Discharge Opioid Dosing and New Opioid Use Disorder After Elective Surgery in Opioid-Naive Adults: An Emulated Target Trial

Introduction: The optimal dose for an initial opioid prescription at post-surgical discharge for opioid-naive elective surgery patients varies across guidelines and is not well established in randomized clinical trials. Its impact on subsequent opioid use disorder remains unclear. Methods: We conducted a retrospective cohort study using electronic health records from an integrated U.S. academic health system (2012-2019) within a two-step target trial emulation framework. Opioid-naive adults undergoing elective surgery and discharged with opioids were included. High (> 200) versus low (≤ 200) total morphine milligram equivalents (MMEs) at discharge were compared using log-binomial regression weighted by stabilized inverse probability of treatment weights. The primary outcome was new opioid use disorder (OUD) within 2 y. Secondary outcomes included emergency department visits, mortality, persistent opioid use at 90 d, and a ≥ 40% decline in estimated glomerular filtration rate within 1 y. Sensitivity analyses tested robustness to alternative follow-up periods and high MME thresholds. Results: Among 61,422 patients (59.4% female; 24.2% aged ≥ 65 y), 47.3% received high total MME (median 300 [IQR, 225-450]) versus low total MME (median 144 [IQR, 90-150]). Within 2 y, 349 patients developed OUD. OUD incidence was higher in the high-MME group than in the low-MME group (7.7 versus 3.9 per 1000; unadjusted RR 1.96, 95% CI 1.58-2.44). After adjustment, high MME remained associated with increased OUD risk (RR 1.66, 95% CI 1.23-2.26). Sensitivity analyses demonstrated dose–response relationships. Conclusions: Higher opioid prescribing at post-surgical discharge was associated with increased risk of new OUD, supporting lower-dose prescribing (≤ 200 total MME).