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Dr. T.R.Chandrashekar
Intensivist, Liver transplantation.
Department of Surgical Gastroenterology
BMC & RI super-specialty Hospital. Bangalore.
Management of Organ Donor
Following Brain Death
Transplantation of Human Organs Act, (THOA) 1994, 2011, 2014
Potential Brain dead DONOR
DONOR Referral
Donor management
Donor consent
Actual
Donation
Brain death testing ,Twice at a interval of 6 hrs
Organ retrieval
Huge Gap
In India around 2.5- 3
lakh patients die of
liver failure due to
cirrhosis
More than 25,000
require transplant
every year
Only 500 liver
transplants for
Indian patients
done per year
2%
Potential deceased donor
 In transplantation center
 In authorised retrieval hospital
 Referral hospital- has to be shifted to transplant
centers according to ROTA of state coordination
committee (ZCCK)
 Intensivist motivates
 Relatives voluntarily agree and contact ZCCK, these
patients are in a "benign neglect” hence risk of shifting
is high
Clinical Triggers That Should Prompt
Notification of the Organ
Procurement Organization
 At the initial indication that a patient has
suffered a non recoverable neurologic injury
(e.g., documented loss of cranial nerve reflexes)
 As soon as a formal “brain death” examination
is contemplated
 Before initiating a discussion that may lead to
withdrawal of life-sustaining therapy
ICU caregivers should notify transplant team within 1 hour after a
patient meets specified clinical triggers.
Clinicians should consider organ donation as part of end of-life
decisions.
WHY TEST?
Where Brain Stem Death (BSD) is suspected, it is
highly desirable to confirm this by Brain Stem
Testing:
• To eliminate all possible doubt regarding
survivability
• To confirm diagnosis for families
• In cases subject to medico-legal scrutiny
• To provide choice regarding organ donation
The declaration of brain death is based on straight-
forward principles:
The presence of unresponsive coma.
The absence of brain stem reflexes.
The absence of respiratory drive after a CO
2
challenge.
(Apnea test)
Ancillary testing ( any one)
Cerebral angiogram (insufficient evidence to recommend use of
CT or MRI angiography)
Hexylmethylpropylene amineoxine single-photon emission CT
Electroencephalography
Transcranial Doppler ultrasonography
If apnea test aborted or still in doubt
GOALS
 Impetus shifts from optimizing cerebral
perfusion pressure to maintaining hemodynamic
stability
 Diagnosing neurologic death (should it occur)
 Preparing the family for devastating news
 Counseling them on end-of-life issues
 Preserving the option of organ donation.
Timing of the Request
for Deceased Organ
Donation
Primary care giver
Intensivist
Transplant coordinators
Separating requests for
donation from the family
notification of brain
death, a process known
as “decoupling” is
advised
Who Should Request Authorization ?
Superior communication
skills, increased time with
families of potential donors,
trained to handle grief
counseling and also superior
knowledge about THOA
“Family consent” is a vague term, and, unlike in some countries,
no hierarchy of relatives has been specified in the rules.
Consent for Organ donation
 A patient’s previously expressed preferences for
organ donation are paramount. ICU clinicians
and coordinator/ ZCCK should retrieve proof
of such authorisation.
 Another clause in from 8
 There are reasons to believe that no near relative
of the said deceased person has objection to any
of his/her organs/tissue being used for
therapeutic purposes.
For organ RetrievalFirst declaration 6 hours interval
Issues with Medico-Legal cases
 Police clearance
 FIR registration station is required to give
clearance and sign the permission for PM
 Post Mortem timings
Delay in PM
Grief stricken families in hospital
Relatives waiting at donors residence
Time pressure for both relatives and
doctors- leads to conflicts
ICU Management
of the Brain Dead Potential Donor
 Stabilize profound physiologic and
homeostatic derangements provoked by BD
 Balance competing management priorities
between different organs
 Avert somatic death and loss of all organs
Clin Infectious Diseases
Delmonico Fl 2000; 31 : 781-786
Routine serological testing of donors
• Antibody to HIV
• Hepatitis B surface antigen
• Antibody to Hepatitis B core antigen
• Antibodyto Hepatiotis B surface antigen
• Antibody to Hepatitis C virus
• Antibody to Cytomegalo Virus
CBC/ ABG
LFT/ RFT/ SE
Coagulation profile/
TEG
Two blood cultures
Urine and sputum
culture
Antibiotics as per cultures if present same may be used for recipients also
Physiologic Changes with Brain Death
Neurologic
Cardiovascular
Pulmonary
Endocrine
Hypothermia
Metabolic
Pro-
inflammatory
state
Incidence of organ involvement
 Hypotension 81%
 Diabetes insipidus 65%
 DIC 28%
 Cardiac dysrrhythmias 25%
 Pulmonary oedema 18%
 Metabolic acidosis 11%
J Heart Lung Transplantation 2004 (suppl)
Competing physiologic needs
Heart: Balanced Fluids, Vasopressin
Kidney: Liberal Fluids, Dopamine
Lungs: Conservative Fluids, No Pressors
Liver: Isotonic fluids
Failure of hypothalamo-pituitary axis
Decline in plasma hormone concentration
ADH, TSH
Impaired TSH secretion
Impaired peripheral conversion of T4
Reduced T3- progressive loss of cardiac
contractility
Increased anaerobic metabolism
Hypoadrenalism
Impairs donors stress response
Cardiovascular collapse
Decreased insulin secretion
Hyperglycaemia
Endocrine changes
Compared to usual care
Society of Critical Care Medicine/American College of Chest
Physicians/Association of Organ Procurement Organizations
Donor Management Task Force
Crit Care Med 2015; 43:1291–1325
Hemodynamic changes with BD
 10-20% donors are lost to cardiovascular collapse as
patient evolves to brain death
 Volume Depletion in BD
 Causes multifactorial
 Underlying medical condition – blood loss, etc
 Prior management – osmotic therapy for ICP
 Neuro-hormonal cascade
 Capillary Leak
 Diabetes Insipidus
 50% of potential BD donors are volume responsive
Muragan, CCM, 2009
Target lactate, ScVO2, TTE, CVP
 General guidelines for adequate IV fluid
resuscitation are as follows:
a. Mean arterial pressure at least 60 mm Hg.
b. Urine output at least 1 mL/kg/hr.
c. Left ventricle ejection fraction at least 45%.
d. Lower vasopressor dose (e.g., dopamine ≤ 10
μg/kg/min).
 Use Isotonic crystalloids ,0.9% saline and
lactated Ringer solution
Vasoactive Medications – Pressors
Noradrenaline in vasodilatory shock
Dopamine
 Traditional 1st line pressor
 1-10 mcg/kg/min
 Inotrope and vasopressor
 Pro – suppresses
inflammation; mitigates
ischemia-reperfusion
injury
 Con – suppresses anterior
pituitary hormone
function
Vasopressin
 Alternative 1st line pressor
 .01-.04 IU/min
 Vasoconstrictor
 Pro – catecholamine sparing
effect; concurrent rx of
DI
 Con - Decreases splanchnic
perfusion
Vasoactive Medications -
Inotropes
 If EF < 45% despite volume
repletion and pressors,
add inotrope
 Dobutamine, Epinephrine
 If EF remains depressed despite inotrope,
consider starting hormonal replacement therapy
(HRT)
Corticosteroid administration
Methyl-prednisolone 1,000 mg IV, 15 mg/kg IV, or 250
mg IV bolus followed by infusion at 100 mg/hr.
Corticosteroid repletion reduces inflammation in
donor livers
 Lower levels pro-inflammatory cytokines – serum,
tissue
 Fewer adhesion molecules in tissue
 Less ischemia-reperfusion injury
 Lower acute rejection rates
Given after blood has been collected for tissue typing as it
has the potential to suppress HLA expression.
AVP ↓-DI
 Polyuria (> 200ml/hr for 3hrs).
 Normal or increased serum osmolality.
 Inappropriately dilute urine (specific gravity < 1.005,
 Urine osmolality < 200 mOsm/kg H2O).
 Hypernatremia (Na+ > 145 mmol/L).
Hypotension -Vasopressin : 1 unit bolus; Infusion at 1-4 units/hr
IF sodium, > 145–150 mmol/L without hypotension, treatment with
Desmopressin should be initiated. ( Nasal Spray)
Bolus IV dose of 1–4 μg, additional 1 or 2 μg every 6 hours
AVP + Desmopressin can be used concurrently in unstable patients
Our protocol -Hormonal
replacement
• Vasopressin : 1 unit bolus; Infusion at 1-4 units/hr
• Triiodothyronine - 4mcg bolus, infusion at 3 mcg/hr (
levothyroxine 100 mcg NG )
• Methlyprednisolone – 1 gram bolus every 12th hrly
• Insulin - 1 unit/hr minimum and titrate
Na < 155 and Glu < 160,
Aim for temperature >36o C
Donor Management Goals
 Develop protocols to optimize donor organ
function and maximize organs per donor
 Borrow concept of “bundles” from other
disease management models
 Represent consensus of physiologic targets
based on expert opinion
 Modest clinical studies to support use
Thank You
Potential organs for retrieval
• Heart
• Lung
• Liver
• Kidney
• Cornea
• Pancreas
• Small bowel
• Vessels, Tissues
Organ Preservation Time
 Heart: 4-6 hours
 Lungs: 4-6 hours
 Liver: 12 hours
 Pancreas: 12-18 hours
 Kidneys: 72 hours
 Small Intestines: 4-6
hours
‘Collateral damage’
 Hormonal
• Diabetes insipidus
 Hypovolaemia
 Hypernatraemia
• T3 / T4 reduces
• ↓ACTH/ cortisol levels
• Blood glucose
 Hypothermia
Organ Donation Past, Present and Future
 Hemodynamic assessments for brain-dead
donors include
 serial determination and interpretation of
 a. Mixed venous oxygen saturation.
 b. Lactate.
 c. Base deficit and acid-base status.
 d. CVP, PAOP, or noninvasive hemodynamic
parameters. TTE TEE ECHO
Our protocol -Hormonal
replacement
• Vasopressin : 1 unit bolus; Infusion at 1-4 units/hr
• Triiodothyronine - 4mcg bolus, infusion at 3 mcg/hr (
levothyroxine 100 mcg NG )
• Methlyprednisolone – 1 gram bolus every 12th hrly
• Insulin - 1 unit/hr minimum and titrate
Temperature
 Temperature regulation lost
 Hypothermia
 Physiological changes
associated with hypothermia
 Sepsis
 Coagulation abnormality
Fluid warmers
Forced air warming blankets
Inspired gas humidification
Minimise exposure to
environmental
temperature
Aim for temperature >36o C
It is imperative that the same rigor that is applied to
the care of living patients be employed in the care
of organ donors.
Metabolic changes with BD
 Hypernatremia
 Caused by volume depletion, Diabetes insipidus
 Na > 170 associated primary non-function (PNF)
of graft liver
 Hyperglycemia
 Caused by insulin resistance and gluconeogenesis
 Glu > 200 associated with PNF of graft pancreas
 Glu > 160 associated with PNF of graft kidney
Pulmonary Changes in BD
 Pulmonary edema
 Neurogenic
 Cardiogenic
 Non-cardiogenic – capillary endothelial leak
 Delayed alveolar fluid clearance
 LPV should be used in all BD

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Management of organ donor following brain death 2016

  • 1. Dr. T.R.Chandrashekar Intensivist, Liver transplantation. Department of Surgical Gastroenterology BMC & RI super-specialty Hospital. Bangalore. Management of Organ Donor Following Brain Death
  • 2. Transplantation of Human Organs Act, (THOA) 1994, 2011, 2014
  • 3. Potential Brain dead DONOR DONOR Referral Donor management Donor consent Actual Donation Brain death testing ,Twice at a interval of 6 hrs Organ retrieval
  • 4. Huge Gap In India around 2.5- 3 lakh patients die of liver failure due to cirrhosis More than 25,000 require transplant every year Only 500 liver transplants for Indian patients done per year 2%
  • 5. Potential deceased donor  In transplantation center  In authorised retrieval hospital  Referral hospital- has to be shifted to transplant centers according to ROTA of state coordination committee (ZCCK)  Intensivist motivates  Relatives voluntarily agree and contact ZCCK, these patients are in a "benign neglect” hence risk of shifting is high
  • 6. Clinical Triggers That Should Prompt Notification of the Organ Procurement Organization  At the initial indication that a patient has suffered a non recoverable neurologic injury (e.g., documented loss of cranial nerve reflexes)  As soon as a formal “brain death” examination is contemplated  Before initiating a discussion that may lead to withdrawal of life-sustaining therapy ICU caregivers should notify transplant team within 1 hour after a patient meets specified clinical triggers. Clinicians should consider organ donation as part of end of-life decisions.
  • 7. WHY TEST? Where Brain Stem Death (BSD) is suspected, it is highly desirable to confirm this by Brain Stem Testing: • To eliminate all possible doubt regarding survivability • To confirm diagnosis for families • In cases subject to medico-legal scrutiny • To provide choice regarding organ donation
  • 8. The declaration of brain death is based on straight- forward principles: The presence of unresponsive coma. The absence of brain stem reflexes. The absence of respiratory drive after a CO 2 challenge. (Apnea test) Ancillary testing ( any one) Cerebral angiogram (insufficient evidence to recommend use of CT or MRI angiography) Hexylmethylpropylene amineoxine single-photon emission CT Electroencephalography Transcranial Doppler ultrasonography If apnea test aborted or still in doubt
  • 9. GOALS  Impetus shifts from optimizing cerebral perfusion pressure to maintaining hemodynamic stability  Diagnosing neurologic death (should it occur)  Preparing the family for devastating news  Counseling them on end-of-life issues  Preserving the option of organ donation.
  • 10. Timing of the Request for Deceased Organ Donation Primary care giver Intensivist Transplant coordinators Separating requests for donation from the family notification of brain death, a process known as “decoupling” is advised Who Should Request Authorization ? Superior communication skills, increased time with families of potential donors, trained to handle grief counseling and also superior knowledge about THOA “Family consent” is a vague term, and, unlike in some countries, no hierarchy of relatives has been specified in the rules.
  • 11. Consent for Organ donation  A patient’s previously expressed preferences for organ donation are paramount. ICU clinicians and coordinator/ ZCCK should retrieve proof of such authorisation.  Another clause in from 8  There are reasons to believe that no near relative of the said deceased person has objection to any of his/her organs/tissue being used for therapeutic purposes. For organ RetrievalFirst declaration 6 hours interval
  • 12. Issues with Medico-Legal cases  Police clearance  FIR registration station is required to give clearance and sign the permission for PM  Post Mortem timings Delay in PM Grief stricken families in hospital Relatives waiting at donors residence Time pressure for both relatives and doctors- leads to conflicts
  • 13. ICU Management of the Brain Dead Potential Donor  Stabilize profound physiologic and homeostatic derangements provoked by BD  Balance competing management priorities between different organs  Avert somatic death and loss of all organs
  • 14. Clin Infectious Diseases Delmonico Fl 2000; 31 : 781-786 Routine serological testing of donors • Antibody to HIV • Hepatitis B surface antigen • Antibody to Hepatitis B core antigen • Antibodyto Hepatiotis B surface antigen • Antibody to Hepatitis C virus • Antibody to Cytomegalo Virus CBC/ ABG LFT/ RFT/ SE Coagulation profile/ TEG Two blood cultures Urine and sputum culture Antibiotics as per cultures if present same may be used for recipients also
  • 15. Physiologic Changes with Brain Death Neurologic Cardiovascular Pulmonary Endocrine Hypothermia Metabolic Pro- inflammatory state
  • 16. Incidence of organ involvement  Hypotension 81%  Diabetes insipidus 65%  DIC 28%  Cardiac dysrrhythmias 25%  Pulmonary oedema 18%  Metabolic acidosis 11% J Heart Lung Transplantation 2004 (suppl)
  • 17. Competing physiologic needs Heart: Balanced Fluids, Vasopressin Kidney: Liberal Fluids, Dopamine Lungs: Conservative Fluids, No Pressors Liver: Isotonic fluids
  • 18. Failure of hypothalamo-pituitary axis Decline in plasma hormone concentration ADH, TSH Impaired TSH secretion Impaired peripheral conversion of T4 Reduced T3- progressive loss of cardiac contractility Increased anaerobic metabolism Hypoadrenalism Impairs donors stress response Cardiovascular collapse Decreased insulin secretion Hyperglycaemia Endocrine changes
  • 20. Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Donor Management Task Force Crit Care Med 2015; 43:1291–1325
  • 21. Hemodynamic changes with BD  10-20% donors are lost to cardiovascular collapse as patient evolves to brain death  Volume Depletion in BD  Causes multifactorial  Underlying medical condition – blood loss, etc  Prior management – osmotic therapy for ICP  Neuro-hormonal cascade  Capillary Leak  Diabetes Insipidus  50% of potential BD donors are volume responsive Muragan, CCM, 2009
  • 22. Target lactate, ScVO2, TTE, CVP  General guidelines for adequate IV fluid resuscitation are as follows: a. Mean arterial pressure at least 60 mm Hg. b. Urine output at least 1 mL/kg/hr. c. Left ventricle ejection fraction at least 45%. d. Lower vasopressor dose (e.g., dopamine ≤ 10 μg/kg/min).  Use Isotonic crystalloids ,0.9% saline and lactated Ringer solution
  • 23. Vasoactive Medications – Pressors Noradrenaline in vasodilatory shock Dopamine  Traditional 1st line pressor  1-10 mcg/kg/min  Inotrope and vasopressor  Pro – suppresses inflammation; mitigates ischemia-reperfusion injury  Con – suppresses anterior pituitary hormone function Vasopressin  Alternative 1st line pressor  .01-.04 IU/min  Vasoconstrictor  Pro – catecholamine sparing effect; concurrent rx of DI  Con - Decreases splanchnic perfusion
  • 24. Vasoactive Medications - Inotropes  If EF < 45% despite volume repletion and pressors, add inotrope  Dobutamine, Epinephrine  If EF remains depressed despite inotrope, consider starting hormonal replacement therapy (HRT)
  • 25. Corticosteroid administration Methyl-prednisolone 1,000 mg IV, 15 mg/kg IV, or 250 mg IV bolus followed by infusion at 100 mg/hr. Corticosteroid repletion reduces inflammation in donor livers  Lower levels pro-inflammatory cytokines – serum, tissue  Fewer adhesion molecules in tissue  Less ischemia-reperfusion injury  Lower acute rejection rates Given after blood has been collected for tissue typing as it has the potential to suppress HLA expression.
  • 26. AVP ↓-DI  Polyuria (> 200ml/hr for 3hrs).  Normal or increased serum osmolality.  Inappropriately dilute urine (specific gravity < 1.005,  Urine osmolality < 200 mOsm/kg H2O).  Hypernatremia (Na+ > 145 mmol/L). Hypotension -Vasopressin : 1 unit bolus; Infusion at 1-4 units/hr IF sodium, > 145–150 mmol/L without hypotension, treatment with Desmopressin should be initiated. ( Nasal Spray) Bolus IV dose of 1–4 μg, additional 1 or 2 μg every 6 hours AVP + Desmopressin can be used concurrently in unstable patients
  • 27. Our protocol -Hormonal replacement • Vasopressin : 1 unit bolus; Infusion at 1-4 units/hr • Triiodothyronine - 4mcg bolus, infusion at 3 mcg/hr ( levothyroxine 100 mcg NG ) • Methlyprednisolone – 1 gram bolus every 12th hrly • Insulin - 1 unit/hr minimum and titrate Na < 155 and Glu < 160, Aim for temperature >36o C
  • 28. Donor Management Goals  Develop protocols to optimize donor organ function and maximize organs per donor  Borrow concept of “bundles” from other disease management models  Represent consensus of physiologic targets based on expert opinion  Modest clinical studies to support use
  • 30. Potential organs for retrieval • Heart • Lung • Liver • Kidney • Cornea • Pancreas • Small bowel • Vessels, Tissues
  • 31. Organ Preservation Time  Heart: 4-6 hours  Lungs: 4-6 hours  Liver: 12 hours  Pancreas: 12-18 hours  Kidneys: 72 hours  Small Intestines: 4-6 hours
  • 32.
  • 33. ‘Collateral damage’  Hormonal • Diabetes insipidus  Hypovolaemia  Hypernatraemia • T3 / T4 reduces • ↓ACTH/ cortisol levels • Blood glucose  Hypothermia Organ Donation Past, Present and Future
  • 34.
  • 35.
  • 36.
  • 37.  Hemodynamic assessments for brain-dead donors include  serial determination and interpretation of  a. Mixed venous oxygen saturation.  b. Lactate.  c. Base deficit and acid-base status.  d. CVP, PAOP, or noninvasive hemodynamic parameters. TTE TEE ECHO
  • 38. Our protocol -Hormonal replacement • Vasopressin : 1 unit bolus; Infusion at 1-4 units/hr • Triiodothyronine - 4mcg bolus, infusion at 3 mcg/hr ( levothyroxine 100 mcg NG ) • Methlyprednisolone – 1 gram bolus every 12th hrly • Insulin - 1 unit/hr minimum and titrate
  • 39. Temperature  Temperature regulation lost  Hypothermia  Physiological changes associated with hypothermia  Sepsis  Coagulation abnormality Fluid warmers Forced air warming blankets Inspired gas humidification Minimise exposure to environmental temperature Aim for temperature >36o C
  • 40. It is imperative that the same rigor that is applied to the care of living patients be employed in the care of organ donors.
  • 41. Metabolic changes with BD  Hypernatremia  Caused by volume depletion, Diabetes insipidus  Na > 170 associated primary non-function (PNF) of graft liver  Hyperglycemia  Caused by insulin resistance and gluconeogenesis  Glu > 200 associated with PNF of graft pancreas  Glu > 160 associated with PNF of graft kidney
  • 42. Pulmonary Changes in BD  Pulmonary edema  Neurogenic  Cardiogenic  Non-cardiogenic – capillary endothelial leak  Delayed alveolar fluid clearance  LPV should be used in all BD