Strategies for the treatment of acute benzodiazepine toxicity in a clinical setting: the role of antidotes

ABSTRACT

Introduction

Although not a potentially life-threatening poisoning, benzodiazepine (BZD) intoxication may be life-threatening in special situations/populations or those with background diseases.

Areas covered

The aim of this review is to evaluate all possible treatment options available in the literature for the management of benzodiazepine poisoning with special attention to antidote administration. We conducted a literature search using PubMed, Google Scholar, EMBASE, and Cochrane central register from 1 January 1980 to 10 November 2021 using keywords ‘benzodiazepine,’ ‘poisoning,’ ‘toxicity,’ ‘intoxication,’ and ‘treatment.’

Expert opinion

Careful patient selection, ideally by a clinical toxicologist, may decrease the complications of flumazenil and add to its efficacy. The cost-to-benefit ratio should be considered in every single patient who is a candidate for flumazenil administration. In case a decision has been made to administer flumazenil, careful consideration of the possible contraindications is essential. We recommend slow administration of low doses of flumazenil (0.1 mg/minute) to avoid complications or withhold the administration with development of first signs of adverse effects. The main treatment of benzodiazepine toxicity is conservative with administration of activated charcoal, monitoring of the vital signs, prevention of aspiration and development of deep vein thrombosis due to prolonged immobilization, and respiratory support.

KEYWORDS:

• Antidote
• benzodiazepine
• contraindications
• GABA
• flumazenil
• Indications
• overdose
• poisoning
• treatment

Acknowledgments

We would like to thank Caroline Copeland for her revisions to an earlier version of this manuscript.

Article highlights

• Pure benzodiazepine poisoning or co-ingestion is extremely common worldwide. The physicians generally prefer to treat benzodiazepine poisoning conservatively mainly due to fear of flumazenil side effects.

• Flumazenil is a great antidote in special circumstances and populations including elderly patients, pregnant patients, those with background disorders, and crowded emergency departments or when the patient refers with grave loss of consciousness and needs a vast work-up.

• The patients should be selected with caution, and flumazenil should not be routinely administered to all patients referred with loss of consciousness.

• To prevent flumazenil complications, it should be given in small (0.1-mg) slow (every one minute) doses to a maximum of 3 mg. Flumazenil administration should be withheld whenever complications start to develop.

• Other treatments including aminophylline and MARS can be used when patients do not respond to flumazenil, but the patient is at increased risk of complications due to prolonged coma.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers of this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

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Additional information

Funding

This paper was not funded.