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New international recommendations aim to bring worldwide consensus to determining brain death in adults and children.

The guideline is an effort to "improve the rigor of and minimize diagnostic errors in brain death, or death by neurologic criteria," said Gene Sung, MD, MPH, of the University of Southern California, who is the corresponding author of the .

"One of the most fundamental concepts of medicine is life and death, but how do you determine if someone has died?" he asked.

This is the first time five different world federations have come together to help develop and endorse a consensus statement about brain death or death by neurologic criteria (DNC), Sung told 乌鸦传媒.

Multiple professional societies including the Society of Critical Care Medicine have endorsed it. The American Academy of Neurology, which called for uniform brain death laws, policies, and practices in its 2019 position statement, affirmed the value of the statement as an educational tool for neurologists.

In the U.S., death by neurologic criteria has been incorporated into legal standards for death in every state following the (UDDA), a model state law approved in 1981.

"Notwithstanding this very important legal innovation, there have been recurrent philosophical and religious objections to DNC," noted Ariane Lewis, MD, of New York University Langone Medical Center in New York City, and co-authors, in an .

The most common objection is that the only "true death" is death by cardiopulmonary criteria, they said. "Some have argued that continuing hormonal functions in an individual who is comatose, has absent brainstem reflexes, and is unable to breathe spontaneously indicates that person is not dead under the UDDA, because they have not lost 'all functions of the entire brain,'" Lewis and co-authors wrote.

Clinicians have contributed to the growing controversy by failing to ensure consistency among hospital DNC guidelines, they added: "As a result, a person could be declared dead at one hospital yet alive at another."

To create their consensus statement, Sung and co-authors conducted literature searches from January 1992 through April 2020. Because high-quality data from randomized clinical trials or large observational studies were lacking, their recommendations also relied on the consensus of contributors and medical societies representing critical care, neurology, neurosurgery, and other fields.

"The determination of brain death/DNC is a clinical diagnosis, and given the implications and consequences of this diagnosis, a conservative approach and criteria are recommended," they wrote.

The diagnosis begins by establishing that the clinical history, etiology, and neuroimaging demonstrate the person has experienced an irreversible devastating brain injury leading to loss of all brain functions, and there are no confounders that could make the person appear to have irreversible brain injury when that's not the case, they said.

Determining brain death/DNC can be done with a clinical examination that demonstrates coma, brainstem areflexia, and apnea, they continued. This is seen when:

• There's no evidence of arousal or awareness to maximal external stimulation, including noxious visual, auditory, and tactile stimulation
• Pupils are fixed in a midsize or dilated position and are nonreactive to light
• Corneal, oculocephalic, and oculovestibular reflexes are absent
• There's no facial movement to noxious stimulation
• The gag reflex is absent to bilateral posterior pharyngeal stimulation
• The cough reflex is absent to deep tracheal suctioning
• There's no brain-mediated motor response to noxious stimulation of the limbs
• Spontaneous respirations aren't seen when apnea test targets reach pH below 7.30 and PaCO₂ equal to or above 60 mm Hg

"If the clinical examination cannot be completed, ancillary testing may be considered with blood flow studies or electrophysiologic testing," the authors wrote. "Special consideration is needed for children, for persons receiving extracorporeal membrane oxygenation, and for those receiving therapeutic hypothermia, as well as for factors such as religious, societal, and cultural perspectives; legal requirements; and resource availability."

The guidelines recommend that consent not be required for apnea testing because of concerns over prolonged somatic support, challenging an emerging trend of families objecting to apnea tests, noted Wade Smith, MD, PhD, of the University of California San Francisco, in . "By doing so, families preclude the diagnosis of death, leading in some instances to prolonged somatic support that many physicians consider unethical," he wrote.

The trend is highlighted in a called Bobby's Law: if passed, physicians may be required to gain consent from surrogates before testing for apnea, Smith said. The proposed legislation is predicated on Simon's Law -- now adopted in Missouri, Kansas, and Arizona -- that requires physicians to involve family members in end-of-life decisions, "an ethic that is sensible," he wrote.

"Ostensibly, families should be asked to provide consent because the apnea test may lead to cardiovascular collapse in some patients, classifying it as procedure with risk," Smith added. "Physicians have argued that apnea testing is part of the neurological examination and it should be performed to establish an important diagnosis (death), allowing them to communicate an honest prognosis."

The World Brain Death Project guidelines "serve as a foundational report for all clinicians involved in determining brain death," observed Robert Truog, MD, MA, of Harvard University, and co-authors in an .

Two steps are necessary to bring these recommendations to the entire international community, they pointed out. "First, evidence to support the existing tests needs to be bolstered, and this may require greater use of advanced neurodiagnostic techniques," Truog and colleagues wrote.

"Second, since much of the world does not have access to advanced technologies, the World Brain Death Project will need to focus on development and validation of tests that rely on the clinical examination and widely available diagnostic tools," they continued. "This will be essential if the capacity for accurately diagnosing brain death/DNC is to become accessible to all clinicians around the world."

One important limitation to this consensus document is that a "lack of high-quality data from randomized clinical trials or large studies prevented the use of GRADE, AGREE, or other formal analytic techniques," Sung and co-authors noted. Another is that the group developed recommendations without including patient partners or direct input from diverse social and religious groups.