Midazolam Dosing and Administration
Procedural Sedation in Adults
For procedural sedation in healthy adults under 60 years, administer 1 mg IV (or no more than 0.03 mg/kg) over 1-2 minutes, with additional 1 mg increments at 2-minute intervals until adequate sedation is achieved; total doses rarely exceed 5-6 mg for routine procedures. 1, 2
Initial Dosing by Age and Risk Status
Healthy adults <60 years: Start with 1-2.5 mg IV over at least 2 minutes, wait 2+ minutes to evaluate effect, then titrate with small increments until slurred speech or desired sedation occurs 1, 2
Adults ≥60 years or debilitated patients: Reduce initial dose by 20% or more; start with no more than 1.5 mg IV over at least 2 minutes, with subsequent doses of no more than 1 mg over 2 minutes 1, 3, 2
ASA III or higher status: Require dose reduction of 20% or more; total doses greater than 3.5 mg are not usually necessary 1, 3, 2
Critical Timing Considerations
- Onset of action: 1-2 minutes after IV administration 1
- Peak effect: 3-4 minutes after IV administration 1, 2
- Duration of effect: 15-80 minutes 1
- Wait time between doses: Minimum 2 minutes to fully evaluate sedative effect before administering additional doses 2
Combination with Opioids
When midazolam is combined with opioids, a synergistic interaction dramatically increases the risk of respiratory depression and apnea, necessitating dose reduction and heightened monitoring. 1, 3
The combination of midazolam and fentanyl produces hypoxemia in 92% of subjects and apnea in 50%, compared to no apnea with midazolam alone 4
Reduce midazolam dose by approximately 30% when used with narcotic premedication 1, 2
Patients ≥60 years receiving concomitant CNS depressants require at least 50% less midazolam 2
Apnea may occur as long as 30 minutes after the last dose of midazolam when combined with opioids 1
Anesthesia Induction
For induction of general anesthesia in unpremedicated adults <55 years, administer 0.3-0.35 mg/kg IV over 20-30 seconds, allowing 2 minutes for effect. 2
Induction Dosing by Patient Category
Unpremedicated adults <55 years: 0.3-0.35 mg/kg IV; resistant cases may require up to 0.6 mg/kg total, though this prolongs recovery 2
Unpremedicated adults ≥55 years: 0.3 mg/kg IV initially 2
Unpremedicated patients with severe systemic disease: 0.2-0.25 mg/kg IV; as little as 0.15 mg/kg may suffice in some cases 2
Premedicated adults <55 years: 0.25 mg/kg IV over 20-30 seconds 2
Premedicated adults ≥55 years (ASA I & II): 0.2 mg/kg IV 2
Premedicated patients with severe systemic disease: As little as 0.15 mg/kg may suffice 2
Continuous Infusion for ICU Sedation
For ICU sedation, administer a loading dose of 0.01-0.05 mg/kg (0.5-4 mg for typical adults) over several minutes, followed by continuous infusion at 0.02-0.10 mg/kg/hr (1-7 mg/hr), titrated to effect. 2
Titrate infusion rate up or down by 25-50% to maintain desired sedation level 2
Decrease infusion rate by 10-25% every few hours to find minimum effective rate and minimize accumulation 2
Dilute 5 mg/mL formulation to 0.5 mg/mL with 0.9% sodium chloride or 5% dextrose 2
Benzodiazepines like midazolam are among the strongest independent risk factors for developing ICU delirium and are associated with worse outcomes compared to non-benzodiazepine sedatives 1, 5
Pediatric Dosing (Non-Neonatal)
Pediatric patients generally require higher mg/kg doses than adults, with younger children (<6 years) requiring the highest doses; calculate doses based on ideal body weight in obese patients. 2
IV Procedural Sedation by Age
6 months to 5 years: Initial dose 0.05-0.1 mg/kg; total dose up to 0.6 mg/kg may be necessary (usually not exceeding 6 mg) 2
6 to 12 years: Initial dose 0.025-0.05 mg/kg; total dose up to 0.4 mg/kg may be needed (usually not exceeding 10 mg) 2
12 to 16 years: Dose as adults; total dose usually does not exceed 10 mg 2
<6 months: Limited data available; particularly vulnerable to airway obstruction and hypoventilation; titrate with small increments and monitor closely 2
IM Sedation for Pediatrics
Doses of 0.1-0.15 mg/kg IM are usually effective and do not prolong emergence 2
For more anxious patients, doses up to 0.5 mg/kg have been used 2
Total dose usually does not exceed 10 mg 2
Pediatric ICU Continuous Infusion
Loading dose: 0.05-0.2 mg/kg IV over at least 2-3 minutes 2
Maintenance infusion: 0.06-0.12 mg/kg/hr (1-2 mcg/kg/min), titrated to effect 2
Seizure Management
For acute seizure management in a 45 kg patient, administer 2.25-4.5 mg IV/IM (0.05-0.10 mg/kg) initially, with a maximum of 4 mg per dose, repeatable every 10-15 minutes as needed. 5
For IV administration, give slowly over 2-3 minutes to avoid oversedation; peak effect occurs at 3-5 minutes 5
For refractory status epilepticus, use loading dose of 0.15-0.20 mg/kg (6.75-9 mg for 45 kg patient) followed by continuous infusion 5
Continuous infusion: Start at 1 mcg/kg/min (0.06 mg/kg/hr), titrate by 1 mcg/kg/min increments every 15 minutes up to maximum 5 mcg/kg/min (0.3 mg/kg/hr) 5
Intranasal Administration
Intranasal midazolam avoids the risk of thrombophlebitis associated with IV diazepam and offers superior amnestic properties. 3
Dose reduction of 20% or more required for patients >60 years and ASA III or greater 3
When combined with opioids, synergistic interaction necessitates midazolam dose reduction 3
Intramuscular Administration
For preoperative sedation in adults <60 years, administer 0.07-0.08 mg/kg IM (approximately 5 mg) up to 1 hour before surgery, injected deep in a large muscle mass. 2, 6
Adults ≥60 years: 2-3 mg (0.02-0.05 mg/kg) IM produces adequate sedation 2
Some older patients may require only 1 mg IM if less critical sedation is needed 2
Onset within 15 minutes, peaking at 30-60 minutes 2
Special Population Considerations
Hepatic and Renal Impairment
- Midazolam clearance is reduced in patients with hepatic or renal impairment, requiring dose reduction 1, 3
Elderly and Obese Patients
Midazolam clearance is reduced in elderly and obese patients 1
Bioavailability increased by approximately 30% in patients using H2-receptor antagonists 1
Critical Safety Monitoring
Respiratory depression is the major side effect of midazolam, with deaths reported particularly when combined with opioids; continuous monitoring with pulse oximetry and immediate availability of airway management equipment is mandatory. 1, 4
78% of deaths associated with midazolam were respiratory in nature, and 57% involved concurrent opioid administration 4
Supplemental oxygen should be administered during procedural sedation 1, 4
Flumazenil (benzodiazepine antagonist) should be immediately available for reversal 1
Monitor for hypotension, especially with rapid administration 5
Serious adverse events occur a median of 2 minutes after final medication administration 1
92% of adverse events occur during the procedure, with 8% occurring after; no primary serious adverse effects occurred >25 minutes after final medication administration in pediatric patients 1
Reversal with Flumazenil
Flumazenil is more effective in reversing benzodiazepine-induced sedation and amnesia than respiratory depression 1
Half-life of flumazenil is 0.7-1.3 hours with average duration of antagonism of 1 hour 1
Re-sedation may occur since midazolam effects may persist for 80 minutes or longer 1
Caution in patients with chronic benzodiazepine use due to risk of inducing withdrawal or seizures 5, 3
Comparative Efficacy
Midazolam is 1.5-3.5 times more potent than diazepam 1
Midazolam has faster onset and shorter duration than diazepam, reducing induction time by average of 2.5 minutes per procedure 1
Fewer adverse events including respiratory depression reported with midazolam compared to diazepam 1
Oral midazolam produces less effective sedation than chloral hydrate for pediatric diagnostic procedures (4-fold increased risk of incomplete procedures) 7