Impact of Perioperative Gabapentin and Pregabalin on Opioid Requirements in Mothers Undergoing C-Section: A Systematic Review and Meta-Analysis
Authors: Faysal Hani , Ogunmuko Kemi H , Daggy Joanne , Haas David 
Published: July 2024

Introduction: Patients undergoing cesarean section (CS) are commonly prescribed opioids as part of their pain control regimens. Enhanced recovery after surgery protocols are utilized to reduce the need for postoperative opioids. Gabapentin is a part of some protocols. The goal of this study is to perform a systematic review and metanalysis of current literature to examine the efficacy of perioperative gabapentin and pregabalin for pain control for patient’s undergoing CS.

Methods: We searched PubMed, MEDLINE, Embase, Scopus, EBSCO, Google Scholar, and ClinicalTrials.gov to identify studies involving perioperative use of Gabapentin and Pregabalin in patients undergoing CS. Characteristics of trials, outcomes measured, and protocols for pain relief were collected and descriptively summarized. The primary outcome was cumulative opioid requirements in the first 48 hours after surgery using mixed morphine equivalents (MME). Secondary outcomes included pain measured with activity using either a visual analog score (VAS) or numerical rating scale (NRS) converted to a 0-10 scale and participant satisfaction on a scale from 0-100. Network meta-analysis which adjusts for the correlation between multiple comparisons within multi-arm studies was implemented with the netmeta package in R software.

Results: We identified 15 individual studies after review of abstracts and full text results. Thirteen studies used gabapentin, while two used pregabalin. The final analyses included 9 RCTs, and 2 observational studies. Most studies used gabapentin as a single dose preoperatively (n=10, 77%), while 2 studies (1 RCT, 1 observational) used the drug pre- and postoperatively after CS, and 1 observational study only used drug post-operatively. All but one study reported pain scores as an outcome and 9 reported MME use. Six studies reported patient satisfaction outcomes. Two observational studies incorporated gabapentin as part of enhanced recovery protocols, both of which saw benefit. Seven of the eight trials using only preoperative gabapentin showed some benefit. Overall, the risk of bias for all studies was low.

From a random effects model for a network meta-analysis approach, treatment with 600 mg of gabapentin, compared to no treatment or placebo, was associated with a decrease in cumulative opioid requirements post-operatively in MME (-20.72, 95% [CI -33.52, -7.93]) when including all study designs. When limiting the analysis to randomized trials, treatment with 300 mg of gabapentin or pregabalin perioperatively also led to reduced opioid use (-4.30, 95% CI [-8.25, -0.36]; -6.90, 95% CI [-8.51, -5.29], respectively). Using the same model for the outcome of pain, 600 mg and 900 mg of gabapentin were associated with lower pain scores (-1.01, 95% CI [-1.98, -0.04] and -2.50, 95% CI [-4.28, -0.71], respectively). From the limited studies that report satisfaction (using gabapentin), satisfaction was higher for those in treatment groups (200 mg/both, 300 mg, and 600 mg), but only the 300 mg level of gabapentin was associated with higher satisfaction (1.35, 95% CI [0.45, 2.24]).

Conclusion/Implications: Accumulating literature shows support for perioperative use of gabapentin or pregabalin as an adjunct for post-CS pain control. Evaluations for optimal protocols, dosing, and safety information in the postpartum period are still needed.