MANAGEMENT OF BRAIN DEATH

Death can bring life is a unique concept new to mankind. The Egyptianswere perhaps the first to believe in it and took elaborate measures topreserves the body by the complex process of embalming. In modern timesthe field of preservation of tissues has constantly looked at newermethods of preserving tissues and organs after death. Preservation ofcells is dependant on the complexity of their function. The morecomplex the function the lesser time the tissues can be preservedoutside the body. Skin, bones, cartilage, arteries and veins areessentially structural tissues and have the ability to be preserved formany years whereas cells of organs like liver, heart, pancreas, lungs, kidneys, intestine can only be preserved for few hrs to a few days. Theconcept of Brain Death is more recent and its acceptance as an entityhas provided a boost to the whole organ donation and transplantprogramme in the world. In brain death patient it is possible topreserve the required hemodynamic stability to keep the critical organsalive by providing them with oxygen and nutrition. Organ donation in abrain death situation is a positive outcome of death which sometimesmaybe unnecessary as it happens in road traffic accident. Over 50% of Brain Death involves young people with head injury due to a roadtraffic accident. The tragedy for the family members of the deceased atthis unnecessary loss of life is immense. Organ donation is perhaps theonly positive outcome of this grave tragedy provided the relativesagree to the process. However one must always remember that thecondition was not invented for the benefit of organ donation and thewishes of the loved ones should always be respected and no pressureshould be put on the relatives to donate. Ideally they should be awareof the concept in advance and should come themselves come forward fororgan donation.

HISTORY OF THE CONCEPT OF BRAIN DEATH

In 1959 two French physicians first recognized Brain Death on patients being ventilated in the intensive care unitsand called it coma depasse (a state beyond coma). In 1968, an Ad HocCommittee of Harvard Medical School defined brain death as irreversible coma with the patient being totally unreceptive andunresponsive with absence of all cranial reflexes and no spontaneousrespiratory efforts during a 3 minutes period of disconnection from theventilator. A matter for debate has been how much of brain needs to beactually dead before death can be diagnosed. Experiments haveconclusively shown that a few cubic centimeters of tissue called brainstem that is located beneath Aqueduct of Sylvius anteriorly andfloor of fourth ventricle posteriorly is the vital section of the brainthat determines consciousness and ability to breathe spontaneously. Ifthis tissue is destroyed it will result in brain death. However incertain countries, the whole brain including the brainstem needs to dieto diagnose this state of irreversible death. This can be a difficultto diagnose and sometimes requires four vessels (carotid and vertebral)angiography and Isotope studies of the cranium. In contrast the teststo diagnose brainstem death are more clinically oriented and over thelast 35 years have stood the test of time. They are simple, clinical, foolproof and capable of confirmation of brain-stem death. In 1988 theIrish working committee on Brain Death in its memorandum said, if thebrainstem is irreversibly lost, what goes on elsewhere in the brain isimmaterial and Life cannot return. 

Patho-physiology

Brain death is similar to physiologicaldecapitation and can result from intra cerebral bleeding or increasein the pressure of the cranium due to a tumor (Fig.1). Increasingintracranial pressure results in coning of the brainstem and ischemialeading to brainstem death. In this situation the heart can continue tobeat if the patient is kept adequately ventilated and hemodynamiclystable. However this situation cannot be maintained indefinitely and inmajority of the situations the patient has hemodynamic instability, electrolyte imbalance and cardiac arrest due to loss of the centralreceptors. 

LEGAL ISSUES 

In the last three decades the concept of brain death has evolved and has had judicial approval in many parts of the world. 
In USA
UK
JAPAN
IRAN
#
Saudi arabia

India in 1994, accepted the concept of brainstemdeath and passed an act to this effect and called it the Transplantation of Human Organ Act (THO). The act also proposed tostop commercial dealing of organs by making regulatory authorities ineach state to look into the whole process of organ donation for bothlive related (or unrelated) and cadaver organ donation andtransplantation.

As health and education are state subjects this acthad to be accepted by various states and paased in their assemblies. Sofar the act has been passed in most of the Indian states, however thereare still a few states that have to accept the act. ( Table .1) 

Brain death certification: As per the Transplantation of Human Organ Act two clinicians who are experts inthe field (like neurologists or neuro-surgeons) are required for braindeath certification. Ethically these clinicians must not have interestin or benefit in any way from transplantation of cadaver donor organs.They are expected to do two sets of tests six hours apart to certifybrain death. One of these two clinicians should be a nominated memberfrom the panel of doctors listed by the State Government for thispurpose. The legal time of death in these circumstances is taken as thesecond set of brainstem death tests. The certification should be doneon laid out forms as per the act. In a medico-legal case a forensicexpert is also required for the certification. The medical director ormedical superintendent of the hospital should finally countercheck andsign the form ( Table-2- Form 8 THO Act). It is only after this hasbeen done should ventilatory support be discontinued or retrieved.

CLINICAL DIAGNOSIS OF BRAIN STEM DEATHThe aim is to establish that the patient has absentbrainstem reflexes and is apnoeic. The testing itself isstraightforward. There are certain preconditions that should have beenfulfilled to make sure that the tests are performed on the rightpatients and at the right time. These are as follows:

1. Patient should be comatose and on ventilatory support.
2. The cause of irreversible structural brain damage should be known
3. Functional reversible causes of a non-functioning brainstem should have been ruled out. These causes include.
1. Primary Hypothermia
2. Alcohol intoxication
3. Neuromuscular blockades (like use of muscle relaxants)
4. Use of central nervous system depressant drugs like use of sedatives
5. Severe metabolic or endocrinal disturbances.
4. Patient should have no circulating therapeutic levels of any drugs that could cause coma
   Establishing loss of 'Brainstem reflexes' at the bedside:- Absence of brain stem function is essential for establishing thediagnosis of Brain death (Figure 2). In a brainstem dead patientcranial nerve reflexes (Table-II) are tested to observe motor responseto a sensory input. The absence of brain stem function is documented byconducting the following tests:
   1. Absence of Pupillary reflex response to light
   2. Absence of Corneal reflexes
   3. Absence of vestibulo-ocular reflex
   4. Absence of cranial nerve response to pain
   5. Absence of gag and cough reflexes

To check for absent pupillary response to light, a bright pentorchlight should be used in a darkened room. It should be made surethat no eye drops to dilate the pupils have been used in the four hourspreviously. The pupils may not be necessarily fixed and dilated in thebrainstem dead patients, however there should be no pupillary responseto light.

To test the corneal reflex moist cotton tipped swab should be usedand firm pressure should be applied to the cornea without damaging it. The vestibulo-ocular reflex testing involves instilling 20ml ofice-cold water into the external auditory canal and looking at eyeballmovements of either eye for about a minute. No eyeball movementindicates absence of reflex. Presence of ruptured eardrums or dischargefrom the ear prevents this test from being performed.

Testing of gag and cough reflex requires temporary disconnectionfrom the ventilator. A cotton tipped swab can be used to stimulate theposterior pharynx to look for a response. Experienced ICU staff usuallynotice a progressive loss of response during the evolution of brainstemdeath when performing the routine suction of airways andoropharynx.

The plantar response may continue to be present in brain deathpatients along with spinal reflexes and should not be tested. Thedecorticate and decerebrate posturing is absent, however on occasionsit may be difficult to differentiate from complex spinal reflexes.

Apnoea Test: The aim of apnoea test is to establishdeath of the respiratory centre in the brainstem (Table III). Itdemonstrates that the spontaneous respiratory response fails to occureven in the absence of stimulatory drive from CO2. For this test thepatient is disconnected from the ventilator for 10 minutes. However, toavoid hypoxia to vital organs, 100% oxygen is given for 5 minutesbefore disconnection of the ventilator. Even during the test period, 100% oxygen is given through a tracheal catheter. In the patient who isbrain dead the carbondioxide tension increase at a rate of 2mm/min (0.3kPa/min) during apnoea testing. If the initial CO2 tension beforetesting is about 40mmHg (5.3 kPa) then arterial CO2 tension after 10minutes is likely to be 60mmHg (8 kPa). However a rise to 50mmHg in CO2tension is acceptable and should provide sufficient stimulatory drivefor spontaneous respiration in an intact respiratory centre. Inpatients with chronic airway disease or severe chest trauma, the apnoeatest may be difficult to perform. 

Role of Cerebral Angiography & EEG for brain death testingfour-vessel angiography is used to show absence of the flow of cerebralblood flow and confirm death of whole brain. However this is cumbersomeinvestigation in an unstable patient and is not done routinely. Nor isit necessary to use EEG to diagnose the condition. If there is anydoubt in the diagnosis of brain death one should not proceed for arequest for organ donation and ventilatory support should be continued. In a case of severe facial trauma or presence of paralyses or severechest trauma routine tests may not be possible and one may require todo special tests like isotope scanning or colour flow duplex scanningof the cranium to confirm brain death. All these tests can havelimitations and can sometimes be inconclusive. In these inconclusivesituations, if organ donation is being contemplated, the patient srelatives should be told about it and the ventilator should only bedisconnected in the operation theatre and organ retrieval started onlyafter cardiac standstill. The Transplantation of Human Organ act doesnot require investigations like cerebral angiography or EEG brain deathcertification.
In children there remains uncertainty about thereliability of clinical brainstem testing. In neonates especiallyorgans for transplantation should not be removed in the first sevendays of life with beating hearts. Radioisotope brain scanning has beenrecommended under the age of one year when brainstem deathcertification is required.