Degradation of benzodiazepines after 120 days of EMS deployment

Neurological Emergencies Treatment Trials investigators

Research output: Contribution to journalArticle

9 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 - Jul 1 2014
Externally publishedYes

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. / Neurological Emergencies Treatment Trials investigators.

In: Prehospital Emergency Care, Vol. 18, No. 3, 01.07.2014, p. 368-374.

Research output: Contribution to journalArticle

Neurological Emergencies Treatment Trials investigators 2014, 'Degradation of benzodiazepines after 120 days of EMS deployment', Prehospital Emergency Care, vol. 18, no. 3, pp. 368-374. https://doi.org/10.3109/10903127.2013.869642
Neurological Emergencies Treatment Trials investigators. / Degradation of benzodiazepines after 120 days of EMS deployment. In: Prehospital Emergency Care. 2014 ; Vol. 18, No. 3. pp. 368-374.
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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.",
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author = "{Neurological Emergencies Treatment Trials investigators} and McMullan, {Jason T.} and Elizabeth Jones and Bruce Barnhart and Kurt Denninghoff and Daniel Spaite and Erin Zaleski and Robert Silbergleit and Daniel Lowenstein and William Barsan and Arthur Pancioli and Valerie Stevenson and Deneil Harney and Donna Harsh and Joy Pinkerton and Allison Kade and Nicholas Siewert and Ashley Pinawin and Catherin Ring and Phebe Brenne and Kay Vonderschmidt and Valerie Durkalski and Yuko Palesch and Catherine Dillon and Keith Pauls and Qi Wu and Wenle Zhao and Robin Conwit and Scott Janis and David Jett and Brandy Fureman and Welch, {Robert D.} and Lynnmarie Mango and Mika, {Valerie H.} and Jenny Atas and Robert Dunne and Douglas Wheaton and Phillip Levy and Velilla, {Marc Anthony} and Robert Sherwin and Brian O'Neil and Angela Groves and Marc Rosenthal and Irene Ewing and Peggy Waymeyer and {Kay Vonderschmidt}, M. and Hamilton Schwartz and Brian Stettler and William Knight and Craig Warden and Lowe, {Robert (Bob)}",
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T1 - Degradation of benzodiazepines after 120 days of EMS deployment

AU - Neurological Emergencies Treatment Trials investigators

AU - McMullan, Jason T.

AU - Jones, Elizabeth

AU - Barnhart, Bruce

AU - Denninghoff, Kurt

AU - Spaite, Daniel

AU - Zaleski, Erin

AU - Silbergleit, Robert

AU - Lowenstein, Daniel

AU - Barsan, William

AU - Pancioli, Arthur

AU - Stevenson, Valerie

AU - Harney, Deneil

AU - Harsh, Donna

AU - Pinkerton, Joy

AU - Kade, Allison

AU - Siewert, Nicholas

AU - Pinawin, Ashley

AU - Ring, Catherin

AU - Brenne, Phebe

AU - Vonderschmidt, Kay

AU - Durkalski, Valerie

AU - Palesch, Yuko

AU - Dillon, Catherine

AU - Pauls, Keith

AU - Wu, Qi

AU - Zhao, Wenle

AU - Conwit, Robin

AU - Janis, Scott

AU - Jett, David

AU - Fureman, Brandy

AU - Welch, Robert D.

AU - Mango, Lynnmarie

AU - Mika, Valerie H.

AU - Atas, Jenny

AU - Dunne, Robert

AU - Wheaton, Douglas

AU - Levy, Phillip

AU - Velilla, Marc Anthony

AU - Sherwin, Robert

AU - O'Neil, Brian

AU - Groves, Angela

AU - Rosenthal, Marc

AU - Ewing, Irene

AU - Waymeyer, Peggy

AU - Kay Vonderschmidt, M.

AU - Schwartz, Hamilton

AU - Stettler, Brian

AU - Knight, William

AU - Warden, Craig

AU - Lowe, Robert (Bob)

PY - 2014/7/1

Y1 - 2014/7/1

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

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