Gabapentin After Surgery Ups Risks in Older Adults

Perioperative gabapentin upped the risk of delirium, new antipsychotic use, and pneumonia in older adults after major surgery, a retrospective study showed.

Risk of delirium — the primary outcome of the study — was 3.4% for older patients who received gabapentin within 2 days after major surgery and 2.6% for those who did not, with a relative risk (RR) of 1.28 (95% CI 1.23-1.34), reported Dae Hyun Kim, MD, ScD, of Brigham & Women’s Hospital and Hebrew SeniorLife in Boston, and colleagues.

Risk of new antipsychotic use was 0.8% versus 0.7%, respectively (RR 1.17, 95% CI 1.07-1.29), and risk of pneumonia was 1.3% versus 1.2% (RR 1.11 95% CI 1.03-1.20), the researchers reported in JAMA Internal Medicine.

“Gabapentin is increasingly used for postoperative pain control to reduce opioid use, although previous research suggested that the analgesic effect of gabapentin is not so great,” Kim told MedPage Today.

“In our clinical experience on the geriatrics service, we have seen several patients who developed delirium after major surgery and those patients were on gabapentin,” he noted. “We conducted this study to see whether patients receiving gabapentin after surgery were more likely to develop delirium than those not receiving gabapentin.”

“Our findings suggest that routine use of gabapentin for postoperative pain control be avoided,” Kim added. “A careful risk-benefit assessment is needed before prescribing.”

Poorly controlled postoperative pain is associated with several complications, including cognitive impairment, delirium, depression, decreased mobility, and longer recovery, observed Zachary Marcum, PharmD, PhD, of the University of Washington in Seattle, and co-authors, in an accompanying editorial.

“Multimodal pain management in the perioperative period is important to minimize the short-term and long-term morbidity associated with opioid use,” the editorialists wrote.

But this study “adds to growing evidence that gabapentin as part of a multimodal pain management approach in the perioperative period is not ideal in older adults because it increases risk of harm with unclear benefits in this population,” Marcum and co-authors pointed out. “While the use of gabapentin may reduce pain and spare opioids in younger populations, the risks in older adults do not seem to outweigh the benefits.”

The findings are “a call to surgical societies and verification programs aimed to improve surgical care in older adults to specifically address the use of gabapentin in consensus statements, including a clear statement about its currently known risks and benefit,” the editorialists wrote. “More globally, this new clinical evidence invites us to reconsider multimodal pain management pathways for older adults, which will require data-driven non-opioid pain management strategies that can be translated into routine clinical practice.”

Kim and colleagues studied diagnostic codes for patients in the Premier Healthcare Database 65 years or older who underwent major surgery at U.S. hospitals within 7 days of hospital admission from January 2009 to March 2018, and did not use gabapentin before surgery.

Of 967,547 patients, 119,087 (12.3%) used perioperative gabapentin within 2 days after surgery. The researchers propensity-score matched 118,936 gabapentin users and an equal number of nonusers. Mean age was 74.5, and 62.7% were women.

Between postoperative day 3 and hospital discharge, the risk of adverse events was lower in gabapentin users before propensity score matching, but increased risks for delirium, new antipsychotic use, and pneumonia were seen for gabapentin users in the matched cohorts.

After matching, the risk differences between gabapentin users and nonusers were 0.75 per 100 persons for delirium, 0.12 per 100 persons for new antipsychotic use, and 0.13 per 100 persons for pneumonia. There was no increased risk of hospital death.

Delirium incidence in this study was lower than previously reported post-surgery incidences of 15% to 25% due to the low sensitivity and high specificity of the study’s delirium identification algorithm, Kim and co-authors noted.

“Moreover, the diagnosis codes for delirium and pneumonia did not have an exact onset date in our data sets; thus, these outcomes may have been present before surgery in some patients,” the researchers acknowledged.