Benzodiazepine overdose

Clinical treatment of overdose is by symptom management. Maintain the patient's airway and respiration, and provide hemodynamic support while excluding other diagnoses. Patients require cardiac monitoring and pulse oximetry with consideration of end tidal CO₂.

Most patients with pure benzodiazepine (BZD) overdose present with mild central nervous system (CNS) depression, particularly sedation with no respiratory depression. Once the diagnosis has been confirmed, they usually require only observation until metabolism of the BZD leads to a natural recovery.

If there is cardiorespiratory depression, pure BZD overdose is unlikely, and treatment should be focused on cardiorespiratory and hemodynamic support, and treating other causes such as alcohol excess or opioid overdose. The American Heart Association states that naloxone should be administered when mixed opioid and BZD overdose is suspected.[1]Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023 Oct 17;148(16):e149-84. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001161 http://www.ncbi.nlm.nih.gov/pubmed/37721023?tool=bestpractice.com Assisted ventilation may be necessary.[33]Bezchlibnyk-Butler JZ, Jeffries JJ. Clinical handbook of psychotropic drugs, 16th ed. Toronto, Canada: Hogrefe & Huber Publishing; 2006. If the patient is hypotensive, ensure adequate fluid resuscitation, and additional measures such as vasopressors if required.

Consult the Poison Center to discuss the patient's presentation, toxicity, and management considerations. Poison Help Opens in new window

Use of activated charcoal is not routinely recommended in the management of poisoned patients, but may be considered if the patient presents to hospital within an hour of ingestion of a toxic dose.[37]Chyka PA, Seger D, Krenzelok EP, et al. Position paper: single-dose activated charcoal. Clin Toxicol (Phila). 2005;43(2):61-87. http://www.ncbi.nlm.nih.gov/pubmed/15822758?tool=bestpractice.com The patient must be conscious and able to protect their airway for safe administration of activated charcoal; therefore, the clinical effects of BZD toxicity often contradict its use.

Treatment recommended for SOME patients in selected patient group

Flumazenil, a benzodiazepine (BZD) antagonist, temporarily reverses central nervous system (CNS) depression; however, the risks of flumazenil often outweigh the benefits and its use is inappropriate for most patients presenting to the emergency department with BZD toxicity.

Flumazenil should only be considered in patients who are known to have pure BZD poisoning and should be avoided where other respiratory depressants are known to have been coingested or if the patient has an undifferentiated coma and medical history, substance use history, and the potential poisons involved are unknown.[1]Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023 Oct 17;148(16):e149-84. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001161 http://www.ncbi.nlm.nih.gov/pubmed/37721023?tool=bestpractice.com

Flumazenil can induce seizures in patients who have a history of seizures, who are dependent on BZDs, or who have also ingested a proconvulsant, such as a tricyclic antidepressant, and is contraindicated in these groups.[34]Haverkos GP, DiSalvo RP, Imhoff TE. Fatal seizures after flumazenil administration in a patient with mixed overdose. Ann Pharmacother. 1994 Dec;28(12):1347-9. http://www.ncbi.nlm.nih.gov/pubmed/7696723?tool=bestpractice.com [35]Spivey WH. Flumazenil and seizures: analysis of 43 cases. Clin Ther. 1992 Mar-Apr;14(2):292-305. http://www.ncbi.nlm.nih.gov/pubmed/1611650?tool=bestpractice.com

The American Heart Association states that flumazenil can be effective in select patients with respiratory depression or respiratory arrest caused by pure BZD poisoning (such as during procedural sedation) who do not have contraindications to flumazenil.[1]Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023 Oct 17;148(16):e149-84. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001161 http://www.ncbi.nlm.nih.gov/pubmed/37721023?tool=bestpractice.com

Flumazenil may prevent the need for intubation and mechanical ventilation; however, it is associated with harm in patients who are at increased risk for seizures or dysrhythmias.

Flumazenil has a shorter half-life than most BZDs and so rapid resedation can occur after apparent recovery. Resedation occurs in approximately 30% of patients, increasing their risk of aspiration and death. Close monitoring is required.[36]Kyong YY, Park JT, Choi KH. Serial monitoring of sedation scores in benzodiazepine overdose. Am J Emerg Med. 2014 Nov;32(11):1438;e5-6. http://www.ncbi.nlm.nih.gov/pubmed/24908447?tool=bestpractice.com