Older adults are increasingly prescribed opioid analgesics and are at increased risk for serious infections. Animal and in vitro studies suggest that certain opioids impair crucial immune functions. As the clinical implications of opioid-induced immunosuppression remains unclear, we sought to determine if opioid use is associated with an increased risk of serious infections in older adults.
We conducted a self-controlled case series analysis on a retrospective cohort of adults ≥ 50 years enrolled in Tennessee Medicaid (1995-2012). We excluded patients with serious medical conditions at baseline, and performed within-person comparisons of the risk of hospitalizations for serious infections during periods of opioid use and non-use using conditional Poisson regression. Serious infections included pneumonia, sepsis, meningitis/encephalitis, cellulitis, endocarditis, pyelonephritis, or infective arthritis/osteomyelitis. Fixed confounders were accounted for by design. Time-varying confounders accounted for included age, seasonality, nursing home residency, and use of glucocorticoids, proton-pump inhibitors, and disease-modifying anti-rheumatic drugs. Secondary analyses classified opioids by new use, immunosuppressive properties, duration of action and morphine equivalent dose. Sensitivity analyses assessed the fulfillment of model assumptions.
Among 70,826 individuals and 391,117 person-years of follow-up, we identified 100,660 hospitalizations for serious infection. The adjusted incidence rate of serious infection was higher during periods of opioid use compared with non-use [incidence rate ratio (IRR): 1.47 (95% confidence interval (CI): 1.43, 1.51)]. The increased risk was highest during new use of opioids [IRR: 2.20 (95% CI: 2.08, 2.32)], immunosuppressive opioid use [IRR: 1.58 (95% CI: 1.50, 1.67)], long-acting opioid use [IRR: 1.82 (95% CI: 1.70, 1.96)] and morphine equivalent dose ≥ 60 mg per day [IRR: 1.58 (95% CI: 1.52, 1.65)] compared to non-use. Results from pre-specified sensitivity analyses were consistent with the primary analysis.
Among older adults enrolled in Tennessee Medicaid, the incidence of hospitalizations for serious infection was higher during opioid-exposed periods compared with periods of non-use.
C. M. Stein, None
E. Mitchel Jr., None
C. G. Grijalva, None
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