Degradation of benzodiazepines after 120 days of EMS deployment

Jason T. McMullan, Elizabeth Jones, Bruce Barnhart, Kurt R Denninghoff, Daniel W Spaite, Erin Zaleski, Bentley J Bobrow

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)368-374
Number of pages7
JournalPrehospital Emergency Care
Volume18
Issue number3
DOIs
StatePublished - 2014

Fingerprint

Benzodiazepines
Lorazepam
Midazolam
Diazepam
Temperature
Southwestern United States
Pharmaceutical Preparations
Status Epilepticus
Environmental Exposure
Hot Temperature
High Pressure Liquid Chromatography

Keywords

  • Benzodiazepines
  • Emergency medical services
  • Temperature

ASJC Scopus subject areas

  • Emergency Medicine
  • Emergency

Cite this

Degradation of benzodiazepines after 120 days of EMS deployment. / McMullan, Jason T.; Jones, Elizabeth; Barnhart, Bruce; Denninghoff, Kurt R; Spaite, Daniel W; Zaleski, Erin; Bobrow, Bentley J.

In: Prehospital Emergency Care, Vol. 18, No. 3, 2014, p. 368-374.

Research output: Contribution to journalArticle

McMullan, Jason T. ; Jones, Elizabeth ; Barnhart, Bruce ; Denninghoff, Kurt R ; Spaite, Daniel W ; Zaleski, Erin ; Bobrow, Bentley J. / Degradation of benzodiazepines after 120 days of EMS deployment. In: Prehospital Emergency Care. 2014 ; Vol. 18, No. 3. pp. 368-374.
@article{71e12b318c1e4afabda44017aef484b7,
title = "Degradation of benzodiazepines after 120 days of EMS deployment",
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",
author = "McMullan, {Jason T.} and Elizabeth Jones and Bruce Barnhart and Denninghoff, {Kurt R} and Spaite, {Daniel W} and Erin Zaleski and Bobrow, {Bentley J}",
year = "2014",
doi = "10.3109/10903127.2013.869642",
language = "English (US)",
volume = "18",
pages = "368--374",
journal = "Prehospital Emergency Care",
issn = "1090-3127",
publisher = "Informa Healthcare",
number = "3",

}

TY - JOUR

T1 - Degradation of benzodiazepines after 120 days of EMS deployment

AU - McMullan, Jason T.

AU - Jones, Elizabeth

AU - Barnhart, Bruce

AU - Denninghoff, Kurt R

AU - Spaite, Daniel W

AU - Zaleski, Erin

AU - Bobrow, Bentley J

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Benzodiazepines

KW - Emergency medical services

KW - Temperature

UR - http://www.scopus.com/inward/record.url?scp=84902972449&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902972449&partnerID=8YFLogxK

U2 - 10.3109/10903127.2013.869642

DO - 10.3109/10903127.2013.869642

M3 - Article

C2 - 24548058

AN - SCOPUS:84902972449

VL - 18

SP - 368

EP - 374

JO - Prehospital Emergency Care

JF - Prehospital Emergency Care

SN - 1090-3127

IS - 3

ER -