials only included participants undergoing elective laparoscopic cholecystectomy and those who were at low anaesthetic risk (ASA I and II). The most commonly used local anaesthetic agent was bupivacaine. Methods of instilling the local anaesthetic varied considerably between trials; this included location and timing of application. The control groups received 0.9% normal saline (69 trials), no intervention (six trials), or sterile water (two trials). One trial did not specify the control agent used. None of the trials provided information on follow-up beyond point of discharge from hospital. Only two trials were at low risk of bias. Seven trials received external funding, of these three were assessed to be at risk of conflicts of interest, a further 17 trials declared no funding.
We are very uncertain about the effect intraperitoneal local anaesthetic versus control on mortality; zero mortalities in either group (8 trials; 446 participants; very low-certainty evidence); serious adverse events (RR 1.07; 95% CI 0.49 to 2.34); 13 trials; 988 participants; discharge on same day of surgery (RR 1.43; 95% CI 0.64 to 3.20; 3 trials; 242 participants; very low-certainty evidence). We found that intraperitoneal local anaesthetic probably results in a small reduction in length of hospital stay (MD −0.10 days; 95% CI −0.18 to −0.01; 12 trials; 936 participants; moderate-certainty evidence). No trials reported data on health-related quality of life, return to normal activity or return to work.
Pain scores, as measured by visual analogue scale (VAS), were lower in the intraperitoneal local anaesthetic instillation group compared to the control group at both four to eight hours (MD −0.99 cm VAS; 95% CI −1.19 to −0.79; 57 trials; 4046 participants; low-certainty of evidence) and nine to 24 hours (MD −0.68 cm VAS; 95% CI −0.88 to −0.49; 52 trials; 3588 participants; low-certainty of evidence).
In addition, we found two trials that were still ongoing, and one trial that was completed but with no published results. All three trials are registered on the WHO trial register.