Note: Due to the short duration of sedation of nonbenzodiazepine hypnotics, a continuous infusion is probably unnecessary in patients intoxicated with these agents (Gunja 2013). Resedation: IV: In the event of resedation, repeat 0.5 to 1 mg doses (administered at 0.1 mg/minute) may be administered at 20-minute intervals if needed maximum cumulative resedation dose: 3 mg in 1 hour (Howland 2019 manufacturer's labeling). If a patient has not responded 5 minutes after a cumulative dose of 5 mg, the major cause of sedation may be due to exposure to additional CNS depressants (eg, opioids). Note: Based on use in benzodiazepine overdose, patients with a partial response to a cumulative dose of 3 mg may rarely require additional titration up to a total dose of 5 mg (although doses >3 mg do not reliably produce additional effects). IV: Initial: 0.2 mg over 2 minutes if the desired level of consciousness is not obtained 30 seconds after the dose, 0.3 mg can be administered over 3 minutes if the desired level of consciousness is still not obtained, 0.5 mg can be administered over 5 minutes and repeated at 1-minute intervals usual cumulative dosage range: 1 to 3 mg usual maximum cumulative dose: 3 mg (Howland 2019 manufacturer's labeling). Limited data available dose based on use in benzodiazepine overdose. Nonbenzodiazepine hypnotic overdose or gabapentin overdose, treatment (off-label use): Note: May consider during the treatment of patients who are experiencing toxicity secondary to a nonbenzodiazepine hypnotic agent (eg, eszopiclone, zaleplon, zolpidem, zopiclone) or gabapentin (Butler 2003 Cienki 2005 Höjer 2002 Lheureux 1990 Patat 1994). Note: After an overdose with high doses of benzodiazepines, the duration of a single dose of flumazenil is not expected to exceed 1 hour if clinically necessary, the period of wakefulness may be prolonged with repeated low IV doses of flumazenil, or by an infusion of 0.1 to 1 mg/hour (off label) (Höjer 1991 Maxa 2003 Weinbroum 1996). Resedation: IV: In the event of resedation, repeat 0.5 to 1 mg doses (administered at 0.1 mg/minute) may be administered at 20-minute intervals as needed maximum cumulative resedation dose: 3 mg in 1 hour (Howland 2019 manufacturer's labeling). If a patient has not responded 5 minutes after a cumulative dose of 5 mg, benzodiazepines are likely not the major cause of sedation sedation may be due to exposure to additional CNS depressants (eg, opioids). Note: Patients with a partial response to a cumulative dose of 3 mg may rarely require additional titration up to a total dose of 5 mg (although doses >3 mg do not reliably produce additional effects). IV: Initial: 0.2 mg over 2 minutes if the desired level of consciousness is not obtained 30 seconds after the dose, 0.3 mg can be administered over 3 minutes if the desired level of consciousness is still not obtained, 0.5 mg can be administered over 5 minutes and repeated at 1-minute intervals usual cumulative dosage range: 1 to 3 mg usual cumulative maximum dose: 3 mg (Howland 2019 manufacturer's labeling). Consider consultation with poison control center or medical toxicologist refer to institutional protocols. Benzodiazepine overdose, treatment: Note: Routine use of flumazenil is controversial, as most benzodiazepine-poisoned patients can be treated successfully with supportive measures alone, and use of flumazenil is associated with a risk of adverse effects (eg, withdrawal seizures, arrhythmias), especially in patients who have co-ingested a proconvulsant or proarrhythmic agent, patients that are physiologically dependent on benzodiazepines, or patients with an underlying seizure disorder (Höjer 1988 Howland 2019 Penninga 2016 Schult 2021).
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