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Comparative Study
. 2014 Jul-Sep;18(3):368-74.
doi: 10.3109/10903127.2013.869642. Epub 2014 Feb 18.

Degradation of benzodiazepines after 120 days of EMS deployment

Jason T McMullan, Elizabeth Jones, Bruce Barnhart, Kurt Denninghoff, Daniel Spaite, Erin Zaleski, Robert Silbergleit; Neurological Emergencies Treatment Trials investigators
Collaborators
Comparative Study

Degradation of benzodiazepines after 120 days of EMS deployment

Jason T McMullan et al. Prehosp Emerg Care. 2014 Jul-Sep.

Abstract

Introduction: EMS treatment of status epilepticus improves outcomes, but the benzodiazepine best suited for EMS use is unclear, given potential high environmental temperature exposures.

Objective: To describe the degradation of diazepam, lorazepam, and midazolam as a function of temperature exposure and time over 120 days of storage on active EMS units.

Methods: Study boxes containing vials of diazepam, lorazepam, and midazolam were distributed to 4 active EMS units in each of 2 EMS systems in the southwestern United States during May-August 2011. The boxes logged temperature every minute and were stored in EMS units per local agency policy. Two vials of each drug were removed from each box at 30-day intervals and underwent high-performance liquid chromatography to determine drug concentration. Concentration was analyzed as mean (and 95%CI) percent of initial labeled concentration as a function of time and mean kinetic temperature (MKT).

Results: 192 samples were collected (2 samples of each drug from each of 4 units per city at 4 time-points). After 120 days, the mean relative concentration (95%CI) of diazepam was 97.0% (95.7-98.2%) and of midazolam was 99.0% (97.7-100.2%). Lorazepam experienced modest degradation by 60 days (95.6% [91.6-99.5%]) and substantial degradation at 90 days (90.3% [85.2-95.4%]) and 120 days (86.5% [80.7-92.3%]). Mean MKT was 31.6°C (95%CI 27.1-36.1). Increasing MKT was associated with greater degradation of lorazepam, but not midazolam or diazepam.

Conclusions: Midazolam and diazepam experienced minimal degradation throughout 120 days of EMS deployment in high-heat environments. Lorazepam experienced significant degradation over 120 days and appeared especially sensitive to higher MKT exposure.

Keywords: benzodiazepines; emergency medical services; temperature.

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Figures

Figure 1
Figure 1
Relative concentrations of benzodiazepines at 120 days as a function of cumulative mean kinetic temperatures (MKT).
Figure 2
Figure 2
Comparison by site of relative concentration of lorazepam and cumulative mean kinetic temperature (MKT) at 30, 60, 90, and 120 days.
See this image and copyright information in PMC

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