Toxicologic Confounders of Brain Death Determination: A Narrative Review

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.