About 10% to 15% of the adult western population have gallstones. Between 1% and 4% become symptomatic each year. Removal of the gallbladder (cholecystectomy) is the mainstay treatment for symptomatic gallstones. More than half a million cholecystectomies are performed per year in the US alone. Laparoscopic cholecystectomy (removal of gallbladder through a keyhole, also known as port) is now the preferred method of cholecystectomy.
Laparoscopic surgery is associated with less pain than open surgery for removal of the gallbladder but postoperative pain is one the major reasons for delayed hospital discharge after laparoscopic cholecystectomy. Administration of painkillers may be an effective way of decreasing the pain after laparoscopic cholecystectomy. The different types of painkillers include those that decrease the inflammation (non-steroidal anti-inflammatory drugs or NSAIDS), which include drugs that are available over-the-counter such as paracetamol and ibuprofen and other drugs that are not available over-the-counter such as diclofenac; opium-like painkillers such as codeine and morphine, and some painkillers that are used to treat fits but also possess the ability to decrease the pain such as gabapentin and pregabalin. The last two classes of drugs are available only as prescription drugs except for low dose codeine in some countries. The benefits and harms of giving painkillers on a regular basis in people undergoing laparoscopic cholecystectomy is unknown. We sought to answer these questions by reviewing the medical literature and obtaining information from randomised clinical trials for benefits (where people are randomly allocated to one of two or more treatment groups) and comparative non-randomised studies for treatment-related harms. We compared the regular use of painkillers with no regular use of painkillers (ie, painkillers were administered as and when required) and the different type of painkillers.
We identified 25 randomised clinical trials involving 2505 people undergoing laparoscopic cholecystectomy. Most participants in the trials were low anaesthetic risk people undergoing planned laparoscopic cholecystectomy. The choice of whether the participants received the different painkillers (or not) was determined by a method similar to the toss of coin so that the treatments compared were conducted in people who were as similar as possible. The treatments in all the included trials were aimed at decreasing the pain after laparoscopic cholecystectomy before the participants reported pain. Participants were allowed to take additional painkillers as required in most of the trials.
There were no deaths in either group in three trials (183 participants) that reported deaths. The differences in the serious complications between the groups was imprecise in all the comparisons. None of the trials reported quality of life or the time taken to return to normal activity. The differences in length of hospital stay and the time taken to return to work was imprecise in all the comparisons that reported these. Pain was lower in the participants who received painkillers compared with those who received controls at 4 to 8 hours and at 9 to 24 hours as measured by the visual analogue scale (a chart that rates the amount of pain on a scale of 1 to 10). This is a modest reduction and is comparable to other methods of pain reduction such as administering local anaesthetics (drugs that numb part of the body, similar to the ones used by the dentist to prevent the people from feeling pain) during the operation. In summary, different painkillers reduce pain scores in low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. However, the decision to use these drugs has to weigh the clinically small reduction in pain against uncertain evidence of serious adverse events associated with many of these agents.
Quality of evidence
The overall quality of evidence was very low.
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.
There is evidence of very low quality that different pharmacological agents including non-steroidal anti-inflammatory drugs, opioid analgesics, and anticonvulsant analgesics reduce pain scores in people at low anaesthetic risk undergoing elective laparoscopic cholecystectomy. However, the decision to use these drugs has to weigh the clinically small reduction in pain against uncertain evidence of serious adverse events associated with many of these agents. Further randomised clinical trials of 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.
While laparoscopic cholecystectomy is generally considered less painful than open surgery, pain is one of the important reasons for delayed discharge after day-surgery and overnight stay following laparoscopic cholecystectomy. The safety and effectiveness of different pharmacological interventions such as non-steroidal anti-inflammatory drugs, opioids, and anticonvulsant analgesics in people undergoing laparoscopic cholecystectomy is unknown.
To assess the benefits and harms of different analgesics in people undergoing laparoscopic cholecystectomy.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and the World Health Organization International Clinical Trials Registry Platform portal (WHO ICTRP) to March 2013 to identify randomised clinical trials of relevance to this review.
We considered only randomised clinical trials (irrespective of language, blinding, or publication status) comparing different pharmacological interventions with no intervention or inactive controls for outcomes related to benefit in this review. We considered comparative non-randomised studies with regards to treatment-related harms. We also considered trials that compared one class of drug with another class of drug for this review.
Two review authors collected the data independently. We analysed the data with both fixed-effect and random-effects models using Review Manager 5 analysis. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI).
We included 25 trials with 2505 participants randomised to the different pharmacological agents and inactive controls. All the trials were at unclear risk of bias. Most trials included only low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. Participants were allowed to take additional analgesics as required in 24 of the trials. The pharmacological interventions in all the included trials were aimed at preventing pain after laparoscopic cholecystectomy. There were considerable differences in the pharmacological agents used and the methods of administration. The estimated effects of the intervention on the proportion of participants who were discharged as day-surgery, the length of hospital stay, or the time taken to return to work were imprecise in all the comparisons in which these outcomes were reported (very low quality evidence). There was no mortality in any of the groups in the two trials that reported mortality (183 participants, very low quality evidence). Differences in serious morbidity outcomes between the groups were imprecise across all the comparisons (very low quality evidence). None of the trials reported patient quality of life or time taken to return to normal activity. The pain at 4 to 8 hours was generally reduced by about 1 to 2 cm on the visual analogue scale of 1 to 10 cm in the comparisons involving the different pharmacological agents and inactive controls (low or very low quality evidence). The pain at 9 to 24 hours was generally reduced by about 0.5 cm (a modest reduction) on the visual analogue scale of 1 to 10 cm in the comparisons involving the different pharmacological agents and inactive controls (low or very low quality evidence).