Usual Dosing of Fentanyl and Midazolam for Anxiolysis
For anxiolysis in adults, the recommended dose is 1-2 mg (0.03 mg/kg) of midazolam IV and 25-50 μg of fentanyl IV, with additional doses titrated to effect. 1
Adult Dosing Guidelines
Midazolam (Versed)
- Initial IV dose: 1-2 mg (or 0.03 mg/kg) administered over 1-2 minutes
- Additional doses: 1 mg increments at 2-minute intervals until adequate anxiolysis is achieved
- Maximum dose: Total dose greater than 6 mg is usually not required
- Dose adjustments:
- Patients >60 years: Reduce dose by at least 20%
- ASA physical status 3 or above: Reduce dose by at least 20%
- Hepatic or renal impairment: Reduce dose by at least 20%
Fentanyl
- Initial IV dose: 50-100 μg
- Additional doses: 25 μg increments every 2-5 minutes until adequate anxiolysis is achieved
- Dose adjustments:
- Elderly patients: Reduce initial dose by 50% or more
Synergistic Effects and Precautions
When midazolam and fentanyl are used in combination, a significant synergistic interaction occurs that increases the risk of respiratory depression and hypoxemia 2. Therefore:
- When using both medications together, reduce the doses of each
- Continuous monitoring with pulse oximetry is essential
- Supplemental oxygen should be available
- Personnel skilled in airway management should be present
Monitoring Requirements
- Continuous pulse oximetry
- Regular blood pressure measurements (every 5 minutes)
- Monitoring of respiratory rate
- Assessment of sedation level
- Availability of reversal agents:
- Flumazenil for midazolam
- Naloxone for fentanyl
Potential Adverse Effects
- Respiratory depression: Most common serious adverse effect, especially when both medications are used together 2
- Hypoxemia: Occurs in up to 92% of patients receiving both medications 2
- Apnea: Occurs in up to 50% of patients receiving both medications 2
- Hypotension: May occur, especially in elderly or debilitated patients
- Upper airway obstruction: Occurs in approximately 42% of patients 3
Special Considerations
- The onset of action for both midazolam and fentanyl is 1-2 minutes when administered intravenously 1
- Peak effect of midazolam is achieved within 3-4 minutes 1
- Duration of effect: midazolam 15-80 minutes; fentanyl 30-60 minutes 1
- Respiratory depression from fentanyl may last longer than its analgesic effect 1
- Observe patients for at least 2 hours after administration of reversal agents to ensure resedation does not occur 1
Pediatric Dosing
For pediatric patients requiring anxiolysis, the median doses used in urgent care settings are:
- Fentanyl: 2.02-2.23 μg/kg intranasal
- Midazolam: 0.19-0.2 mg/kg intranasal 4
Remember that the combination of midazolam and fentanyl creates a potent drug interaction that significantly increases the risk of respiratory depression. Always have appropriate monitoring and resuscitation equipment immediately available when administering these medications.