Midazolam Dosing and Administration for Sedation
Initial Dosing for Procedural Sedation
For healthy adults under 60 years undergoing endoscopic or procedural sedation, start with 1 mg IV administered over 1-2 minutes, then titrate with additional 1 mg doses at 2-minute intervals until adequate sedation is achieved, with a total dose rarely exceeding 6 mg. 1, 2
Adult Dosing Protocol
- Initial dose: 1 mg IV (or no more than 0.03 mg/kg) injected slowly over 1-2 minutes 1
- Titration: Additional 1 mg doses (or 0.02-0.03 mg/kg) may be given at 2-minute intervals 1
- Maximum total dose: Usually does not exceed 6 mg for routine endoscopic procedures 1
- Onset: 1-2 minutes with peak effect at 3-4 minutes 1
- Duration: 15-80 minutes 1
Critical Dose Reductions Required
Patients over 60 years or ASA physical status III or greater require at least 20% dose reduction, starting with no more than 1.5 mg over 2 minutes, with total doses usually not exceeding 3.5 mg 1, 2. The elderly metabolize midazolam more slowly and are at significantly higher risk for respiratory depression 1.
When co-administered with opioids (fentanyl, meperidine), reduce midazolam dose by at least 20-30% due to synergistic respiratory depression effects 1, 3, 2. This combination dramatically increases the risk of apnea and respiratory arrest 2.
Additional mandatory dose reductions 1, 3:
- Hepatic or renal impairment: Reduce by at least 20% (clearance is significantly reduced) 1, 3
- Patients on H2-receptor antagonists: Reduce dose due to 30% increased bioavailability 1, 3
- Obese patients: Clearance is reduced, requiring dose adjustment 1
Pediatric Dosing
Age-Specific IV Dosing for Procedures
Children 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 but usually does not exceed 6 mg 2, 4
Children 6-12 years: Initial dose 0.025-0.05 mg/kg IV; total dose up to 0.4 mg/kg may be needed but usually does not exceed 10 mg 2, 4
Children 12-16 years: Dose as adults, though total dose usually does not exceed 10 mg 2
Infants under 6 months: Extremely limited data; titrate with very small increments as this population is particularly vulnerable to airway obstruction and hypoventilation 2
Continuous Infusion for ICU Sedation
For intubated pediatric patients in ICU settings, initiate with a loading dose of 0.05-0.2 mg/kg IV over 2-3 minutes, followed by continuous infusion at 0.06-0.12 mg/kg/hr (1-2 mcg/kg/min) 2. However, current evidence strongly favors minimizing benzodiazepine use in ICU settings due to increased delirium risk and worse outcomes compared to propofol or dexmedetomidine 3.
Neonates: Do not use loading doses; start infusion at 0.03 mg/kg/hr (<32 weeks) or 0.06 mg/kg/hr (>32 weeks) 2. Never administer by rapid injection in neonates due to risk of severe hypotension and seizures, particularly with concomitant fentanyl 2.
Critical Safety Monitoring
Respiratory depression can occur up to 30 minutes after the last dose of midazolam, requiring extended monitoring 1, 3. Deaths from respiratory arrest have been reported, particularly when combined with opioids 1.
Mandatory Safety Requirements 2
- Continuous pulse oximetry and cardiac monitoring throughout procedure and recovery
- Immediate availability of resuscitation equipment: bag-valve-mask, intubation equipment, oxygen, suction
- Personnel trained in airway management must be present
- For pediatric deep sedation: A dedicated monitor (separate from the proceduralist) is required 2
- Flumazenil must be immediately available for reversal 3
- Minimum 2-hour observation period after last dose 1
Alternative Routes
Intramuscular: 0.07-0.08 mg/kg IM (approximately 5 mg) for preoperative sedation in healthy adults under 60, administered up to 1 hour before surgery; onset within 15 minutes, peaking at 30-60 minutes 2
Oral: For pediatric premedication, 0.25-0.5 mg/kg orally provides effective sedation with response rates of 56-98%, though higher doses increase risk of over-sedation 5
Common Pitfalls to Avoid
- Never administer as rapid IV bolus: Always inject slowly over at least 2 minutes and wait an additional 2+ minutes between doses to assess effect 1, 2
- Do not use 5 mg/mL formulation for sedation: The 1 mg/mL formulation facilitates safer, slower titration 1, 2
- Avoid in patients with chronic opioid use without dose adjustment: These patients may have altered tolerance 1
- Do not assume recovery based on alertness alone: Amnestic effects may persist after sedation wears off 1