ACMT Position Statement: Toxicology Issues in Determining Brain Death

September 26, 2017, 9:11 pm


ACMT Position Statement: Determining Brain Death in Adults After Drug Overdose. Neavyn MJ et al. J Med Toxicol 2017;13:271-273.

Full Text

The American Academy of Neurology guidelines on determining brain death in adults states that the clinician can not make such a determination unless he or she can  “[e]xclude the presence of a CNS-depressant drug effect by history, drug screen, calculation of clearance using 5 times the drug’s half-life (assuming normal hepatic and renal function), or, if available, drug plasma levels below the therapeutic range.”

Excluding drug effect in these cases is not at all straightforward, and this position statement — developed by the American College of Medical Toxicology and endorsed by both the American Academy of Clinical Toxicology and the Society of Critical Care Medicine — discusses the crucial nuances that must be considered.

The authors note that a drug screen can neither exclude intoxication nor establish a clinical significant depressant effect. They also point out that while a period of 5 half-lives in generally considered time enough for a drug to be essentially eliminated from the system, in overdose situations all bets are off. In overdose, standard assumptions about rates of drug absorption and elimination go out the window. In addition, with massive overdose, the amount of drug remaining in the CNS can still be clinically significant. For example, although baclofen has a half-life of 2 -4 hours, one reported case of baclofen-induced coma mimicking brain death lasted for 7 days.

Although determination of brain death is an extremely complex matter, there are 3 essential components:

  1. establishing a clear, irreversible and proximate cause
  2. demonstrating lack of brain function, and
  3. eliminating reasonable possibility toxic etiology

In a 2013 column in Emergency Medicine News, I reported on a case from Syracuse NY where a 41-year-old woman was declared brain dead and sent to the operating suite on her 5th hospital day so that her vital organs could be harvested. Just as the surgical procedure was beginning, she opened her eyes and began to look around at the OR lights. Afterwards when she was able to give a history she admitted taking a massive overdose of baclofen. When the case was reviewed, it was determined that the clinical team had neither established a clear alternative explanation for brain death, nor established lack of brain function. If the principles stressed in this brief position statement had been adhered to, this near catastrophe could have been avoided.

Related Posts:

TPR Podcast #4: Poisoning and the diagnosis of brain death

Official report about overdose patient who awoke in OR just before surgeons
harvested her organs

Hospital fined after overdose awakes just before surgeons harvest her organs



  1. Rama Says:

    Why not mandate cerebral blood flow absence as the criteria

  2. Leon Gussow Says:


    Good question. Lack of cerebral blood flow (at least as visualized on angiogram) is caused by cerebral edema. This can result both in false positives — transient and reversible early edema — and false negatives — irreversible cellular injury without massive edema.