Protocol-Based Management of Medication Confounders in Brain Death Determination: A Multi-Institutional Review

Determination of death by neurologic criteria (DNC) relies on clinical examination, provided no confounding conditions affect reliability. Current guidelines require patients to be free of confounders before neurologic testing but do not specify how these confounders should be assessed or managed. This lack of specificity may lead to variability in practice and uncertainty in protocol implementation. The objective of this study was to review institutional protocols for DNC determination across hospitals in the United States and evaluate how they address medication confounders and the role of ancillary testing.

To further explore variability observed in our initial national survey sent to the Neurocritical Care Society membership, we conducted a follow-up study requesting exact DNC protocol language from respondents willing to provide additional details. Participants submitted protocol excerpts related to medication confounders, ancillary testing, reversal agents, and practitioner responsibilities, which were de-identified and analyzed using artificial intelligence (AI)-assisted qualitative theme extraction with subsequent investigator review for accuracy.

Responses were obtained from 18 of 23 U.S. institutions (78%), nearly all of which were urban centers with neurology and neurocritical care services. Analysis identified several recurring themes. Protocols consistently emphasized pharmacokinetic clearance strategies, most commonly the use of elimination half-lives, drug levels, and toxicology screening, to exclude medication confounders. Ancillary testing was generally reserved for situations in which clinical examination could not be safely performed and was often discouraged as a substitute for drug clearance. Reversal agents were infrequently addressed and, when included, were typically described as optional. Additional variability was observed in patient-specific considerations, practitioner responsibilities, and the presence of supporting drug appendices.

Institutional DNC protocols demonstrate substantial variability in how medication confounders are assessed, despite most sites requiring medication review. These findings highlight the need for clearer, evidence-based protocols to ensure reliable DNC determinations in the presence of potential medication confounders.