BASICS

OF ORGAN DONATION & MANAGEMENT OF BRAIN DEAD DONOR

Dr.T.Venkatachalam. MD.,DA,

Madras Medical College & Rajiv Gandhi Govt General Hospital Chennai

 What is brain death? total, irreversible Brain death -results from

loss of all brain funcGons including the brainstem due to total necrosis of the cerebral neurons following loss of blood ow and oxygenaGon Due to a severe head injury, illness or disease. A person's heart will sGll beat for a period of Gme aMer they become "brain dead".

The purpose of Brain death cerGcaGon

1. To determine whether to conGnue the life support

systems or not. 2. If suitable, plan for organ retrieval. 4. PaGents could be supported for longer periods, as criGcal care management of potenGal organ donors is crucial in maximizing the number and the quality of transplanted organs.

 1. Irreversible Coma 2. Irreversible loss of brainstem reexes 3. Loss of respiratory Centre funcGon 4. DemonstraGon of loss of intracranial blood ow.

Brain death is established by documentaGon of

ResponsibiliGes of the physician determining brain death

The diagnosis of brain death is primarily clinical. No other tests are required if the full clinical examinaGon, including each of two assessments of brainstem reexes and the single apnea test is conclusively performed.

Clinical tes9ng for brainstem func9on: STEP-1

Evaluate the irreversibility and poten8al causes of coma

STEP II
Ini8ate the hospital policy for no8fying the next of kin. STEP III
Conduct and document the rst clinical assessment of brain stem reexes.

Clinical tesGng for brainstem funcGon- cont.

STEP- IV Interval observaGon period: 6 hour observaGon period is sucient in adults and children over the age of 1 year.

Clinical tesGng for brainstem funcGon- cont.

STEP- V Repeat clinical assessment of brainstem reexes: STEP-VI Apnoea test: The apnoea test is performed aMer the II examinaGon of brainstem reexes.

Clinical tesGng for brainstem funcGon- cont.

STEP: VII Conrmatory tesGng as indicated When it is impossible to complete the clinical examinaGon, then a conrmatory test is required.

Clinical tesGng for brainstem funcGon- cont.

STEP: VIII Reasonable AccommodaGon STEP: IX CerGcaGon of brain death: Medical record documenta9on: All phases of the determinaGon of brain death should be documented in the medical record

Clinical tesGng for brainstem funcGon- cont.

STEP:X Withdraw cardio-respiratory support in accordance with hospital policies including those for organ donaGon. When organ donaGon is contemplated, paGent is shiMed to the theatre with venGlatory support and venGlaGon/anaesthesia conGnued Gll the organs are harvested and then cardio respiratory support is withdrawn.

BRAIN DEATH MAINTENANCE

Organ transplantaGon is considered the opGmal treatment for appropriate paGents with end stage organ dysfuncGon. The mismatch between supply and demand results in more paGents dying on the transplant waiGng list. the criGcal care management of potenGal organ donors is crucial in maximizing the number and the quality of transplanted organs.

The duGes of the criGcal care physician

Early idenGcaGon of brain death CerGcaGon of brain death The responsibility to oer the paGents family the opportunity to donate organs / Gssues. ObligaGon to unknown recipients to provide the best possible organs and Gssue.

BRAIN DEATH MAINTENANCE

The standards of medical management of the potenGal organ donor should be the same as those of any brain injured paGent unGl the irreversibility of injury is conrmed FuGle brain oriented therapy should then be disconGnued but other aspects of intensive care should be conGnued unGl it is certain that organ donaGon will not occur & the family are aware that support is to be withdrawn.

GENERAL MEDICAL CRITERIA

1. Age 0-75yrs. 2. Has suered irreversible loss of brain funcGon. 3. Has been maintained on venGlator with intact circulaGon. 4. Has no H/O malignancy except primary brain / skin malignancy 5. Has no major untreated sepsis. 6. No major signicant system specic disease (cardiac, pulmonary, liver) 7. No signicant infecGous disease. 8. Cause of death not due to massive poisoning with potenGal for transplant organ dysfuncGon (cyanide, co etc.)

EXCLUSION CRITERIA FOR ORGAN DONATION

1. HIV/HepaGGs B/C posiGve donors. (Please refer to transplant co-coordinator for individual assessment) 2. Any malignancy other than primary skin / CNS lesion. 3. H/O treatment with human pituitary growth hormone and other hormones of pituitary origin. 4. Untreated bacterial, viral, fungal infecGon. 5. Family H /O demenGa.

INVESTIGATIONS
Before I brain death test Blood GP, CBC, LFT, RFT AMer gemng consent HIV, Hbs Ag, AnG HCV, CMV, VDRL Kidney donor - HLA typing, USG kidney Liver USG Liver Heart - 12lead ECG, ECHO, if donor is >50yrs coronary angiogram Lung CXR, ABG, bronchoscopy.

CLINICAL MANAGEMENT OF THE ORGAN DONOR

Severe brain injury and brain death create a variety of extra cerebral organ manifesta2ons including: 1. Autonomic storm 2. Neuro endocrine hormone deciencies 3. Systemic inammatory response syndrome (SIRS) 4. Neurogenic pulmonary edema (NPE) 5. Myocardial stunning 6. Electrolyte and 7. Immunologic derangements.

CLINICAL MANAGEMENT OF THE ORGAN DONOR

The challenge for ICU physician is maintaining adequate organ perfusion and metabolism. Maximal ICU management strategies should be employed to bring out improved outcomes: larger number of organs transplanted Longer recipient survival Gmes Improved organ funcGon following transplantaGon.

 ALTERATION OF CEREBRAL PHYSIOLOGY AND ITS EFFECTS ON CVS:

Rapidly expanding supra tentorial lesion SwiMly progressing brain edema Upper brain looses funcGon (level of consciousness) Increase ICT Transtentorial herniaGon DistorGon of post fosse / Infra tentorial compartment Pressure on the PONS Cushings response (HT, brady cardia, wide pulse pressure)

ALTERATION OF CEREBRAL PHYSIOLOGY AND ITS EFFECTS ON CVS-2

Cushings response
(HT, brady cardia, wide pulse pressure)

ICT caudal spread Ischemia of medulla / Brainstem (vagal / cardio motor nuclei) Central autonomic dysfuncGons

ALTERATION OF CEREBRAL PHYSIOLOGY AND ITS EFFECTS ON CVS-3

Autonomic storm: HR, BP, SVR Catecholamine surge Cardiac work load
Myocard .02 ConsumpGon, vasoconstricGon ( end org.perfusion)

Catecholamines fall to levels below Normal within 20mts of brain death Autonomic collapse sympatheGc ouulow SVR Catecholamines CO End organ perfusion

I Phase

MANAGEMENT

duraGon of haemo dynamic surge

unpredictable - close monitoring without aggressive Rx

(a) Thresholds: sys Bp > 160mm Hg

MAP > 90mmHg

(b) Preferred therapy SNP 0.5 5 mcg / kg / min

Esmolol -100-500mcg / kg bolus followed by 100- 300 mcg / kg/min.

II Phase Hypotension may occur due to

MANAGEMENT

Catecholamine depleGon / sympatheGc drive Volume depleGon due to diureGcs- Mannitol, Frusemide used in the Rx of cerebral edema ConGnuous blood loss from injuries Insensible uid loss. Diabetes Insipidus Metabolic / Endocrine abnormaliGes Hypothermia Myocardial dysfuncGon

MANAGEMENT OF HYPOTENSION
Rapid replacement of circulaGng Blood Volume- colloids / crystalloids. Titrated to a CVP (8-10mmHg) Goal Bp- Syst. (100mmHg) MAP - 60-70mmHg HR < 100beats / min Ionotropes

Vasopressin 1unit bolus

Dopamine - <10mcg/kg/min Dobutamine - <10mcg/kg/min Despite the fact that Dopamine has been tradiGonally used for the circulatory support of the cadaveric donor, there is move towards Vasopressin. The ACC recommends vasopressin as the iniGal therapy for cardiovascular support.

- 0.5-4 units/hr.(0.01-0.04unit/min)

Second line agents for haemodyamic support: Norepinephrine

Epinephrine Phenylephrine

 Expert consensus recommends CVP monitoring in every potenGal

MONITORING

organ donor.

A pulmonary catheter should not be placed aMer brain death for extra cerebral organ perfusion consideraGons. Indica8ons for PA catheter Ind : (1) 2D Echo EF 40% (2) PaGents requiring - : Dopamine > 10mcg /kg /min Vasopressor support EscalaGon of supports Targets: PCWP 12 -14mmHg CI - >2.4 l /min/m2 SVR - 800 1200 dynes /sec /cm-5 Brady arrhythmias: In the brain dead paGents, heart is de nervated and resistant to atropine. Rx - TitraGon of Dopamine Small does of i.v. Adrenaline (0.05 0.1mg)

RESPIRATORY SYSTEM
The Consequences of brain death on gas exchange and lung funcGon may be profound. Brain death is associated with systemic inammaGon. In addiGon: Lung func9on can deteriorate due to: Lung injury (Release of pro inammatory cytokines) AspiraGons Pulmonary contusions / pneumonia Volutrauma / Barotrauma Pul. micro emboli V/Q mismatch Neurogenic pul. edema.

Neurogenic Pulmonary edema

Catecholamine surge Intense vasoconstricGons SVR

ShiMing of uid from periphery to central circulaGon

Acute in LA pressure Pul capillary pressure

Intense adrenergic Altera9on of Pulmonary s9mula9on pul. Capillary edema Permeability

 INTERVENTIONS FOR PULMONARY STABILITY 1. Aggressive pulmonary care ReposiGoning (Q 2hrly) Chest physiotherapy , sucGoning & Oral hygiene.
2. Careful uid management - CVP guided uid therapy to avoid pul. Edema. 3. VenGlaGon strategies : --Fi02 Gtrated to keep 02 sat 95% --Pao2 80 mmHg , PH 7.35 -7.45 , Paco2 35 - 45 mmHg --PEEP 5cm H20, TV 6- 8 ml/kg, PIP <30cm H20 4. IntervenGon of the inammatory process. Methyl Prednisolone 15 mg/kg (diminish the systemic inammatory response& improve oxygenaGon 5. Bronchoscopy in every lung organ donor for therapeuGc bronchial toileGng and for isolaGon of potenGal pathogens. 6. AnGmicrobial therapy should be tailored to bronchial wash gram stain or culture results. Empiric anGbioGcs not recommended.

 EFFECTS ON ENDOCRINE & METABOLIC ACTIVITY DYSFUNCTION OF HYPOTHALAMOPITUITARY AXIS

Due to hypo thalamo pituitary axis disrupGon, neuro endocrine deciencies occur. 1. Posterior hypothalamic pituitary deciency

Diabetes Insipidus (DI) Up to 90% of donors have low or undetectable vasopressin (ADH) levels. Diabetes Insipidus : Urine output >500ml/hr, Sr.Na >155meq/l U.SP.Gravity <1.005 , Sr.Osmolality > 305mosm/l Treatment Volume replacement (with hypotonic saline or 5% Dextrose in water DI in isolaGon can be treated with a conGnuous infusion of vasopressin or intermi~ent i .v vasopressin infusion should be the rst choice, when * Haemodynamic support with vasopressin required *CombinaGon hormonal therapy indicated.

 Highly selecGve v2 receptor acGvity Longer half life Potent anG diureGc acGon Minimal Vasopressor acGvity Dosage- Loading 8ng/kg Infusion 4ng/kg /hr Arginine vasopressin Have both vasoconstrictor/ ADH eect.
(treat DI as well as lowering the Vasopressor requirement for the donor)

Desmopressin (DDAVP)

Bolus 1 unit Infusion 0.01 0.04 unit /min. Dose Gtrated to a SVR of 800 1200 dyns/cm 5

ANTERIOR HYPOTHALAMIC PITUITARY DEFICIENCY adrenal and thyroid

2. Thyroid & 3. Adrenal insuciency: This steroid deciency is implicated in Deciency of normal stress response and hypotension. The inammatory process results in up regulaGon of cytokines producGon in the organs to be transplanted, increasing the immunogenicity post transplant. Management: Methyl Prednisolone -15mg / kg/24hrly Improves lung funcGon Improved oxygenaGon Improved survival in organ recipients.

 Thyroid hormone, vasopressin, Methylprednisolone Combined therapy is used in donor with Echocardiographic assessment of EF 40% or haemodynamic instability. ConsideraGon should be given to its use in all donors. 1. T3 4mcg bolus / Infusion 3mcg / hr 2. Methyl Prednisolone 15mg/Kg/ Q24 hrly 3. Vasopressin 1 unit bolus i.v infusion 0.01 0.04 units /min

TRIPLE HORMONAL THERAPY

4) Insulin deciency Glycemic control with insulin infusion Gtrated to a blood glucose target of 6-8 mmol /Lt (100 to 140 mg %) (5) Hypothermia Consequences of Hypothermia: Arrhythmias, Myocardial depression ( CO) , (L) shiM of ODC (impaired 02 delivery) Cold diuresis ( ability of kidneys to concentrate urine), Coagulopathies. Management: TherapeuGc intervenGons to maintain a core temperature of 350C External warming devices Warming blankets Warmed i.v uids Heated humidied gases Consider thyroid replacement.

ANTERIOR HYPOTHALAMIC PITUITARY DEFICIENCY INSULIN

TRANSFUSION THRESHOLDS
Acceptable targets for Hb, Platelets, and Coagula8on Parameters. A Hb target of 9 10g % is most appropriate to opGmize cardiopulmonary funcGon in the face of haemodynamic instability. Hb 7 g % is the lowest acceptable limit for ICU management of stable donors. Coagulopathy

Cause: Release of thromboplasGn from injured brain issue DiluGonal coagulopathy Hypothermia

There are no dened targets for platelets / INR / PTT.

RENAL SYSTEM
Maintain systolic blood pressure consistently above 80 90 mmHg

HEPATIC SYSTEM
DepleGon of liver glycogen occurs in 12hrs following brain death. Provision of both glucose and insulin may improve glycogen storage as well as improve Glycemic control. Hypernatremia (Sr.Na>155mmol/l) causes accumulaGon of idiogenic osmoles within the liver and leads to graM dysfuncGon.

THANK YOU Dr.T.Venkatachalam. MD.,DA. Professor of Anaesthesia, Madras Medical College & Govt General Hospital, Chennai