Perioperative gabapentin use associated with adverse outcomes for older adults

1. In this cohort study, perioperative gabapentin for multimodal analgesia in older adults undergoing major surgery was associated with an increased risk of delirium, new antipsychotic use, and pneumonia.

Evidence Rating Level: 2 (Good)

Following surgery, multimodal nonopioid analgesia is being used more frequently, with high quality evidence showing improved pain control and decreased opioid use associated with multimodal analgesia. Gabapentin is recommended as a component of nonopioid analgesia; however, recent studies have raised concerns about marginal benefits and possible side effects including perioperative delirium. This retrospective cohort study aimed to investigate the association of perioperative gabapentin use with adverse effects in older adults undergoing major surgery. This study included adults aged 65 years or older from the Premier Healthcare Database, which covers approximately 25% of annual inpatient admissions in the US, who underwent major surgeries within 7 days of hospital admission. The primary study outcome was delirium, as per the diagnostic code, and secondary outcomes include new antipsychotic use, pneumonia, and in-hospital death. In total, 967,547 patients were eligible to initiate gabapentin for perioperative pain management, and 119,087 (12.3%) received gabapentin in the perioperative period. With respect to the primary outcome, after propensity score matching, gabapentin users had an increased risk of delirium (4040 [3.4%] vs 3148 [2.6%]; RR, 1.28 [95% CI, 1.23-1.34]; RD, 0.75 [95% CI, 0.61-0.89] per 100 persons), new antipsychotic use (944 [0.8%] vs 805 [0.7%]; RR, 1.17 [95% CI, 1.07-1.29]; RD, 0.12 [95% CI, 0.05-0.19] per 100 persons), and pneumonia (1521 [1.3%] vs 1368 [1.2%]; RR, 1.11 [95% CI, 1.03-1.20]; RD, 0.13 [95% CI, 0.04-0.22] per 100 persons) when compared to gabapentin nonusers. There was no significant difference in in-hospital deaths between gabapentin users and nonusers. With subgroup analysis, the associations of gabapentin use with delirium, new antipsychotic use, and pneumonia were consistent. A major limitation of this study was the use of diagnostic codes, which is better at identifying hyperactive delirium, typically associated with a poorer outcome than hypoactive or normoactive delirium, which may result in type II error. Overall, perioperative gabapentin use was associated with an increased risk of delirium, new antipsychotic use, and pneumonia, but not in-hospital death in adults aged 65 years or older after a major surgical procedure. Previous research has encouraged the use of multimodal analgesia following surgery, including gabapentin, but the findings of this study suggest that use of gabapentin perioperatively for pain control increases the risk of adverse events. As a cohort study, study findings are limited in their interpretation, but provide valuable preliminary findings that may hopefully cause clinicians to rethink gabapentin use, especially in older adults at high risk of delirium (i.e., previous cognitive impairment).

Click to read the study in JAMA Internal Medicine

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