National cohort study of opioid analgesic dose and risk of future hospitalization

BACKGROUND: High daily and total doses of opioid analgesics (OAs) increase the risk for drug overdose and may be risks for all-cause hospitalization. OBJECTIVE: To examine the association of OA dose measures with future all-cause hospitalization. DESIGN/PATIENTS: Cohort study of 87,688 national health maintenance organization enrollees aged 45 to 64 years with noncancer pain who filled ≥2 OA prescriptions from January 2009 to July 2012. METHODS: Outcomes were all-cause hospitalization and hospital days in 6-month intervals after the first OA was filled. In generalized linear mixed models, we examined interactions of 5 daily OA dose categories and 5 total dose categories in each 6-month interval adjusted for demographics, clinical conditions, psychotropic drugs, and current hospitalization. For high total OA doses, percentage of days covered by OA prescriptions in 6 months was examined. RESULTS: Over 3 years, an average of 12% of subjects were hospitalized yearly for a mean 6.5 (standard deviation=8.5) days. Compared with no OAs, adjusted odds of future hospitalization for high total opioid dose (>1830 mg) were 35% to 44% greater depending on daily dose category (all P<0.05), but total OA dose ≤1830 mg had weak or no association with future hospitalization regardless of daily OA dose. For high total OA doses, odds of hospitalization were 41% to 51% greater for categories of percentage of time on OAs above >50% (>3 months) versus no OAs (all P<0.05). Similar effects were observed for hospital days. CONCLUSIONS: Higher total OA doses for >3 months within a 6-month period significantly increased the risk for all-cause hospitalization and longer inpatient stays in the next 6 months.