Abstract
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. To evaluate the association between perioperative coadministration of gabapentinoids and opioids with inpatient opioid-related adverse events in surgical patients. 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. Gabapentinoids (gabapentin or pregabalin) coadministered with opioids starting the day of surgery vs opioid therapy without gabapentinoids. 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. 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. 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.
Highlights
Amid the ongoing opioid epidemic in the United States, physicians are increasingly turning to multimodal pain management strategies
The primary analysis yielded the adjusted hazard ratio of 1.95, and the number needed to treat for an additional overdose to occur was 16 914 patients
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; the absolute risk of adverse events was low
Summary
Amid the ongoing opioid epidemic in the United States, physicians are increasingly turning to multimodal pain management strategies When effectively implemented, such strategies have been shown to improve the quality of care, decrease hospital stay, and reduce opioid use.[1,2,3] In the postoperative setting, the 3 most common nonopioid pharmacologic analgesics used in multimodal pain management include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and gabapentinoids.[2] While acetaminophen and NSAIDs have been coadministered with opioids for decades, the use of gabapentinoids is relatively recent. Gabapentinoids (gabapentin and pregabalin) are anticonvulsant medications, commonly used for the treatment of chronic neuropathic pain Their off-label use as adjuvant analgesics following surgery has been found to decrease postoperative pain and opioid consumption[4,5,6] and is increasing. Given the increasing use of gabapentinoids perioperatively and the lack of clinical data on their safety when coadministered with opioids for postoperative analgesia, we conducted a population-based cohort study in a large, nationwide database of US hospital admissions to assess whether coadministration of gabapentinoids with opioids is associated with increased risk of opioidrelated adverse outcomes, including opioid overdose, in surgical patients
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