Flumazenil Dosing for Midazolam (Versed) Reversal
For reversal of midazolam-induced sedation, administer flumazenil at an initial dose of 0.2 mg IV over 15 seconds, followed by additional 0.2 mg doses at 60-second intervals as needed, up to a maximum total dose of 1 mg. 1
Adult Dosing Protocol
- Initial dose: 0.2 mg IV (2 mL) administered over 15 seconds 1
- Wait 45 seconds to assess response 1
- If desired level of consciousness is not achieved, administer additional doses of 0.2 mg at 60-second intervals 1
- Maximum total dose: 1 mg (10 mL) 1
- Most patients respond to doses between 0.6 mg to 1 mg 1
Special Considerations
- In cases of resedation (occurs in 3-9% of patients), repeated doses may be administered at 20-minute intervals 1, 2
- For repeat treatment, no more than 1 mg should be administered at any one time, and no more than 3 mg should be given in any one hour 1
- Administer through a freely running intravenous infusion into a large vein to minimize injection site pain 1
Pediatric Dosing (>1 year of age)
- Initial dose: 0.01 mg/kg (up to 0.2 mg) IV over 15 seconds 1
- Additional doses: 0.01 mg/kg (up to 0.2 mg) at 60-second intervals if needed 1
- Maximum total dose: 0.05 mg/kg or 1 mg, whichever is lower 1
Mechanism and Duration of Action
- Flumazenil competitively antagonizes benzodiazepine effects at the GABA-A receptor complex 2
- Onset of action occurs within 1-2 minutes, with peak effect at 3-4 minutes 2
- Average duration of antagonism is approximately 1 hour 2
- Since midazolam effects may persist for 80 minutes or longer, re-sedation may occur 2
Efficacy and Limitations
- Flumazenil is more effective in reversing benzodiazepine-induced sedation and amnesia than respiratory depression 2, 3
- Respiratory depression reversal occurs approximately 120 seconds after IV administration 2
- While flumazenil reverses sedative effects, it may only partially reverse respiratory parameters 3, 4
- In clinical trials, 78% of patients receiving flumazenil became completely alert 1
Cautions and Contraindications
- Use cautiously in benzodiazepine-dependent patients due to risk of inducing acute withdrawal 5
- Avoid rapid administration which may increase adverse effects 2
- Monitor for resedation, especially with larger doses of midazolam (>20 mg), longer procedures (>60 minutes), or when multiple anesthetic agents were used 1
- Be prepared to provide respiratory support regardless of flumazenil administration 6
Monitoring After Administration
- Continuously monitor oxygen saturation as respiratory depression may not be completely reversed 6, 3
- Assess level of consciousness at regular intervals for at least 2 hours after administration 6, 7
- Extended monitoring may be necessary in patients with hepatic impairment due to prolonged midazolam effects 5, 6