Transcript Dr. Mary Warner, Maximizing Donation Through

Optimizing Organ Donation
Donor Alliance Organ Donation Summit
December 8, 2015
Mary Laird Warner, MD, FCCP
Chairman, 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
109,08
3
15,54
1
1,046
4,264
1,576
49
268
2,039
133,8
66
Total
Colorad
o
1,962
695
11
44
48
19
2,779
Total
http://optn.transplant.hrsa.gov
Updated 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) = 8
Heart, Lungs (2), Kidneys (2), Liver, Pancreas,
Small Intestine
Donation after Cardiac Death (DCD) = 5
Lungs (2), Kidneys (2), Liver
Physiologic Changes with Brain Death
Cardiovascular
Metabolic
Neurologic
Endocrine
Pulmonary
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 Statement
Critical 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 - Pressors
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)
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 had
Lower dose and shorter duration pressor needs
No 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
Kotsch, 2008
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
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 gtt
T3: 4 mcg IV bolus, 3 mcg/hr IV gtt
MacDonald, 2012
3 hormone replacement
for 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 year
Mason, 1993
Insulin therapy in BD
• Glucose > 160 associated with reduced posttransplant renal graft function
• Glucose > 200 associated with reduced posttransplant 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 ventilation
Lung 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, 1999
Angel, 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
none
Results:
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 antibiotics
Small bowel decontamination regimen
Broad-spectrum iv antibiotic prophylaxis
• Avoid use of SB from patients with prolonged shock/
resuscitation or GI bleeding
Competing physiologic needs
Heart: Balanced Fluids,
Vasopressin
Lungs: Conservative Fluids,
No pressors
Kidney: Liberal Fluids,
Dopamine
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 goals
MAP 60 – 100 mm Hg
ABG pH 7.30 – 7.45
CVP 4 – 10 mm Hg
PaO2: FiO2 > 300
EF > 50%
Na 135 - 160 mEq/L
Pressor < 1; low dose
Glu < 150 mg/dL
Thyroid hormone
UOP 0.5 – 3 mL/kg/hr
J Trauma. 2011 Oct;71(4):990-5
Crit Care Med. 2012 Oct;40(10):2773-80
Am 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 had
More 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 consent
33% at 12-18 hrs
48% at time of recovery
• Independent predictors of > 4 OTPD
7+/9 DMG met at consent, recovery
Change in DMG at 12-18 hr
Donor age
Serum 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
Alkhafaji, R, 2015
• Glycemic control – conventional vs intensive
glycemic control effects on renal graft
function
Niemmann, in press
Organ Viability Research Project
at 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 HHS
OTPD > 3.75
Timely referral rate > 97%
Questions?
Thank You