Human Organ Transplant Act

Indian parliament in July 1994 formulated HOTA to regulate transplant activities in India. This was necessitated by acts of selling and buying organs prevalent at the time and which had brought Indian medical system into disrepute all over the world.

This act immediately came into force in Goa, Himachal Pradesh, Maharashtra and Union Territories. This had to be ratified by various states before it could be applied to the rest of the country. Some of these states took a very long time before the act was applied.

In 2014, the act has been almost totally revised. The main aim of the act is to regulate all transplant activities, provide stringent punishment to offenders indulging in organ sales and traffic, clarify the confusing points in previous act and add grandparents to the list of near relatives. It also enhanced punishment to the offenders. This act also sought to encourage cadaver donation by various means.

This law further clarified the duties of Incharge in ICUs and made it mandatory for them to apply provisions of brain death and ask relatives if they are willing for cadaver donation in case a person had not prior to his death pledged to donate his organs.

This act also included nonmedical people (from police, judiciary, teaching professions etc) to become members of the authorizing committees. These committees decide whether a willing donor in case of living donor can donate his organs. These committees are also tasked with ascertaining financial position of the donors, motivation for donating an organ and seeing that organs are not sold or bought for transplant purposes. The committees also satisfy themselves in case of spouses that the donation is voluntary and without pressure.

The act provides for periodic review of the hospitals allowed to carry out transplant activity and publish their results of transplants undertaken by these. Various states have started their websites to regulate organ allocation and maintain a list of patients awaiting organ transplant.

The success of the act will depend on how meticulously and honestly the spirit of the act influences the transplant activity in the country.

FEVER

Body temperature in humans is regulated by an area of the brain called hypothalamus. The thermoregulatory center here keeps the core body temperature within a closely set limit. The body temperature varies by 0.5 ◦ C during a 24 hour period being lowest at about 6 A.M. and maximum at about 4 to 6 P.M.

A temperature of > 37.2◦ C in the morning at 6 and > 37.7 ◦ C in the afternoon is considered to suggest the occurrence of fever.

In most fevers, the body temperature is set at a higher level by increased level of Prostaglandin E in the blood and brain tissues in the hypothalamus. This occurs due to the production of various chemicals in the body.

In cases of infection or inflammation, various cytokines (IL -1, IL-6, TNF etc.) cause a rise in PGE. This may be mediated by production of various toxins e.g. Endotoxins, TSST etc. Once the temperature is set at a higher level, more heat is produced in the body and less is dissipated. This leads to higher core temperature.

The mechanisms for decreasing heat loss from the skin is by vasoconstriction (narrowing of blood supply to the skin). This allows less heat to be lost by the skin and is perceived as cold skin. More heat is produced by increased muscle contraction (shivering) or added heat production from the liver by increasing metabolism. These soon result in a higher body temperature. In most fevers, diurnal variations continue.

Covering the body by blankets raises the temperature faster as heat dissipation is no longer available.

Hyperthermia is a condition where body temperature is elevated without a higher “set point “ for the temperature in the brain. This can be rapidly fatal and in this condition, antipyretics do not work. This occurs either because heat is not lost from the body due to excessive insulation or environmental temperatures are very high as in heat stroke. Sometimes the cooling mechanism by sweating fails due to a skin condition. Metabolic derangements may also continuously produce heat. The use of drug “ECSTASY” and atropine may result in hyperthermia. Treatment is by rapid cooling by immersion in Ice, cooling blankets etc.

In hyperpyrexia, the temperature Is >41.5 ◦ C. However the set point is higher and treatment with antipyretics lowers the temperature. This can occur in severe infections and some diseases of the brain. Malignant hyperthermia is another condition in which temperatures are very high. Usually, there is a history of intake of drugs acting on CNS. This condition can also be very dangerous.

Treatment of fever is undertaken in common fevers if the temperature is >40 ◦ C or if headaches, body aches etc are troublesome. If temperatures are only moderately elevated, the antipyretics may not be required.

The antipyretics in common use are acetaminophen, aspirin, nimesulide and ibuprofen. These act by Cyclooxygenase inhibition which reduces PGE levels.  Quinine can also decrease temperature. Along with this, cooling by external means may be required in some cases. If antipyretics are taken, taking them in frequent doses reduces the discomfort due to “chills and rigors”.

Causes of Fever

Infections usually viral are a common cause of a fever. Most are self-limiting and last for a few days to 2 weeks. Bacterial, fungal and protozoal infections are also very common. Malaria, HIV, TB, Chickenpox, rubella, measles, picorna viruses, influenza are examples of infectious fevers.

Other causes of fever are inflammatory diseases, malignancies, drugs, metabolic conditions and various others. If the body’s defense mechanisms are lowered (due to low WBCs ), infections may become very dangerous. The rise of temperature does not correlate well with the severity of infections. In children, temperatures swing over wider ranges and settle as rapidly as they rise.

Brain Death

More than half of organ transplants in the world are carried out on organs obtained from deceased donors. In 1959 the term brain death came into vogue to describe patients who have a permanent cessation of brainstem or brain functions which are required to integrate functioning of the organism as a whole. Some tissues may still be “live” and can continue to grow in laboratories for indefinite periods. However, the organism as a whole does not live once brain death has occurred.

Conventionally brain death had been ascertained once the heart has stopped beating. However, a few heartbeats may occur for some time after the cessation of cardiac function and a few gasps may be seen. This criterion of clinical death has been replaced in most countries of the world by the concept of brain death.

In modern ICUs once brain death has occurred, spontaneous breathing does not occur. Hence patients are on ventilators and most require support to maintain blood pressure ( vasopressors).

What is brain death?

Brain death is the cessation of brain function and almost always accompanied by the stoppage of blood flow to the brain. This is in most cases due to injury as in road traffic accidents, falls or elsewhere. It is also a common result of subarachnoid bleed (bleeding inside the covering of brain in the cranial cavity).

How is brain death diagnosed?

Diagnosis of brain death requires expertise and experience.

Prerequisites for diagnosing brain death are

  • Cause of injury to the brain should be known and compatible with brain death.
  • Poisoning and drug intoxication should be excluded
  • The body temp should be above 36 C.
  • There should be no severe electrolyte or metabolic state (sugar, sodium, CO2 and O2 level)
  • Blood pressure should be >100 mm systolic

Clinical Examination :

Neurological examination reveals coma,

The absence of all reflexes originating from the brain stem.

The absence of motor activity originating from the brain (spinal cord reflexes and some involuntary movements may be seen)

Apnea test may be carried out by stopping mechanical ventilation, waiting for CO2 levels to rise and observing for spontaneous breathing. Oxygen is usually given at a high pressure before carrying out this test.

Laboratory Investigations:

These include

Tests to see absent blood flow. The methods employed may be MR Angiography, CT angiography, Nuclear scans, Trans Cranial Doppler etc

EEG and brain stem evoked potentials to ascertain activity.

These tests are usually carried out by more than one clinician. Neurologists, neurosurgeons, physicians, intensive care doctors, anesthesiologists are usually experienced in these tests. These tests are repeated after a time interval to ensure that the changes are indeed reproducible and permanent.

Most countries have their own definitions, examination patterns and requirements before brain death is declared including the qualifications of doctors declaring the same. It is equated with clinical death in most countries. However, the lack of clarity is apparent as yet there are no universally applicable guidelines.

Organs for various transplantation purposes can be obtained once brain death is declared and other laws and relatives permitting the same. The organs thus retrieved are in a reasonably healthy state as organ perfusion has continued till the retrieval and ischemia time is least.