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

High daily and total doses of opioid analgesics (OAs) increase the risk for drug overdose and may be risks for all-cause hospitalization.

To examine the association of OA dose measures with future all-cause hospitalization.

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.

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.

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.

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.