Toxicologic Confounders of Brain Death Determination: A Narrative Review
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REVIEW ARTICLE
Toxicologic Confounders of Brain Death Determination: A Narrative Review Lauren Murphy1,2* , Hannah Wolfer1 and Robert G. Hendrickson1,2 © 2020 Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society
Abstract The aim of this narrative review is to describe the toxicologic confounders of brain death currently reported in the literature to offer guidance for physicians assessing brain death after a toxic exposure. We established an a priori definition of a “brain death mimic” as an unresponsive, intubated patient missing some, but not all brainstem reflexes. We completed a review of the literature utilizing MEDLINE and EMBASE to find case reports of patients of all ages in English, French, and Spanish meeting the criteria and hand searched the references of the results. We recorded xenobiotic dose, duration of physical exam suggesting brain death, and how the cases failed to meet full brain death criteria, when available. Fifty-six cases representing 19 different substances met the a priori definition of brain death mimic. Xenobiotic toxicities included: snake envenomation (13), baclofen (11), tricyclic antidepressants (8), bupropion (7), alcohols (4), antiepileptic agents (3), barbiturates (2), antidysrhythmics (2), organophosphates (2), and one case each of magnesium, succinylcholine, tetrodotoxin, and zolpidem. All patients except one survived to discharge and the majority at their baseline physical health. The most common means by which the cases failed brain death examination prerequisites was via normal neuroimaging. The xenobiotics in this review should be considered in cases of poisoning resulting in loss of brainstem reflexes and addressed before brain death determination. Brain death diagnosis should not be pursued in the setting of normal cerebral imaging or incomplete evaluation of brain death prerequisites. Keywords: Brain death, Drug overdose, Drug toxicity, Coma, Abnormal reflex Introduction Brain death in the USA is defined as the death of an individual due to irreversible loss of all functions of the entire brain, including the brainstem [1, 2]. It is a clinical diagnosis that is based on a prerequisite assessment that eliminates the potential for confounding factors, followed by a physical exam, and concluded with apnea testing [2]. This procedure, when interpreted and followed correctly, excludes the possibility for a brain death “mimic” or a “reversible” brain death state. A brain death mimic may be suggested, however, when the clinical exam of a patient exhibits absent brainstem reflexes but in whom *Correspondence: [email protected] 1 Department of Emergency Medicine, Oregon Health and Science University, Medical Toxicology, Portland, OR, USA Full list of author information is available at the end of the article
confounders have not yet been addressed or eliminated. While many xenobiotics may cause coma in overdose, relatively few are known to cause respiratory failure and even fewer the loss of cranial nerve reflexes. The American Acade
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