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Brain death guidelines are not accurate enough
When death isn’t what it seems Life-saving technology is calling into question the guidelines doctors use to determine brain death Linda Geddes
IT’S 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. “On being moved to the operating room table, the anaesthetist noticed that he was coughing,” 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 – 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, DOI: 10.1097/ CCM.0b013e3182186687). At issue is a treatment called therapeutic hypothermia, which Webb’s patient had. It involves cooling the body to about 33 °C to minimise damage to tissues and brain cells caused by oxygen deprivation after a cardiac arrest. 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
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. “There 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,” 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
8 | NewScientist | 8 October 2011
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. “Each state and each individual hospital can develop their own guidelines,” 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’ ability to breathe unaided (Neurology, DOI: 10.1212/01.wnl.0000296278.59487. c2). Even if international consensus can’t be reached, a national standard on brain death is needed, says Greer. “You have people using outdated guidelines and there can be misdiagnosis, our worst nightmare.”
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 – 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, “there’s mounting evidence that markers considered to be extremely reliable may not behave the same way in patients who have been through hypothermia”, says Christine Wijman 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 33µg/l, the usual cut-off for predicting that a patient may not awaken (The Neurologist, DOI: 10.1097/NRL.0b013e318224ee0e). Cooling the brain can depress the firing of neurons, and it may also delay the destruction, or recovery, of neurons. “The neurons might be stunned, but they’re not dead,” says David Greer of Yale University School of Medicine. “Drugs can also stick around for much longer, and once patients [regain a normal body
ANTOINE ROSSET/SCIENCE PHOTO LIBRARY
THIS WEEK
In this section n Twist in King Tut’s club foot tale, page 10 n Can police stop crimes that haven’t happened? page 11 n Cellphones spark innovation in Africa, page 21
temperature], these drugs may become much more active.” 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. “Clinical criteria alone may not be adequate to determine brain death after cardiac arrest, especially when therapeutic hypothermia is employed.” Since Webb published his case report in June, it has prompted a flurry of correspondence, both from neurologists who share Webb’s concerns about the existing guidelines (see “Brain dead in one country but not another”), and those who believe he simply misinterpreted them. “If these authors had stayed to the
“If you test too soon you may not think that they will wake up when there is a chance that they will” letter of the American Academy of Neurology guidelines they would not have misdiagnosed this patient,” says Greer. “If there’s anything that could potentially be influencing the examination, you don’t declare someone.” Andrea Rossetti of the University of Lausanne in Switzerland isn’t so sure. “This is the real world. You have protocols, but you also have human beings applying them. It’s important that such cases are brought into the open, to warn others to take care.” Brain death aside, most agree that doctors need new rules to help them predict recovery from coma after hypothermia has been used. “There’s an urgent need for new guidelines for neurologists,” says Rossetti. “It 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’t wake up when there is still a chance that –In the balance– they will.” n
2011 Arctic ozone hole was biggest ever IN the first three months of this year, a hole in the ozone layer over the Arctic grew twice as big as the previous record. The Arctic ozone layer suffers a little damage every winter, but the effect is normally short-lived. “This is a clear step beyond that,” says atmospheric chemist Neil Harris of the University of Cambridge. As the measurements came in, ozone researchers began to debate whether the loss could be compared to that seen over the Antarctic. “It’s the first time we’ve even discussed that question,” says Harris. Between 18 and 20 kilometres up, over 80 per cent of the existing ozone was destroyed – twice that in the previous record-setting winters of 1996 and 2005, says Nathaniel Livesey of the Jet Propulsion Laboratory in Pasadena, California (Nature, DOI: 10.1038/nature10556). The Arctic ozone hole will have allowed more ultraviolet radiation through than before, but it is unlikely anyone has been seriously harmed, says Bruce Armstrong of the University of Sydney, Australia. Atmospheric scientists are now trying to work out why the hole grew so large and whether it will open again. Livesey and his colleague Michelle Santee say the hole formed because the stratosphere remained cold for several months longer than usual. The cold air allowed water vapour and nitric acid to condense into stratospheric clouds, which catalysed the conversion of chlorine into forms that destroy ozone. Climate change could be part of what is keeping the stratosphere cool. That may be counter-intuitive, but global warming occurs only at the bottom of the atmosphere. “Climate change warms the surface but cools the stratosphere,” Harris says. In 2007, the Intergovernmental Panel on Climate Change concluded that the stratosphere had been cooling since 1979. Michael Marshall n 8 October 2011 | NewScientist | 9
IT’S 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. “On being moved to the operating room table, the anaesthetist noticed that he was coughing,” 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 – 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, DOI: 10.1097/ CCM.0b013e3182186687). At issue is a treatment called therapeutic hypothermia, which Webb’s patient had. It involves cooling the body to about 33 °C to minimise damage to tissues and brain cells caused by oxygen deprivation after a cardiac arrest. 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
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. “There 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,” 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
8 | NewScientist | 8 October 2011
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. “Each state and each individual hospital can develop their own guidelines,” 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’ ability to breathe unaided (Neurology, DOI: 10.1212/01.wnl.0000296278.59487. c2). Even if international consensus can’t be reached, a national standard on brain death is needed, says Greer. “You have people using outdated guidelines and there can be misdiagnosis, our worst nightmare.”
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 – 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, “there’s mounting evidence that markers considered to be extremely reliable may not behave the same way in patients who have been through hypothermia”, says Christine Wijman 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 33µg/l, the usual cut-off for predicting that a patient may not awaken (The Neurologist, DOI: 10.1097/NRL.0b013e318224ee0e). Cooling the brain can depress the firing of neurons, and it may also delay the destruction, or recovery, of neurons. “The neurons might be stunned, but they’re not dead,” says David Greer of Yale University School of Medicine. “Drugs can also stick around for much longer, and once patients [regain a normal body
ANTOINE ROSSET/SCIENCE PHOTO LIBRARY
THIS WEEK
In this section n Twist in King Tut’s club foot tale, page 10 n Can police stop crimes that haven’t happened? page 11 n Cellphones spark innovation in Africa, page 21
temperature], these drugs may become much more active.” 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. “Clinical criteria alone may not be adequate to determine brain death after cardiac arrest, especially when therapeutic hypothermia is employed.” Since Webb published his case report in June, it has prompted a flurry of correspondence, both from neurologists who share Webb’s concerns about the existing guidelines (see “Brain dead in one country but not another”), and those who believe he simply misinterpreted them. “If these authors had stayed to the
“If you test too soon you may not think that they will wake up when there is a chance that they will” letter of the American Academy of Neurology guidelines they would not have misdiagnosed this patient,” says Greer. “If there’s anything that could potentially be influencing the examination, you don’t declare someone.” Andrea Rossetti of the University of Lausanne in Switzerland isn’t so sure. “This is the real world. You have protocols, but you also have human beings applying them. It’s important that such cases are brought into the open, to warn others to take care.” Brain death aside, most agree that doctors need new rules to help them predict recovery from coma after hypothermia has been used. “There’s an urgent need for new guidelines for neurologists,” says Rossetti. “It 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’t wake up when there is still a chance that –In the balance– they will.” n
2011 Arctic ozone hole was biggest ever IN the first three months of this year, a hole in the ozone layer over the Arctic grew twice as big as the previous record. The Arctic ozone layer suffers a little damage every winter, but the effect is normally short-lived. “This is a clear step beyond that,” says atmospheric chemist Neil Harris of the University of Cambridge. As the measurements came in, ozone researchers began to debate whether the loss could be compared to that seen over the Antarctic. “It’s the first time we’ve even discussed that question,” says Harris. Between 18 and 20 kilometres up, over 80 per cent of the existing ozone was destroyed – twice that in the previous record-setting winters of 1996 and 2005, says Nathaniel Livesey of the Jet Propulsion Laboratory in Pasadena, California (Nature, DOI: 10.1038/nature10556). The Arctic ozone hole will have allowed more ultraviolet radiation through than before, but it is unlikely anyone has been seriously harmed, says Bruce Armstrong of the University of Sydney, Australia. Atmospheric scientists are now trying to work out why the hole grew so large and whether it will open again. Livesey and his colleague Michelle Santee say the hole formed because the stratosphere remained cold for several months longer than usual. The cold air allowed water vapour and nitric acid to condense into stratospheric clouds, which catalysed the conversion of chlorine into forms that destroy ozone. Climate change could be part of what is keeping the stratosphere cool. That may be counter-intuitive, but global warming occurs only at the bottom of the atmosphere. “Climate change warms the surface but cools the stratosphere,” Harris says. In 2007, the Intergovernmental Panel on Climate Change concluded that the stratosphere had been cooling since 1979. Michael Marshall n 8 October 2011 | NewScientist | 9