- Benzodiazepines are used for numerous acute states in the emergency department, especially seizures and agitation
- IV access is often not available for patients with seizures or agitation and alternative routes must be considered; the drug of choice may change depending on the route of administration
- This handout will focus on the pharmacokinetics of the two most utilized benzodiazepines in the emergency department, lorazepam and midazolam
|Dose||Sedation: 0.5-2 mg Seizure: 4mg||Sedation: 5-2mg Seizure: 0.5 -2mg (not preferred)||Sedation: 0.5-2mg Seizure: 0.2mg/kg (not preferred)||Sedation: 5mg Seizure:10mg or 0.2mg/kg; max 10mg||Sedation: 0.1mg/kg Seizure: 0.2mg/kg; max 10mg|
|Onset||2-10 min (longer for anticonvulsant)||20-30 min||3-5 min||15 min||10 min|
|Duration||3 – 6 hours for seizures, up to 8 hours for sedation||6 – 8 hours||< 2 hour||2-6 hour||20-30 min|
|Pros /Cons||Pro: Fastest onset||Pro: No IV access needed Con: erratic absorption||Con: short duration, potential for recurrence of agitation/seizure||Pro: No IV access needed||Pro: Least invasive administration Con: small volumes (max 1mL each nare), high concentration drug needed|
|Concentrations available (at GHS)||2mg/mL||2mg/mL||1mg/mL 5mg/mL||1mg/mL 5mg/mL||5mg/mL|
Jlpruitt@gmh.edu; firstname.lastname@example.org For educational purposes only
|Overview of Evidence|
|Author, year||Design/ sample size||Intervention & Comparison||Outcome|
|Nobay 2004||Prospective, double-blind, randomized N=95||IM midazolam vs. IM haloperidol vs. IM lorazepam for agitation||Mean time to sedation (min) Lorazepam: 32.3 (±20) Midazolam: 18.3 (±14) Haloperidol: 28.3 (±25) *lorazepam dropped from study due to significantly longer time to sedation and awakening|
|Silbergleit 2012||Prospective, double-blind, randomized, non-inferiority N= 893||IM midazolam versus IV lorazepam for seizure||Seizures absent at time of arrival to ED IM midazolam: 73.4% IV lorazepam: 63.4% Statistically significant for non-inferiority Faster time to drug administration of IM midazolam was offset by the faster onset of IV lorazepam|
|Haut 2016||Systematic Review N=75 studies||Compared time to administration and time to seizure termination for multiple different benzodiazepines given by various routes||Median time to seizure termination IV: 0.3-5.7 min IM: 1.1-7.9 min IN: 2.3-7.5 min 10 studies showed faster time to administration with IM/IN administration over IV or rectal administration, 7 of which were statistically significant|
|Owusu 2019||Retrospective cohort N= 50||IV lorazepam vs. IN midazolam for seizure||Median time to seizure termination IV lorazepam (N=27): 3.3 min (IQR 1.2-62.4) IN midazolam (N=23): 3.2 min (IQR 0.1-28.5) There was no difference in the number of repeat benzodiazepine doses required or time to administration|
- The initial agent used does not have to be the definitive agent for treatment. Utilizing alternative routes in order to obtain IV access in agitation/convulsing patients is often the safest for both the patient and staff members. It may also allow therapy to be initiated faster than waiting to obtain IV access.
- A lack of literature directly comparing all routes of administration for all benzodiazepines should not limit utilization. Important differences exist in pharmacokinetics of each drug and route of administration that may be beneficial for specific populations and disease states.
- Lorazepam. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Accessed 2020, February 24. http://www.micromedexsolutions.com/
- Midazolam. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Accessed 2020, February 24.
- Lorazepam. Lexicomp [online database].Hudson, OH. Woltes Kluwer Clinical Drug Information, Inc. Accessed 2020, February 24. http://www.online.lexi.com 4. Midazolam. Lexicomp [online database].Hudson, OH. Woltes Kluwer Clinical Drug Information, Inc. Accessed 2020, February 24. http://www.online.lexi.com
- Nobay, et al. Acad Emerg Med. 2004;11(7):744-49.
- Haut, et al. Epilepsy & Behavior. 2016;63:109-17.
- Silbergleit, et al. NEJM. 2012;366(7):591-600.
- Owusu, et al. Epilepsy & Behavior. 2019;98:161-67.