What is the recommended dosing for intramuscular midazolam (Versed) for acute agitation?

IM Midazolam Dosing for Acute Agitation

For acute agitation in adults, administer midazolam 5 mg intramuscularly, which achieves adequate sedation in approximately 75-85% of patients within 15-20 minutes. 1, 2

Standard Adult Dosing

• The recommended IM dose is 5 mg for adults with acute agitation 3, 4, 1
• Onset of action occurs at 10-15 minutes IM, with peak effect at 15-30 minutes 3
• Duration of sedation is approximately 1-2 hours IM 3
• A second 5 mg dose may be administered if inadequate sedation after 15-20 minutes, though this was only required in 12.8% of patients in one large study 4

Pediatric Dosing (Non-Neonatal)

For children, the IM dose is 0.1-0.15 mg/kg, which provides effective sedation without prolonging emergence 5

• Ages 6 months to 5 years: Initial dose 0.05-0.1 mg/kg IV (total dose up to 0.6 mg/kg may be necessary, usually not exceeding 6 mg) 3, 5
• Ages 6-12 years: Initial dose 0.025-0.05 mg/kg IV (total dose up to 0.4 mg/kg, usually not exceeding 10 mg) 3, 5
• Ages 12-16 years: Dose as adults, though total dose usually does not exceed 10 mg 3, 5
• For IM administration specifically: 0.1-0.15 mg/kg is usually effective; doses up to 0.5 mg/kg have been used for more anxious patients, with total dose usually not exceeding 10 mg 5

Comparative Effectiveness

Midazolam 5 mg IM is superior to haloperidol (5 mg or 10 mg), ziprasidone 20 mg, and possibly olanzapine 10 mg for rapid sedation at 15 minutes 1

• At 15 minutes, midazolam achieved adequate sedation in 30% more patients than haloperidol 5 mg, 28% more than haloperidol 10 mg, 18% more than ziprasidone, and 9% more than olanzapine 1
• Combination therapy with midazolam 5 mg plus droperidol 5 mg IV is even more effective than midazolam alone, achieving adequate sedation in 85% of patients at 10 minutes 2, 6
• For methamphetamine-related agitation specifically, midazolam-droperidol combination sedated 85.3% of patients at 10 minutes versus 46.7% with droperidol alone 6

Critical Safety Considerations

Respiratory depression is the primary concern and occurs in approximately 1% of patients, typically when combined with opioids 7, 4

• Have flumazenil immediately available to reverse life-threatening respiratory depression, though note it will also reverse anticonvulsant effects and may precipitate seizures 3, 8
• Monitor oxygen saturation continuously for at least 30 minutes after administration, as respiratory depression can occur up to 30 minutes post-dose 8, 9
• Hypotension occurred in only 0.5% of patients in one large series 7
• Adverse events overall are uncommon: intubation (0.5%), hypoxemia (1%), extrapyramidal effects (0.3%) 1

Dose Adjustments

Reduce the dose by at least 20-50% in the following situations: 8

• Elderly or debilitated patients: Use 2.5 mg IM initially 3, 8
• Hepatic or renal impairment (eGFR <30): Reduce dose by at least 20% due to decreased clearance 8
• Concurrent opioid use: Reduce midazolam dose by at least 20% due to synergistic respiratory depression risk 8, 5
• Patients on H2-receptor antagonists: Reduce dose due to 30% increased bioavailability 8

Common Pitfalls to Avoid

• Do not administer as a rapid IV bolus - give over 2-3 minutes IV to avoid oversedation 5
• Paradoxical agitation occurs in approximately 6-10% of patients, particularly in younger children and those with developmental disabilities 3, 9
• Wait the full 15-20 minutes before redosing IM - midazolam takes approximately three times longer than diazepam to achieve peak effect 5
• Do not exceed 10 mg total dose in most clinical situations 3, 5
• Combining with other CNS depressants dramatically increases respiratory depression risk 8, 9

Route Comparison

IM and intranasal routes are equally effective (71% vs 75.4% adequate sedation, p=0.24), making IN administration a reasonable alternative when IV/IM access is difficult 4