Midazolam Administration Routes
Midazolam should be administered intravenously or intramuscularly only, as these are the FDA-approved routes with established safety and efficacy data. 1
FDA-Approved Routes of Administration
Intravenous (IV) Administration
- Primary route for procedural sedation and anesthesia induction 1
- Onset of action occurs within 1-2 minutes, with peak effect at 3-4 minutes 2
- Initial dose in healthy adults <60 years: 1 mg (or ≤0.03 mg/kg) injected slowly over 1-2 minutes 2
- Additional 1 mg doses may be given at 2-minute intervals until adequate sedation achieved 2
- Must be administered slowly over at least 2 minutes to avoid severe hypotension, particularly in neonates and when combined with opioids 1
Intramuscular (IM) Administration
- Alternative route when IV access unavailable 3
- Recommended dose for preoperative sedation: 0.07-0.1 mg/kg given IM one hour before surgery 4
- Provides reliable absorption with rapid onset 3, 5
Non-FDA Approved Routes (Off-Label Use)
While the FDA explicitly states that "the safety and efficacy of midazolam following nonintravenous and nonintramuscular routes of administration have not been established" 1, several alternative routes are used in clinical practice:
Intranasal Administration
- Used primarily for acute seizure management 6
- Demonstrated anxiolysis and sedation effects 7
- Requires dose reduction in patients with hepatic impairment or concurrent CNS depressants 6
Oral Administration
- Undergoes extensive first-pass metabolism with only 50% bioavailability 3
- Less effective than chloral hydrate for pediatric procedural sedation 7
- Dose: 0.1-0.15 mg/kg for conscious sedation 4
Buccal Administration
- Bioavailability of 74.5% with maximum plasma concentration at 30 minutes 8
- Avoids first-pass metabolism compared to oral route 8
Subcutaneous Administration
- Recommended by the European Society of Medical Oncology at lower doses (0.5-1 mg) in elderly, frail, or COPD patients 9
Critical Safety Warnings for All Routes
Respiratory Depression Risk
- Can occur up to 30 minutes after last dose administration 2, 1
- Risk dramatically increased when combined with opioids due to synergistic interaction 9, 1
- Flumazenil must be immediately available for reversal 9
Dose Reduction Requirements
- Reduce dose by ≥20% in patients >60 years or ASA physical status ≥III 2
- Reduce dose by ≥20% when co-administered with opioids 9
- Reduce dose in hepatic/renal impairment due to decreased clearance 9, 1
- Reduce dose by 30% in patients on H2-receptor antagonists 9
Intra-arterial Injection Precaution
- Avoid intra-arterial injection and extravasation - limited reports include local reactions and seizure activity 1
Continuous Infusion (ICU Setting)
- Minimize benzodiazepine use in ICU due to increased delirium risk and worse outcomes compared to propofol or dexmedetomidine 9
- If used: maintenance infusion 0.02-0.1 mg/kg/hr (1-7 mg/hr initially) 9
- For breakthrough agitation: bolus equal to 1-2 times hourly infusion rate every 5 minutes 9
- If 2 boluses needed within 1 hour, double the infusion rate 9