Brain death....what is it?

Anatomy of the brain

Traditionally, a person who does not have a beating heart and is not breathing is considered to have died. However with the advent of mechanical ventilation, a person who is not spontaneously breathing can be oxygenated for a significant period of time using a mechanical ventilator.

The human brain is the command & co-ordination center of all body activities. It consists of four parts: the cerebral cortex, the cerebellum, the mid-brain and the brain-stem (pons & medulla oblongata).
The cerebral cortex has multiple functions importantly cognition, sensation, purposeful movement, wakefulness, thinking, speech and memory. The mid-brain among others is responsible for pupillary function and eye movement as it houses the centres controlling nerves responsible for these reflexes. The cerebellum controls co-ordinated movements, gait and balance. The brain stem houses centres for all the other cranial nerves including those for conjugated eye movement, corneal reflex, tracheal and conjugated eye movements. The medulla oblongata houses the critical breathing and vasomotor centres that are responsible for spontaneous breathing and maintenance of coordinated heartbeat and circulation.

It follows therefore that irreversible and major damage to the brain function is incompatible with life. Due to autonomic reflex and local mechanisms, some organs including the heart may continue to function for a period ranging from hours to weeks, but long term survival is precluded in the absence of coordination provided by the brain.
The hallmarks of lack of brain and in particular brain-stem activity are
Deep coma ( absence of spontaneous movement, absence of response to deep pain)
Absence of spontaneous breathing
Loss of reflexes coordinated by nerves in the mid-brain & brain stem ie corneal reflex, pupillary reaction, cough & gag reflex, dolls eye reflex, cold caloric reflex

Such severe damage to the brain can result from various causes
Brain hemorrhage
Brain hypoxia (Due to cut-off of oxygen supply)
Brain injury
Rise in pressure in and around the brain (intra-cranial pressure) due to infection or tumours

Once the damage to the brain becomes irreversible, despite having a heart beat, the individual is unable to perceive any stimulus, unable to awaken, unable to move and has no spontaneous breathing. Such a person is considered to be Dead by neurological criteria or Brain dead.

It is important to differentiate this situation form other neurological syndromes like Persistent Vegetative State  or Minimally responsive state. The fundamental difference is that in these other conditions, brain stem function is partially or totally preserved despite the lack of response to stimuli and hence brain death is often also referred to as Brain stem death to emphasize the irreversible loss of brain stem functions.

To diagnose a comatose person on mechanical ventilator to have suffered brain death, the proximate cause of brain injury should be known or identifiable and irreversibility should be established. Generally to diagnose this condition clinically, one should reliably rule out presence of shock (severe reduction in blood pressure), hypothermia (body temperature <35 administration="" also="" anaesthesia="" be="" br="" intake="" narcotics="" of="" or="" out.="" ruled="" should="" soporifics=""> To establish that an individual has undergone Brain death the following is deemed necessary and sufficient

Deep coma (no spontaneous movement or response to call )
Absence of cranial nerve reflexes (corneal reflex, pupillary reaction to light, corneal & tracheal/pharyngeal reflex, dolls eye reflex)
Absence of spontaneous respiration despite rise in CO2 (Apnea test)

The Apnea test is mandatory for the declaration of brain-stem death. After ruling out hypothermia and hypoxia, the individual is pre-oxygenated and is disconnected from the ventilator and oxygen is delivered at 6L/min through a catheter into the trachea after baseline arterial blood gas analysis. Close watch is maintained for spontaneous chest wall movements due to respiratory excursions or actual breaths. After 8 minutes, the individual is reconnected  to the ventilator and arterial blood gases are analysed. If there is no spontaneous respiration despite adequate rise in PCO2 levels (usually 60 mm mercury or 20mm rise above baseline) during disconnection, the test is positive and irreversible brain stem damage is confirmed.

Most experts agree that in a case ( excluding infants) where cause of brain injury is not drug overdose or poisoning, a six hour period is sufficient to gauge for signs of recovery before brain death can be confirmed.

Other tests like EEG, Cranial doppler, Cerebral angiography, Evoked potential study or SPECT are not required to diagnose brain death but may be performed when the testing is equivocal.

With the advent of severe brain stem dysfunction, normal body function is severely deranged. Significant and progressive alterations occur in cardiovascular, metabolic, immune and endocrine systems that if untreated can lead to rapid progression to cardiac arrest.

 Rapid rise in the intracranial pressure can lead to herniation of the brain stem and pressure on the vasomotor centre causing instant cessation of circulation and cardiac death. Slower rises compromise blood flow to the brain and evoke initially a  fall in heart rate followed by sympathetic storm characterised by rapid heart rate and rise in blood pressure. Eventually heart damage and lack of blood supply to the vasomotor centre lead to collapse and cardiac arrest.
Process of brain stem death also leads to deranged function of the pituitary gland leading to reduction in thyroid hormone, anti-diuretic hormone (ADH) and cortisol release.  This derangement (in particular ADH) causes significant changes in ability of body to maintain temperature, blood glucose level and fluid electrolyte balance without significant extraneous support. Diabetes insipidus-like state induced by lack of ADH causes massive urinary water losses leading to cellular dehydration and rise in sodium levels. Brain death also leads to hyper-activation of the immune system, white cell activation and release of inflammatory substances like cytokines in the blood, similar to those seen in a systemic inflammatory response (SIRS) to infection. This further leads to loss of vascular tone, reduced blood supply to cells and shunting further depriving organs of blood and oxygen eventually leading to cell death. All these mechanisms are activated immediately after brain stem injury but the speed of impact may vary and with adequate monitoring and support, hours to days may elapse before circulatory collapse and cardiac arrest. However once brain death is established, recovery is impossible and cardiac arrest is only a matter of time.