Perioperative gabapentin in cardiac, thoracic, or abdominal surgery: insights from a large pragmatic randomized trial

Gabapentinoids, including gabapentin and pregabalin, were originally developed as anticonvulsant medications but have been widely repurposed for perioperative pain management based on their effects on nociceptive processing. Although the exact mechanism for analgesic effects is still unclear, the perioperative rationale for gabapentinoid use rests on their potential to blunt early central sensitization, reduce opioid requirements, and mitigate opioidrelated adverse effects after surgery (1). A recent systematic review and metaanalysis reported statistically significant reductions in 24-hour postoperative pain scores and opioid consumption with gabapentin compared with placebo, as well as higher patient satisfaction (2). However, the authors noted substantial heterogeneity across studies related to dosing, timing, and surgical populations.

Despite widespread use, uncertainty persists regarding the clinical relevance of gabapentinoids in major surgery. Reductions in opioid consumption have not consistently translated into clinically meaningful improvements in pain scores, functional recovery, or vomiting, or length of stay (LOS) (2,3). Concerns have emerged regarding adverse effects such as, dizziness, sedation, and respiratory depression, particularly when combined with opioids (4-7). These competing signals have contributed to variability in guideline recommendations and review papers, and underscore the need for large trials in major surgery (8-13),

A recent large pragmatic randomized controlled trial (RCT) adds high-quality evidence to our understanding of perioperative pain management in major surgery. In the Gabapentin for Pain Management after Major Surgery (GAP) trial, Baos et al. randomized 1,196 adults undergoing cardiac, thoracic, or abdominal surgery to receive perioperative gabapentin (600 mg preoperatively followed by 300 mg twice daily for 2 days) or placebo, in addition to standard multimodal analgesia (14). The primary outcome was hospital LOS, and secondary outcomes included postoperative pain, opioid consumption, adverse health events, health-related quality of life.

The RCT found no clinically meaningful difference in LOS between the gabapentin and placebo groups. Although gabapentin was associated with modest reductions in in-hospital opioid consumption—approximately one quarter to one third in thoracic and abdominal surgery—these reductions were small in absolute terms and largely confined to the first 48 hours after surgery. Improvements in acute pain scores were minimal. Gabapentin did not improve postoperative quality of life or reduce opioid use after discharge. Patients receiving gabapentin reported a higher incidence of pain at 4 months. Importantly, the modest opioid reductions did not translate into fewer adverse events, so that the authors concluded that gabapentin should not be used routinely as part of perioperative analgesic regimens for major cardiac, thoracic, or abdominal surgery.

The GAP trial has several notable strengths that meaningfully advance the perioperative analgesia literature. First, the RCT evaluated perioperative gabapentin in major surgery, enrolling 1,196 patients across multiple centers. This large sample size provided adequate statistical power to detect clinically relevant differences in outcomes, addressing a key limitation of prior gabapentinoid studies that were often underpowered (2). In addition, the multicenter design enhances the external validity and generalizability of the findings by capturing a diverse patient population and varying perioperative care environments. This can reduce the influence of center-specific practices or biases.

Second, the GAP trial employed a pragmatic design embedded within routine clinical care, with gabapentin administered alongside standard multimodal analgesia rather than under highly controlled experimental conditions. The choice of LOS as the primary outcome is reasonable, as it captures the net effect of gabapentin on recovery, integrating analgesic efficacy, adverse effects, and complications into a single clinically meaningful endpoint. This approach moves beyond surrogate outcomes such as short-term opioid consumption and aligns closely with outcomes that matter to patients, clinicians, and health systems.

Third, the RCT included three distinct high‑risk surgical populations—cardiac, thoracic, and abdominal surgery—thereby enhancing the generalizability of its findings. These procedures are associated with postoperative pain, opioid exposure, and postoperative pulmonary complications. By stratifying the total cohort by surgical type and formally testing for interactions, the investigators were able to assess whether any potential benefit of gabapentin was procedure-specific, rather than assuming a uniform effect across heterogeneous surgeries.

Despite its many strengths, the GAP trial has important limitations that warrant careful consideration when interpreting its findings. First, although gabapentin showed statistically significant reductions in in-hospital opioid consumption, the clinical meaning of this opioid reduction is uncertain. The absolute differences in opioid use were modest, largely confined to the first 48 postoperative hours, and did not persist after discharge. Moreover, the modest opioid-sparing effect of gabapentin was not uniform across surgical populations. In the GAP trial, no reduction in opioid consumption was observed in the cardiac surgery subgroup, whereas small reductions were seen in thoracic and abdominal surgery. Importantly, these reductions did not translate into fewer opioid‑related adverse events, improved recovery, or shorter hospital stay, calling into question whether opioid consumption alone is an adequate surrogate for meaningful patient benefit.

Second, improvements in pain scores were minimal between the gabapentin and placebo groups, which is consistent with other RCTs (2). The largest differences in numeric rating scale pain scores occurred within the first 24 hours after surgery, with the gabapentin group reporting pain scores that were 0.81 points lower at rest [95% confidence interval (CI): −1.12 to −0.51] and 0.82 points lower on movement (95% CI: −1.20 to −0.44) at 1 hour postoperatively. However, such small differences may be less meaningful to patients. Moreover, gabapentin did not reduce the incidence or severity of longer-term pain and was paradoxically associated with a higher proportion of patients reporting pain at 4 months after surgery. Of note, there is no clear biological plausibility by which perioperative gabapentinoids would increase long-term postoperative pain. Thus, this finding might be explained by statistical variability or residual error and should be interpreted cautiously.

Third, while the GAP trial provides reassuring data regarding serious adverse events, it may not have been adequately powered to detect clinically important harms. Gabapentinoids have been associated with somnolence and respiratory depression, and observational studies have linked their perioperative use to increased postoperative pulmonary complications in major surgeries (4,15,16). In the GAP trial, reported rates of somnolence and respiratory depression were low and similar between groups. Of note, these outcomes relied on routine clinical reporting rather than systematic physiologic monitoring, raising the possibility of underdetection. Additionally, the trial did not assess postoperative pulmonary complications as a distinct outcome, which is relevant in major surgeries (17,18).

Finally, the dose and duration of gabapentin used in the GAP trial may not represent the optimal regimen for efficacy or safety. Higher doses or longer courses might yield greater analgesic effects but would likely increase adverse effects, while lower doses may further diminish any benefit. Moreover, The GAP trial used a fixed gabapentin regimen, consisting of 600 mg preoperatively followed by 300 mg twice daily for two postoperative days, without adjustment for age, renal function, or other patient-specific factors. As such, the trial does not resolve ongoing uncertainty regarding patient selection, dosing strategies, or whether specific subgroups might derive net benefit from perioperative gabapentinoid use.

In summary, this large pragmatic RCT demonstrates that, in patients undergoing major cardiac, thoracic, and abdominal surgery, adding gabapentin to multimodal analgesia modestly reduces early opioid use without improving pain, recovery, or hospital LOS. As multimodal analgesia continues to expand in perioperative care, these findings highlight the need to prioritize high-quality evidence over theoretical opioid-sparing rationale, and suggest that the routine use of gabapentin as an adjunctive analgesic warrants careful reconsideration.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, AME Surgical Journal. The article has undergone external peer review.

Peer Review File: Available at https://asj.amegroups.com/article/view/10.21037/asj-2026-1-0008/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://asj.amegroups.com/article/view/10.21037/asj-2026-1-0008/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Hurley RW, Cohen SP, Williams KA, et al. The analgesic effects of perioperative gabapentin on postoperative pain: a meta-analysis. Reg Anesth Pain Med 2006;31:237-47. [Crossref] [PubMed]
2. Verret M, Lauzier F, Zarychanski R, et al. Perioperative Use of Gabapentinoids for the Management of Postoperative Acute Pain: A Systematic Review and Meta-analysis. Anesthesiology 2020;133:265-79. [Crossref] [PubMed]
3. Molla YD, Alemu HT. The Role of Gabapentin in Enhanced Recovery After Surgery (ERAS) for Patients Undergoing Abdominal Procedures, A Systematic Review and Meta-Analysis. Health Sci Rep 2025;8:e70813. [Crossref] [PubMed]
4. Bykov K, Bateman BT, Franklin JM, et al. Association of Gabapentinoids With the Risk of Opioid-Related Adverse Events in Surgical Patients in the United States. JAMA Netw Open 2020;3:e2031647. [Crossref] [PubMed]
5. Ohnuma T, Raghunathan K, Ellis AR, et al. Effects of Acetaminophen, NSAIDs, Gabapentinoids, and Their Combinations on Postoperative Pulmonary Complications After Total Hip or Knee Arthroplasty. Pain Med 2020;21:2385-93. [Crossref] [PubMed]
6. Ohnuma T, Raghunathan K, Moore S, et al. Dose-Dependent Association of Gabapentinoids with Pulmonary Complications After Total Hip and Knee Arthroplasties. J Bone Joint Surg Am 2020;102:221-9. [Crossref] [PubMed]
7. Sarac BA, Schoenbrunner AR, Brower KI, et al. Analysis of Adverse Effects of Multimodal Gabapentin in Abdominal Wall Reconstruction. Plast Reconstr Surg 2022;149:733-9. [Crossref] [PubMed]
8. Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain 2016;17:131-57. [Crossref] [PubMed]
9. Lemoine A, Alber A, Joshi GP, et al. Pain management after open thoracotomy 2025: procedure-specific postoperative pain management (PROSPECT) recommendations. Anaesthesia 2026;81:541-55. [Crossref] [PubMed]
10. Bourgeois C, Oyaert L, Van de Velde M, et al. Pain management after laparoscopic cholecystectomy: A systematic review and procedure-specific postoperative pain management (PROSPECT) recommendations. Eur J Anaesthesiol 2024;41:841-55. [Crossref] [PubMed]
11. Uten T, Chesnais M, van de Velde M, et al. Pain management after open colorectal surgery: An update of the systematic review and procedure-specific postoperative pain management (PROSPECT) recommendations. Eur J Anaesthesiol 2024;41:363-6. [Crossref] [PubMed]
12. Maeßen T, Korir N, Van de Velde M, et al. Pain management after cardiac surgery via median sternotomy: A systematic review with procedure-specific postoperative pain management (PROSPECT) recommendations. Eur J Anaesthesiol 2023;40:758-68. [Crossref] [PubMed]
13. Saffari TM, Saffari S, Brower KI, et al. Management of Acute Surgical Pain in Plastic and Reconstructive Surgery. Plast Reconstr Surg 2024;153:838e-49e. [Crossref] [PubMed]
14. Baos S, Lui M, Walker-Smith T, et al. Gabapentin for Pain Management after Major Surgery: A Placebo-controlled, Double-blinded, Randomized Clinical Trial (the GAP Study). Anesthesiology 2025;143:851-61. [Crossref] [PubMed]
15. McGauvran MM, Ohnuma T, Raghunathan K, et al. Association Between Gabapentinoids and Postoperative Pulmonary Complications in Patients Undergoing Thoracic Surgery. J Cardiothorac Vasc Anesth 2022;36:2295-302. [Crossref] [PubMed]
16. Ohnuma T, Krishnamoorthy V, Ellis AR, et al. Association 'Between Gabapentinoids on the Day of Colorectal Surgery and Adverse Postoperative Respiratory Outcomes. Ann Surg 2019;270:e65-7. [Crossref] [PubMed]
17. Davies OJ, Husain T, Stephens RCM. Postoperative pulmonary complications following non-cardiothoracic surgery. BJA Education 2017;17:295-300. [Crossref]
18. Fischer MO, Brotons F, Briant AR, et al. Postoperative Pulmonary Complications After Cardiac Surgery: The VENICE International Cohort Study. J Cardiothorac Vasc Anesth 2022;36:2344-51. [Crossref] [PubMed]