The 60-day temperature-dependent degradation of midazolam and Lorazepam in the prehospital environment.

TitleThe 60-day temperature-dependent degradation of midazolam and Lorazepam in the prehospital environment.
Publication TypeJournal Article
Year of Publication2013
AuthorsMcMullan JT, Pinnawin A, Jones E, Denninghoff K, Siewart N, Spaite DW, Zaleski E, Silbergleit R
Corporate AuthorsNeurological Emergencies Treatment Trials investigators
JournalPrehosp Emerg Care
Date Published2013 Jan-Mar
ISSN Number1545-0066
KeywordsAnticonvulsants, Chromatography, High Pressure Liquid, Drug Stability, Drug Storage, Emergency Medical Services, Humans, Linear Models, Lorazepam, Midazolam, Multicenter Studies as Topic, Off-Label Use, Randomized Controlled Trials as Topic, Status Epilepticus, Temperature, United States

<p><b>BACKGROUND: </b>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.</p><p><b>OBJECTIVE: </b>This study evaluated temperature-dependent degradation of lorazepam and midazolam after 60 days in the EMS environment.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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 R(2) -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 R(2) 0.278). The difference between the temperature dependence of degradation of midazolam and lorazepam was statistically significant (T = -5.172, p &lt; 0.001).</p><p><b>CONCLUSIONS: </b>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.</p>

Alternate JournalPrehosp Emerg Care
PubMed ID23148574
PubMed Central IDPMC4111795
Grant ListU01 NS056975 / NS / NINDS NIH HHS / United States
U01NS056975 / NS / NINDS NIH HHS / United States
U01NS059041 / NS / NINDS NIH HHS / United States
UL1 TR000077 / TR / NCATS NIH HHS / United States
Faculty Reference: 
Kurt Denninghoff, MD
Daniel W. Spaite, MD