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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

ParameterLorazepam IVLorazepam IMMidazolam IVMidazolam IMMidazolam IN
DoseSedation: 0.5-2 mgSedation: 0.5-2 mgSedation: 0.5-2 mgSedation: 2.5-5 mgSedation: 0.1 mg/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%
Concentrations available2 mg/mL2 mg/mL1 mg/mL, 5 mg/mL1 mg/mL, 5 mg/mL5 mg/mL

Evidence

Author, yearDesign / sample sizeIntervention & ComparisonOutcome
Klein 2018Prospective observational study, N=737IM haloperidol 5 mg; IM ziprasidone 20 mg; IM olanzapine 10 mg; IM midazolam 5 mg; IM haloperidol 10 mgAt 15 minutes, midazolam resulted in a greater proportion of patients adequately sedated (Altered Mental Status Scale <1) compared with all other drugs
Martel 2005Prospective, double-blind, randomized, N=201IM droperidol 5 mg; IM midazolam 5 mg; IM ziprasidone 20 mgAdequate 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 2004Prospective, double-blind, randomized, N=95IM midazolam; IM haloperidol; IM lorazepamMean 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 2001Prospective, double-blind, randomized, N=201IM olanzapine 10 mg; IM lorazepam 2 mg; PlaceboAt 2 hours, olanzapine significantly greater reduction in scores on all agitation scales compared with patients treated with either placebo or lorazepam
Battaglia 1997Prospective, double-blind, randomized, N=98IM haloperidol 5 mg; IM lorazepam 2 mg; IM haloperidol + lorazepamPatients who received combination treatment showed significantly greater reduction in symptoms compared to those receiving lorazepam. No significant difference from haloperidol group
Wyant 1990Observational, N=15IM midazolam 5 mg; IM haloperidol 10 mg; IM sodium amytal 250 mgMidazolam 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

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Lorazepam vs Midazolam for Acute Agitation. Pharmacy Friday Pearls. jlp2.pdf