Brain death

Introduction

For as long as medical practice has existed, the layperson has required of medical practitioners that they be knowl­edgeable about death. For centuries, laypeople and doctors alike have accepted cessation of respiration and heartbeat as the classical signs of death. Advances in cardiopulmonary resuscitation and modern mechanical ventilation have made obsolete the traditional clinical definition of death with a small but significant harvest of irreversibly brain-damaged patients. The worst form of such damage led to the concept of ‘coma depasse’, first defined by Mollaret and Goulon in 1959. As the number of patients with artificially maintained ventilation and circulation increased, they became to be regarded as a potential source of donor organs. These two developments occurred parallel to but independently of each other, and the diagnosis of brain death did not arise because of the need for donor organs.

The presence of an irreversibly damaged brain in a body in which ventilation and circulation were being maintained by artificial means presented a state in need of a definition. Mollaret and Goulon were the first to investigate this state in their paper ‘Le coma depasse’. Many terms for this and other states for which it has been mistaken have been suggested or used, of which the following ate the most commonly encountered: cerebral death, brainstem death, brain death, coma depasse, irre­versible coma, cortical death, persistent vegetative state and locked-in syndrome.

The high cost of maintaining patients in intensive therapy units (ITUs) and the premium on such limited resources has led significantly to the re-evaluation and management of such states. Nursing and medical staff morale, as well as the emo­tional toll on relatives, ate very real considerations. As these patients may now be potential essential organ donors their care has acquired medicolegal and ethical significance. It is not the primary task of a doctor to provide organs for transplantation but neither is it to deny patients in need of transplant surgery. Before a patient can be considered as having suffered irreversible brain damage, it is mandatory that a positive diagnosis be made of the pathogenesis of this damage. To produce coma, pathological processes must affect the brain diffusely or encroach upon its deep central structures.

Three major groups of lesions can be differentiated:

       suptatentotial lesions;

       infratentorial lesions;

  metabolic disorders — which widely depress or interrupt brain function, including anoxia, ischaernia, infections, toxins and essential deficiencies.

The disintegration of function following progressive herniation will end in cessation of spontaneous respiration leading to hypoxic cardiac arrest. If ventilation and circula­tion are maintained artificially, the heart, kidneys and liver may continue to function for some hours or days but after btainstem death has occurred, cardiac arrest will follow within 2 weeks.

Since Mollaret and Goulon, several committees and reviewers have sought to establish unequivocal and appropriate clinical and EEG criteria for brainstem death based on retrospective analysis of patients who died. The first was the Harvard group who included EEG as part of their criteria. This was later deemed unnecessary by both the Minnesota and British Groups. The latter are as follows.

Before diagnosing brain death several preconditions should be satisfied:

  there should be no doubt that the patient’s condition is due to irremediable brain damage of known aetiology (Fig. 35.48);

the patient should be in a coma on a ventilator because spontaneous respiration has been inadequate or ceased altogether;

  conditions and drugs which simulate brain death have to be excluded and, if necessary, drug levels measured to ensure that there is no reversible cause for coma. Some drugs (e.g. thiopentone) may take days to be cleared from the system.

Potentially reversible circulatory, metabolic and endocrine disturbances must have been excluded as the cause for the continuation of unconsciousness. It is recognised that circulatory, metabolic and endocrine disturbances are a likely accompaniment of btainstem death (e.g. hypernatraemia and diabetes insipidus) but these are the effect rather than the cause of that condition and do not preclude the diagnosis.

The tests should be performed by two physicians of not less than 5 years’ registration, who are not members of a transplant team and at least one of whom is a consultant. The tests are designed to assess brainstem functioning as it is the reticular activating system in the brainstem which is responsible for activating the rest of the cerebrum.

  1.       The pupils should be fixed and unresponsive to changes in the intensity of incidental light.

2.       There should be no corneal reflex.

3.       The vestibulo-ocular reflexes should be absent. No eye movements should be observed while at least 50 ml of cold water is infused over each eardrum. Clear access to the membrane must be established by direct inspection.

4.       No motor responses within the cranial nerve distribution can be elicited by adequate stimulation of any somatic area. There is no limb response to somatic pressure, bearing in mind that movements mediated at a spinal level might still be possible.

5.       There is no gag reflex to bronchial stimulation by a catheter placed down the trachea.

6.       No respiratory movements appear when the patient is disconnected from the mechanical ventilator. During this test it is necessary for the arterial Cd2 to exceed the threshold for respiratory stimulation, that is the PaCO2 should reach 6.65 kPa. This should be ensured by measurement of the blood gases. The patient should first be preoxygenated with 100 per cent 02 for 10 minutes (then with 5 per cent CO2 in 02 for 10 minutes — if CO2 is available). The ventilator should then be disconnected for 10 minutes while 6 litres per minute 02 via a catheter is infused into the trachea.

If no respiratory effort has been detected and other signs of brainstem dysfunction have been demonstrated the patient may be considered brain dead.

Studies of hundreds of patients in several countries have found that not a single body displaying the criteria of brain death outlined gained any neurological recovery. Despite full and repeated efforts at resuscitation all such reported patients have suffered asystole within days or rarely weeks of the diagnosis. Interestingly in 37 instances the EEG retained at least fragments of electrical activity at a time when the patient was diagnosed as brain dead. In contrast to this, Jennet has shown that of the patients surviving prolonged coma, none ever met the criteria for brainstern death at any stage. Although not all agree, most religious and ethical bodies have expressed themselves in sympathy with the concept that death of the brain signifies death of the person. Pope Pius XII proclaimed in 1958 that the pro- -nouncement of death was the responsibility of the church, stating that when illnesses reached hopeless proportions, death should not be medically opposed by extraordinary measures.

It is imperative that conditions simulating brain death be excluded.

Drug intoxication

CNS-depressant drug poisoning may cause total loss of cerebral function and electrocerebral silence for more than 50 hours followed by complete recovery. Self-induced drug poisoning often involves several drugs, frequently in combination with alcohol. Toxicology screening is not always available and frequently levels do not correlate with the clinical state. Serum concentrations often lag behind brain concentrations.

Hypothermia

The core temperature tends to drop when the brainstem ceases to function. That hypothermia may cause an isoelec­tric EEG is a theoretical rather than a practical issue. What is important is that hypothermia should be excluded as the cause rather than the result of the coma.

Electrical injury

This may be an important cause of coma, apnoea and fixed pupils.

Brainstem encephalitis

This is a rare form of encephalitis characterised by rapid ophthalmoplegia, ataxia and areflexia with apnoea and coma in severe cases. Although the clinical state may suggest brain death, these patients do not comply with the basic prerequisite of an incontrovertible diagnosis and the physician should be concerned with diagnostic and therapeutic measures rather than speculating about irreversible coma.

Ancillary tests

Ever since the concept of brain death arose, efforts have been made to establish the diagnosis electrophysiologically, the reason being to seek an objective nonclinical mode of diag­nosis free of error or bias. These tests are not available in all hospitals and those which have proved to be indisputable indicators of brainstem death have usually occurred in patients in whom the diagnosis was never in doubt. They are listed for completeness and not because they replace clinical testing:

EEG;

  scalp electrornyograms;

  evoked potentials;

  brainstem auditory evoked potentials;

  somatic evoked potentials;

  lower oesophageal contractility;

  arteriovenous 02 difference;

cerebral blood flow;

  ocular microtremor.

There is strong evidence that EEG silence for greater than 12 hours in a normothermic patient having had no drugs is not compatible with neurological recovery. Silverman reviewed 2560 isoelectric EEGs lasting for up to 24 hours. Only three patients in this group, all of whom overdosed on CNS antidepressant drugs, recovered cerebral function. Testing in an ITU setting is technically difficult owing to interference. The presence of a few fragments of electrocerebral activity is of dubious significance. Return of EEG activity after silence has also been reported.

NB: an EEG does not measure brainstem function. Drugs may cause coma with reversible true electrocerebral silence.

Cessation of cerebral blood flow in patients with raised ICP was first described by Riishede and Ethelberg in 1953. It is a significant indicator of brain death particularly where CT scanning is not available. It is caused by ICP rising above the MAP and by progressive vascular obstruction caused by autolysis in respirator brain (Fig. 35.49).

Ocular microtrernor is one of three fixational eye movements measured using the isoelectric strain gauge technique and is an indicator of brainstem activity. Studies by Coakley and Bolger (1999) have shown that this tremor is absent in patients with the diagnosis of brainstem death.

If the viability of certain organs is to be maintained for possible harvesting, mechanical ventilation can be continued and the circulation artificially supported with a clear under­standing, however, that these measures are not therapeutic but continued in order to maintain a cadaver in a perfused state. A member of the transplantation team is summoned and all further medical and administrative care of the poten­tial donor should be carried out by them. The request for organ donation must come from the transplant team and not those treating the primary pathology. The staff taking care of the patient declining to brain death have a special respon­sibility towards the relatives who are going through a very harrowing time. For the layperson it is still a macabre concept to speak of death of a person in whom the heart is still beating.