Pregabalin can decrease acute pain and morphine consumption in laparoscopic cholecystectomy patients: A meta-analysis of randomized controlled trials

Abstract

Background: Pregabalin has been used as an adjunct for the management of acute pain in laparoscopic cholecystectomy. This meta-analysis aimed to illustrate the efficacy and safety of pregabalin for pain management following laparoscopic cholecystectomy.

Methods: In March 2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, and Google databases. Data on patients prepared for laparoscopic cholecystectomy in studies that compared pregabalin versus placebo were retrieved. The primary endpoints were the visual analog scale (VAS) score with rest or mobilization at 6, 12, and 24 hours and total morphine consumption. The secondary outcomes were the morphine-related complications (i.e., nausea, vomiting, dizziness, somnolence, headache, pruritus, urine retention, respiratory depression, and blurred vision). Continuous outcomes were expressed as the weighted mean difference (WMD) with a corresponding 95% confidence interval (CI), and discontinuous outcomes were expressed as a risk ratio (RR) with a corresponding 95% CI.

Results: Twelve clinical studies with 938 patients (gabapentin group = 536, control group = 402) were ultimately included in the meta-analysis. Pregabalin was associated with reduced pain scores with rest at 6, 12, and 24 hours, which corresponded to a reduction of 11.27 points at 6 hours, 9.46 points at 12 hours, and 3.99 points at 24 hours on a 100-point VAS. Moreover, pregabalin was associated with reduced pain scores with mobilization at 6, 12, and 24 hours, which corresponded to a reduction of 8.74 points, 5.80 points and 6.37 points at 6, 12, and 24 hours, respectively, on a 110-point VAS. Furthermore, pregabalin reduced the occurrence of nausea and vomiting. There were no significant differences in the occurrence of respiratory depression, pruritus, dizziness, blurred vision, and headache.

Conclusions: Pregabalin was efficacious in the reduction of postoperative pain, total morphine consumption, and morphine-related complications following laparoscopic cholecystectomy. In addition, a high dose of pregabalin was more effective than a low dose. The dose of pregabalin differed across the studies, and the heterogeneity was large. More studies are needed to verify the optimal dose of pregabalin in laparoscopic cholecystectomy patients.

Figure 1

Flowchart of study search and inclusion criteria.

Figure 2

(A) The risk of bias graph. (B) Risk of bias summary of included randomized controlled trials. +, no bias; −, bias; ?, bias unknown.

Figure 3

Forest plots of the included studies comparing the VAS with rest at 6 hours. VAS = visual analog scale.

Figure 4

(A) Funnel plot of VAS with rest at 6 hours. (B) Begg's test of VAS with rest at 6 hours. VAS = visual analog scale.

Figure 5

Sensitivity analysis of the VAS with rest at 6 hours. VAS = visual analog scale.

Figure 6

Forest plots of the included studies comparing the VAS with rest at 12 hours. VAS = visual analog scale.

Figure 7

Forest plots of the included studies comparing the VAS with rest at 24 hours. VAS = visual analog scale.

Figure 8

Forest plots of the included studies comparing the VAS with mobilization at 6 hours. VAS = visual analog scale.

Figure 9

Forest plots of the included studies comparing the VAS with mobilization at 12 hours. VAS = visual analog scale.

Figure 10

Forest plots of the included studies comparing the VAS with mobilization at 24 hours. VAS = visual analog scale.

Figure 11

(A) Scatter plot showing the relationship between the dose of pregabalin and the VAS with rest at 6 hours; (B) scatter plot showing the relationship between the dose of pregabalin and the VAS at 12 hours; (C) scatter plot showing the relationship between the dose of pregabalin and the VAS at 24 hours. VAS = visual analog scale.

Figure 12

Forest plots of the included studies comparing the total morphine consumption.

Figure 13

Forest plots of the included studies comparing the occurrence of, (A) nausea; (B) vomiting; (C) respiratory depression; (D) pruritus; (E) dizziness; (F) blurred vision.

Figure 14

Forest plots of the included studies comparing the occurrence of headache.