Saved by the Bell: Drugs that Mimic Death

Crime writers frequently ask me to suggest a poison that will mimic natural death. The answer to this question provides the premise for the Dr. Lily Robinson novels. As a covert assassin using poison, Lily attempts to mimic her target's underlying medical condition by finding a poison that will kill her foil and yet avoid suspicion that the death is intentional rather than a natural one.

Yet some poisons might make someone appear dead when they are not. Putting crime writing aside, what if a person has taken a medication either willfully or accidentally, that renders them “almost dead” and leads them to be declared dead even though they are still alive? I think back to a case I was consulted on where the “deceased” was found in a bathtub of cold water and transported to the medical examiner. The combination of the cold water and the drug she had taken before she fell unconscious in the bathtub simulated death. The medical examiner was quite surprised when the “deceased” woke up in the morgue. As Edgar Allen Poe said, “The boundaries which divide Life from Death are at best shadowy and vague. Who shall say where the one ends, and where the other begins?”

How do we know for certain that a patient is dead, specifically, brain dead? The phrase “saved by the bell” originated in 19th-century boxing, where a boxer, close to losing a round, could be saved from defeat when the bell rang, and each boxer was sent to his corner. However, at the same time, people were worried (and rightly so) about being buried alive. Other than looking for a breath on the mirror, listening for heart sounds, or checking a pulse, there wasn’t the array of medical tests we have available today that could determine true brain death. Safety coffins in various forms existed in the 19th century, and although the true origin of the phrase “saved by the bell” is attributed to boxing, it also persists in the context of premature burial. A string attached to the “deceased's” finger could be used to ring a bell outside the coffin in the event the individual woke up, alerting those with oversight, thus preventing burial alive. Today, given that many conditions and drugs can mimic death, medical professionals are careful before someone is declared brain dead and subsequently sent to the morgue or to a surgical suite for organ harvesting.

The current neurological criteria for brain death/death by neurological criteria are quite complicated and written for medical professionals. Brain death implies the loss of all brain function, including the brainstem. Irreversible loss. For those interested in the details, the guidelines, published in 2023, can be found in Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Guideline. ⁽¹⁾ I am only commenting on the toxicological aspects of this discussion—that is, drugs that are respiratory depressants, for example, that can confound brain function, misleading caretakers to assume death when in reality, the patient is alive (reversible loss of brain function). This is both an interesting and frightening prospect.

Barely detectable blood pressure, breath sounds scarcely audible, or hypothermia can confuse the picture. A 2021 scientific article reviewed cases of xenobiotics (chemicals not normally found in the body) that, in overdose, were found to mimic brain death. The report identified snake venom, baclofen, tricyclic antidepressants, bupropion, alcohols, antiepileptic drugs, and barbiturates as the most common culprits. Other drugs identified included organophosphates and one case each of magnesium, succinylcholine, tetrodotoxin, and zolpidem.⁽²⁾ The concern is with poisonings that result in the loss of brainstem reflexes.

In the review article, baclofen was the second most frequent confounder of brain death after snake venoms (envenomation in the United States from snakes is not the problem it is in India). Baclofen is a muscle relaxant used to reduce spasms or tight muscles. It acts at the central nervous system (the brain) and is given to patients suffering from multiple sclerosis or spinal cord lesions. At doses of a gram or more, symptoms that mimicked brain death lasted from hours to days.

I’ve already written about tetrodotoxin (see The Poison Blog: What was in the Apple the Evil Queen gave Snow White), a toxin found in the Pufferfish and the Blue-Ringed Octopus, as well as in other animal species. Tetrodotoxin is a potent neurotoxin that blocks voltage-gated sodium channels, thereby preventing nerve-to-muscle communication. Paralysis of the diaphragm and intercostal muscles stops breathing, and death occurs by suffocation.

When determining brain death, it is imperative to exclude intoxication, particularly those drugs that can depress the central nervous system.^(1,3) To ensure that intoxication is not a confounding factor, serum and urine drug screens are performed as indicated, therapeutic or subtherapeutic serum concentrations of specific drugs are determined not to contribute to the neurologic state, at least five half-lives of a drug have passed (that is, the time it takes to eliminate the drug by fifty percent, which depends on kidney and liver function, age and also takes into account body temperature), and that phenobarbital (if administered clinically) is below the limits of detection.

Brain death/death by neurological criteria is complex and rigorous. The medical profession has taken care to provide guidelines to help determine the end of life. Poisoning may confound the issue, but with awareness, it can be addressed. For the crime writer, it can be exploited.

1.      Greer DM, Kirschen MP, Lewis A, et al. Pediatric and adult brain death/death by neurologic criteria consensus guideline: report of the AAN guidelines subcommittee, AAP, CNS, and SCCM. Neurology. 2023;101(24):1112-1132.

2.      Murphy, L., Wolfer, H., & Hendrickson, R. G. (2021). Toxicologic Confounders of Brain Death Determination: A Narrative Review. Neurocritical Care, 34(3), 1072-1089. https://doi.org/10.1007/s12028-020-01114-y

3.      Lewis, A., Kirschen, M. P., & Greer, D. (2023). The 2023 AAN/AAP/CNS/SCCM Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Practice Guideline A Comparison With the 2010 and 2011 Guidelines. Neurology: Clinical Practice 2023;13:e200189. doi:10.1212/CPJ.0000000000200189