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 CO2

challenge.

(Apnea test)

Ancillary testing ( any one) Cerebral angiogram (insufficient evidence to recommend use of CT or MRI angiography)Hexylmethylpropylene amineoxine single-photon emission CTElectroencephalographyTranscranial 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 OrganDonation

Primary care giverIntensivistTransplant

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 Retrieval

First 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 PMGrief stricken families in hospitalRelatives 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/ ABGLFT/ RFT/ SECoagulation profile/ TEGTwo blood culturesUrine and sputum culture

Antibiotics as per cultures if present same may be used for recipients also

Physiologic Changes with Brain Death

Neurologic

Cardiovascular

Pulmonary

EndocrineHypothermia

MetabolicPro-

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 axisDecline in plasma hormone concentrationADH, TSH

Impaired TSH secretionImpaired peripheral conversion of T4Reduced T3- progressive loss of cardiac contractilityIncreased anaerobic metabolism

HypoadrenalismImpairs donors stress responseCardiovascular collapse

Decreased insulin secretionHyperglycaemia

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 – PressorsNoradrenaline 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/hrIF 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 hoursAVP + 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 titrateNa < 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

Critical care management of potential organ donors is crucial in maximizing the number and the quality of transplanted

organs

Goal is to provide adequate oxygen supply and tissue perfusion – Target MAP : 65-75

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 warmersForced air warming

blanketsInspired gas

humidificationMinimise 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