Perioperative Gabapentin Use and In-Hospital Adverse Clinical Events Among Older Adults After Major Surgery

Abstract

Importance: Gabapentin has been increasingly used as part of a multimodal analgesia regimen to reduce opioid use in perioperative pain management. However, the safety of perioperative gabapentin use among older patients remains uncertain.

Objective: To examine in-hospital adverse clinical events associated with perioperative gabapentin use among older patients undergoing major surgery.

Design, setting, and participants: This retrospective cohort study using data from the Premier Healthcare Database included patients aged 65 years or older who underwent major surgery at US hospitals within 7 days of hospital admission from January 1, 2009, to March 31, 2018, and did not use gabapentin before surgery. Data were analyzed from June 14, 2021, to May 23, 2022.

Exposures: Gabapentin use within 2 days after surgery.

Main outcomes and measures: The primary outcome was delirium, identified using diagnosis codes, and secondary outcomes were new antipsychotic use, pneumonia, and in-hospital death between postoperative day 3 and hospital discharge. To reduce confounding, 1:1 propensity score matching was performed. Risk ratios (RRs) and risk differences (RDs) with 95% CIs were estimated.

Results: Among 967 547 patients before propensity score matching (mean [SD] age, 76.2 [7.4] years; 59.6% female), the rate of perioperative gabapentin use was 12.3% (119 087 patients). After propensity score matching, 237 872 (118 936 pairs) gabapentin users and nonusers (mean [SD] age, 74.5 [6.7] years; 62.7% female) were identified. Compared with nonusers, gabapentin users had 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, 0.75 [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), but there was no difference in in-hospital death (362 [0.3%] vs 354 [0.2%]; RR, 1.02 [95% CI, 0.88-1.18]; RD, 0.00 [95% CI, -0.04 to 0.05] per 100 persons). Risk of delirium among gabapentin users was greater in subgroups with high comorbidity burden than in those with low comorbidity burden (combined comorbidity index <4 vs ≥4: RR, 1.20 [95% CI, 1.13-1.27] vs 1.40 [95% CI, 1.30-1.51]; RD, 0.41 [95% CI, 0.28-0.53] vs 2.66 [95% CI, 2.08-3.24] per 100 persons) and chronic kidney disease (absence vs presence: RR, 1.26 [95% CI, 1.19-1.33] vs 1.38 [95% CI, 1.27-1.49]; RD, 0.56 [95% CI, 0.42-0.69] vs 1.97 [95% CI, 1.49-2.46] per 100 persons).

Conclusion and relevance: In this cohort study, perioperative gabapentin use was associated with increased risk of delirium, new antipsychotic use, and pneumonia among older patients after major surgery. These results suggest careful risk-benefit assessment before prescribing gabapentin for perioperative pain management.

Figure 1.. Flowchart of Study Population Selection

POD indicates postoperative day.

Figure 2.. Subgroup Analysis of the Association Between Perioperative Gabapentin Use and Delirium Diagnosis and New Antipsychotic Use

Propensity score matching was performed within each subgroup. The propensity score model included demographic information, insurance type, admission characteristics, surgery type, combined comorbidity score, comorbidities, inpatient medication use and procedures before or on postoperative day 2, hospital-level characteristics, geographic region, and calendar year. Combined comorbidity index (CCI) scores range from −2 to 26, with higher scores indicating greater risk of death. All P values are for heterogeneity. Markers indicate estimates, with horizontal lines indicating 95% CIs. MME indicates morphine milligram equivalent; RD, risk difference; and RR, risk ratio.

Figure 3.. Subgroup Analysis of the Association Between Perioperative Gabapentin Use and Pneumonia and In-Hospital Death

Propensity score matching was performed within each subgroup. The propensity score model included demographic information, insurance type, admission characteristics, surgery type, combined comorbidity score, comorbidities, inpatient medication use and procedures before or on postoperative day 2, hospital-level characteristics, geographic region, and calendar year. Combined comorbidity index (CCI) scores range from −2 to 26, with higher scores indicating greater risk of death. All P values are for heterogeneity. Markers indicate estimates, with horizontal lines indicating 95% CIs. MME indicates morphine milligram equivalent; RD, risk difference; and RR, risk ratio.