“Alcohol detox” is a common presentation to acute medical services and is usually managed via standardised guidelines and protocols. We present a case of chlordiazepoxide toxicity, requiring repeated bolus doses and subsequently 24 hours of an intravenous infusion of flumazenil in response to guideline directed management of an alcohol withdrawal state.  The use of prolonged flumazenil infusions to treat benzodiazepine toxicity is infrequently described. Chlordiazepoxide is metabolised in the hepatic microsomal pathway and hepatic impairment can lead to accumulation of toxic metabolites, which may have been the explanation for toxicity in this case. In patients at risk of liver dysfunction we advise the use of benzodiazepines not requiring phase 1 oxidative metabolism, such as lorazepam or oxazepam.

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References

1. Guideline Development Group. Alcohol-use disorders: diagnosis and management of physical complications: National Institute for Health and Care Excellence Clinical Guideline 100. London, National Institute for Health and Care Excellence, 2010.
2. Benson G, McPherson A, Reid S. An alcohol withdrawal tool for use in hospitals. Nursing Times. 2012; 108: 15-17.
3. Katzung BG. Basic and Clinical Pharmacology, 7th edition. New York, Appleton & Lange, 1998. Pg 357.
4. Weinbroum AA, Flaishon R, Sorkine P, et al. A risk-benefit assessment of flumazenil in the management of benzodiazepine overdose. Drug Safety. 1997; 17: 181-196.
5. Kumar CN, Andrade C, Murthy P. A randomized, double-blind comparison of lorazepam and chlordiazepoxide in patients with uncomplicated alcohol withdrawal. J Stud Alcohol Drugs. 2009; 70: 467-474.
6. Cheymol G. Clinical pharmacokinetics of drugs in obesity. An update. Clin Pharmacokinet. 1993; 25: 103-114.
7. Maxa JL, Ogu CC, Adeeko MA, et al. Continuous-infusion flumazenil in the management of chlordiazepoxide toxicity. Pharmacotherapy. 2003; 23: 1513-1516.
8. Al-Halawani M, Sen P, Abdeen Y, et al. Continuous intravenous flumazenil infusion in a patient with chlordiazepoxide toxicity and hepatic encephalopathy. J Emerg Trauma Shock. 2015; 8: 58-60.
9. Grimm G, Ferenci P, Katzenschlager R, et al. Improvement of hepatic encephalopathy treated with flumazenil. Lancet. 1988; 2: 1392-1394.
10. Brammer G, Gibly R, Walter FG, et al. Continuous intravenous flumazenil infusion for benzodiazepine poisoning. Vet Human Toxicol. 2000; 42: 280-281.
11. Guglielminotti J, Maury E, Alzieu M, et al. Prolonged sedation requiring mechanical ventilation and continuous flumazenil infusion after routine doses of clorazepam for alcohol withdrawal syndrome. Intensive care Med. 1999; 25: 1435-1436.
12. Gueye PN, Lofasso F, Borron SW, et al. Mechanism of respiratory insufficiency in pure or mixed drug-induced coma involving benzodiazepines. Clinical Toxicology. 2002; 40: 35-47.
13. Höjer J, Baehrendtz S, Magnusson A, et al. A placebo-controlled trial of flumazenil given by continuous infusion in severe benzodiazepine overdosage. Acta Anaesthesiol Scand. 1991; 35: 584-590.
14. Weinbroum A, Rudick V, Sorkine P, et al. Use of flumazenil in the treatment of drug overdose: a double-blind and open critical study in 110 patients. Crit Care Med. 1996; 24: 199-206.
15. Chern CH, Chern TL, Wang LM, et al. Continuous flumazenil infusion in preventing complications arising from severe benzodiazepine intoxication. Am J Emerg Med. 1998; 16: 238-241.
16. Spivey WH. Flumazenil and seizures. Analysis of 43 cases. Clin Ther. 1992; 14: 292-305.
17. Burr W, Sandham P, Judd A. Death after flumazenil. British Med J. 1989; 298: 1713.