Article In Brief
An international team of critical care experts reviewed an extensive trove of medical literature on brain death and developed a set of recommendations for establishing criteria that can be applied worldwide.
It took 18 section leaders and 45 scientists and clinicians poring through 700 articles and reviewing 45 recommendations to arrive at a consensus of what brain death is and how it should be determined when someone is dead.
The World Brain Death Project was a massive undertaking to attempt to have one set of brain death guidelines that hospitals and medical organizations agree with, and will use.
As it stands now, hospitals, medical examiners, states, and countries have their own rule books they use when determining brain death. And this variability raises a number of questions about brain death itself and whether the systems in place promote trust in the medical system or open it up to legal and ethical debate.
“We recognized there are a number of states and countries that are determining brain death differently,” said the senior author Gene Yong Sung, MD, MPH, director of neurocritical care and the stroke division at University of Southern California.
“We wanted to minimize the differences by asking the question: What is needed to determine who is brain dead and what are the minimum things that clinicians should do? We started with a foundation of all the issues surrounding brain death and what the world community knows at this time in history. Maybe we will think differently when new science comes around but this is what we agree on today. We are not coming up with a grand concept but looking at what we know to be true right now about what it means to be brain dead.”
The neurologic criteria for brain death guidelines were published on August 3 in JAMA.
Nearly 24 world federations and 30 major medical societies, including the AAN, have either affirmed or endorsed the recommendations. (The AAN affirmed the tool as an educational reference for neurologists.)
“There has been a lot of talk about doing this for quite some time,” said Dr. Sung. “The World Health Organization (WHO) started to do something but it wasn't the project we hoped it would be,” explained Dr. Sung.
Defining Brain Death
A really good neurological exam is at the core of this document, raising these among other questions: Is the brain functioning or not? Is the patient in a coma? Is there any function left in the brainstem? Does the brain retain its ability to help the body breathe?
“It is so straightforward,” said Dr. Sung. “Answering these questions is the start of the core of the clinical brain death determination.”
The document includes details on how to carry out a thorough brain death/death by neurologic criteria examination. Dr. Sung added, however, that it is also important that the person has suffered a serious traumatic injury that can lead to brain death.
“You can have someone with certain drugs on board, or hypothermia, or paralysis that can look like brain death but is not,” he explained.
Included in the document are discussions on issues surrounding brain death: Is brain death a legal definition or a medical one? What about religious beliefs about determining whether someone is brain dead?
“There are still a number of countries that do not have processes in place to make a determination of brain death,” Dr. Sung said. “Having a consensus of what brain death is will help.”
Dr. Sung and his colleagues reached out to professional medical societies, including the World Federation of Intensive and Critical Care, World Federation of Pediatric Intensive and Critical Care Societies, World Federation of Neurology, World Federation of Neurosurgery, and the World Federation of Critical Care Nurses. They helped identify experts in brain death/death by neurologic criteria to review the literature on brain death published from January 1992 to April 2020.
Section leaders were the primary authors for each of 13 topics. Others on the team reviewed the draft recommendations at multiple points during the development of the document.
This extensive project led to recommendations that the committee feels could be used anywhere in the world when clinicians have to determine whether someone meets the criteria for a brain death.
Before evaluating a patient for brain death/death by neurologic criteria, the clinician must establish a neurologic diagnosis to determine whether there is a complete and irreversible loss of all brain function. This can be done with a clinical examination that demonstrates coma, brainstem areflexia, and apnea.
This includes eight measures, as outlined in the recommendations:
- 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 is 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 is no brain-mediated motor response to noxious stimulation of the limbs;
- Spontaneous respirations are not observed when apnea test targets reach pH <7.30 and PaCO2 >/= 60 mm Hg.
The clinical exam should be enough to make a determination of brain death, said Dr. Sung. If the clinical exam can't be completed, ancillary testing “may be considered with blood flow studies or electrophysiologic testing. Other ancillary tests, including MRI or CT scans were not part of the recommendations because the scientific evidence was just not strong enough,” he added.
There is a lengthy supplemental section that includes recommendations in special cases, including death of a child, people receiving extracorporeal membrane oxygenation, and for those receiving therapeutic hypothermia. There are also detailed recommendations for brain death that take into account religious, societal, and cultural perspectives. The document also talks about legal requirements; and includes resources for more advanced decision making.
For the most part, medical societies endorsed the recommendations, said Dr. Sung, adding that a few stated that they wanted to use more advanced ancillary tests.
“This is a historical document,” said Stephan Mayer, MD, professor of neurology and neurosurgery, and director of neurocritical care and emergency neurology services at Westchester Medical Center Health Network in Valhalla, New York.
“How brain death is defined has been decided locally all over the world. Every hospital has its own criteria, their own rules,” he said.
“About 85 percent of it is the same: Something damaged the brain and there is no evidence of brain function and the patient doesn't breathe on his own and you have excluded anything that could reverse it. As far as the other 15 percent, most of these rules are unnecessary and overly complicated. They are things that impede the entire noble purpose of the brain death concept.”
One of the reasons that critical care doctors want expediency in the process is to pave the way for organ transplant, Dr. Mayer said. Many hospitals require two examiners to call a brain death and there is often a waiting or observation period between the first determination and a second confirmation. It can add six hours or longer to the process, which leaves families in limbo and a person's healthy organs on the fringe for harvesting. “There is no rationale for these rules. Can someone become un-brain dead in a six-hour period?”
These rules limit the population of transplanted organs, he added.
“The AAN created useful guidelines in 2010 and still the variability among hospitals is wide in spite of this document,” said David Y. Hwang, MD, FAAN, associate professor in the division of neurocritical care and emergency neurology at Yale School of Medicine. “This new set of international guidelines represents another beginning, and we will have to see how many hospitals, states, and countries adopt them.”
“At the end of the day, one of the first rules for brain death determination is to make sure that the patient's pathological process is not reversible,” Dr. Hwang added.
“If you believe that, then a waiting period for another doctor's confirmation is theoretically redundant. You don't want brain death criteria to lead to anything arbitrary,” said Dr. Hwang, who is the chair of the organ donation program at Yale.
The variability in protocols from hospital to hospital creates medical as well as legal and ethical uncertainties, said Thaddeus Mason Pope, JD, PhD, HEC-C, director of the Health Law Institute and professor of law at the Mitchell Hamline School of Law in Saint Paul, MN. Dr. Pope co-authored an editorial on the new guidelines in JAMA Neurology and is one of the 45 scientists who worked on the World Brain Death Project.
Among those questions: Should doctors be required to ask permission to do a clinical brain death examination? What if family members object to stopping mechanical ventilation that keeps their loved one breathing? What are the rights and duties of hospitals and doctors?
The Uniform Declaration of Death Act (UDDA) was written in 1981 and has been adopted by almost every state, Dr. Pope pointed out. The American Medical Association and the American Bar Association signed off on it, and it is meant to guide state lawmakers and clinicians. The UDDA offers two definitions to declare someone dead: Irreversible cessation of circulatory and respiratory functions; or the irreversible cessation of the entire brain, including the brain stem.
“There is a gap between what the law requires and what neurologists do,” said Dr. Pope. “We are calling people dead when some areas of the brain are still working. The problem is that even if a patient satisfies everything on the checklist, the hospital doesn't always require what the law demands. Death is one of those things where there needs to be uniformity and consistency. That is what determines public trust in what it means to be brain dead by neurologic criteria.”
Dr. Pope added: “The one thing everyone agrees about death is that we can't have any false positive cases.”
Robert D. Truog, MD, the Frances Glessner Lee professor of medical ethics, anesthesia & pediatrics, and director of the Center for Bioethics at Harvard Medical School, and his colleagues also wrote an editorial in JAMA.
“This report should be a call for our profession, as well as federal and state lawmakers, to reform our laws so that they are consistent with our diagnostic criteria,” he said. “The most straightforward way of doing this would be to change US law and adopt the British standard of brainstem death, and then refine our testing to make the diagnosis of irreversible apneic unconsciousness as reliable and safe as possible.
“Most important is that there be a clear and logical consistency between the definition of death and the tests that are used to diagnose it.”
He added that there has been “a longstanding myth that ‘death’ can only be defined and diagnosed by doctors. In truth, death may be understood from a multitude of perspectives—theological, philosophical, and cultural, among others. The notion that death can be diagnosed purely on the basis of the loss of neurological functioning—brain death—is very reasonable for many people. But we should recognize that not everyone agrees with this, and their views deserve respect as well.”
Drs. Sung, Mayer, Pope, Hwang, and Truog had no relevant disclosures.