Midazolam Continuous Infusion Dosing
For ICU sedation, start with a loading dose of 0.01-0.05 mg/kg IV over several minutes, followed by a maintenance infusion of 0.02-0.1 mg/kg/hr (approximately 1-8 mg/hr), titrated to the lightest effective sedation level using validated scales. 1, 2
Critical Context: Benzodiazepines Are Not First-Line
- Non-benzodiazepine sedatives (propofol or dexmedetomidine) should be used as first-line agents for ICU sedation due to midazolam's association with increased delirium (76.6% vs 54%), longer mechanical ventilation (5.6 vs 3.7 days), increased ICU length of stay, and higher mortality. 3
- Midazolam should only be used when non-benzodiazepine sedatives are contraindicated or as rescue sedation, with recent studies showing median doses as low as 0.0026-0.00476 mg/kg/hr when used alongside propofol or dexmedetomidine. 3
Standard ICU Infusion Protocol
Loading Phase:
- Administer 0.01-0.05 mg/kg IV over several minutes (typically 2-5 mg for a 70 kg patient). 2, 3
- Alternative loading approach: 0.05-0.15 mg/kg over 1 minute for more rapid sedation. 4
Maintenance Infusion:
- Start at 0.02-0.1 mg/kg/hr (1-8 mg/hr for most adults). 5, 2
- Titrate in small increments every 15-30 minutes to achieve target sedation (RASS -1 to 0 preferred). 3
- Typical effective infusion rates range from 0.5-1.5 mcg/kg/min (0.03-0.09 mg/kg/hr). 6
Pharmacokinetic Considerations
Onset and Duration:
- Onset of action: 1-2 minutes IV with peak effect at 3-4 minutes. 5, 1
- Duration of single dose: 15-80 minutes, but accumulation occurs with continuous infusion. 5, 3
- Elimination half-life: 2-4 hours in healthy patients, but prolonged to 4.4 hours with continuous infusion. 7, 6
Accumulation Risk:
- Midazolam accumulates in skeletal muscle and fat with repeated dosing, prolonging duration of effect. 3
- Active metabolites can accumulate, particularly in renal impairment (up to 72 hours with severely reduced GFR). 5
Dose Adjustments for Special Populations
Elderly (≥60 years) or ASA III+ patients:
Hepatic or renal impairment:
- Reduce doses due to decreased clearance. 5, 1, 3
- Monitor closely for prolonged sedation from metabolite accumulation. 5
Obese patients:
Concomitant opioid use:
- Reduce midazolam dose by 30% due to synergistic respiratory depression. 1, 2
- Fentanyl 25-300 mcg/hr is commonly co-administered, necessitating lower midazolam doses. 5
Monitoring and Safety
Essential monitoring:
- Continuous oxygen saturation monitoring is mandatory. 2
- Apnea risk persists up to 30 minutes after last dose or discontinuation of infusion. 5, 2
- Rapid administration significantly increases apneic episodes. 5
Reversal agent:
- Have flumazenil 0.25-0.5 mg IV immediately available. 1, 2
- Administer in 0.1-0.3 mg incremental boluses for reversal. 5
- Re-sedation may occur since flumazenil half-life (0.7-1.3 hours) is shorter than midazolam's. 5
Discontinuation and Recovery
Awakening times:
- After short-term infusion (<24 hours): awakening in 1-2 hours. 8
- After prolonged infusion: awakening may take 3-4 hours or longer depending on cumulative dose. 6
- Target plasma concentration for adequate sedation: 150-200 ng/mL. 8, 6
Special Context: End-of-Life Care
For withdrawal of life-sustaining measures in benzodiazepine-naïve patients:
- Initial bolus: 2 mg IV over 5 minutes. 2, 3
- Maintenance: 1 mg/hr, titrated to symptom control with no dose ceiling. 2, 3
- Rescue boluses: equal to or double the hourly rate every 5 minutes as needed. 3
Common Pitfalls to Avoid
- Do not use midazolam as first-line ICU sedation when propofol or dexmedetomidine are available—this is associated with significantly worse outcomes. 3
- Avoid rapid bolus administration which dramatically increases respiratory depression risk. 5
- Do not assume rapid awakening after prolonged infusions—accumulation in fat and muscle delays recovery. 3, 6
- Monitor for propylene glycol toxicity if using lorazepam instead, though this is not an issue with midazolam itself. 5