In the majority of cases, declaring a patient’s death in a clinical setting is a relatively straightforward affair. In the most common cases of cardio-respiratory death (also called cardio-pulmonary death), after all efforts to resuscitate the patient have failed, most healthcare systems require a five-minute observation by a doctor or senior nurse to confirm various factors, including no respiratory effort, no palpable central pulse and a lack of pupillary response to light, before death can be declared.
But the march of progress in medical science since WWII has drastically improved clinicians’ ability to keep patients breathing and their hearts beating through external ventilation and advanced life support. As a result, the medical community shifted its focus in the post-war decades to a new designation of death for patients whose vital organs can be kept functioning but without consciousness or any hope of recovery – brain death, sometimes referred to as death by neurologic causes.
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“That’s how the concept of brain death started, in the 1950s,” says Dr Gene Sung, director of neurocritical care at Los Angeles County + USC Medical Center in California and steering committee member of the World Brain Death Project. “After CPR [cardiopulmonary resuscitation], ACLS [advanced cardiovascular life support] and mechanical ventilators were developed, when people were resuscitated and getting ventilation, they still never woke up, and in fact their bodies started decomposing after a while.
“Then people starting saying, ‘Ah, this is brain death.’ The brain isn’t functioning, and the body will never get better as a result. We’re better and better at doing other things with the body, but you can’t transplant a new brain, and people still die by brain death.”
Common causes of brain death are often the same events that cause cardio-respiratory death, including cardiac arrest, stroke and blood clots, all of which can block oxygenated blood from reaching the brain, which cannot survive without it.
While mechanical ventilation and life support systems can sometimes prevent immediate death, if there’s no function or hope of recovery in the body’s central processor, the point of no return has already been crossed. Other major causes of brain death include severe head injuries, brain haemorrhages, tumours and infections such as encephalitis.
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By GlobalDataDiagnosing brain death: a painful process
In this hinterland that seems to exist – to the non-clinical observer, at least – between life and death, there are complications involved with making a determination of brain death. The first and most obvious is making a clear distinction between brain death and a patient who is in a vegetative state. Vegetative patients harbour some hope of recovery because their brain stem remains functional, potentially giving some form of consciousness, as well as usually allowing unaided breathing.
Under guidelines in the UK’s NHS, for a patient to even be considered for a diagnosis of brain death, they must satisfy three criteria: they must be unconscious and unresponsive to outside stimulation; their breathing can only be maintained by a mechanical ventilator; and there must be clear evidence that serious and incurable brain damage has occurred. A clinical examination (along with ancillary tests if needed) is then carried out to confirm the diagnosis, which in the UK must be carried out by two senior doctors.
A thorough clinical exam is often the only thing that is required to legally declare brain death. “This is a clinical diagnosis,” says Sung. Nevertheless, various technologies and techniques are routinely employed for ancillary testing if further confirmation is required.
He continues: “The ancillary tests that we recommend are a conventional angiogram, so putting a dye into a vessel and seeing if blood goes into the brain – if no blood goes into the brain, well that’s a dead organ. Also, a nuclear medicine study – you inject radioisotope into the body and see if there’s any isotope that’s taken up in the brain.
“There are also electrical studies. Electroencephalogram (EEG) is the test that’s been used the longest since brain death was first defined. But we feel that EEG can be confounded, because now in the intensive care unit there’s so much more electrical noise around because of all the different technologies used routinely in the ICU. EEG in combination with other electro-physiological studies – that’s our recommendation.”
Of course, just as in the acrimonious debate over when life begins, raw emotion and religious convictions muddy the waters when it comes to making a determination of brain death. There have been a range of controversies surrounding brain death declarations – some have objected to legally defining a non-functional brain stem as death, citing various bodily functions that can be maintained in a ‘brain-dead’ state, while some conspiracies argue that brain death is a convenient designation to facilitate organ donation.
The sense of mistrust may be best exemplified by the case of Jahi McMath, a 13-year-old girl from California who was diagnosed with brain death and issued a death certificate in 2013 after post-surgical complications. McMath’s family rejected the diagnosis, and after taking legal action, removed McMath for continued life support, despite Children’s Hospital Oakland’s arguments that this would constitute futile treatment of an already-deceased person.
A second death certificate was issued for McMath nearly five years later in June 2018, when she was removed from life support following internal bleeding due to kidney and liver failure.
Trust issues: setting consistent standards in brain death
Part of the mistrust around brain death may stem from the lack of understanding about this diagnosis – for example, it’s not unknown for a patient to make small movements in the arms or torso after brain death. These movements are caused by spinal reflexes and don’t involve the brain at all, but it’s certainly understandable that distraught families would refuse to accept death in a loved one who has seemingly shown signs of recovery.
Perhaps a more important factor is the variation in practice and protocol for declaring brain death, which has led to significant differences in how it is approached between and even within countries. Sung has direct experience of these differences, even between hospitals in the same health system.
“When I first came to University of Southern California (USC), we have two main hospitals, and the two hospitals’ [brain death] protocols, even with the same university staff, were slightly different,” Sung says.
“In the US, the majority of states only require one examiner,” he continues. “Four states, including my state of California, require two doctors to do two separate brain death examinations. So you could be determined as brain-dead in one state, but it may not suffice to be declared brain-dead in another state.”
The mistrust and confusion surrounding brain death – and the fact that varying clinical practices might be contributing to it – is what inspired Sung and the World Brain Death Project to publish a consensus paper in JAMA this summer to help harmonise global standards in this area. He describes the 300-page paper, with 17 appendices, as something of a foundational textbook on brain death, which could inform policy changes in developed countries and guide the development of brain death policies in around half of the countries in the world that currently lack them.
The paper certainly has the backing of a broad swathe of the medical community – it is endorsed by the world federations of intensive care, paediatric intensive care, neurology, neurosurgery and critical care nurses, as well as 33 medical societies from 25 countries.
“Showing there is this worldwide understanding and acceptance and agreement about brain death first, and then how to determine brain death – it shows that it’s not a random process that’s different in each little locality, and that this is really a worldwide and accepted document,” Sung says.
The role of technology in brain death
As well as laying out in detail the accepted best practices in determining brain death – broadly speaking, that a good clinical exam is the only thing needed in most patients, with various ancillary tests to be used in more complex cases – the consensus paper also compiles instances in which brain death exams may be misled. A particularly important factor is hypothermia, which may be used as a treatment to protect the brain after cardiac arrest.
“That leads to complications because lowering the temperature also lowers metabolism,” says Sung. “So if there are other drugs used to sedate patients or paralyse patients, those drugs stay in the system longer. And with hypothermia itself, the lower temperatures can actually lower brain function, and so you can’t do a clinical examination if the temperature’s too low. Our recommendation is you should wait a minimum of 24 hours after the temperature returns to normal.”
The paper also extensively covers the technologies that play a role in accurately determining brain death. While the techniques listed above – as well as transcranial doppler ultrasound, another method of assessing blood flow in the brain – are well established in the field, Sung says other technologies are being investigated or used, which could be effective but as yet lack definitive supporting evidence.
“People have used infrared technologies to try to look at blood flow, and that could be used in brain death determination,” he says. “Some people have been using magnetic fields for looking at edema and flow. The problems with those are that, again, in what situations can they be used and when can they not be used? The aetiology of the brain death, is it making that particular technology not work? There are also imaging studies looking at the function of the brain.
“So, what are situations where this could be accurate, and which situations not accurate, in terms of showing when there’s irreversible damage to the brain? These [new] technologies, that’s great – that’s medicine, that’s science. New things are developed all the time and we have to incorporate them. But they need to be properly studied before they’re incorporated.”
Of course, conducting wide-ranging studies on the effectiveness of various technologies in brain death determination is an expensive endeavour, and with a field like brain death, there’s precious little profit motive for private industry to foot the bill.
“If anyone’s interested in doing those studies, they’re going to have to find some kind of unusual funding,” says Sung. “It probably won’t come from industry, because there’s little profit for them to make.”
Sung adds that the feedback on the consensus paper from the medical community to date has been very positive, with no criticism of the science behind its guidance. But even with the standards set, the task of applying them worldwide begins now, and it might be an even stiffer challenge.
“There are questions about how we can proceed further, to help minimise these differences,” Sung says. “We’ve always understood this would be a difficult process, especially for a lot of developed countries that have had longstanding processes for determination [of brain death], and how and why would they change their protocols now? Those are some issues that we’re trying to address.”
