The American Pain Society (APA) guidelines on the management of postoperative pain suggest components of multimodal pain regimen for commonly performed surgeries (e.g., thoracotomy, open laparotomy, total hip replacement, total knee replacement, spinal fusion, cesarean section, CABG) which largely consists of opioids, non-steroidal anti-inflammatory drugs (NSAIDs) and/or acetaminophen, gabapentin or pregabalin, and intravenous (IV) ketamine. The guidelines did not provide the protocol, given that the exact components of multimodal pain regimens depend on the individuals and surgical procedures involved. [1]
The American Society of Anesthesiologists (ASA) guidelines for acute pain management in the perioperative setting strongly recommend around-the-clock acetaminophen, COX-2 selective NSAIDs, or nonselective NSAIDs for postoperative multimodal pain management. Regional blockade with local anesthetics and calcium channel alpha-2 antagonists (i.e., gabapentin and pregabalin) is suggested as part of the postoperative management as well. This guideline considers acute pain as pain that is present in a surgical patient after a procedure that may be the result of trauma from the procedure or procedure-related complications. [2]
The Enhanced Recovery After Surgery (ERAS®) Guideline for postoperative care in gynecologic/oncology surgery has identified gabapentin as an option for reducing postoperative pain, opioid consumption, and side effects. However, there is no established optimal dose or frequency of administration for gabapentin as part of an enhanced recovery after surgery (ERAS) protocol. [3]
A 2023 meta-analysis examined the efficacy of gabapentin on postoperative pain scores and opioid consumption in laparoscopic cholecystectomy. A total of 19 randomized controlled trials (RCTs) involving 2,068 patients were evaluated. Patients were 18-60 years old and underwent laparoscopic cholecystectomy. Gabapentin was given 1 or 2 hours before the surgery, with doses varying across the studies. The primary outcome was assessed based on data from 7 RCTs (n= 382 patients), finding cumulative pain scores in the first 24 hours was significantly lower in patients treated with gabapentin compared to placebo (mean difference [MD] -1.19; 95% confidence interval [CI] -1.39 to 0.99; p<0.00011; I2 = 96%). Secondary outcomes assessed included opioid consumption, time to first rescue analgesia, incidence of postoperative nausea and vomiting (PONV), incidence of sedation, and incidence of somnolence. Gabepentin reduced postoperative opioid consumption by an average of 3.51 mg (MD -3.51; 95% CI -4.67 to -2.35; p<0.00001; 9 RCTs; n= 1,096). The time to first analgesia rescue was significantly longer with gabapentin compared to placebo (210.9 minutes longer for time to first rescue; MD 210.9; 95% CI 76.90 to 344.91; p= 0.002; 5 RCTs, n= 330). The incidence of PONV was lower in gabapentin compared to placebo (35% vs. 55%; risk ratio [RR] 0.64; 95% CI 0.52 to 0.78; p<0.00001; 4 RCTs; n= 507). There was no difference in the incidence of sedation (RR 1.70; 95% CI 0.62 to 4.65; p= 0.31) or incidence of somnolence (RR 1.26; 95% CI 0.91 to 1.74; p= 0.16) between gabapentin and placebo. Lastly, no difference was seen in the incidence of respiratory depression (RR 0.43; 95% CI 0.007 to 2.84; p= 0.38). This pooled evidence indicates that gabapentin can significantly reduce postoperative pain in the first 24 hours after surgery, lower the overall opioid consumption, and reduce the incidence of PONV. There were little or no effects on the incidence of sedation, somnolence, and respiratory depression. Gabapentin may be considered as a component of multimodal management of patients undergoing laparoscopic surgery. [4]
A 2023 systematic review and meta-analysis evaluated the efficacy and safety of preoperative gabapentin in bariatric surgical patients. Four articles were included, with a total of 283 participants who completed surgery via a laparoscopic approach; all patients had a body mass index >35 kg/m2. Studies varied in the type of bariatric surgery (e.g., sleeve gastrectomy or gastric bypass), dose of gabapentin (e.g., 100 or 1,200 mg), and timing of gabapentin administration (2 hours before surgery, immediately before surgery, or during surgery). Gabapentin use significantly reduced the cumulative pain score (0-10 pain scale) within the first 24 hours post-surgery by an average of 1.04 (MD -1.04; 95% CI -1.45 to 0.63; p<0.00001; I2= 90%); however, there was notable heterogeneity that did not resolve after a subgroup and sensitivity analysis. There was a reduction in overall morphine equivalent use by 7.89 mg (MD -7.89; 95% CI 13.56 to 2.2; p= 0.006; I2= 97%). Gabapentin use was not found to impact the incidence of postoperative nausea and vomiting (RR 0.61; 95% CI 0.38 to 1.00; p= 0.05; I2= 3%), dizziness (RR 1.01; 95% CI 0.40 to 2.54; p= 0.99; I2= 0%), or headache (RR 0.76; 95% CI 0.25 to 2.30; p= 0.62; I2= 0%). Incidence of sedation could not be evaluated due to variable data. This study was limited in that it had high levels of heterogeneity, imprecision of the effect size, and potential publication bias. This study found gabapentin to be beneficial in the management of postoperative bariatric surgery; however, additional studies with homogeneity and larger sample sizes would help to support this study’s results. [5]
A 2020 review on pain management in plastic surgery suggests gabapentin can be given the night before an operation (usually 600 mg) and as a preoperative dose (300 mg) to reduce total opioid use and pain scores within the first 24 postoperative hours. Options for postoperative use include 300 mg TID in patients younger than 65 years (or BID if older than 65 years), but there is a lack of evidence on post-surgery gabapentin dosing and/or effectiveness. [6]
Another 2020 meta-analysis on managing acute postoperative pain suggests there is no clinically significant analgesic effect for the perioperative use of gabapentinoids, nor was there any effect on preventing postoperative chronic pain. This analysis included 281 RCTs (N = 24,682 participants) comparing gabapentinoids to controls for postoperative surgical pain. The studies initiated either gabapentin or pregabalin between 1 week before surgery to 12 hours postoperation. Results found that gabapentinoid administration resulted in slightly lower postoperative pain scores up to 48 hours after surgery, but not at 72 hours. The authors deemed this to not be clinically significant, as the results ranged below the minimally important difference (10 points out of 100) for each time point. Gabapentinoid use also lowered postoperative nausea and vomiting, but was associated with more dizziness and visual disturbance. The authors conclude that results do not support the routine use of pregabalin or gabapentin for the management of postoperative pain in adult patients. The results of this analysis come with high heterogeneity, owing to the diversity of surgery types, differences in dosage/timing of gabapentinoid use, and the variety of comparators (placebo, active controls, and standard of care). [7]
Based on a review article, animal data illustrate inhibition of visceral nociception and gastrointestinal (GI) function by gabapentin; however, limited clinical human data are available to support the findings in such animal studies. A study showed that despite no significant reduction in the baseline average daily pain scores between the placebo and gabapentin groups in irritable bowel syndrome (IBS) patients, gabapentin significantly increased sensory thresholds for pain (p=0.048). The authors call for larger clinical studies to be conducted to establish its benefits in alleviating visceral pain. [8]
A 2022 RCT evaluated the efficacy of gabapentin and duloxetine in patients with moderate to severe knee osteoarthritis (OA). The study included 150 patients who were randomized to receive gabapentin (300-600 mg/day), duloxetine (30-60 mg/day), or acetaminophen (1000-2000 mg/day) over three months. Both gabapentin and duloxetine significantly reduced pain severity scores, measured by visual analogue scale (VAS), compared to acetaminophen at one month and three months (p<0.001), with no significant difference between gabapentin and duloxetine. Functional status scores, measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), decreased significantly more with gabapentin and duloxetine than with acetaminophen by three months (p<0.001), with gabapentin reaching maximal effect by three months. Early improvements in pain and function were faster with duloxetine. Adverse events occurred in 9/50 (18%) of gabapentin patients (dry mouth, drowsiness, fatigue) and 8/50 of duloxetine patients, with none in the acetaminophen group. Overall, these findings indicate that gabapentin can provide significant pain relief and functional improvement in knee OA, with a delayed onset of effect relative to duloxetine. [9]