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.

Salicylate toxicity after undetectable serum salicylate concentration: a retrospective cohort study.

BACKGROUND: Salicylates are usually rapidly absorbed and quickly measurable in serum. An undetectable serum salicylate concentration ([ASA]) may occur early after ingestion and may be interpreted as evidence of non-exposure and not repeated. Although cases of delayed salicylate detection are reported rarely, the risk factors associated with this phenomenon are not known. RESEARCH QUESTION: What factors are associated with an early undetectable [ASA] in salicylate poisoning? METHODS: Records from a single regional poison center were searched from 2002 to 2016 for cases of salicylate toxicity treated with bicarbonate and [ASA] > 30 mg/dL. Cases were excluded if initial [ASA] was obtained >4 h after presentation. Case information, serial [ASA], and outcomes were recorded and compared between groups. RESULTS: A total of 313 records met all criteria with 11 initially undetectable [ASA] (3.5%) and 302 detectable [ASA] (96.5%). Time of first [ASA] occurred sooner in the undetectable [ASA] group (89 vs. 137 min, p = 0.011) while time to peak [ASA] was longer (640 vs. 321 min, p < .001). The longest interval between ingestion and undetectable [ASA] was 225 min. Peak [ASA] and reported mean ingested dose were similar in both groups (45 vs. 50 mg/dL, p = NS; 19.7 g vs. 32.9 g, p = NS). Coingestion of agents that delay gastric emptying were similar in both groups (18% [2/11] vs. 25% [76/302], p = NS, chi-square). Hemodialysis was performed in 9% (1/11) of undetectable [ASA] patients and 5.6% (17/302) of detectable [ASA] patients (p = NS, chi-square). A single death occurred in the entire cohort in a patient with an initially detectable [ASA]. DISCUSSION: In this series, a small but significant proportion (3.5%) of patients who developed [ASA] > 30 mg/dL had an initially undetectable [ASA]. Those with an undetectable [ASA] were measured earlier after ingestion with a longer time to peak [ASA]. However, neither coingestion of agents prolonging gastric emptying nor reported dose ingested was different between groups. Formulation was infrequently recorded but one undetectable [ASA] did ingest a non-enteric coated product. Limitations include the small number of patients with undetectable [ASA], use of single poison center data and partial data on co-ingestants and aspirin formulation. CONCLUSIONS: [ASA] may be undetectable early after an overdose and need for serial [ASA] in the evaluation of salicylate ingestion should be further explored. Additional research is needed to determine any causative factors and the optimal timing of [ASA] measurements.