Association of Gabapentinoids With the Risk of Opioid-Related Adverse Events in Surgical Patients in the United States

Abstract

Importance: The use of gabapentinoids in multimodal postoperative analgesia is increasing; however, when coadministered with opioids, these drugs may potentiate central nervous system and respiratory depression.

Objective: To evaluate the association between perioperative coadministration of gabapentinoids and opioids with inpatient opioid-related adverse events in surgical patients.

Design, setting, and participants: This cohort study used propensity score trimming, stratification, and weighting of adults admitted for a major surgery between October 2007 and December 2017 who were treated with opioids on the day of surgery and included in the Premier Research database. Data analysis was conducted from February to April 2020.

Exposure: Gabapentinoids (gabapentin or pregabalin) coadministered with opioids starting the day of surgery vs opioid therapy without gabapentinoids.

Main outcomes and measures: Primary outcome was opioid overdose. Secondary outcomes included respiratory complications, unspecified adverse effects of opioid use, and a composite of these 3 outcomes. Patients were followed up for as long as 30 days from the day of surgery until deviation from the initial treatment regimen or discharge.

Results: Gabapentinoids with opioids were administered to 892 484 of 5 547 667 eligible admissions (16.1%; mean [SD] age, 63.5 [11.8] years; 353 315 [39.6%] men). Among the 4 655 183 patients who received opioids only, the mean (SD) age was 63.7 (14.7) years, and 1 913 284 (41.1%) were men. Overall, 441 overdose events were identified, with absolute risks of 1.4 per 10 000 patients with gabapentinoid exposure and 0.7 per 10 000 patients receiving opioids only. Following propensity score trimming, the cohort included 737 383 patients exposed to gabapentinoids and 3 002 480 patients receiving opioids only. The primary analysis yielded the adjusted hazard ratio of 1.95 (95% CI, 1.49-2.55), and the number needed to treat for an additional overdose to occur was 16 914 patients (95% CI, 11 556-31 537 patients). Adjusted hazard ratios for secondary outcomes were 1.68 (95% CI, 1.59-1.78) for respiratory complications, 1.77 (95% CI, 1.61-1.93) for unspecified adverse effects of opioids, and 1.70 (95% CI, 1.62-1.79) for the composite outcome. The results were consistent across sensitivity analyses and subgroups identified by key clinical factors.

Conclusions and relevance: In this real-world cohort study of patients who underwent major surgery, concomitant use of gabapentinoids with opioids was associated with increased risk of opioid overdose and other opioid-related adverse events; however, the absolute risk of adverse events was low.

Figure 1.. Study Cohort

Exposure to medications was measured by medication charge codes.

Figure 2.. Association Between Concomitant Exposure to Gabapentinoids and Opioids and Opioid Overdose Among Subgroups

MME indicates morphine milligram equivalent. ^aOrthopedic surgeries included hip arthroplasty, knee arthroplasty, laminectomy or spinal fusion, and a surgery for hip fracture or dislocation.