Perioperative gabapentin use after major surgery is associated with increased delirium

Reference

Park CM, Inouye SK, Marcantonio ER, et al. Perioperative gabapentin use and in-hospital adverse clinical events among older adults after major surgery. JAMA Intern Med 2022;182(11):1117-1127.

Synopsis

Using a healthcare database of small to medium hospitals across the United States, these investigators identified patients 65 years and older who had undergone major surgery within 7 days of a hospital admission. Patients who died or were discharged by postoperative day 2, those who may have been taking gabapentin prior to surgery, and those who had other indications for or contraindications to gabapentin were excluded. The exposure of interest was perioperative gabapentin use, defined as any dose of gabapentin administered from postoperative day 0 to day 2. The primary outcome was delirium. Out of almost 1 million eligible patients, 119,087 received perioperative gabapentin. Three-quarters of them had orthopedic surgery. Compared with nonusers, the gabapentin users were younger, more likely to be female, and had a lower comorbidity index. Propensity score matching was used to create 118,936 pairs of gabapentin users and nonusers. Baseline characteristics were similar in the propensity-matched cohort. Use of gabapentin was associated with increased risks of delirium (3.4% vs 2.6%; relative risk [RR] 1.28; 1.23 - 1.34), pneumonia (1.3% vs 1.2%; RR 1.11; 1.03 - 1.20), and new antipsychotic use (0.8% vs 0.7%; RR 1.17; 1.07 - 1.29). There was no statistically significant difference between the 2 groups for in-hospital mortality. This study had limitations, primarily that the database the authors used did not contain information about pre-admission medication use (the authors used different surrogate methods to infer prior gabapentin use). Additionally, as this is an observational study, unmeasured confounders may have played a role, despite the use of propensity matching. Ultimately, you would need to treat 125 older patients with perioperative gabapentin to result in one extra case of delirium — a number needed to harm that is not terrible but should give you pause before you prescribe.