Dr. Sunil Shroff, MS, FRCS ( UK). Dip. Urol ( Lond.).
Dr. S Mahendran, MD, General Medicine
The concept of 'Brain Death' is important for those involved in organ transplantation, however this condition was not invented for the benefit of organ donation. The head injury due to road traffic accident can account for almost 50% of Brain Deaths. Organ donation is perhaps the only positive outcome of this grave tragedy, provided the relatives agree to the process.
EVOLUTION OF THE CONCEPT OF BRAIN DEATH
History: Two French physicians in 1959 first recognized "Brain Death" on patients being ventilated in the intensive care units and called it coma depasse (a state beyond coma). In 1968, an Ad Hoc Committee of Harvard Medical School defined brain death as 'irreversible-coma' with the patient being totally unreceptive and unresponsive with absence of all cranial reflexes and no spontaneous respiratory efforts during a 3 minutes period of disconnection from the ventilator.
How much of brain needs to be actually dead before death can be diagnosed has been debated over the years. Experiments have shown that a few cubic centimeters of tissue called "brainstem" which is located beneath "Aqueduct of Sylvius" anteriorly and "floor of fourth ventricle" posteriorly is the vital section of the brain that determines consciousness and ability to breathe spontaneously. Destruction of this tissues is what determines brain death. However in certain countries, the whole brain including the brainstem needs to die to diagnose the state of 'irreversible death' and requires four vessels (carotid and vertebral) angiography and Isotope studies of the cranium. This can be a cumbersome exercise to undertake in an intrinsically unstable patient. In contrast, the tests that determine brainstem death are more clinical and over the last 30 years have proven to be simple, clinical, foolproof and capable of confirmation. In 1988, the Irish working committee on 'Brain Death' in its memorandum said, if the brainstem is irreversibly lost, what goes on elsewhere in the brain is immaterial and 'Life cannot return'.
In the last three decades this concept evolved and has had judicial approval in many parts of the world. India in 1994, accepted the concept of brainstem death and passed an act to this effect and called it the "Transplantation of Human Organ Act" (THO). The act also proposed to stop commercial dealing of organs by making regulatory authorities in each state to look into the whole process of organ donation for both live related (or unrelated) and cadaver organ donation and transplantation.
Patho-physiology: This situation of 'physiological decapitation' can be caused by any pathology that increases in the pressure within the confines of the cranium. Usually this happens as a result of bleeding from rupture of a vessel or a tumor (Fig.1). Increase in the intracranial pressure usually results in coning of the brainstem and ischemia leading to brainstem death. In this situation the heart can continue to beat and keep the circulation of some of the essential organs going provided the patient is kept adequately ventilated and hemodynamic stable. However this state can be only maintained temporarily and cardiac asystole occurs in all the patients.
Legal Aspects in brain death certification: As per the 'Transplantation of Human Organ Act' two clinicians who are experts in the field (like neurologists or neuro-surgeons) are required for brain death certification. Ethically these clinicians must not have interest in or benefit in any way from transplantation of cadaver donor organs. They are required to do two sets of tests six hours apart to certify brain death. One of these two clinicians should be a nominated member from the panel of doctors listed by the State Government for this purpose. The legal time of death in these circumstances is taken as the second set of brainstem death tests. The certification should be done on the laid out forms as per the THO act. In a medico-legal case a forensic expert is also required for the certification. The medical director or medical superintendent of the hospital should finally countercheck and sign the form (Table-I - Form 8. THO Act) . It is only after these formalities have been completed, should ventilatory support be discontinued or organs retrieved.
DIAGNOSIS OF BRAIN STEM DEATH
The aim is to establish that the patient has absent brainstem reflexes and is apnoeic. The testing itself is straightforward. There are certain preconditions that should have been fulfilled to make sure that the tests are performed on the right patients and at the right time. These are as follows:
- Patient should be comatose and on ventilatory support.
- The cause of irreversible structural brain damage should be
known
Functional reversible causes of a non-functioning brainstem
should have been ruled out. These causes include.
- rimary Hypothermia
- Alcohol intoxication
- Neuromuscular blockades (like use of muscle relaxants)
- Use of central nervous system depressant drugs like use of sedatives
- Severe metabolic or endocrine disturbances.
- Patient should have no circulating therapeutic levels of any drug that could cause coma
Establishing Loss of 'Brainstem Reflexes' at the Bedside: - Absence of brain stem function is essential for establishing the diagnosis of Brain death (Fig -2). In the situation of brain stem death the patient's cranial nerve reflexes (Table-II) are tested to observe their motor response to a sensory input. The absence of brain stem function is documented by conducting the following five tests:
- Absence of Pupillary Reflex Response to Light
- Absence of Corneal Reflexes
- Absence of Vestibulo-Ocular Reflex
- Absence of Cranial Nerve response to Pain
- Absence of Gag and Cough Reflexes
Pupillary Reflexes: To check for absent pupillary response to light, a bright pen torchlight should be used in a darkened room. It should be made sure that no eye drops to dilate the pupils have been used in the four hours previously. The pupils may not be necessarily fixed and dilated in the brainstem dead patients, however there should be no pupillary response to light.
Corneal Reflexes: A moist cotton tipped swab should be used and firm pressure should be applied to the cornea without damaging it.
Vestibulo-Ocular Reflexes: testing involves instilling 20ml of ice-cold water into the external auditory canal and looking at eyeball movements of either eye for about a minute. No eyeball movement indicates absence of reflex. Presence of ruptured eardrums or discharge from the ear prevents this test from being performed.
'Gag and Cough Reflexes' Test: requires temporary disconnection from the ventilator. A cotton tipped swab can be used to stimulate the posterior pharynx to look for a response. Experienced ICU staff usually notice a progressive loss of response during the evolution of brainstem death when performing the routine suction of airways and oropharynx.
Grimacing of the face to a painful stimulation is a normal response and this is absent in brainstem death situation. A firm supra-orbital pressure( trigeminal nerve) should be used to check this cranial reflex. Pin pricks should not be used to test this response.
Doll's Head Eye Phenomenon: (testing for oculo-cephalic reflex) This is one test that can be done to know if the brainstem is still alive. If this test is positive than other tests to establish brain death can be postponed. One may need to disconnect the patient from the ventilator for 15 to 20 second to perform this test. To do this test the physician holds the patient's head between his hands and move the head from side to side through 1800. The clinician should hold the head to one side for 3 to 4 seconds and look at the simultaneous eye movement to that side. A similar movement is done to the opposite side and eye movement is noticed. In a normal fully alert individual and in a cadaver the eyes move with the head and there is only a very fractional delay. If the cerebral hemispheres are damaged but brainstem is still alive there will be a obvious deviation of the eyes to the opposite side for a second or two followed by a "release phenomenon" when the eyes will get realigned to the side of the head. This test should not be done if cervical fracture is suspected.
The plantar response may continue to be present in brain death patients along with spinal reflexes and should not be tested. The decorticate and decerebrate posturing is absent, however on occasions it may be difficult to differentiate these from complex spinal reflexes.
Apnoea Test: The aim of apnoea test is to establish death of the respiratory centre in the brainstem (Table III). This is the ultimate test to establish brainstem death. It demonstrates that the spontaneous respiratory response fails to occur even in the absence of stimulatory drive from CO2. For this test the patient is disconnected from the ventilator for 10 minutes. However, to avoid hypoxia to vital organs, 100% oxygen is given for 5 minutes before disconnection from the ventilator. Even during the test period, 100% oxygen is given through a tracheal catheter. In the patient who is brain dead the carbondioxide tension increase at a rate of 2mm/min (0.3 kPa/min) during apnoea testing. If the initial CO2 tension before testing is about 40mmHg (5.3 kPa) then arterial CO2 tension after 10 minutes is likely to be 60mmHg (8 kPa). However a rise to 50mmHg in CO2 tension is acceptable and should provide sufficient stimulatory drive for spontaneous respiration in an intact respiratory centre. In patients with chronic airway disease or severe chest trauma, the apnoea test may be difficult to perform.
Role of Cerebral Angiography & EEG for brain death testing: Four-vessel angiography is used to show absence of cerebral blood flow and confirm death of whole brain. However this test is not done routinely as it is a cumbersome investigation to undertake in an unstable patient. Nor is it necessary to use EEG to diagnose the condition. If there is any doubt in the diagnosis of brain death one should not proceed for a request for organ donation and ventilatory support should be continued. In case of severe facial trauma or presence of paralyses or severe chest trauma, routine tests may not be possible and one may require to do special tests like isotope scanning or colour flow duplex scanning of the cranium to confirm brain death. All these tests can have limitations and can sometimes be inconclusive. In these inconclusive situations, if organ donation is being contemplated, the patient's relatives should be told about it and the ventilator should only be disconnected in the operation theatre and organ retrieval started only after cardiac standstill. The Transplantation of Human Organ act does not require investigations like cerebral angiography or EEG for brain death certification.
In children there remains uncertainty about the reliability of clinical brainstem testing. In neonates especially, organs for transplantation should not be removed in the first seven days of life with beating hearts. Radioisotope brain scanning has been recommended under the age of one year when brainstem death certification is required.
