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Management of the Potential Organ Donor

Management of the Potential Organ Donor. Kenneth E. Wood, D.O. Professor of Medicine and Anesthesiology Senior Director of Medical Affairs Director of Critical Care Medicine and Respiratory Care The Trauma and Life Support Center University of Wisconsin Hospital and Clinics.

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Management of the Potential Organ Donor

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  1. Management of the Potential Organ Donor Kenneth E. Wood, D.O. Professor of Medicine and Anesthesiology Senior Director of Medical Affairs Director of Critical Care Medicine and Respiratory Care The Trauma and Life Support Center University of Wisconsin Hospital and Clinics

  2. DisclaimerNo Financial SupportSlides Available by Requestkew@medicine.wisc.edu

  3. Maximal Utilization and Optimal Management of Potential Organ Donors • Surveillance to identify patients with severe neurologic injury likely to progress to brain death • Standardized method for brain death declaration • Uniform request for consent • Optimal medical management of donor

  4. Optimal Medical Management of the Potential Organ Donor • Continued intensity of support • Focus shift from cerebral protective strategies to optimizing donor organs for transplantation • Simultaneous critical care to organs of multiple patients • Critical period • Facilitates donor somatic survival • Maintains organs to be procured best condition • Donor management impact recipientfunction

  5. Role of Clinical Care Team in Donation • Donor Medical Management = Critical Care Management • Integrative multi-disciplinary collaborative approach between OPO and Clinical Care Team • Intensivists • Pulmonary Consultants • Cardiac Consultants • Nursing • Respiratory • Hemodynamics • Ventilatory Management • Echocardiography • Diagnostic Procedures • Donor Management Team/Defined Champions • Donor Family Support

  6. Cardiac Transplant Continuum Mechanism • Catecholamine • Hypothesis • Autonomic Surge • MVO2 supply demand imbalance • Endocrinopathy •  Coronary perfusion • Aerobic  Anerobic NEURO INJURY BRAIN DEATH DONOR • Fluids • Immunomodulators catecholamines • Vasopressin • Thyroid hormone • Steroids • Insulin Approach • Standard • Pretreatment ? • Sympathetic antagonists • Calcium blockers • Cardiac sympathectomy

  7. Improvement of Donor Myocardial Function After Treatment of Autonomic Surge During Brain Death • Defined by Systolic BP > 200 mmkg and tachycardia > 140 beats/min. • Observed in 63% • Duration 1.2 hours (30 min-6hr) • Followed by  BP which never occurred when AS absent • AS less with head injury • Treated with esmolol, urapidil or nicardipine • Treatment independently associated with EF > 50% Audibert Transplantation 2006;82:1031-1036

  8. Complications of Brain Death and Impact on Organ Retrieval “…hypothesized that brain death related complications would have no effect on the number of organs donated if an aggressive donor management protocol was in place.” • Vasopressor requirement 97.1% • Coagulopathy 55.1% • Thrombocytopenia 53.6% • Diabetes Insipidus 46.4% • Cardiac ischemia 30.4% • Lactic acidosis 24.6% • Renal failure 20.3% • ARDS 13% Salim Am Surgeon 2006;72:377-381

  9. Aggressive Donor Management and Organ Donor Shortage Salim 2006;61:429-435

  10. 40% (21) MAP < 55 (mean 47 mmHg) despite inotropic support 19% (10) CVP > 15 (mean 18 mmHg) 4% (2) inotropes > 20 (mean 25 ug/Kg/min) 25% (13) PCWP > 15 (mean 20 mmHg) 12% (6) LVSWI < 15 (mean 12.8 gm) MAP > 60 mmHg CVP < 12 mmHg PCWP < 12 mmHg LVSWI > 15 gm Inotropes < 5 ug/Kg/mm Transforming Unacceptable Donors Potential Multi-organ Donors (150) Acceptable 65% (98) Unacceptable 35% (52) Outcomes Optimum Management • Invasive monitoring • Bolus steroids (15mg/Kg/MP) • Insulin/glucose • Argine vasopressin 1U bolus and 1.5 U/hr • Tri-iodothyronine 4 ug bolus and 3 ug/hr • 44/52 “unacceptable” donors yielded transplantable organs • 84% alive (13-48 months) • 92% of initially unacceptable organs were capable of functional resuscitation Wheeldon J Heart Lung Txp 1995; 14:734-742

  11. Donor Management TrialHormonal Therapy Randomization T3 0.8 ug/Kg Bolus Followed by 0.113 μg/Kg/hr T3 And Methyl-prednisolone Placebo Methyl-prednisolone 1000 mg Bolus Venkateswaran Eur Heart J 2009

  12. Marginal Functional Hemodynamic Effects of Adjunctive Hormonal Therapy • MAP < 70 mmHg • with • CVP or PCWP > 14 mmHg • and • CI < 2.4 L/min • Dopamine > 5 μg/Kg/min • or • Norepi > 0.06 μg/Kg/min • or • Epi > 0.03 μg/Kg/min • CVP < 12 mmHg • PCWP < 14 mm Hg • CI > 2.5 L/min • Minimal vasoactive support • No gross LVH or palpable CAD on inspection Brain Stem Death (80) • Trauma 24% • Vascular event/tumor 64% • Hypoxia/Infection 13% Management Brain Death Coning OR Consent Management HRT Retrieval 10.7 hrs 2 hrs 1 hr 5.9 hrs 12.7 hrs 6.9 hrs 19.6 hrs Venkateswaran Eur Heart J 2009

  13. Hemodynamic Parameters for Entire Trial Cohort Venkateswaran Eur Heart J 2009

  14. Cardiac Index and Treatment Venkateswaran Eur Heart J 2009

  15. Donor Heart Function and Thyroid Function • 58% Low free T3 or T4 • 18% co-existent low TSH • Initial CI no different with low T3 or T4 • CI ↑ regardless of initial T3 or T4 or T3 Tx Venkateswaran Eur Heart J 2009

  16. Cardiac Index and Pre-Tx Thyroid Venkateswaran Eur Heart J 2009

  17. Association between NE withdrawal and cardiac functional improvement 60% (48/80) initially receiving NE Significantly lower LVSWI (43.5 vs 36.6) Vasopressin introduced 60/80 → NE withdrawn in 26/48 or reduced to 0.06 μg/Kg/min Donor Heart Function and Norepinephrine Norepi Vasopressin Venkateswaran Eur Heart J 2009

  18. Hemodynamic Effects of Adjunctive Hormone Therapy Trial Donors (80) 50% Non-Marginal at Initial Assess (40) 50% Marginal at Initial Assess (40) • 35% Unsuitable at End Assessment (14) • CAD (5) • RV Dysfunction (5) • LV Dysfunction (4) 65% Suitable at End Assessment (26) 35% Suitable at End Assessment (14) • 65% Unsuitable at End Assessment (26) • CAD (15) • RV Dysfunction (6) • LV Dysfunction (5) 71% Retrieved for TXP (10) 58% Retrieved for TXP (15) Total Suitable at End Assessment (40) • 37% Non-Txp (15) • No Recipient (10) • Age > 60 (3) • Poor Donor Txp (2) 63% Hearts Txp (25) Venkateswaran Eur Heart J 2009

  19. Donor Management “Active donor management improves circulatory function and has the capacity to increase the yield of suitable hearts from the existing pool of potential donors. Neither T3 nor MP, alone or in combination, appears fundamental to this improvement.” Venkateswaran Eur Heart J 2009

  20. Donor Management “Our study demonstrates that not only may donor circulatory status be improved by active management but also there is the potential to increase the yield of transplantable hearts if decisions on organ acceptance are deferred until a period of resuscitation and assessment is complete. Active donor management with PAFC monitoring is the cornerstone of this objective but this has implications for planning donor retrieval services. The simple introduction of hormone therapy is not a substitute for the detailed haemodynamic assessment and management of the potential heart donor.” Venkateswaran Eur Heart J 2009

  21. Role of Brain Death in Donor Lung Injury Neurogenic Pulmonary Edema • “Blast Injury Theory” → Hemodynamic mechanism • Sympathetic surge • Transient massive ↑ hydrostatic pressure with structural damage to capillary endothelium • Sympathetic alteration of capillary permeability • Cytokines → TNF IL-1 activate endothelial cells to express adhesion molecules and mediate production of IL-8 → neutrophil activator → bind to endothelial cells → migrate to interstitium/alveolar spaces → release ROS and proteolytic enzymes ↑ SVR ↓CO ↑LAP Left ↑ Pvc ↑ VR ↑PAP ↑Pul Volume Right Inflammatory Response Alvonitis Trasnaplantation 2003; 75:1928-1933

  22. Potential Lung Donor Unacceptable Lungs “Marginal” Lungs Ideal Lungs • PaO2/FiO2 > 300 • PEEP = 5cmH2O • Clear chest x-ray • Age < 55 • Tobacco < 20 pk/yr • Absence of trauma, surgery, aspiration, secretions, malignancy purulent secretions Baseline Status Acquired reversible Alveolar Flooding Aspiration Atelactasis

  23. Impact of Donor Management Protocol on Lung Donation and Recipient Outcomes Education • Transplant Pulmonologists and OPO staff training sessions on Donor selection and management • Emphasis upon every donor as a lung donor • Request and consent should be attempted for every donor • Education regarding donor management strategies Angel AJRCCM 2006;174:710-716

  24. Impact of Donor Management Protocol on Lung Donation and Recipient Outcomes Active Management • Recruitment Maneuvers • Pressure control ventilation 25 cm H2O and PEEP 15 cm H2O for 2 hours • Switch to conventional volume control mode with TV 10 ml/kg and PEEP 5 cm H2O • Fluid balance • Minimized use of crystalloids • Diuretics to maintain neutral or negative balance • Aspiration risk • Elevated head of bed to 300 • Inflate ET balloon to 25 cm H2O • Bronchosopy with BAL to eval CXR area of infiltrate Angel AJRCCM 2006;174:710-716

  25. PaO2/FIO2 > 300 No infiltrates No copious purulent secretions No bronchoscopically demonstrated aspiration Age > 55 years Pack years > 20 History of pulmonary disease Severe chest trauma Mechanical ventilation > 4 days Positive gram stain of tracheal or BAL fluids Impact of Donor Management Protocol on Lung Donation and Recipient Outcomes Absolute Extended • Ideal • All absolute criteria • No extended criteria • Extended • All absolute criteria • One or more extended criteria • Poor • Did not satisfy ALL absolute criteria Poor Ideal Poor Extended Angel AJRCCM 2006;174:710-716

  26. Impact of Donor Management Protocol on Lung Donation and Recipient Outcomes Angel AJRCCM 2006;174:710-716

  27. Impact of Donor Management Protocol on Lung Donation and Recipient Outcomes Angel AJRCCM 2006;174:710-716

  28. Early Donor Management Increases Retrieval Rate of Lung for TXP TRIAL NON - TRIAL Venkateswaran Ann Thorac Surg 2008; 85: 278-86

  29. Early Donor Management Increases Retrieval Rate of Lungs for TXP Management Points • Commenced Management • 2 hours post consent • 12.5 hours post brain death and continued for 6.9 hours • Respiratory Management • Bronchoscopy early • TV 10 ml/Kg PEEP 5 cm H2O • Frequent Suctioning • Volume recruitment by turning every 2 hours • Active hemodynamic management • Specific algorithms for • CI > 2.5 L/min m2 • CVP and PCWP < 12 mm Hg • MAP 65-85 • SVR 800-1200 dynes/cm/sec-5→ vasopressin • Fluid Resuscitation • Small amount blood (Hgb > 10 g/dl), gelatin or colloid • 376 ml of colloid /27 ml crystaloid Venkateswaran Ann Thorac Surg 2008; 85: 278-86

  30. Early Donor Management Increases Retrieval Rates of Lungs for TXP Management Outcomes • Respiratory function – deteriorated • ↓ PaO2/FIO2 • ↑ EVLWI and PVPI • PaO2/FIO2 rose after final inspection • Bronchoscopy • Abnormalities in 20 donors • BAL positive cultures in 31 donors • Methylprednisolone • No effect on any absolute indicator • Associated with reduced accumulation of EVLWI and lower pre-retrieval PCWP • Did not improve EVLWI in marginal • Norepinephrine → PaO2 / FIO2 ratio deteriorated and EVLWI increased significantly NOT prevented by withdrawal of NE Venkateswaran Ann Thorac Surg 2008; 85: 278-86

  31. Early Donor Management Increases Retrieval Rate for Lungs for TXP Potential Lung Donors (182) Non Trial Lungs (244) Trial Lungs (120) MP(30) T3 + MP(28) T3 (34) Placebo (28) Non-MP Lungs (62) MP Donors (58) 44.8% Lungs Retrieval (26/58) 35.5% Lungs Retrieval (22/62) 27% Lungs Transplanted (66/244) 40% Lungs Transplanted (48/120) Venkateswaran Ann Thorac Surg 2008; 85: 278-86

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