Introduction

  • Benzodiazepines are used for numerous acute states in the emergency department, especially agitation
  • IV access is often not available for patients with 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 for acute agitation.

Clinical Detail

Lorazepam IVLorazepam IMMidazolam IVMidazolam IMMidazolam IN
DoseSedation: 0.5-2 mgSedation: 0.5-2mgSedation: 0.5-2mgSedation: 2.5-5mgSedation: 0.1mg/kg
Onset2-10 min
(longer for anticonvulsant)		20-30 min3-5 min5-15 min10 min
Duration3-6 hours for seizures, up to 8 hours for sedation6-8 hours<2 hour1-2 hour20-30 min
Bioavailability100%83-100%100%90%44%
Pros/ConsPro: Fastest onsetPro: No IV access needed
Con: erratic absorption		Con: short duration, potential for recurrence of agitation/seizurePro: No IV access neededPro: Least invasive administration
Con: small volumes (max 1mL each nare), high concentration drug needed
Concentrations available2mg/mL2mg/mL1mg/mL
5mg/mL		1mg/mL
5mg/mL		5mg/mL

Evidence

Author, yearDesign/sample sizeIntervention & ComparisonOutcome
Klein
2018		Prospective observational study
N=737		IM haloperidol 5 mg
IM ziprasidone 20 mg
IM olanzapine 10 mg
IM midazolam 5 mg
IM haloperidol 10 mg		At 15 minutes, midazolam resulted in a greater proportion of patients adequately sedated (Altered Mental Status Scale <1) compared with all other drugs
Martel,
2005		Prospective, double-blind, randomized
N=201		IM droperidol 5 mg
IM midazolam 5 mg
IM ziprasidone 20 mg		Adequate sedation was achieved at 15 minutes in patients receiving midazolam compared to 30 minutes for droperidol and ziprasidone
There was no difference in respiratory depression that clinically required treatment with supplemental oxygen
Nobay
2004		Prospective, double-blind, randomized
N=95		IM midazolam
IM haloperidol
IM lorazepam		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
Meehan,
2001		Prospective, double-blind, randomized
N=201		IM olanzapine 10 mg
IM lorazepam 2mg
Placebo		At 2 hours, olanzapine significantly greater reduction in scores on all agitation scales compared with patients treated with either placebo or lorazepam
Battaglia
1997		Prospective, double-blind, randomized
N=98		IM haloperidol 5 mg
IM lorazepam 2 mg
IM haloperidol + lorazepam		Patient who received combination treatment showed significantly greater reduction in symptoms compared to those receiving lorazepam
No significant difference from haloperidol group
Wyant
1990		Observational
N=15		IM midazolam 5 mg
IM haloperidol 10 mg
IM sodium amyta 250 mg		Both midazolam was significantly more effective than haloperidol in controlling motor agitation

Conclusions

  • Midazolam has a quick onset, reliable IM absorption, and evidence that supports its use an effective pharmacologic agent for acute agitation which could lead clinicians to argue that midazolam is more efficacious than lorazepam for acute agitation.

References

  • 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.
  • http://www.micromedexsolutions.com/
  • Nobay, et al. Acad Emerg Med. 2004;11(7):744-49.
  • Wyant M, et al. Psychopharmacol Bull 1990; 26:126 -9.
  • Meehan K, et al.. J Clin Psychopharmacol. 2001;21(4):389-397.
  • Battaglia J, et al. Am J Emerg Med. 1997;15(4):335-340.
  • Knott JC, et al. Ann Emerg Med. 2006;47(1):61-67.
  • Martel M, et al. Acad Emerg Med. 2006 Feb;13(2):233].
  • Klein LR, et al. Ann Emerg Med. 2018;72(4):374-385.
Tags:lorazepam midazolam acute agitation benzodiazepine