The Risk of Serious Opioid-Related Harms Associated With Discharge Opioid and Non-Opioid Analgesic ‎Regimens Among Patients Hospitalized With Long-Bone Fracture

Background: Opioid prescription is often indicated for patients hospitalized with a long-bone fracture. Patients with a long bone fracture may have elevated risk of serious opioid-related events (SOREs). Concomitant prescribing of non-opioid analgesics may be a strategy to reduce opioid prescribing needs and opioid-related harms, though evidence of their benefit is limited.

Objectives: To compare the risk of SOREs among patients with low- and high-dose discharge opioid regimens with and without non-opioid analgesic pain prescriptions after long bone fracture.

Methods: We identified a retrospective cohort of opioid-naïve patients aged 18-65 admitted with long bone fracture (Merativ® MarketScan; 2013-2020). We stratified patients into categories based on analgesic prescriptions filled within first 6 weeks after discharge: no analgesic, non-opioid analgesic only, opioid analgesic only, and both an opioid and non-opioid analgesic. We further stratified the opioid analgesic groups based on low- or high (relative to the median) total opioid prescription dose. Non-opioid analgesics included gabapentins, muscle relaxants, and non-steroidal anti-inflammatory drugs. Follow-up began on day 43 after discharge until the earliest possible outcome: enrollment loss, death, 1 year follow-up, or evidence of a SORE. SOREs included new persistent opioid use (filling >90-day supply within a 180-day period), opioid use disorder (coded diagnosis or prescription fill/procedure code for methadone or buprenorphine), or opioid-related overdose. We estimated adjusted hazard ratios (aHR) for the SORE outcome of each discharge analgesic regimen while accounting for baseline demographics, hospitalization characteristics, and pain indications.

Results: Of 36,420 patients, most filled an opioid prescription alone (54.8%), or in combination with a non-opioid analgesic (24.2%). Approximately 18.4% had no analgesic prescription and 2.6% a non-opioid analgesic alone. The median total opioid dose was 675 MME among those filling opioid analgesics. The overall rate of SOREs was 5.11 per 100 person-years. In the adjusted model, compared to not filling an analgesic, the risk of SOREs was lower among those with a low total opioid dose without concomitant non-opioid analgesic use (aHR:0.47,CI:0.37-0.60) but not for those with concomitant use (aHR:0.95;CI:0.0.73-1.22). For those with a high total opioid dose, the risk of SORE was significantly higher both with (aHR:4.00;CI:3.38-4.74) and without non-opioid prescriptions (aHR:2.05;CI:1.72-2.45).

Conclusions: Filling a non-opioid analgesic in combination with an opioid was not associated with a decreased risk of SOREs after long bone fracture.