Shock is a common reason for medical intensive care unit admission, with septic and cardiogenic accounting for most of the etiologies. However, the potential severity of adverse side effects of drugs indicates that any medication should be carefully scrutinized for potential pharmacokinetic and pharmacodynamic interactions that may result. We herein report the case of a life-threatening shock mimicking successively anaphylactic, cardiogenic, and septic shock, which was finally related to disulfiram ethanol reaction. Indeed, disulfiram ethanol reaction is known to provoke unpleasant symptoms through vasodilatation in various organs. However, extreme manifestations of vasodilatory shock may lead to circulatory failure and lactic acidosis. Because of large prevalence of alcoholism and disulfiram medication, emergency physicians and medical specialists should be aware of this life-threatening condition, with its misleading presentation.

A 65-year-old man was referred to our intensive care unit (ICU) for shock. This patient reported no medical history except chronic alcohol abuse and was strictly asymptomatic until lunchtime, when he drunk 500 mL of wine. Half an hour later, he suddenly fainted and was transferred to the emergency department. Consciousness almost returned to normal, but blood pressure was 80/60 mm Hg, heart rate was 110 beats per minute, whereas respiratory rate was 25 breaths per minute and oxygen saturation 99% as he was breathing room air. Temperature was 36°C. Medical examination was only remarkable for diffuse erythema on his chest and face, without mucosal swelling or pruritus. Anaphylaxis was nonetheless suspected, and the patient immediately received intravenous epinephrine (0.1 mg) and aggressive intravenous fluid resuscitation. Worsening circulatory failure required high-dose (0.8 μg/kg per minute) norepinephrine infusion. Electrocardiography (ECG) was suggestive of acute myocardial infarction on ECG (Fig..Fig.), but coronary angiography was strictly normal. Because of hypothermia (35.5°C) and intense shivering, a toxic shock syndrome was evoked, and intravenous broad-spectrum antibiotics combining ceftriaxone and clindamycin were started. The patient was then transferred to the ICU. Laboratory results revealed metabolic acidosis (pH 7.33; bicarbonates, 17.2 mmol/L; and arterial blood lactate, 8.7 mmol/L), but procalcitonin, high-sensitivity troponine, and other routine laboratory tests were strictly within normal ranges. Blood ethanol concentration was 0.9 g/L 6 hours after ingestion. Whole-body computed tomographic scan was unremarkable. Transthoracic echocardiography revealed a hyperkinetic left ventricle without other abnormality. Further interrogation revealed that the patient erratically self-medicated with disulfiram and that he had ingested 500 mg of disulfiram 1 hour before alcohol intake. His circulatory status dramatically improved, and norepinephrine was gradually weaned within 2 hours after ICU admission. Cutaneous manifestations, lactic acidosis, and ECG abnormalities also resolved within 6 hours. All bacteriological samples remained sterile, and antibiotics were discontinued. The patient was discharged home the day after, without any medication. The diagnosis of severe “disulfiram ethanol reaction” (DER) was retained.

Used for more than half a century, disulfiram is thought as a safe adjunctive therapy in alcohol detoxication. Hepatic alcohol dehydrogenase metabolizes alcohol to acetaldehyde, which is then converted to acetate by aldehyde dehydrogenase. As disulfiram inhibits aldehyde dehydrogenase, alcohol-induced acetaldehyde may accumulate to blood levels of 5- to 10-fold higher than those observed during the metabolism of alcohol alone [1x[1]Hine, C.H., Burbridge, T.N., Macklin, E.A. et al. Some aspects of the human pharmacology of tetra-ethylthiuramdisulfide (antabus). J Clin Invest. 1952; 31: 317–325

CrossRef | PubMedSee all References][1]. High-concentration acetaldehyde acts as a potent vasodilatory component and is responsible for the unpleasant side effects of DER. Indeed, coingestion of alcohol and disulfiram provokes unpleasant manifestations of headache, flushing, or nausea. The time-course of DER parallels with blood acetaldehyde levels, which peak within 1 hour after ethanol challenge and disappear in a few hours [[1]x[1]Hine, C.H., Burbridge, T.N., Macklin, E.A. et al. Some aspects of the human pharmacology of tetra-ethylthiuramdisulfide (antabus). J Clin Invest. 1952; 31: 317–325

CrossRef | PubMedSee all References, [2]x[2]Yourick, J. and Faiman, M. Comparative aspects of disulfiram and its metabolites in the disulfiram-ethanol reaction in the rat. Biochem Pharmacol. 1989; 38: 413–421

CrossRef | PubMed | Scopus (30)See all References]. Moreover, and as a matter of concern, disulfiram inhibits dopamine β-hydroxylase, resulting in reduced levels of norepinephrine. Thus, direct vasodilatation and depletion of endogenous catecholamines concur to cardiovascular collapse. Besides shock-related tissue dysoxia, specific mitochondrial toxicity due to the accumulation of acetaldehyde could further explain lactic acidosis and transient myocardial dysfunction [3x[3]Ma, H., Li, J., Gao, F., and Ren, J. Aldehyde dehydrogenase 2 ameliorates acute cardiac toxicity of ethanol. J Am Coll Cardiol. 2009; 54: 2187–2196

PubMed | Scopus (48)See all References][3]. Fomepizole, an alcohol dehydrogenase inhibitor, has been described as an effective treatment during severe DER [4x[4]Sande, M., Thompson, D., and Monte, A.A. Fomepizole for severe disulfiram-ethanol reactions. Am J Emerg Med. 2012; 30: 262.e3–262.e5

Abstract | Full Text | Full Text PDF | Scopus (9)See all References][4] but was not retained in our case because of rapid improvement of patient's condition.

Despite relevant pathophysiology and high prevalence of alcoholism, severe vasodilatatory shock in alcoholic patients treated with disulfiram has been rarely reported [[5]x[5]Jerónimo A, Meira C, Amaro A et al. Choque cardiogênico por dissulfiram. Arquivos Brasileiros de Cardiologia 2009;92(3).

See all References, [6]x[6]Motte, S., Vincent, J.-L., Gillet, J.-B. et al. Refractory hyperdynamic shock associated with alcohol and disulfiram. Am J Emerg Med. 1986; 4: 323–325

Abstract | Full Text PDF | PubMed | Scopus (8)See all References, [7]x[7]Amireche, N., Petit, J.-S., Bankole, E. et al. Effet antabuse sévère aggravé par la dopamine. Ann Fr Anesth Reanim. 2011; 30: 150–152

CrossRef | PubMed | Scopus (2)See all References], and only 1 case has described ST-segment depression [8x[8]Milne, H.J. and Parke, T.R.J. Hypotension and ST depression as a result of disulfiram ethanol reaction. Eur J Emerg Med. 2007; 14: 228–229

CrossRef | PubMed | Scopus (8)See all References][8]. Our case emphasizes the need to include drug interaction in the differential diagnosis of any shock, to avoid unnecessary and invasive procedures or therapeutics. Especially, DER should be suspected in an alcoholic patient presenting with miscellaneous manifestations mimicking anaphylaxis, complicated myocardial infarction, or toxinic shock. Emergency physicians and medical specialists should be aware of this life-threatening condition because of its misleading presentation.