What is the treatment for benzodiazepine (BZD) intoxication?

Treatment for Benzodiazepine Intoxication

For benzodiazepine overdose, the primary treatment is supportive care with airway management, while flumazenil should only be used in select patients with pure benzodiazepine poisoning who don't have contraindications to its use. 1

Initial Management

• Establish and maintain an open airway as the first priority, providing bag-mask ventilation followed by endotracheal intubation when appropriate to address hypoxemia and hypercarbia 1, 2
• Address hypoxemia and hypercarbia promptly as these are the primary mechanisms of tissue injury and death in benzodiazepine overdose 1, 2
• Contact a regional poison center (1-800-222-1222 in the US) for expert guidance on management 1

Supportive Care

• Provide standard airway management, support of breathing, and treatment of hypotension, dysrhythmias, or cardiac arrest according to local guidelines 1, 2
• Consider internal decontamination by lavage and activated charcoal if the patient presents early after ingestion 3, 4
• Monitor vital signs, prevent aspiration, and avoid deep vein thrombosis due to prolonged immobilization 4

Flumazenil Use

Indications

• Consider flumazenil for select patients with respiratory depression/respiratory arrest caused by pure benzodiazepine poisoning who do not have contraindications 1
• Flumazenil is reasonable in low-risk presentations such as pediatric exploratory ingestions and iatrogenic overdoses during procedural sedation 1

Contraindications

• Avoid flumazenil in patients with:
  • Chronic benzodiazepine dependence (risk of withdrawal) 1, 3
  • History of seizure disorders 3
  • Suspected or known co-ingestion of tricyclic antidepressants or other dysrhythmogenic drugs 3
  • Cardiac arrest related to benzodiazepine poisoning (no benefit) 1
  • Undifferentiated coma due to risk of complications 2, 3

Dosing

• For adults with suspected benzodiazepine overdose 3:
  • Initial dose: 0.2 mg IV over 30 seconds
  • If no response after 30 seconds, give 0.3 mg IV over 30 seconds
  • Further doses of 0.5 mg can be given at 1-minute intervals up to a cumulative dose of 3 mg
  • Most patients respond to a cumulative dose of 1-3 mg
• For pediatric patients >1 year 3:
  • Initial dose: 0.01 mg/kg (up to 0.2 mg) IV over 15 seconds
  • If no response after 45 seconds, additional doses of 0.01 mg/kg can be given at 60-second intervals
  • Maximum total dose: 0.05 mg/kg or 1 mg, whichever is lower

Administration Technique

• Administer through a freely flowing intravenous infusion into a large vein to minimize pain or inflammation at the injection site 3
• Administer as a series of small injections (not as a single bolus) to control the reversal of sedation to the desired endpoint 3

Special Considerations

• If combined opioid and benzodiazepine poisoning is suspected, administer naloxone first (before flumazenil) for respiratory depression 1, 2
• The effects of flumazenil may wear off before a long-acting benzodiazepine is completely cleared from the body, potentially leading to resedation 3
• For patients who resedated after initial response, repeated doses may be given at 20-minute intervals if needed 3, 5
• For repeat treatment, no more than 1 mg should be given at any one time, and no more than 3 mg should be given in any one hour 3

Monitoring After Treatment

• Observe patients for at least 2 hours after the last dose of flumazenil 3
• Longer observation periods are required for patients who received long-acting benzodiazepines (such as diazepam) or large doses of short-acting benzodiazepines 3
• Monitor for potential adverse effects including seizures, dysrhythmias, anxiety, agitation, and withdrawal symptoms 3, 6

Alternative Treatments

• In rare cases with severe intoxication in patients with impaired metabolism (e.g., liver disease), hemadsorption has been reported as an effective method to eliminate benzodiazepines 7

Common Pitfalls to Avoid

• Failing to recognize mixed overdoses, especially with opioids, which can significantly increase toxicity 2, 6
• Administering flumazenil too rapidly, which increases the risk of adverse effects 3, 4
• Underestimating the potential for resedation after initial response to flumazenil, particularly with long-acting benzodiazepines 3
• Using flumazenil as a substitute for proper airway management and supportive care 3