A detailed presentation on Brain Death and Ongan transplantation.
Criteria for Brain Death are explained in detail. Legislative laws regarding the organ transplant, organ preservation are also explained.
Hemostasis Physiology and Clinical correlations by Dr Faiza.pdf
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BRAIN DEATH AND ORGAN TRANSPLANTATION
1. BRAIN DEATH AND ORGAN
TRANSPLANTATION
DR. ARTI ANAND PGY3, S3
MODERATORS
DR. SHAJI THOMAS, DIR. PROFESSOR, S3
DR. ASHISH ARSIA, PROFESSOR, S3
2. SYNOPSIS
⢠BRAIN DEATH - CRITERIA
⢠LEGISLATURE REGARDING BRAIN DEATH IN INDIA
⢠ORGAN TRANSPLANTATION â BASIC PRINCIPLES
⢠CADAVER DONATION AND HUMAN ORGAN TRANSPLANT ACTS
⢠ETHICAL AND MEDICOLEGAL ASPECTS OF ORGAN TRANSPLANTATION
⢠ORGAN TRADING AND PREVENTION
3. BRAIN DEATH
⢠The history of brain death dates back to late 19th century, when many
authors reported cessation of respiration but continued heartbeat in
patients of cerebral diseases with increased intracranial pressure.
⢠In 1968, Harvard Medical School published a landmark report, âthe
definition of irreversible coma.â It defined the criteria for determining
brain death as apneic coma and absence of elicitable brain-stem
reflexes for a period of 24 hours as confirmed by an
electroencephalogram
⢠In 1994, India enacted a law to legalize brain-stem death.
4. ⢠India follows the UK concept of brain-stem death and the Transplantation
of Human Organs (THO) Act was passed by Indian parliament in 1994
which legalized the Brain-stem death.
⢠Despite this, the brain-death is not promptly declared in India due to lack
of awareness and doubts about the legal procedure of certifying brain-
death.
⢠Throughout history, across cultures, the moment of death is held in great
fascination. The change in status from living person to corpse is not a
mere clinical phenomenon; it has profound psychological, legal, moral,
religious, and economic implications.
⢠Diagnosis of brain-stem death is required to discontinue artificial
ventilation and to ask legal consent for organ donation from relatives.
5. DEFINITION OF BRAIN DEATH
The WHO, Global Glossary of Terms and Definitions on Donation and
Transplantation, 2009, defines brain stem death as: âIrreversible
cessation of cerebral and brain stem function; characterized by
absence of electrical activity in the brain, blood flow to the
brain, and brain function as determined by clinical assessment
of responses. The three essential findings in brain death are
â Coma, absence of brainstem reflexes, apnea.
6. CAUSES OF BRAIN DEATH
MOST COMMON -
⢠Direct trauma with head injury (e.g.., RTA)
⢠Subarachnoid hemorrhage
⢠Ischemic stroke
OTHERS â
⢠Intracerebral hemorrhage
⢠HIE, etc.
7. ⢠In India, as per section 3(b) of THOTA, a panel of four
physicians including the treating physician, a physician
representing the treating hospital, an independent specialist,
and a neurologist or neurosurgeon is convened to determine
brain stem death along with the registered medical practitioner
in charge of that hospital.
⢠Assessment of brain stem reflexes should be done using a series
of tests, which are to be repeated within an interval of 6
hours by a panel of four doctors. It is mandatory that all four
doctors witness these tests done 6 hours apart.
⢠The apnea test is the last brain stem reflex test to be performed,
and that too, only if the previous tests confirm that there are no
more brain stem reflexes. At this stage, informed written consent
is to be obtained by the doctor.
8. DETERMINATION OF BRAIN DEATH
1. Identification of history and examination findings that provides a clear
etiology of the brain dysfunction â identification of a proximate cause.
2. EXCLUSION of any condition that might confound the examination of
cortical and brain stem functions â includes
Shock/ hypotension, hypothermia (<32deg),
Drugs (like anesthetic agents, neuroparalytic drugs, methaqualone,
barbiturates, benzodiazepines, amitriptyline, alcohol, trichloroethylene),
Brain stem encephalitis, Guillaine barre syndrome,
hepatic and uremic encephalopathy,
severe hypophosphatemia.
1. Complete neurological examination to determine brain death
9. NEUROLOGICAL EXAMINATION TO
DETERMINE BRAIN DEATH
1. Examination of the patient â absence of spontaneous breathing,
posturing, seizures, shivering, response to verbal stimuli, response to
noxious stimuli
2. Absent pupillary reflexes â direct and consensual
3. Absent Corneal, oculocephalic, gag reflexes
4. Absent Oculovestibular reflex â 20-50ml ice water irrigated into the
EAC with elevation of head to 30 degrees
5. Failure of heart rate to increase by more than 5bpm after 1-2mg
atropine given IV (indicates absent vagus function)
6. Absent respiratory efforts in spite of hypercarbia- (apnea test)
Prerequisites- core temp >36.5 C/ euvolemia with positive fluid balance
over last 6 hrs./ PCO2 >40mmHg/ PO2>200mmHg.
10. APNEA TEST
⢠Patient is pre-oxygenated with 100% oxygen for 10 minutes
⢠A pulse oximeter is connected, the ventilator is disconnected and 100%
O2 delivered at 6L/min into the trachea- a catheter is placed through the
ET tube close to the level of the carina
⢠Any respiratory movements is looked for closely.
⢠After 8 minutes, arterial PO2, PCO2, pH are measured. The ventilator is
then reconnected.
11. ⢠If respiratory movements are absent, and PCO2 > 60mmHg, the apnea test
is positive. (i.e., the person is brain dead).
⢠If any respiratory movements are observed, it does not support the
diagnosis of brain death.
⢠NOTE- if at any point during the testing, if systolic bp gets <90 mmHg/
pulse oximeter shows significant oxygen desaturation/ cardiac arrhythmias
develop, the ventilator is immediately reconnected. The above blood tests
are taken to determine PCO2 elevation.
12. ASSESSMENT OF BRAINSTEM REFLEXES
1. Pupils â no response to bright light.
2. Pupil size â mid-dilated (4mm) or dilated (9mm) â CN 2,3
3. Ocular movements - oculocephalic reflex, oculovestibular reflex â CN 8,3,6
4. Facial sensations and facial motor response â corneal reflex, jaw reflex, grimace to
deep pressure on nail bed/ supraorbital ridge/ TM joint â CN 5, 9
5. Pharyngeal and tracheal reflexes â stimulation of posterior pharynx, cough
response on tracheobronchial suctioning.
13. CLINICAL OBSERVATIONS COMPATIBLE
WITH BRAIN DEATH
The following may be occasionally seen and should not be misinterpreted as
presence of brainstem function
1. Spontaneous limb movements other than pathological flexion or extension
response
2. Respiration-like movements â shoulder elevation, adduction, back arching,
intercostal expansion without significant tidal volumes
3. Sweating, flushing, tachycardia
4. Normal blood pressure without pharmacological support or sudden increases
in blood pressure
5. Deep tendon reflexes, superficial abdominal reflexes, triple flexion response
6. Babinskiâs reflex
14. ⢠The diagnosis of brain death is primarily clinical. If the full clinical
examination and assessment of brain stem reflexes and apnea test is
positive, brain death is said to be confirmatory.
⢠The facility must make diligent efforts to notify the patientâs kin that the
process for determining brain death is underway. Religious or moral
objections if any, should be noted.
⢠In some patients, with skull or cervical injuries or in cardiovascular
instability, it may be impossible to complete parts of the assessment
safely. In such cases, confirmatory tests verifying brain death is
necessary. The confirmatory tests are â angiography (absence of
intracerebral filling at the level of carotid bifurcation or circle of Willis),
EEG (absence of electrical activity during at least 30 minutes of recording) ,
nuclear brain scanning (absence of uptake of radioisotope in brain
parenchyma), Transcranial Doppler ultrasonography
15.
16.
17. Brain (stem) death needs to be differentiated from persistent vegetative
state
18. LAWS AND RULES GOVERNING ORGAN
DONATION AND TRANSPLANTATION IN
INDIA
19. ⢠India is currently having a cadaver donation rate of 0.05 to 0.08 per
million population.
⢠There are currently over 120 transplant centers in India performing
approximately 3,500 to 4,000 kidney transplants annually. Out of these
transplant centers, four centers undertake approximately 150 to 200 liver
transplants annually while some of these centers also do an occasional
heart transplant. Presently, approximately 50 liver transplants are done
from deceased donors and the rest are from living donors
20. ⢠Kidneys
⢠Liver
⢠Heart
⢠Lungs
⢠Intestine
⢠Pancreas
⢠Cornea
⢠Skin
⢠Cartilage/ ligaments
⢠Bones/ tendons
⢠vessels
LIVE ORGAN DONATION
WHAT ORGANS CAN A DECEASED
(CADAVER) DONOR DONATE?
⢠Single kidney (most common)
⢠Part of the liver
21. ORGAN DONATION
There are three variants of consent in practice in relation to organ harvesting.
⢠1. âopt-inâ consent. A person's agreement to allow something to happen to him
made with full knowledge of the risks involved
⢠2. âopt-outâ consent. Under presumed consent, the decedent would be
âpresumedâ to be willing to have their organs harvested on death.
⢠3. The third is âmandated choice,â where all adults are required to express their
preferences regarding donation at the time they execute a state-regulated
task and their decisions would be controlling.
In India, we follow the âopt-inâ form of consent for retrieval of organs from
deceased
22. TYPES OF LIVING ORGAN DONATION
⢠LIVING NEAR RELATED DONORS â only immediate blood relations
are accepted â parents, siblings, children, spouse, grandparents
and grandchildren.
⢠LIVING NON- NEAR RELATIVE DONORS â They can donate only for
the reason of attachment or affection towards the recipient.
⢠SWAP DONORS â in cases where living near-relative donor is
incompatible with the recipient, donors between two such pairs
are swapped.
23. ORGAN TRANSPLANTATION
⢠The role of a transplant coordinator is only to assist the registered medical
practitioner in examining and verifying the authorization given by the
deceased and or obtaining the consent for removal of organ from the legal
heir or the person who is in lawful possession of the body of the deceased
person
⢠The role of the transplant coordinator is also to counsel the family members
of the deceased person about organ donation and also to coordinate the
process of donation and transplantation.
⢠According to the Section 14 (4) of THOTA, hospitals engaged in transplants
and related activities are required to register and obtain registration from
the appropriate authority appointed for the purpose of the Act
24. Main provisions of THO act includes â
1. For living donation â first degree relatives who can donate without any
formalities include â mother, father, sisters, son, daughter and spouse.
They are required to provide proof of their relationship by genetic
testing and/or by legal documents.
2. Formation of an authorization committee in each state that â approves
or rejects transplants between recipients and donors other than a first
relative, to regulate the removal, storage and transplantation of human
organs by hospitals licensed to do the same by the authority.
25. ⢠The gazette states that before removing a human organ from the body of a
donor before his death, a medical practitioner should satisfy himself that
the donor has given authorization in Form 1(A) if the relative is a close
relative i.e., a mother, father, brother, sister, son, or daughter. Form 1(B) is
used for a spouse and Form 1(C) is used for other relatives.
⢠The donor is in a proper state of health and is fit to donate the organ.
The registered medical practitioner should then sign a certificate stating
the same.
⢠The relationship between the donor and recipient also needs to be
examined to the satisfaction of the Registered Medical Practitioner in
charge of the transplant center
26. ⢠The medical practitioner also has to confirm that the person lawfully in
possession of the dead body has signed a certificate.
⢠The practitioner shall, before removing a human organ from the body of a
person in the event of brain-stem death, confirm that the certificate is
signed by all the members of the board of medical experts and in case of
brain-stem death of a person of less than 18 years of age, it is also signed
by either of the parents.
⢠When the proposed transplant is between persons related genetically (first
degree relative) then tissue typing is done along with other documentary
evidence.
⢠If the relationship is not conclusively established after evaluation of the
above evidence, direct further medical tests may be given like â test for
HLA by PCR based DNA testing methods/ test for human leukocyte
antigen-DR beta genes by PCR based DNA methods.
27. CADAVER DONATION
⢠According to THOTA of India, if any human organ is to be removed from
the body of a deceased person, the registered medical practitioner shall
first conduct an examination of the body.
⢠No authority shall be given for removal of any human organ from the body
of a deceased person if the medical practitioner believes, that an inquest
may be required to be held in relation to the body.
⢠In the case of a dead body lying in a hospital or prison and not claimed by
an near relatives of the deceased within 48 hours from the time of death,
the authority for removal of human organs from the deceased body can be
given by the person in charge, or by an employee of the institution.
28. ORGAN PRESERVATION
⢠Organ preservation is the supply line for organ transplantation.
⢠The Liver, Pancreas and Kidney can be successfully preserved for up to 2
days by flushing the organs with the University of Wisconsin organ
preservation solution and storing them in hypothermia (0 â 5 degrees)
⢠The UW solution contains a number of cell impermeable agents (lacto
bionic acid, raffinose, hydroxyethyl starch) that prevent cell swelling
during cold ischemic storage. It also contains agents that may stimulate
recovery of normal metabolism upon reperfusion
⢠Intrathoracic organs like Lungs and the Heart are less well preserved,
especially not for more than 8 hours.
29. PREVENTION OF ORGAN TRADING
In accordance with the THO act amendment of 2011, section 19
Whoever
⢠Makes or receives any payment for the supply of, or for an offer to supply, any human tissue or
⢠Offers to supply any human tissue for payment or
⢠Seeks to find person willing to supply for payment and human tissue or
⢠Initiates or negotiates any arrangement or control of a body of persons, whether a society/firm/company,
whose activities consist of or include the initiation or negotiation of any arrangement or
⢠Publishes or distributes or causes to be published of distributed any advertisement â inviting persons to
supply for payment of any human tissue or
⢠Abets in the preparation or submission of false documents including giving false affidavits to establish
that the donor is making the donation of human tissue as a near relative
SHALL BE PUNISHABLE WITH IMPRISONMENT FOR A TERM WHICH SHALL BE NOT LESS THAN ONE
YEAR, BUT MAY EXTEND TO THREE YEARS AND SHALL BE LIABLE TO A FINE WHICH SHALL NOT BE LESS
THAN FIVE LAKH RUPEES BUT WHICH MAY EXTEND TO TWENTY-FIVE LAKH RUPEES.
30. Considering the success of organ transplants and that organ transplants are
the only hope for end stage organ failures; in view of acute shortage of
organs and availability of a large number of brain dead patients as potential
organ donors; we must promote the timely diagnosis and declaration of
brain dead patients. It will allow the organ transplantation to gift a life
31. REFERENCES
1. David M. Greer, âDetermination of Brain Deathâ N Engl J Med 2021;
385;2554-61.
2. Aboubakr M, Yousaf MIK, Alameda G. Brain Death Criteria. [Updated 2021
Dec 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;
2022 Jan.
3. Anant Dhanwate âBrainstem death: A comprehensive review in Indian
perspectiveâ Indian J Crit Care Med 2014 Sep; 18(9): 596â605.
4. Government of India. Transplantation of Human Organs Act, 1994. 1994
5. Goila AK, Pawar M. The diagnosis of brain death. Indian J Crit Care Med.
2009 Jan-Mar;13(1):7-11. doi: 10.4103/0972-5229.53108. PMID: 19881172;
PMCID: PMC2772257.