Pre-Operative Single 150 Mg Dose of Pregabalin for Postoperative Pain Management in Laparoscopic Cholecystectomy: A Systematic Review and Meta-Analysis

Technical Summary: Pre-Operative Single 150 Mg Dose of Pregabalin for Postoperative Pain Management in Laparoscopic Cholecystectomy

Problem Statement
Postoperative pain following laparoscopic cholecystectomy (LC) remains a significant clinical challenge, with up to 80% of patients experiencing moderate-to-severe acute pain within the first 24 hours. This pain profile compromises recovery, extends hospital stays, and increases healthcare costs. While opioids are a conventional component of analgesia, their utility is limited by adverse effects such as respiratory depression, nausea, and dependence risks. Consequently, multimodal analgesia incorporating non-opioid adjuncts has become the gold standard. Although pregabalin, a gabapentinoid, has shown promise in pre-emptive analgesia, the efficacy of a standardized 150 mg preoperative dose specifically for LC has not been clearly established, particularly given conflicting evidence regarding lower doses (50–75 mg) which have demonstrated limited value as stand-alone agents.

Methodology
This study is a systematic review and meta-analysis conducted in accordance with PRISMA guidelines and the Cochrane Handbook. The authors searched PubMed, Web of Science, Google Scholar, and the Cochrane Library for Randomized Controlled Trials (RCTs) published between 2008 and May 2025.

• Inclusion Criteria: The review focused on patients undergoing LC who received a single preoperative oral dose of 150 mg pregabalin compared to a placebo. Only RCTs were included.
• Data Extraction: Two reviewers independently screened articles and extracted data regarding sample sizes, demographics, timing of administration, and outcomes including Visual Analogue Scale (VAS) pain scores at 2 and 24 hours, total fentanyl and tramadol consumption, time to first rescue analgesic, and adverse events (nausea, vomiting, headache, sedation).
• Quality Assessment: Methodological quality was assessed using the Jadad scale, with scores ≥3 indicating high-quality studies.
• Statistical Analysis: A random-effects model was employed to calculate Standardized Mean Differences (SMD) for continuous variables (pain scores, opioid consumption) and Risk Ratios (RR) for dichotomous variables (adverse events). Heterogeneity was quantified using the $I^2$ statistic. Sensitivity analyses (leave-one-out) were performed to test the stability of the results. Publication bias assessment via funnel plots was omitted due to the inclusion of fewer than 10 studies.

Key Contributions and Results
The analysis synthesized data from seven high-quality RCTs involving 450 patients (225 in the pregabalin group, 225 in the placebo group).

• Primary Outcome (Pain Scores): Pooled analysis of four studies reporting 24-hour VAS scores demonstrated that preoperative 150 mg pregabalin significantly reduced pain compared to placebo (SMD = –0.80; 95% CI: –1.42 to –0.18; p = .01). However, heterogeneity was high ($I^2$ = 81%). Sensitivity analysis confirmed the robustness of these findings, with the pooled effect remaining stable even when individual studies were sequentially removed.
• Secondary Outcomes (Opioid Consumption): Pregabalin significantly reduced opioid requirements.
  • Fentanyl: Significant reduction (SMD = –1.24; p = .002), though with high heterogeneity ($I^2$ = 87%).
  • Tramadol: Significant reduction (SMD = –4.21; p = .002), with very high heterogeneity ($I^2$ = 93%).
• Safety and Adverse Events:
  • Sedation: Ramsay sedation scores showed a slight, non-significant increase in the pregabalin group (SMD = 0.36; p = .09).
  • PONV: A non-significant trend toward reduced postoperative nausea and vomiting was observed (RR = 0.74; p = .10).
  • Headache: A non-significant increase in headache risk was noted (RR = 1.56; p = .67).

Significance and Claims
The authors conclude that a single preoperative 150 mg oral dose of pregabalin is an effective and well-tolerated adjunct for perioperative analgesia in patients undergoing laparoscopic cholecystectomy. The study claims that this specific dosage meaningfully reduces postoperative pain intensity and opioid consumption (fentanyl and tramadol) while maintaining an acceptable safety profile without inducing excessive sedation or significantly increasing adverse events.

The paper positions these findings as supporting the integration of 150 mg pregabalin into multimodal analgesia protocols, particularly within Enhanced Recovery After Surgery (ERAS) frameworks. The authors argue that this dosage offers an optimal balance between bioavailability and central nervous system penetration, avoiding the diminishing returns of higher doses or the limited efficacy of lower doses. While acknowledging limitations such as high statistical heterogeneity and the small number of included studies, the authors assert that the results provide a practical strategy to optimize postoperative outcomes in minimally invasive general surgery. They call for further prospective trials to validate these findings across broader surgical populations.