IT鈥橲 a nightmarish scenario: a 55-year-old man, pronounced dead after a cardiac arrest, is minutes away from organ donation when he begins to show signs of life. 鈥淥n being moved to the operating room table, the anaesthetist noticed that he was coughing,鈥� says neurologist Adam Webb of Emory University School of Medicine in Atlanta, Georgia, who initially pronounced the man brain dead.
It transpired that the man had also regained corneal reflexes and was breathing 鈥� both signs of a functioning brainstem. Although the man later died, his case has reignited a debate about whether clearer guidelines are needed to determine brain death (Critical Care Medicine, ).
At issue is a treatment called therapeutic hypothermia, which Webb鈥檚 patient had. It involves cooling the body to about 33 掳C to minimise damage to tissues and brain cells caused by oxygen deprivation after a cardiac arrest.
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Since the publication of two landmark papers in 2002 in The New England Journal of Medicine, increasing numbers of hospitals are using therapeutic hypothermia. It saves lives, but the technique muddies the waters when it comes to determining brain death. It is also making it harder to predict who is likely to recover from a coma.
Cardiac arrest is a leading cause of death in western countries, affecting around 295,000 people each year in the US alone. Just 15 per cent of people survive as far as hospital and of these around 80 per cent will fall into a coma. Only a third regain consciousness, and they may have brain damage.
Doctors use a number of standard indicators to help them with the prognosis for people in a coma. These include ways to assess brainstem reflexes 鈥� whether the pupils respond to light, for example, and electrophysiological markers, such as applying an electrical stimulus to the wrist and looking for a response in the brain. Doctors also measure levels of a protein called neuron-specific enolase (NSE) in the blood, which is released by dying neurons.
However, 鈥渢here鈥檚 mounting evidence that markers considered to be extremely reliable may not behave the same way in patients who have been through hypothermia鈥�, says of Stanford Stroke Center in Palo Alto, California.
For example, in a study of 45 coma patients treated with hypothermia, two patients whose eye response reflexes suggested that they were unlikely to wake up, ultimately regained consciousness. Eleven patients who initially had a poor motor response also woke up. In a different study, four patients regained consciousness out of 42 who had an NSE level greater than 33渭g/l, the usual cut-off for predicting that a patient may not awaken (The Neurologist, ).
Cooling the brain can depress the firing of neurons, and it may also delay the destruction, or recovery, of neurons. 鈥淭he neurons might be stunned, but they鈥檙e not dead,鈥� says of Yale University School of Medicine. 鈥淒rugs can also stick around for much longer, and once patients [regain a normal body temperature], these drugs may become much more active.鈥�
These issues may also make it harder to determine brain death. Although US guidelines say doctors should exclude confounding factors before deciding on brain death, Webb says the guidelines need to be made more specific. 鈥淐linical criteria alone may not be adequate to determine brain death after cardiac arrest, especially when therapeutic hypothermia is employed.鈥�
Since Webb published his case report in June, it has prompted a flurry of correspondence, both from neurologists who share Webb鈥檚 concerns about the existing guidelines (see 鈥淏rain dead in one country but not another鈥�), and those who believe he simply misinterpreted them.
鈥淚f these authors had stayed to the letter of the American Academy of Neurology guidelines they would not have misdiagnosed this patient,鈥� says Greer. 鈥淚f there鈥檚 anything that could potentially be influencing the examination, you don鈥檛 declare someone.鈥�
of the University of Lausanne in Switzerland isn鈥檛 so sure. 鈥淭his is the real world. You have protocols, but you also have human beings applying them. It鈥檚 important that such cases are brought into the open, to warn others to take care.鈥�
Brain death aside, most agree that doctors need new rules to help them predict recovery from coma after hypothermia has been used. 鈥淭here鈥檚 an urgent need for new guidelines for neurologists,鈥� says Rossetti. 鈥淚t is about life and death. If you test someone too soon after they have warmed up, you may not get a response and think that someone won鈥檛 wake up when there is still a chance that they will.鈥�
鈥淚f you test too soon you may not think that they will wake up when there is a chance that they will鈥�
Brain dead in one country but not another
Although doctors agree that a person is dead when their brain is dead, there is no international consensus on how this should be decided.
鈥淭here can be differences in the procedural aspects of brain death determination that would make a patient brain dead in Germany, but not in the US,鈥� says Adam Webb of Emory University School of Medicine in Atlanta, Georgia (see main story).
Brain death is generally defined as irreversible coma with absent brainstem reflexes. Ten years ago, Eelco Wijdicks of the Mayo Clinic in Rochester, Minnesota, compared criteria for brain death in 80 countries and found widespread variability in the methods used. Of the 70 countries that had published guidelines, 59 per cent required a test to see if the person could breathe unassisted, while half required more than one doctor to examine the patient. Extra tests, like an EEG, were required in 40 per cent of countries (Neurology, vol 58, p 20).
Even within the US, guidelines can vary. 鈥淓ach state and each individual hospital can develop their own guidelines,鈥� says David Greer of Yale University. He compared guidelines between 50 top US hospitals and found differences in the attention paid to confounding factors and how they assessed patients鈥� ability to breathe unaided (Neurology, ). Even if international consensus can鈥檛 be reached, a national standard on brain death is needed, says Greer. 鈥淵ou have people using outdated guidelines and there can be misdiagnosis, our worst nightmare.鈥�
