Editorial I

Death and its diagnosis by doctors

G. R. Park

John Farman Intensive Care Unit, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UKE-mail: gilbertpark{at}doctors.org.uk

There is no legal definition of death in the UK; the law accepts the opinion of a suitably experienced, registered medical practitioner to say when a person is dead. Training in the diagnosis of death is often taught on the wards as a practical skill. Once qualified, doctors often start diagnosing death almost immediately as a pre-registration house officer on the ward. Formal guidelines on how to diagnose death in this situation are rare. Undergraduate medical textbooks seem to ignore the topic. On looking up ‘death’ in the index of Kumar and Clark,1 I found only one reference to brain death; Davidson’s,2 Medicine at a Glance,3 and Chamberlain’s Symptoms and Signs4 had nothing; and Hutchison’s Clinical Methods5 spoke about confidentiality after death and described brain death and organ donation, but had nothing on cardiovascular death. Of the small selection I looked at, only the Oxford Textbook of Medicine6 had a description of how to confirm both cardiovascular and brain stem death, and this was repeated in the Oxford Handbook of Clinical Medicine.7

The diagnosis of cardiovascular death relies on signs that have been used for many centuries. Apnoea has been a cardinal sign of death. Mirrors and feathers have been used for centuries to confirm the absence of breathing. Once breathing stops, then cardiac arrest usually follows and can be confirmed by the absence of heart sounds. Lack of cardiorespiratory function results in hypoxic death of organs such as the brain, with the associated pupillary dilation. In addition, the patient looks dead with central cyanosis, pallor, and loss of consciousness.

Death, often regarded as an event, is not one but rather a process. Loss of consciousness from cerebral hypoxia after cardiac arrest occurs in seconds. Other functions of the brain may take minutes to stop. Some organs may take hours to stop functioning while connective tissues can take days to die.

As medicine has progressed, so it has started to interfere with the process of dying. First cures and other treatments were found for diseases that prevented or delayed death. More recently, the ability to support vital functions such as breathing and prevent cardiac arrest has changed the process of death. If the brain is considered to be the person then it can die, but vital functions are still supported by mechanical ventilation and other treatments, so that cardiorespiratory arrest does not occur. In such circumstances the person is dead, but the body is not cyanosed, it remains warm, the chest moves with ventilation and the heart beats. However, treatment is futile and merely prolongs the patient’s dying process. This adds to the distress caused to the relatives and uses expensive ICU resources to no advantage. To prevent this, various guidelines8 9 have been developed around the world to help clinicians identify brain death and prevent suffering of the relatives and futile treatment. Afterwards, brain (stem) death was used to confirm death in potential heart-beating organ donors. More formal guidelines for brain stem death rather than cardiorespiratory death were deemed necessary because of the complexities of death while receiving ‘high tech’ medicine, which might make diagnosis more difficult.

In the UK, the Royal Colleges issued a Code of Practice on how to diagnose brainstem death in 1976 and have regularly updated it.1012 This Code is based on clinical criteria, rather than tests such as electroencephalographic activity of the brain, or measurement of cerebral blood flow. It is the implementation by clinicians of the Code of Practice for the diagnosis of brain stem death that has been surveyed by Bell and colleagues13 in this issue of the British Journal of Anaesthesia. On first reading of this paper, some might feel alarm that the Code is not being followed correctly. There is no doubt that there is room for improvement, but are the results as bad as they may seem?

The first thing to remember is that the diagnosis of any form of death is not always straightforward. A decapitated corpse is without question dead, but some doctors will still feel the need to listen to the heart; to do what they have been taught to do and always done to confirm death. However, the apparently pulseless, apnoeic skier rescued from an avalanche may just be suffering from profound hypothermia and make a full recovery. In such a patient, a perfunctory listening to the heart will be unlikely to detect a heart beat and death may be wrongly diagnosed. The same types of diagnostic problems exist with brain (stem) death. Take, for example, the victim of a high speed motorcycle vehicle accident, who was not wearing a helmet. The initial cranial computed tomography (CT) scan shows gross cerebral oedema, but no surgical lesion. Serial CTs go on to show prolonged, brainstem herniation. This person is also self evidently dead. Again brain stem death tests are often done—just to be sure. Conversely, consider the person with perhaps a hypoxic brain injury, with only a small amount of oedema. They have been sedated because they were initially struggling against the ventilator and have been aggressively dried out to ‘treat’ their aspiration pneumonia. It is much more difficult to declare brain (stem) death in this case. Thus the variation in how the tests are done may just reflect individual practice based, not on science, but on ritual, what has been taught, and being seen to do what is expected.

Because of the difficulties in diagnosing death in patients receiving mechanical ventilation there is a need for guidance; no matter how skilful or artful any of us may be. Nobody would deny that guidelines, applied in context, are extremely valuable. In medicine, this form of guidance can be viewed as an expert consultation, to be weighed in conjunction with other information and in the context of each individual patient. Indeed, the Code of Practice does not and should not replace clinical judgment, which must be tailored to the particular needs of each clinical situation. Within the Code are some examples of some of the problems that may need specific deviation from it. An example is apnoea testing in a patient with chronic pulmonary disease who may not breathe if they are made hyperoxic. One thing that the history of medicine teaches us is that expert opinion at any given time can be very wrong and slavish adherence to such opinion will also be wrong.

Some of the variation in this study is probably based on a lack of knowledge, not necessarily by the clinician but by medicine as a whole. Sedative drugs are one example. Their elimination by the critically ill patient is very variable both between patients and even within the same patient over time.14 15 Unlike administration of a single dose or short infusion of a drug during anaesthesia, plasma concentrations can be misleading after a sedative drug has been infused for days and may not correlate with effect. Indeed, in one report of two patients who had taken an overdose of diazepam and became unconscious, the plasma concentration when they were discharged 48 h later, awake, greatly exceeded that associated with profound clinical sedation.16

As we cannot be certain about the effects of drugs in such circumstances, it seems logical to wait. How long you wait will depend on patient factors (such as age, illness and occurrence of organ failure), the drug and how much drug was given. As Bell’s paper shows,13 with all these variables it is not surprising there are differences between clinicians when faced with a questionnaire. I have made a study of the problems associated with the use of sedatives and analgesics over the years and would find it impossible to make a set of rules that cover every drug, in every patient, with every type of pre-existing disease. To me, the use of antagonistic agents, such as naloxone and flumazenil seem sensible after one set of tests has shown brain (stem) death. They should not be used before, as their use is associated with instability in the cerebral perfusion pressure.17 An alternative is to use agents that, at the moment, appear devoid of the risk of accumulation even after prolonged administration, such as remifentanil.18

A further reason for the variability is the use of a postal questionnaire. While a useful instrument for surveys, it is limited. Thus one asks about practice in a complex situation but only allows one answer, when in truth there is more than one.

Some parts of the survey also show uncertainty in the minds of the doctors doing the tests. An intracranial pressure equal to or greater than mean arterial pressure must eventually result in brain death (assuming that the monitoring equipment is accurate), yet only 12% of respondents thought this was sufficient to diagnose brain (stem) death. Is this the equivalent of listening to the heart in the decapitated corpse?

There are some parts of the current Code of Practice that are unclear, and despite knowledge that they are unclear these have not been addressed. For example, two doctors have to do the tests, but ambiguity about whether it needs to be done once or twice by each doctor exists. Some argue it is unnecessary to repeat tests you have done once especially when confirmed by another doctor. Others prefer to confirm their own findings. Future versions of the Code of Practice should address these issues.

Transplantation of organs from beating heart donors relieves the suffering of thousands of patients each year. However the Code of Practice is modified, it has to provide certainty that the patient is dead but avoid unnecessary delay and loss of organs. After all, we could just support every patient until the heart stops. This is clearly not proper. Not only will it cause distress to the relatives and result in expensive, futile treatment it will also result in the loss of many organs for transplantation. Delay causes loss of organs through the donor becoming unsuitable or because the relatives withdraw consent during the wait.

Stricter adherence to the Code of Practice is a seemingly easy solution, but how can this be done? This problem has been addressed many times when trying to get doctors to follow evidence-based medicine. In one study,19 obstetricians were given a guideline from their National Society showing that vaginal delivery was possible and safe after Caesarean section in many patients. The control group were given no more information. A further group had their practice audited regularly and were shown the results. The final group had a ‘champion’ (opinion leader) for vaginal delivery after Caesarean section who supplied more information, arranged meetings, and made regular formal and informal contact with colleagues. Over the next 2 yr, the results were followed. Only those with a champion showed an increase in the vaginal delivery group (Fig. 1).



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Fig 1 Impact of audit and opinion leader methodology in changing medical practice. The first year, 1987, is the year before the 2 yr of study. Reproduced with permission from Lomas and colleagues,19 and the publishers of JAMA.

 
Perhaps the answer is to do away with clinical testing altogether, and use confirmatory physiological tests and imaging more. Demonstrating that cerebral blood flow is absent by using cerebral angiography will involve moving the patient to the x-ray department and a delay while this is arranged and done with a resource implication. Bedside tests such as the EEG may avoid this problem, but are unreliable. Electrical activity may continue after cerebral blood flow has stopped. Newer bedside tests such as the transcranial Doppler,20 and possibly measurement of oxygen saturation in the jugular bulb,21 hold some potential to contribute to the diagnosis.

I fear that, unless the medical profession makes its own improvements, legislation will be introduced to force us. In some countries, such as France and Chile, organ retrieval and transplantation have only been allowed by special hospitals, approved by the Government since the start of transplantation. In the UK, should this be extended to allow only specially trained and certified doctors to perform brain death tests? This would undoubtedly introduce delay into the system causing more distress to the relatives and waste of resources.

Care of the damaged brain has moved on since the first Code was written in 1976. Even since the last one in 1998 there have been changes.22 23 It is probably time for the Code of Practice to be looked at again, especially as there is so much variation in the ways of testing for this condition within Europe.24 It needs to be clearer and easier to follow, for example how many tests and by whom. Perhaps during a rewriting process we should also recognize that one size does not fit all. As in so many other areas of medicine, clinical tests do benefit from help (such as antagonistic agents) and investigations (such as the use of transcranial Doppler), in a similar way to practice in the USA.8 Whatever we do must allow us to apply flexibility so that the right tests can be done in each patient matching the cause of the presumed brain (stem) death and its treatment. This would allow us to be sure that the patient is dead and avoid long waits to exclude any residual effects of drugs. It would also avoid situations, such as the manipulation of serum sodium, merely to put ticks in boxes.

I do not believe that any deficiencies identified in this study have resulted in misdiagnosis of brain stem death, but rather a failure to apply properly the Code of Practice. I do believe that the way we do testing now has led to delay in diagnosing brain (stem) death. However, we should address the issues raised in this paper carefully, but quickly, to allay any concerns that may be generated in the public’s minds.

Declaration of interest

The author has been a member of a transplant team for 20 yr and is a Non-Executive Director of United Kingdom Transplant. The views expressed in this editorial are his personal opinions.

References

1 Kumar P, Clark M. Clinical Medicine. London: W.B. Saunders, 2002

2 Haslett C, Chilvers E, Boon NA, Colledge NR. Davidson’s Principals and Practice of Medicine. Edinburgh: Churchill Livingstone, 2003

3 Davey P. Medicine at a Glance. Oxford: Blackwell, 2002

4 Ogilvie C, Evans CC. Chamberlain’s Symptoms and Signs in Clinical Medicine. Bristol: IOP Publishing Ltd, 1987

5 Swash M. Hutchison’s Clinical Methods. London: W.B. Saunders, 2002

6 Warrell DA, Cox TM, Firth JD, Benz EJ jr. Oxford Textbook of Medicine. Oxford: Oxford University Press, 2003

7 Longmore M, Wilkinson I, Torok E. Thinking about medicine. In: Oxford Handbook of Clinical Medicine. Oxford: Oxford University Press, 2003; 1–19

8 Harvard Medical School: Ad Hoc Committee. A definition of irreversible coma. JAMA 1968; 205: 337–9[CrossRef][Medline]

9 Mollaret P, Goulon M. Le coma depasse (memoire preliminaire). Rev Neurol 1959; 101: 3–5

10 Conference of Medical Royal Colleges and their Faculties in the UK (Statement issued by the Honorary Secretary on October 11, 1976). Diagnosis of brain death. Br Med J 1976; 2: 1187–8[Medline]

11 Conference of Medical Royal Colleges and their Faculties in the UK (Statement issued by the Honorary Secretary on January 15, 1979). Diagnosis of brain death. Br Med J 1979; 1: 372[ISI][Medline]

12 Academy of Medical Royal Colleges. A Code of Practice for the Diagnosis of Brain Stem death, 1998

13 Bell MD, Moss E, Murphy PG. Brain-stem death testing in the UK—time for reappraisial. Br J Anaesth 2004; 92: 633–40[Abstract/Free Full Text]

14 Shelly MP, Mendel L, Park GR. Failure of critically ill patients to metabolise midazolam. Anaesthesia 1987; 42: 619–26[ISI][Medline]

15 Park GR. Molecular mechanisms of drug metabolism in the critically ill. Br J Anaesth 1996; 77: 32–49[Free Full Text]

16 Greenblatt DJ, Woo E, Allen MD, Orsulak PJ, Schader RI. Rapid recovery from massive diazepam overdose. JAMA 1977; 240: 1872–4[ISI]

17 Chiolero RL, Ravussin P, Anderes JP, Ledermann P, de Tribolet N. The effects of midazolam reversal by RO 15–1788 on cerebral perfusion pressure in patients with severe head injury. Intensive Care Med 1988; 14: 196–200[ISI][Medline]

18 Breen D, Wilmer A, Bodenham A, et al. Offset of pharmaco dynamic effects and safety of remifentanil in intensive care unit patients with various degrees of renal impairment. Critical Care 2004; 8: R21–R30[CrossRef][ISI][Medline]

19 Lomas J, Enkin M, Anderson GM, Hannah WJ, Vayda E, Singer J. Opinion leaders vs audit and feedback to implement practice guidelines. Delivery after previous Cesarean section. JAMA 1991; 265: 2202–7[Abstract]

20 Hadani M, Bruk B, Ram Z, Knoller N, Spiegelmann R, Segal E. Application of transcranial doppler ultrasonography for the diagnosis of brain death. Intensive Care Med 1999; 25: 822–8[CrossRef][ISI][Medline]

21 Diaz-Reganon G, Minambres E, Holanda M, Gonzalez-Herrera S, Lopez-Espadas F, Garrido-Diaz C. Usefulness of venous oxygen saturation in the jugular bulb for the diagnosis of brain death: report of 118 patients. Intensive Care Med 2002; 28: 1724–8[CrossRef][ISI][Medline]

22 Hutchinson PJ, Seeley HM, Kirkpatrick PJ. Factors implicated in deaths from subarachnoid haemorrhage: are they avoidable? Br J Neurosurg 1998; 12: 37–40[CrossRef][ISI][Medline]

23 Patel HC, Menon DK, Tebbs S, Hawker R, Hutchinson PJ, Kirkpatrick PJ. Specialist neurocritical care and outcome from head injury. Intensive Care Med 2002; 28: 547–53[CrossRef][ISI][Medline]

24 Haupt WF, Rudolf J. European brain death codes: a comparison of national guidelines. J Neurol 1999; 246: 432–7[CrossRef][ISI][Medline]





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