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How to perform a BD exam and improve donor management Panayiotis N. Varelas, MD, PhD Director Neuro-ICU Senior Staff Neurology / Neurosurgery Henry Ford.

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Presentation on theme: "How to perform a BD exam and improve donor management Panayiotis N. Varelas, MD, PhD Director Neuro-ICU Senior Staff Neurology / Neurosurgery Henry Ford."— Presentation transcript:

1 How to perform a BD exam and improve donor management Panayiotis N. Varelas, MD, PhD Director Neuro-ICU Senior Staff Neurology / Neurosurgery Henry Ford Hospital Associate Professor of Neurology Wayne State University Detroit, MI

2 Topics for discussion Management before BD is declared How BD exam is performed How to approach the family Management after BD is declared I have received speaker honoraria and holds stock options from The Medicines Company. The same company has sponsored research for which he served as primary investigator. He also receives royalties from the publication of the book Seizures in the ICU, is an editorial board member of Neurocritical Care and is serving in the advisory board of Gift of Life of Michigan. Potential conflicts: I have received speaker honoraria and hold stock options from The Medicines Company, which has sponsored my research. I also receive royalties from the publication of the book Seizures in the ICU, I am an editorial board member of Neurocritical Care and serving in the advisory board of Gift of Life of Michigan.

3 HFH Management Recommendations BEFORE BD Declaration

4 These recommendations are to be discussed, agreed upon and ordered by the ICU Primary Team (Senior Staff) and collaboratively implemented by the ICU Primary team, Gift of Life representative, and ICU nursing. These recommendations are not orders and should not be used as such. If a decision is made to utilize one or more of these recommendations, an order must be written by the physician. Methods for attaining goals are just recommendations – they should not be used if they are contraindicated to the patient’s condition or contrary to patient’s /family’s advance directives

5 HFH Management Recommendations BEFORE Brain Death Declaration MAP maintained ≥ 60 mmHg – Prevent Hypotension Keep CPP > 70, if an ICP monitor is in place –Maintenance IV Fluid: 0.9% NS with 20 mEq ml/hr. (Saline may need to be adjusted for Na+ greater than 160, see below.) –For hypovolemia: Bolus with 500mL 0.9% NS until MAP sustains ≥60 mmHg. –Start Dopamine and titrate to maintain MAP ≥ 60 mmHg (max 20 mcg/kg/min). Always notify the physician when starting pressors or inotropes or transfusing blood products. –If Dopamine is at 20 mcg/kg/min, CVP greater than 10, and MAP/CPP remains less than 60 mmHg, consider norepinephrine infusion. Titrate to clinical effect (max 20 mcg/min) –If Hct ≤ 25%, recommend 1 unit of PRBC’s over 1 hour, repeat as necessary to maintain HCT ≥ 25% or hemoglobin > 7.0.

6 HFH Management Recommendations BEFORE Brain Death Declaration Hypertension –Use IV Hydralazine prn. Avoid beta-blockers. Hypothermia –Warming blanket to maintain core body temp between 36.5° – 37.2° C, except for pts with induced-hypothermia. Diabetes Insipidus (DI) –For urinary output greater than 4 mL/kg/hr X 2 hrs AND Na+ > 155 and rising, recommend Vasopressin drip or replace urine output mL/mL: If Na+ > 160, use Half NS (0.45%) for replacement If Na+ ≤ 160, use NS 0.9% for replacement Always notify the physician if pt hypotensive (CPP 90)

7 HFH Management Recommendations BEFORE Brain Death Declaration Hypoxemia –Titrate FiO2 to maintain SaO 2 greater than 98% or PaO 2 > 300 on FiO –Tidal Volume at 6 mL/kg –Add PEEP of 5-8 cmH2o –Rate adjusted to maintain normal pH ( ) –Suction and turn patient q 1-2 hrs –Initiate Chest Percussion and Vibration q 1-2 hrs –Albuterol Nebulizers: 2.5mg q 4 hrs.

8 How to perform a BD exam?

9 Current BD criteria in the US Responsibility left to individual institutions: Each hospital has to develop its own criteria, based on State laws  criteria based on “accepted medical standards”, based on President’s Commission (1981), Uniform Determination of Death Act (UDDA, 1993), AAN (2010) or other Societies recommendations, which are “advisory” and carrying the weight of “guidelines” rather than standards

10 HFH: determination of brain death Determination of “death by brain criteria” in accordance with MI law Two different physicians, licensed in MI: 1) The primary senior staff physician 2) Senior staff from Neurology or NS or designated physician under direct supervision, i.e resident, fellow

11 Determination of brain death - Process GCS ≤ 5 GOL notified within 1 hour If All prerequisites are met Clinical evaluation:  Cerebral unresponsiveness: deep, irreversible coma  Absence of brainstem reflexes  Absence of respiration (Apnea test) ± Confirmatory testing

12 Determination of brain death - Prerequisites Established & sufficient cause of irreversible coma Age  7 days Exclusion of any complicating condition confounding clinical assessment:  Absence of deep sedation or peripheral nerve or muscle dysfunction, i.e., (+) TOF, if NM blockade  ToxScreen: ETOH < 80mg%,  < 10  g/ml, drugs?  Temp-core  32.2 o C (90 o F)  SBP  90 mmHg or MAP > 60 mm Hg or age-specific normotensive range in children  Severe electrolyte, acid-base or endocrine disturbances

13 Suspicion of drugs – toxins? Administer antidotes Narcotics  naloxone Benzodiazepines  flumazenil Carbon monoxide  oxygen Carbon disulfide, cyanide, hydrogen sulfide  amyl nitrite Declare brain death if traces of drug are found below therapeutic level Unable to quantify drug/poison  observe for x 5 half lives Unknown, but high suspicion  48 hrs observation, if no   confirmatory study Wijdicks Brain Death 2001

14 Pitfall: Effect of hypothermia on sedative metabolism Figure A shows the time course changes in concentration of Midazolam in brain-injured patients undergoing hypothermic therapy As shown in (A) concentration of the agent increased linearly until Body Temp reached 35 °C, after which the levels decrease profoundly when Body Temp rose to 36 °C, even during continuous administration of Midazolam. (B) Depicts the time course changes in concentration of Midazolam in brain-injured patients with normothermic therapy. In the figure, the concentration of the agent increased at 24 h after administration, then plateaued from 72 h, lasting until 216 h, during continuous infusion. Fukuoka et al, Resuscitation 2004

15 Clinical Examination - Coma Lack of responsiveness to supraorbital nerve, nail-bed or TMJ pressure Pitfalls:  Uncoordinated, non-integrated into posturing responses = i.e. 2 o to spinal cord reflexes  Partial eye opening in response to ipsilateral nipple twisting 5 sec later (sympathetic fibers to Muller’s muscle?) (Santamaria et al., 1999)

16 Clinical Examination - Reflexes Mid-position (4-6 mm) or dilated pupils Pitfalls: Drugs that influence pupils:  Topical application of mydriatics  Atropine in IV doses 0.03 mg/kg  slight mydriasis, but (+) reaction to light (Goetting et al., 1991)  Escalating doses of non-depolarizing paralytics lead from reversible   to non-reversible mydriasis (Schmidt et al., 2000)

17 Clinical Examination - Reflexes Oculocephalic reflex (Cervico-occular, COR) Cold calorics (VOR) Pitfalls:  or absent if:  Toxic levels of aminoglycosides, tricyclics, anticholinergics, antiepileptics  Orbital edema  Battle’s sign (ipsilaterally)

18 Clinical Examination - Reflexes Corneal, blinking to threat Grimacing to pain, jaw reflex  Pitfall: facial myokymia/fibrillation from muscle denervation may mimic facial movements Nasal tickle (V 2 - XI) Gag, cough Over-breathing Atropine test:  tachycardia (↑ HR > 3%) to 2-3mg IV atropine (Huttemann et al., ICM 2000)

19 Apnea test Always with the second BD exam Pre-oxygenation 100% FiO 2 PaCO 2 target: 60 mmHg or [baseline + 20] PaCO 2  by 3-6 mm Hg/min Hypothermia (  CO 2 production, left shift O 2 dissociation curve)  normothermia Hypotension  SBP goal 90 mm Hg Pre-admission or “normal” level for the pt

20 Apnea test - Solutions Unable to complete the test??  repeat after correcting the problem  clinical exam + confirmatory test  use tricks:  CO2 augmentation (1 L/min) – PaCO 2 > 60 mmHg within 2 min (Lang, 1995)  Bulk diffusion (set rate = 0, CPAP = 0, 100% FiO 2, L/min continuous flow) - 22/24 pts completed the test (al Jumah et al., 1992)  T-piece (12 L/min) with CPAP valve (10 cm H 2 O) – less desaturation with T-piece compared to cannula inside ETT or T-piece alone (Levesque et al., CCM 2006)  ADVICE: perform apnea test even if pt on high FiO 2 and draw ABGs as O 2 Sat reaches 90%!

21 HFH: determination of brain death - Observation period between 2 clinical exams Structural brain lesions: 2 Clinical exams  6 hours + apnea  optional ConfTest Catastrophic structural brain lesion: 1 exam + ConfTest (CBF test) + apnea Ischemic/anoxic injury: 2 Clinical exams  24 hours + apnea  optional ConfTest (for ex. if neuroimaging inconclusive)

22 HFH: determination of brain death - Observation period between 2 clinical exams (continue) Children 1 year – 18 years: 2 Clinical exams  12 hours + apnea (  optional ConfTest) Children 2 months – 1 year: 2 Clinical exams  24 hours + apnea + ConfTest Neonates 7 days – 2 months: 2 Clinical exams  48 hours + apnea + ConfTest (2 EEGs 48 hours apart or CBF study, if equivocal) Pregnant women: no BD exam or test, until confirmation of viability of fetus

23 Confirmatory tests may be required Confirmatory Tests “are recommended”: 1.Normal or inconclusive CTOH/MRI 2.COPD or sleep apnea- ? chronic  PaCO 2 3.Inconclusive or indeterminable apnea test 4.Children 5.Inability to perform full clinical exam 6.Severe facial trauma (ex. Racoon eyes)

24 Relevant racoon eyes And NOT…

25 Confirmatory tests may be required (continue) 7. Preexistent abnormal/surgical pupil 8.Severe cranial neuropathies 9.Toxic/therapeutic level of CNS depressants, neuromuscular blocking agents, aminoglycosides, anticholinergics 10.(?) complex/integrated motor activity 11.Injury as a result of crime (not at HF!) 12. If only one brain death exam is required Henry Ford!!)

26 Electroretinogram

27 SPECT with 99mTc-HMPAO 99mTc scintigraphy

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29

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31 Clinical Questions 1. Are there patients who fulfill the clinical criteria of brain death who recover brain function? 2.What is an adequate observation period to ensure that cessation of neurologic function is permanent? 3.Are complex motor movements that falsely suggest retained brain function sometimes observed in brain death? 4.What is the comparative safety of techniques for determining apnea? 5.Are there new ancillary tests that accurately identify patients with brain death?

32 BRAIN DEATH Approaching the family AND NOT DISCUSSING ABOUT DONATION!!!

33 Consent rates Average national consent rate 45-50% Early referral when BD is imminent Suitability for donation relies on OPO (Franz et al., 1997, DeJong et al., 1998)

34 Consent rates Factors improving donation rates: 1.Discussion in a quite environment 2. Trained requester (i.e., OPO) 3.Decoupling = family understands & accepts BD before any donation mentioned (Gortmaker et al., 1998) 4.Within 30 min after BD notification (because if simultaneous  donation rate  by 20-40% !) (Niles & Mattice, 1996)

35 NICU Brain Death and Organ Donation Request Policy (Helms et al. Neurology 2004) Donation was not discussed prior to brain death Brain death declared according to hospital and AAN policies Family informed and brain death process explained by treating attending physician Physician does not bring up donation to family and leaves the room Procurement coordinator (OPO) makes the request

36 Organ and tissue donation consent rates 21 months before and 21 months after the institution of policy change (Helms et al. Neurology 2004) Before % After % Odds ratio, 95% CI p value NICU Eye , Bone & Tissue , * Solid organs , Total , * Other units Eye , Bone & Tissue , Solid organs , Total ,

37 Approaching the family 1.Let family know that the 1 st BD is done and a 2 nd will be performed at X time. 2.No mention about donation ! 3.If family asks about it, refer them to GOL 4.After the 2 nd exam (or after the only BD exam), discuss again with family and explain the results and that the pt is irreversibly and legally dead. 5.Allow time for them to absorb the info, introduce GOL to them and then leave the room

38 Approaching the family 6.If the family decides for donation and consent is signed  GOL takes over  Help GOL with tests, procedures 7.If the family decides against donation  pt is disconnected from vent within 1 hour

39 Time from declaration to VF- asystole Time (hours) to asystole Study No of patients< >72 Jorgensen %25%13% Mohandas and Chou %20%16%8% Hicks and Torda %20% Narimazie %40% Jennett et al %31%11%23% Ouaknine “Generally between 1 and 7 days” Kaste et al “On average 24 hours” Nishimura “On average six days” Goulon “Up to 128 hours” Kenneth Wood, DO, University of Wisconsin, Pallis ABC of Brain Stem Death 1996

40 Medical management after BD Integrative, multi-disciplinary and collaborative approach between OPO and Critical Care Team Pre-BD management, aiming at brain function preservation, may compromise other organs and contradict the post-BD/donor management Aggressive donor management may allow up to 84% of initially unsuitable donors to yield transplantable organs (Wheeldon et al., J Heart Lung Transpl 1995)

41 Kenneth Wood, DO, University of Wisconsin

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43 Hemodynamic Effects of Sympathomimetics MAPPCWPCOSVRHR Dobutamine Dopamine – moderate 5-10 mcg/kg/min Dopamine – high > 10 mcg/kg/min Isoproterenol Norepinephrine Epinephrine CO – cardiac output; HR – heart rate; MAP – mean arterial pressure; PCWP – pulmonary capillary wedge pressure; SVR – systemic vascular resistance.

44 Organ Donor - Heart Myocardial Dysfunction Sympathetic Surge Myocardial necrosis secondary to catecholamines Hormone Depletion Subendo Ischemia Low circulating levels thyroid and cortisol impair function Decreased coronary perfusion pressure precipitates ischemia impairing myocardial function Kenneth Wood, DO, University of Wisconsin

45 Changes in Ejection Fraction with Serial Echocardiograms (16) Zaroff J Heart Lung Txp 2003; 22: Ejection Fraction Time (hours)                              

46 Donor Management Assessment Palac Prog Transplant 2003; 13:42-46 Brain dead patient (< 65 years old) Assess ventricular function by echocardiogram Norm al Ejection function  45% Pulmonary artery catheter placement Persistently abnormal* Patient age Cardiac catheterization < 40 years Consider dobutamine echocardiography (viability study) Reversible dysfunction No reversible dysfunction Proceed to transplant Not a donor > 40 years Normal Abnormal** Normal Repeat echocardiography within 12 hours

47 Kenneth Wood, DO, University of Wisconsin

48 Hormonal Therapy (BD Animal Models) MYOCARDIAL Aerobic  Anaerobic Anaerobic  Aerobic Function   ATP   Creatine   Phosphate   Glycogen   Lactate   SYSTEMIC UTILIZATION Glucose   Pyruvate   Palmitate   Lactate   Free fatty acids   Pre- TreatmentPost Treatment Insulin Cortisol T 3 Novitzky Cryobiology 1987; 24: 1-10 Novitzky Transplantation 1988; 45:32-36

49 Rescue Hormone Therapy 1 ampule 50% dextrose – 20 u insulin 2 grams methylprednisolone 20  g levothyroxine  infusion 10  g/h Vasopressor ug/kg/min Heart rate beats/min Oxygen consumption ml/min/m Oxygen extraction %1618 If  10  g/kg/min Vasoactive Support POSTPRE Salim Arch Surg 2001; 136:

50 Rosendale Transplantation 2003;75: Aggressive Pharmacologic – Hormonal Replacement

51 Ware & Matthay, NEJM 2005 Pulmonary Edema

52 Role of Brain Death in Donor Lung Injury “Blast Injury Theory” → Hemodynamic mechanism Sympathetic surge Transient massive ↑ of hydrostatic pressure with structural damage to pulmonary capillary endothelium Sympathetic alteration of capillary permeability Cytokines → TNF , IL-1 activate endothelial cells to express ICAM-1 and neutrophil migration to interstitium/alveolar spaces → release ROS and proteolytic enzymes ALI/ARDS in 15-20% of severely brain-injured pts Neurogenic Pulmonary Edema Inflammatory Response Left Right ↑ Pvc ↑ VR ↑PAP ↑Pul Volume ↑ SVR ↓ CO ↑LAP Alvonitis Trasnaplantation 2003; 75: Infection – atelectasis - hemo/pneumothorax

53 Neurogenic Pulmonary Edema in 11 chacma baboons  ICP  Autonomic Storm Catecholamine Excess Intense Vasoconstriction Redistribution blood to RA/RV SVR  537% Adjustment to  VR by  CO R MAP  196% PA flow  25% Aortic flow  42% LV failure mPAP  (14  34mmHg)  LAP (8-52mmHg) Capillary blood flow arrest Blood pooling -72% of total circ. volume in lungs Blast injury-disruption of anatomic integrity of pulm capillaries Right CircuitLeft Circuit Exceeds for 1 minute Novitzky Ann Thorac Surg 1987; 43: Kenneth Wood, DO, University of Wisconsin

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55 Management of Respiratory Function in the Organ Donor Goals of mechanical ventilation FiO 2 : 0.40 PaO 2 > 100 mmHg; or PaO 2 > 300 on 100% FiO 2 PaCO 2 : mmHg Arterial pH, Tidal volume: ml/kg of predicted body weight PEEP: 5 cm of water Peak airway pressure: < mm Hg CVP 6-8 mm Hg or PAWP 8-12 mm Hg Recruitment maneuver: prone or CPAP 40 cm H 2 O x 30 sec, repeated q 20 min x3 Kirschbaum & Hudson, Prog Transpl 2010

56 Management of Respiratory Function in the Organ Donor Goals of bronchoscopy Evaluate anatomy; Assess for foreign body and assist in removal Define and locate aspirated material or apparent infection; Clearance of secretions Goals of pulmonary hygiene Prevent atelectasis with the use of q 2-4 hr ETT & supraglottic suction, percussion, postural drainage and lung-expansion techniques; Bronchodilators; Paralytics Use of anti-infective & anti-inflammatory therapy Use of antibiotics based on results of Gram’s staining of aspirated secretions Methyl-prednisolone 15 mg/kg IV plus 15 mg/kg IV q 6 hrs Naloxone 8 mg IV to minimize Neurogenic Pulmonary Edema (?) Kirschbaum & Hudson, Prog Transpl 2010

57 Hanna, K. et al. Arch Surg 2011;146: Partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FIO2) ratios on admission to the intensive care unit and following 100% oxygen challenge Retrospective, all potential donors within a 5-year period 20 pts on ACV & 25 pts on APRV ACV: RR breaths/min, TV 5-10ml/kg, 40%, PEEP 5 APRV: 6-10 breaths/min, inspir pressure cm H2O and 40% Donated lungs: 7/40 (18%) in ACV vs 42/50 (84%) in APRV (p < 0.001)

58 Management of Liver donors Increased recipient death or re-transplantation: ABO incompatibility High Na+ levels (> 155 mEq/L) Long cold ischemia time Large platelet transfusions Prolonged recipient PTT Ploeg et al., Transplant 1993; Figueras et al., Transplant 1996; Kutsogiannis et al., Can J Anaesth 2006

59 Management of Kidney donors + Immunomodulatory effects of catecholamines Low dose dopamine (< 10  g/kg/min) or epinephrine or vasopressin (< 0.04 U/min) Colloids can be used (hydroxyethyl starch) Avoid SBP < mm Hg Keep urine output > 1 ml/kg/hr Avoid nephrotoxic drugs Deman at al., Nephrol Dial Transplant 1999; Dictus et al., Clin Transplant 2009

60 Intensivist-Led Management of Brain-Dead Donors Is Associated with an Increase in Organ Recovery for Transplantation Singbartl et al, Am J Transpl 2011 In the before period, 66 out of 210 (33%) potentially available organs vs. 113 out of 258 (44%) potentially available organs in the after period, p = 0.008

61 Island of KEA, Greece


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