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.

World Liver Day...ode to the liver

19th April is celebrated every year as the World Liver Day.

The liver is a vital organ of the body and performs more than 500 known vital functions. On this World Liver Day let us pledge to take good care of our good friend the liver

 Pablo Neruda immortalized the importance of the liver in his'Ode to the liver' in Spanish that has been translated in English below

Modest, organized friend, underground worker, let me give you the wing of my song, the thrust of the air, the soaring of my ode: it is born of your invisible machinery, it flies from your tireless confined mill, delicate powerful entrail, ever alive and dark.
While the heart resounds and attracts the music of the mandolin, there, inside, you filter and apportion, you separate and divide, you multiply and lubricate, you raise and gather the threads and the grams of life, the final distillate, the intimate essences.

Submerged viscus, measurer of the blood, you live full of hands and full of eyes, measuring and transferring in your hidden alchemical chamber.
Yellow is the matrix of your red hydraulic flow, diver of the most perilous depths of man, there forever hidden, everlasting in the factory, noiseless.

And every feeling or impulse grew in your machinery, received some drop of your tireless elaboration, to love you added fire or melancholy, let one tiny cell be in error or one fiber be worn in your labor and the pilot flies into the wrong sky, the tenor collapses in a wheeze, the astronomer loses a planet.
Up above, how the bewitching eyes of the rose and the lips of the matinal carnation sparkle! How the maiden in the river laughs!

And down below, the filter and the balance, the delicate chemistry of the liver, the storehouse of the subtle changes: no one sees or celebrates it, but, when it ages or its mortar wastes away, the eyes of the rose are gone, the teeth of the carnation wilted and the maiden silent in the river.
Austere portion or the whole of myself, grandfather of the heart, generator of energy: I sing to you and I fear you as though you were judge meter, implacable indicator, and if I can not surrender myself in shackles to austerity, if the surfeit of delicacies, or the hereditary wine of my country dared to disturb my health or the equilibrium of my poetry, from you, dark monarch, giver of syrups and of poisons, regulator of salts, from you I hope for justice: I love life: Do not betray me! Work on!

Do not arrest my song.

Organ retrieval to get caught in even more red tape
Organ retrieval is possible under current Indian law only from brain dead individuals. The only thing that can cause brain death in a medico legal case is severe head injury. Declaration of brain death unequivocally mandates that the cause of the brain injury must be clear and the circumstances known. All this gobbledygook about poisoning cases being prospective donors is totally irrelevant in the context of brain death. Injuries can be photographed and highly accurate imaging can reveal all that a forensic scientist needs in most cases to establish a cause of death. Injured organs in any case are unsuitable for transplantation and most centres will not be willing to accept donors who have penetrating chest or abdominal trauma. In such circumstances, in the larger interest of judicial process, a forensic team may be asked to be present. This entire process is so devoid of reason and logic that it would be funny if it did not threaten to endanger he lives of hundreds of patients needing life saving transplants. The rates of organ donation in India are already abysmally low and such mindless caveats are the last thing needed.