The 60-Day Temperature-Dependent Degradation of Midazolam and Lorazepam in the Prehospital Environment

Abstract

Background. The choice of the optimal benzodiazepine to treat prehospital status epilepticus is unclear. Lorazepam is preferred in the emergency department, but concerns about nonrefrigerated storage limits emergency medical services (EMS) use. Midazolam is increasingly popular, but its heat stability is undocumented.Objective. This study evaluated temperature-dependent degradation of lorazepam and midazolam after 60 days in the EMS environment.Methods. Lorazepam or midazolam samples were collected prior to (n = 139) or after (n = 229) 60 days of EMS deployment during spring–summer months in 14 metropolitan areas across the United States. Medications were stored in study boxes that logged temperature every minute and were stored in EMS units per local agency policy. Mean kinetic temperature (MKT) exposure was derived for each sample. Drug concentrations were determined in a central laboratory by high-performance liquid chromatography. Concentration as a function of MKT was analyzed by linear regression.Results. Prior to deployment, measured concentrations of both benzodiazepines were 1.0 relative to labeled concentration. After 60 days, midazolam showed no degradation (mean relative concentration 1.00, 95% confidence interval [CI] 1.00–1.00) and was stable across temperature exposures (adjusted R2 –0.008). Lorazepam experienced little degradation (mean relative concentration 0.99, 95% CI 0.98–0.99), but degradation was correlated to increasing MKT (adjusted R2 0.278). The difference between the temperature dependence of degradation of midazolam and lorazepam was statistically significant (T = –5.172, p < 0.001).Conclusions. Lorazepam experiences small but statistically significant temperature-dependent degradation after 60 days in the EMS environment. Additional study is needed to evaluate whether clinically significant deterioration occurs after 60 days. Midazolam shows no degradation over this duration, even in high-heat conditions.