Optimizing Organ Donation Donor Alliance Organ Donation Summit December 8, 2015 Mary Laird Warner,...
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Transcript of Optimizing Organ Donation Donor Alliance Organ Donation Summit December 8, 2015 Mary Laird Warner,...
Optimizing Organ Donation
Donor Alliance Organ Donation SummitDecember 8, 2015
Mary Laird Warner, MD, FCCPChairman, Quality Medical Executive Committee
Swedish Medical Center
Associate Professor, Critical Care and Pulmonary Medicine, National Jewish Health
Disclosures - I have no financial conflicts of interest to disclose.
Level of evidence - Levels 1, 2, 3
Outline • Discuss the scope of organ donation needs
• Review physiologic changes of brain death
• Discuss ICU care of the brain dead organ donor
• Discuss bundling of Donor Management Goals (DMG)
• Review results from DMG protocol at Swedish Medical Center
The Need
• Every 10 minutes, someone is added to the national organ transplant waiting list.
• On average, 22 people die each day waiting for an organ transplant.
• The gap between supply and demand of transplanted organs continues to widen.http://optn.transplant.hrsa.gov
Updated 11.27.2015
Gap between patients waiting for transplant and available organs
http://optn.transplant.hrsa.gov
The Numbers:Patient Waiting List for Donated Organs
Site Kidney Liver Pancreas K/P Heart Lung H/L Bowel
United States
109,083
15,541
1,046 2,039 4,264 1,576 49 268
133,866Total
Colorado
1,962 695 11 44 48 19
2,779 Total
http://optn.transplant.hrsa.govUpdated 11.27.2015
How can we bridge the donor gap?
Maximize the number of organs transplanted per donor (OTPD)
Goal per HHS/ HRSA = 3.75
Organs available by Donor Type
Donation after Brain Death (BD) = 8Heart, Lungs (2), Kidneys (2), Liver, Pancreas, Small Intestine
Donation after Cardiac Death (DCD) = 5Lungs (2), Kidneys (2), Liver
Physiologic Changes with Brain Death
Neurologic
Cardiovascular
Pulmonary
Endocrine
Metabolic
Hemodynamic Changes with BD
Brainstem herniation causes ischemia that progresses in rostral – caudal direction– Midbrain - parasympathetic activation
Bradycardia– Medulla - sympathetic activation
Vasoconstriction, hypertension– Spinal cord – sympathetic deactivation Vasodilation, circulatory shock
Hemodynamic changes with BD• 10-20% donors are lost to cardiovascular collapse
as patient evolves to brain death
• 50% of potential BD donors are volume responsive
• Pro-inflammatory state, increased cytokine IL-6
• Resultant shock causes– Progressive organ failure– Fewer OTPD– Lower survival of transplanted organs
Muragan, CCM, 2009
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
Pulmonary Changes in BD
• Pulmonary edema– Neurogenic– Cardiogenic– Non-cardiogenic – capillary endothelial leak– Delayed alveolar fluid clearance
Hormonal changes with BD
• Catecholamine storm
• Ischemia to pituitary and hypothalamus depletes AVP, cortisol, thyroid hormones– Diabetes insipidus – up to 90% BD patients– Hypocortisolism– Hyothyroidism
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
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
Management of the potential organ donor in the ICU: SCCM, ACCP, AOPO Consensus StatementCritical Care Medicine 2015
• First US expert report• Multidisciplinary, multi-institutional • Review of available evidence from
observational studies and case series• Form of consensus statement• Practical guideline for care of organ donor
Crit Care Med 2015; 43: 1291-1325
Circulatory support• Physiologic goals – Target euvolemia – MAP > 60 mm Hg– UOP > 1 mL/kg/hr– EF > 45%– Low pressor dose – Dopamine 1-10 mcg/kg/hr
• Volume Resuscitation – Crystalloid – NS or LR - for volume replacement– Colloids – for acute volume expansion– Avoid Hydroxyethyl starch (HES)
Vasoactive Medications - PressorsDopamine• 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)
Hemodynamic Monitoring
• Static measurement – Central venous, PA catheter– ScVO2
– Lactate– Base deficit– Serial CVP, PAOP, CO, CI
• Dynamic measurements – Pulse contour analysis• Echo – Transthoracic (TTE) vs Transesophagael (TEE)– EF
Vasoactive support:Treating AVP deficiency
• Hypotension despite volume repletion– AVP - Vasopressin - .01-.04 IU/min
• Diabetes insipidus (DI)– UOP > 3 mL/kg/hr– U Osm < 200 mOsm/kg H2O or S Osm > 305– Serum Na > 145 mmol/L– Desmopressin – 1-4 mcg IVP, then 2 mcg IV Q 6 hrs
• AVP treatment associated with – Decreased pressor and inotrope need– increased rate of organ recovery
Corticosteroids for vasoactive support
CORTISOME study: Prospective, randomized study of low dose hydrocortisone effect on resuscitation of BD donors
Subjects: 259 BD organ donors
Intervention: Hydrocortisone (HC) vs none
Results: Patients receiving HC hadLower dose and shorter duration pressor needsNo difference in transplantation or graft survival
Pinsard, 2014
Corticosteroid Therapy for Immunomodulation
• 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
• Conflicting results in cardiac, lung, renal grafts
• Recommended dose: Methylprednisolone– 1000 mg IV, 250 mg IV, or 15 mg/kg IV bolus– 100 mg/hr IV infusion
Kotsch, 2008
Thyroid hormone replacement for vasoactive support
Conflicting evidence over years:16 retrospective studies / case series suggested
T3/T4 infusion improved cardiac index
Meta- analysis of 4 RCTs of 209 donors No effect on cardiac index
Recommendation: Consider thyroid replacement for hemodynamically unstable BD donors or for EF < 45%
Dose: T4: 20 mcg IV bolus, 10 mcg/hr IV gttT3: 4 mcg IV bolus, 3 mcg/hr IV gtt
MacDonald, 2012
3 hormone replacementfor vasoactive support of BD Donor
Multicenter, retrospective study by UNOS of 10,292 BD donors using 3-drug HRT cocktail (AVP, methylprednisolone, T3/T4)
• 22.5% higher OTPD compared to controls• Increased probability organ donation – Kidney, heart, liver, lung and pancreas
• Increased probability of organ survival at 1 yearMason, 1993
Insulin therapy in BD• Glucose > 160 associated with reduced post-
transplant renal graft function• Glucose > 200 associated with reduced post-
transplant pancreas graft function• Potential to deplete graft B-islet cells• No large studies to guide recommendations
• Recommend: Serum glucose < 180 mg/dL
Pulmonary support• Physiologic goals– Arterial pH 7.3 – 7.45 – PaO2/FiO2 > 300
• Avoid excessive fluid resuscitation– Target CVP 4 – 6 mm Hg
• Avoid Vasopressors
• Ventilator strategy – Conventional – high VT 10-12 mL/kg IBW + low PEEP– Lung Protective – low VT 6 mL/kg IBW + mod PEEP
Lung Protective Ventilation in BD organ donors
RCT of 118 BD patients randomized to 6 hrs of randomized vs conventional ventilationLung protective ventilation: (VT 6-8 mL/kg IBW + PEEP 8-10 cm H2O) + recruitment maneuvers + apnea test on CPAP
Conventional ventilation: (VT 10-12 mL/kg + PEEP 5 cm H2O) + no recruitment maneuvers + apnea test off ventilator
Results: Lung protective ventilation resulted in Higher percentage transplantable lungs (95 vs 54%, P < 0.001)Higher number lungs transplanted (54 vs 27%, p = 0.004)Lower inflammatory biomarkers (IL-6, Soluble TNF receptors)
Mascia, 2010
Salvage maneuvers to improve lung recovery for transplantation
Donor management protocol improve lung recovery rate 3 fold• Conservative fluid strategy/ diuresis• Lung recruitment maneuvers• Early therapeutic bronchoscopy• Chest physiotherapy Q 4hrs
Salvage ventilator modes improve lung recovery rate 3-4 fold
– Bilevel 25/15– Airway pressure release ventilation (APRV)
Gabbay, 1999Angel, 2006
Hanna, 2001
Renal Support• Physiologic goals - Euvolemia
– CVP 4-10 mm Hg– UOP > 1 mL/kg/hr
• Resuscitate with crystalloids or colloids
• Avoid HES– Delayed graft function– Elevated serum Cr at PTD 10
• Single, low-dose pressor use– Dopamine as pressor of choice– AVP may increase renal procurement
Effect of donor pretreatment with dopamine on graft function after kidney transplantation
RCT, open-label, parallel study of 264 brain dead donors of 487 kidneys from 60 European centers, 2004-2007. Intervention: low dose DA = 4 mcg/kg/min vs noneResults:
Donors receiving dopamine were less likely to require dialysis (24.7% vs 35.4%, p 0.01)
Multiple dialyses associated with renal graft failure at 3 years. HR 3.61 (2.39-5.45)
Schnuelle, 2009
Organ-specific management:Liver
• Na > 155 in graft liver risks swelling upon transplantation
• Na > 155 in donor associated with– Increased need for re-transplantation at 30d– Increased allograft failure at 90d
• Recommend: Serum Na < 155
Organ-specific management:Pancreas and Small Intestine
• Target Euvolemia
• Provide 3x HRT – enhances pancreatic utilization
• Target serum glucose < 180 mg/dL
• Continue enteral nutrition
• Prophylactic antibioticsSmall bowel decontamination regimenBroad-spectrum iv antibiotic prophylaxis
• Avoid use of SB from patients with prolonged shock/ resuscitation or GI bleeding
Competing physiologic needs
Heart: Balanced Fluids, Vasopressin
Kidney: Liberal Fluids, Dopamine
Lungs: Conservative Fluids, No pressors
Liver: Isotonic fluids
Protocols to maximize OPTD
• Donor Management Goals (DMGs)• Order sets• Intensivist-led organ donor management
Donor Management Goals (DMG)• Develop protocols to optimize donor organ
function and maximize OTPD• Borrow concept of “bundles” from other
disease management models• Represent consensus of physiologic targets
based on expert opinion• Modest clinical studies to support use
Donor management goalsMAP 60 – 100 mm Hg
CVP 4 – 10 mm Hg
EF > 50%
Pressor < 1; low dose
Thyroid hormone
ABG pH 7.30 – 7.45
PaO2: FiO2 > 300
Na 135 - 160 mEq/L
Glu < 150 mg/dL
UOP 0.5 – 3 mL/kg/hrJ Trauma. 2011 Oct;71(4):990-5
Crit Care Med. 2012 Oct;40(10):2773-80Am Surg 2010 Jun; 76 (6): 587-94
Retrospective UNOS Region 5 DMG Study
• Study of protocolized DMG care of 320 BD donors• Results
Overall OTPD = 3.6 + 1.6
Donors with 8+/10 DMG hadMore OTPD (4.4 vs 3.3, p<0.001)More likely 4+ OPTD (70% vs 39%, p < 0.001)
Achieving 4 specific DMGs independently predicted > 4 OTPD– CVP 4 - 10 mm Hg (OR 1.9)– EF > 50% (OR = 4.0)– P:F > 300 (OR = 4.6)– Na 135 – 160 mEq/L (OR = 3.4)
J Trauma. 2011 Oct;71(4):990-5
Prospective Region 5 UNOS DMG Study• Study of protocolized care and time dependency of meeting DMG goals
in 380 SCD donors
• Overall OPTD = 3.6 + 1.7
• 7+/9 DMG met improved over time:15% at time of consent33% at 12-18 hrs48% at time of recovery
• Independent predictors of > 4 OTPD7+/9 DMG met at consent, recoveryChange in DMG at 12-18 hrDonor ageSerum creatinine Crit Care Med. 2012 Oct;40(10):2773-80
UNOS Region 11 Prospective DMG Study• Prospective study of 805 SCD donors, 2685 total, including ECD, DCD
• OPTD– 2.85 - 2.96 when < 8 DMGs met– 3.34 - 3.44 when all 8 DMGs met
• Lung transplants increased 2.4x when all 8 DMGs met
• DMGs associated with highest OTPD– Low VP use– P:F > 200– CVP 4-10
• DMGs associated with recovery of specific organs– Heart: Na, low VP use– Lung: CVP, P:F– Pancreas: glucose control
Am Surg 2010 Jun; 76 (6): 587-94
Intensivist-led management• University of Pittsburgh study• Intensivist-led organ donor support team• Pre-post study design (n= 35 pre/ 45 post)• Results– Increased total organs recovered (66/210 vs
113/258)– Increased lungs recovered (8/70 vs 21/86)– Increased kidneys recovered (31/70 vs 52/86)– Increased OTPD ( 1.9 vs 2.6) Singbartl, 2011
Future Directions• MOniToR Trial – Monitoring Organ donors to
improve Transplant Results
• Glycemic control – conventional vs intensive glycemic control effects on renal graft function
Alkhafaji, R, 2015
Niemmann, in press
Organ Viability Research Projectat Swedish Medical Center
• Focus: Collect data of 9 DMGs from time of BD declaration to DA management
• Goal: Develop protocol for donor management to increase OTPD > 3.75
• Scope: – Baseline study period 2010-2012– Prospective study, starting June 2013
Swedish Medical Center: Organ and Tissue Donation
2010 2011 2012 2013 2014 October 2015
Organ Donors
18 14 20 22 14 11
BD/DCD 17/1 11/3 15/5 19/3 12/2 8/3
%DCD 6% 21% 25% 14% 14% 27%
Tissue 53 62 84 115 79
Eye 96 95 80 88 81
HHS goal: DCD > 10% donors
Swedish Medical Center: Organ Transplant Rate
2010 2011 2012 2013 2014 October 2015
Organ Donors
18 14 20 22 14 11
Total Organs
61 44 58 70 45 33
OTPD 3.39 3.14 2.94 3.18 3.21 3.3
Timely Referral
91% 96% 98% 97% 97% 91%
National Goals from HHSOTPD > 3.75Timely referral rate > 97%
Thank You
Questions?