The Use of Benzodiazepine Receptor Agonists and the Risk of Hospitalization for Pneumonia: A Nationwide Population-Based Nested Case-Control Study

Abstract

The relationship between the use of benzodiazepine-receptor agonists (BZRAs) and the risk of hospitalization for pneumonia remains inconclusive. This study aimed to explore the association between BZRA use and hospitalization for pneumonia in a general population. This population-based nested case-control study used Taiwan's National Health Insurance Research Database between 2002 and 2012. We included only new users who did not have any BZRA prescriptions on record in the preceding 2 years and identified 12,002 subjects who were hospitalized for pneumonia (International Classification of Diseases, Ninth Revision codes 480-486, and 507) and 12,002 disease risk score-matched control subjects. A logistic regression model was used to determine the association of BZRA use and hospitalization for pneumonia. The exposure date, dose-response relationship, and class of BZRAs were comprehensively assessed. Current BZRA exposure was associated with hospitalization for pneumonia (adjusted OR [aOR],1.86; 95%CI, 1.75-1.97). Benzodiazepine hypnotic agents (aOR, 2.42; 95%CI, 2.16-2.71) had a higher risk of pneumonia than did benzodiazepine anxiolytic agents (aOR, 1.53; 95%CI, 1.44-1.63) or nonbenzodiazepine hypnotic agents (aOR, 1.60; 95%CI, 1.46-1.76). The pneumonia risk was increased with ultrashort-acting and short- to intermediate-acting agents, a higher defined daily dose, and the number of BZRAs used. Among individual BZRAs examined, midazolam had a higher risk (aOR, 5.77; 95%CI, 4.31-7.73) of hospitalization for pneumonia than did the others. This study suggests that there is a dose-response relationship between current BZRA use and the risk of hospitalization for pneumonia. In addition, benzodiazepine hypnotic agents, especially midazolam, present a greater risk of hospitalization for pneumonia. These findings reinforce the importance of a careful analysis of the benefits vsthe risks of BZRA use.