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Management of the Potential Organ Donor Cardiac and Pulmonary

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Title: Management of the Potential Organ Donor Cardiac and Pulmonary


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

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Maximal Utilization and Optimal Management of
Potential Organ Donors
  • Surveillance
  • Declaration
  • Consent

Medical Management
4
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

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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
Neurocardiogenic Injury
Pathophysiology Catecholamine Hypothesis
  • Severity of initial event predicts myocardial
    necrosis
  • Phase response to event
  • Neural phase ? within hours
  • Humoral phase ? inflammatory cytokines ? days
  • Contractile dysfunction
  • Unique apical sparing distribution
  • Systolic dysfunction 10 - 28 diastolic
    dysfunction 71
  • Reversible in majority of cases

normal perfusion
abnormal sympathetic innervation
Banki Curr TX Opt CVM 2003 5 451-458
8
Neurogenic Cardiac Injury-SAH
MIBG
MIBI
Mean EF
Zaroff Curr Tx Opt CVM 20035451 Banki Circ
20051123314-3319 Tung Stroke 200435548-553
9
Pituitary Changes in Head Trauma
Ceballos Alabama Med J 19663185-198
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Endocrine Failure After Traumatic Brain Injury
Pathophysiology
  • Diminished input from cortical structures/brainste
    m secondarily affecting HPA
  • Release of hormones (catecholamines, somatomedin)
    with neuroendocrine effects altering HPA
  • Systemic Processes ? 1/2 Failure
  • Inflammation Hypoxia
  • Infection Hypotension
  • Direct Injury to Hypothalamns/Pituitary
  • Compression 2 to edema, skull Fx, hemorrhage,
    ?ICP
  • Sella turcica ? rigid dural covering
  • Vascular Supply
  • Anterior Pituitary ? long hypophyseal portal
    veins
  • Post Pituitary ? Inferior hypophyseal artery from
    internal carotid

Powner Neurocritical Care 2006 5
61-70 Schneider J Neuro Trauma 2005 22 937-946
12
Endocrine Failure After Traumatic Brain Injury
  • Anterior pituitary dysfunction prevalence 301
  • Abnormal function in one anterior pituitary axis
    in 532
  • Estimated incidence hormonal reduction3
  • Adrenal 15 Vasopressin 3 - 37
  • Thyroid 5 - 15 Gonadal 25 - 80
  • Growth Hormone 18
  • Associations3
  • Basilar Skull Fracture Hyponatremia
  • Hypothalamic edema Hypotension
  • Prolonged unresponsiveness
  • Schneider J Neurotrauma 2005 22 937-946.
  • Dimopoulou Int Care Med 2004 30 1051-1057.
  • Powner Neurocritical Care 2006 5 61-70.

13
Pituitary Dependent Changes in Critical Illness
Van den Berghe J Clin Endocrinol Metab
1998831827-1834
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Organ Donor
  • Myocardial Dysfunction

Sympathetic Surge
Hormone Depletion
Coronary Perfusion
  • Myocardial necrosis secondary to catecholamines
  • Low circulating levels thyroid and cortisol
    impair function
  • Decreased coronary perfusion pressure
    precipitates ischemia impairing myocardial
    function

16
Improvement of Donor Myocardial Function After
Treatment of Autonomic Surge During Brain Death
  • Defined by Systolic BP gt 200 mmkg and tachycardia
    gt 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 gt 50

Audibert Transplantation 2006821031-1036
17
Improvement of Donor Myocardial Function After
Treatment of Autonomic Surge During Brain Death
Audibert Transplantation 2006821031-1036
18
Brain Death Autonomic StormCardiac Allograft
Vasculopathy1,2
Coronary vasoconstriction Focal myocardial
necrosis Subendocardial ischemia
Endothelial injury
  • Explosive mode of brain death 3
  • Greater intimal thickening of coronary arteries
  • Higher incidence of sudden death, myocardial
    infarctions, need for re-vascularization
  • Domino Transplant
  • Reduced incidence of coronary artery disease in
    recipients of domino hearts compared to
    recipients of cadaveric hearts 4

1. Segel J Heart Lung Txp 200221804-811 2.
Szabo Transplantation 2002731847-48 3. Mehra J
Am Coll Cardiol 200443806-811 4. Anyanwu J
Heart Lung Txp 200322281-286
19
Standardized Donor Management
Declaration - Consent
Eval
Management
Referral
Recovery
General Management Laboratory and Diagnostic
Tests Respiratory Therapy Treatments IV Fluids
and Medications
Organs Recovered
Organs Transplanted
?10.3 per 100 donors
  • ?3.3 total organs per 100 donors
  • ?11.3 per 100 donors

Rosendale American Journal of Transplantation,
2002 2 761-768
20
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 200672377-381
21
Complications of Brain Death and Impact on Organ
Retrieval
There was no significant effect of complications
on the average number of organs harvested with
the exception of an increase in the organs
harvested in the presence of Diabetes Insipidus
Salim American Surgeon 2006377-381
22
Aggressive Donor Management and Organ Donor
Shortage
Salim 200661429-435
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Vasopressors
  • Adverse Outcomes
  • High dose dopamine ? ATN1
  • Dopamine and ADH ? impaired kidney transplant2
  • Dopamine gt 5 mg/kg/min ? detrimental kidney3
  • Dopamine ? mortality heart transplant4
  • High Dopamine impairs liver5
  • Preserved Outcomes
  • Dopamine/epi not risk factor for delayed function
    renal6
  • Dopamine gt 10 mg/kg/min no effect kidney7
  • Dopamine and NE beneficial8
  • High dose dopamine no effect liver9
  • Dopamine at a agonist doses no influence on
    liver, kidney, hearts pediatric donors10
  • Whelchel Txp Proced 1986 18 523-527
  • Schneider Txp 1983 36 110-111
  • Marshall Surgery 1996 120 663-665
  • Wahlers J Heart Lung Txp 1991 10 22-27
  • Yamoaka Txp Int 1990 78-81
  • Koing Txp 1997 63 1620-1628
  • Mackenzie Ann Surg 1991 213 143-150
  • Schnuelle Kid Int 1999 56 738-746
  • Gonzalez Hepatology 1994 565-573
  • Finfer Int Care Med 1996 22 1424-1432

34
Cardiac Catecholamine ControversyAdverse Effects
  • Biochemical, histopath, functional effects
  • High energy substrate depletion 1
  • Intramyocardial noradrenaline depletion
  • Myocardial beta-adrenoceptor downregulation 2
  • Outcomes
  • Higher dose dopamine 3
  • Higher inotropic support 4
  • Norepinephrine ( not dopamine) predicts initial
    non-function 5

1. Sakagoshi J Heart Lung Txp 1992111054-60
2. Pinelli Ann Thorac Surg 1995601729-34 3.
Wahlers J Heart Lung Txp 19911022-28 4.
Young J Heart Lung Txp 199413353-58 5.
Schunelle Transplantation 200172455-60
35
Cardiac Catecholamine ControversyRationale for
Beneficial Effects
  • Profound decrease in circulating catecholamines
    post autonomic storm 1
  • Loss of vascular tone
  • Reduction in inotropy
  • Fosters reliance on fluids
  • Limited period of hemodynamic stability 2
  • Further impairs RV function 3
  • Risks lung procurement
  • Counteracts ? catecholamine levels and maintains
    perfusion pressure gradients/inotropy
  • Immunomodulatory effects 4
  • Biochem, histopath, function outcome NOT
    associated with catecholamines 5,6

1. Powner J Heart Lung Txp 1992111046-49 2.
Chen CCM 1992241352-57 3. Bittner CHEST
19951081358 4. Schnuelle Kid Int
199956788-92 5. DeMeester J Heart Lung Txp
2001201099-1102 6. Fyfe Circulation
199387230-235
36
Donor Catecholamine Use
4 yr Survival
Combo
One
None
  • Immunomodulatory effect
  • Organ variance

Schnuelle Transplantation 2001 72455-63
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Hormonal CocktailsThe Good, the Bad and the Ugly
40
Potential Organ Donor ManagementHormonal Therapy
(Human)T3- Cortisol- Insulin
Standard (26)
Hormone (21)
  • Unsuitable TXP 20
    0
  • Dopamine ug/Kg/min 14 ? 19
    27 ? 13
  • CV Fxn ?
    ? 2x Cardiac output
  • EKG abnormal Persisted
    Improved
  • MAP ?
    56mmHg ?86mmHg (? 53)
  • CVP ?
    11mmHg ? 7mmHg (? 35)
  • HR ?
    67 ? 91 (? 35)
  • HCO3 Required ? 100
    ? 95
  • Lactate NR
    5.1 ? 2.4 (? 52)
  • Temp ?
    330 ? 360

Novitzky Transplantation 1987 43852-854
41
Thyroid Hormone Donor Management
Study
Design

Intervention
Outcome
Powner Prog in Txp 2005 15 202-207
42
Thyroid Hormone Donor Management
Study
Design

Intervention
Outcome
Powner Prog in AP 2005 15 202-207
43
Rescue Hormone Therapy
? 10ug/kg/min Vasoactive Support
  • 1 ampule 50 dextrose 20 u insulin
  • 2 grams methylprednisolone
  • 20 ?g levothyroxine ? infusion 10 ?g/h
  • Vasopressors
  • No cardiovascular collapse

POST
PRE
Vasopressor ug/kg/min 11.1 6.4 Heart rate
beats/min 120 113 Oxygen consumption
ml/min/m2 107 123 Oxygen extraction 16 18
Reduction ? All (4 hours)
Cessation ? 53
Salim Arch Surg 2001 1361377-80
44
Aggressive Pharmacologic Donor Management
  • Methylprednisolone
  • Vasopressin
  • Triiodothyronine or L-thyroxine

Hormonal Resuscitation (701)
Non-Hormonal Resuscitation (10,292)
Rosendale Transplantation, 2003 75 482-487
45
Hormonal Resuscitation Cardiac Outcomes
3 Hormonal Resuscitation
Non-3 Hormonal Resuscitation
  • 46 reduced odds of death with 30 days
  • 48 reduced odds of early dysfunction
  • Steroids alone or steroids plus triiodothyronine
    or L-thyroxine significantly reduced prolonged
    graft function

Rosendale Transplantation, 2003 75 482-487
46
Hormonal Resuscitation Cardiac
Drugs Combinations (4543)
Drugs
a3HR, three-drug hormonal resuscitation T3,
triiodothyronine T4, L-thyroxine.
Rosendale Transplantation 2003751336-1341
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Physiologic Actions of Glucocorticoids
Metabolic
Supply energy/substrate
  • Increase blood glucose
  • Stimulates free fatty acid release from adiopose
  • Stimulates amino acid release from proteins

Maintenance of cardiac contractility and vascular
tone
Cardiovascular
  • Required for normal cardiovascular reactivity to
  • Angiotensin II, epinephrine, norepinephrine
  • Required for synthesis of N K ATP and
    catecholamines/ receptors
  • Decrease production of nitric oxide

Anti-inflammatory and Immunosuppressive
  • Influence most cells participating in
    immune/inflammation rxn
  • Decrease accumulation and function of cells at
    site of inflammation
  • Modulate production of cytokines
  • Increase release of anti-inflammatory factors ?
    IL-1 receptor antagonist, soluable TNf receptor
    IL-10
  • Block transcription for synthesis of mediators

49
Hormonal Changes/Immune Activation
Lopau Txp Int 2000 (suppl 1) S282-S285
50
Impact of LV Dysfunction on Cardiac Donor
Transplant Rates
Potential Heart Donors (223)
Not Transplanted 44 99/223
Transplanted 56 124/223
Cath 8 8/99
Medical 50 50/99
Logistics 13 13/99
Echo 28 26/99
  • Multivariable analysis ? ejection fraction most
    significant predictor of non-use with odds ratio
    of 1.48 per 5 decrease in ejection fraction
  • Efforts to improve yield should focus upon
    prevention or reversal of LV dysfunction

Zaroff J Heart Lung Txp 2003 22334-337
51
Myocardial Dysfunction in Brain DeathClinical,
Echocardiographic and Pathologic Features
  • Echocardiographic systolic dysfunction, 42
  • Not predicted by clinical, EKG or head CT
    characteristics
  • Ventricular arrhythmias more common, 32
  • Dysfunction segmental SAH ICH?apex spared
  • Dysfunction segmental/global trauma/CNS illness
  • Poor correlation between echocardiographic
    distribution of dysfunction and path findings

Dujardin, J Heart Lung Txp 2001 20350-357
52
Temporal Changes in LV Systolic Fxn in Heart
Donors Serial Echocardiography
  • Retrospective review of all donors with ejection
    fractions lt 50 or regional wall abnormalities on
    initial echo that underwent serial echo (16)
  • 13 of 16 initial EF lt 50 improvement in 12 with
    average EF 41 ? 56
  • Medical management
  • Guidelines mandate hemodynamic monitoring
  • Inotropes (15/16 received dopamine)
  • CVP goal 5-8 mmHg
  • Prior to 1st echo correct ? volume status,
    acidosis, hypoxia, hypercarbia, electrolyte
    abnormalities and anemia
  • 75 received corticosteroids
  • NONE received thyroid hormone
  • Responders ? transplanted with 92 survival at
    16 months

Zaroff J Heart Lung Txp 2003 22383-388
53
Myocardial Reversibility (21 y.o. male, victim
of GSW
6 hours
Courtesy of Wayne Babcock and CTDN
54
Donor Management Assessment
Brain dead patient (lt65 years old)
Assess ventricular function by echocardiogram
Normal
Ejection function ? 45
Pulmonary artery catheter placement
Patient age
Repeat echocardiography within 12 hours
lt 40 years
gt 40 years
Persistently abnormal
Normal
Consider dobutamine echocardiography (viability
study)
Cardiac catheterization
Abnormal
Normal
Reversible dysfunction
No reversible dysfunction
Proceed to transplant
Not a donor
Abnormal echocardiogram is defined as a left
ventricular ejection fraction lt 0.45
Abnormal
cardiac catheterization is defined as obstructive
coronary artery disease with one or more lesions
gt 50 in a main coronary artery
Palac Prog Transplant 2003 1342-46
55
Transforming Unacceptable Donors
Potential Multi-organ Donors (150)
Acceptable 65 (98)
Unacceptable 35 (52)
  • MAP gt 60 mmHg
  • CVP lt 12 mmHg
  • PCWP lt 12 mmHg
  • LVSWI gt 15 gm
  • Inotropes lt 5 ug/Kg/mm
  • 40 (21) MAP lt 55 (mean 47 mmHg) despite
    inotropic support
  • 19 (10) CVP gt 15 (mean 18 mmHg)
  • 4 (2) inotropes gt 20 (mean 25 ug/Kg/min)
  • 25 (13) PCWP gt 15 (mean 20 mmHg)
  • 12 (6) LVSWI lt 15 (mean 12.8 gm)

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 14734-742
56
Left Ventricular Function
AoP RAP (mmHg)
Vasodilation Normalize Preload
Reduce Inotropes Reduce Preload
Vasodilation
Vasodilation Normalize Preload Increase Inotropes
Optimum Hemodynamics
Vasoconstrict
Vasoconstrict Normalize Preload
Vasoconstrict Normalize Preload Increase Inotropes
Normalize Preload Increase Inotropes
Nomogram A
Cardiac Output (1/min)
Potter J Heart Lung Txp 1995 1459-65
57
Donor Management Assessment
Brain dead patient (lt65 years old)
Assess ventricular function by echocardiogram
Normal
Ejection function ? 45
Pulmonary artery catheter placement
Patient age
Repeat echocardiography within 12 hours
lt 40 years
gt 40 years
Persistently abnormal
Normal
Consider dobutamine echocardiography (viability
study)
Cardiac catheterization
Abnormal
Normal
Reversible dysfunction
No reversible dysfunction
Proceed to transplant
Not a donor
Abnormal echocardiogram is defined as a left
ventricular ejection fraction lt 0.45
Abnormal
cardiac catheterization is defined as obstructive
coronary artery disease with one or more lesions
gt 50 in a main coronary artery
Palac Prog Transplant 2003 1342-46
58
Stress Echo Eval Reversible BD Myocardial
Dysfunction
Group I (n 23)
Group IIa (n 4)
Group IIb (n 3)
p Value
plt0.01 versus group 1 plt0.01 versus group
llb. Data are expressed as mean ? SD
Kono Am J Card 1999 84578-572
59
Stress Echo Eval Myocardial Dysfxn
Brain Dead Patients (30)
Fractional Short ? 30 (23)
Fractional Short lt 30 (7)
Dobutamine Stress Echo
Responsive (3)
Non-responsive (4)
normalized
Kono Am J Card 1999 84578-572
60
Consensus Conference Cardiac Recommendations
  • Extracardiac factors
  • Age gt 55 used selectively (LVH-ischemia time
    synergistic)
  • Size 70 Kg suitable
  • Structural abnormalities
  • Mild LVH (? 13 mmHg by echo) does not preclude
    txp
  • Txp inadvisable if LVH gt 13 mm and EKG criteria
  • Valvular and congenital abnormalities
    contraindication
  • Bench repair MR/TR, bicuspid aortic secundum
    ASD
  • Cardiac catheterization
  • Male 35-45 and female 35-50 if
  • Hx of cocaine use
  • ? 3 risk factors for CAD
  • Hypertension, diabetes, dyslipidemia
  • Family hx premature CAD, tobacco
  • Male 46-55 and females 51-55
  • Angio recommendation
  • High risk recipient ? consider if angio cannot be
    obtained
  • Age gt 55
  • Angio strongly recommendation

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Pathophysiology of Lung Donor
Unknown history
Mechanical ventilation
  • Occupational
  • Infectious
  • Tobacco
  • Aspiration
  • Pulmonary contusion
  • Shock
  • Resuscitation
  • Atelectasis
  • Pneumonia
  • Baro/Volu-trauma
  • Pulmonary Embolism
  • Oxygen toxicity
  • Neurogenic pulmonary edema
  • Inflammatory response

Causative event
Brain death physiology
63
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 751928-1933
64
Potential Organ Donor ManagementNeurogenic
Pulmonary Edema
  • ?
    ICP ? Autonomic Storm
  • Catecholamine
    Excess
  • Intense
    Vasoconstriction
  • Redistribution blood to RA/RV
    SVR?? 537
  • Adjustment to ? VR by ? COR
    MAP ? 196
  • PA flow ? 25 CVP ?
    Aortic flow? 42 LV failure
  • mPAP ? (14 ?34mmHg) ? LAP
    (8-52mmHg)
  • Capillary
    blood flow arrest
  • Blood
    pooling-72 circ. volume lungs
  • Blast
    injury-disruption anatomic

Right Circuit
Left Circuit
Exceeds for 1 minute
Novitzky Ann Thorac Surg 1987 43288-294
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Pulmonary Donor Inflammation
Open lung biopsy
  • Non-traumatic brain death
  • Neutrophil infiltration correlated BAL

Bronchoalveolar lavage
Brain Death
Controls
Neutrophil concentration 31.85 3 Lavage
IL-8 1282 pg/ml 85 pg/ml Lavage
GRO-? 12,588 pg/ml 102 pg/ml Lung mRNA
IL-8 59.7 27.5
IL-8
GRO- ?
Fisher Lancet 1999 3531412-13
68
Donor Inflammation ? Recipient Outcome
Donor
Recipient
  • IL-8 expression
  • Neutrophil infiltration
  • Graft Function
  • Survival
  • IL-8 signal in donor correlated with
  • neutrophils BAL donor
  • degree of impairment graft oxygenation
  • development of severe early graft dysfxn
  • early recipient mortality

Fisher Am J Respir CCM 2001 163259-65
69
100
?
?
?
?
10
?
?
?
?
?
?
?
?
?
?
1
?
?
?
?
?
?
Donor BAL IL-8 ng/ml
?
?
0.1
?
?
0.01
?
Y -0.077X 1.716
0
0 100 200 300 400
500 600
Lowest PaO2/FiO2 in Recipient (mmHg)
Fisher Am J Respir CCM 2001 163259-65
70
20
15
5
Interleukin-8 in Donor BAL ng/ml
4
3
2
1
0
Effective Early Graft Dysfunction (n16)
Severe Early Graft Dysfunction (n9)
Fisher Am J Respir CCM 2001 163259-65
71
20
15
5
Interleukin-8 in Donor BAL ng/ml
4
3
2
1
0
Survivors gt 6 months (n19)
Early Deaths (n6)
Fisher Am J Respir CCM 2001 163259-65
72
Potential Lung Donor
Unacceptable Lungs
Marginal Lungs
Ideal Lungs
  • PaO2/FiO2 gt 300
  • PEEP 5cmH2O
  • Clear chest x-ray
  • Age lt 55
  • Tobacco lt 20 pk/yr
  • Absence of trauma, surgery, aspiration,
    secretions, malignancy purulent secretions

Baseline Status
Acquired reversible
Alveolar Flooding
Aspiration
Atelactasis
73
Donor Lung Pathology
Donor Series (77)
Suitable 47 (36)
Non-suitable 53 (41)
  • 14 minor pulmonary abnormalities
  • pulmonary emboli
  • extensive over- inflation
  • 40 significant pulm disease
  • 25 bronchopneumonia
  • 15 lungs (12 donors) suitable ? not transplanted
  • mild emphysema
  • grade II pulm hypertension
  • hemorrhage
  • focal bronchopneumonia
  • mild interstitial fibrosis

Finfer Int Care Med 1996 221424-32
Single Lung Donors
Group B (3)
Group A (9)
Husain J Heart Lung Txp 1993 12932-9
74
Assessment of Lungs Rejected and Implications for
Donor Selection
Study Donors (29)
Regional Donors (312)
Reason for rejection
  • 83 (24/29) no or mild pulmonary edema
  • 74 (17/23) intact alveolar fluid clearance
  • 62 (16/29) normal or mildly abnormal histology

41 of rejected lungs potentially suitable for
txp
Ware LANCET 2002 360619-620
75
Objective Assessment of Criteria for Selection of
Donor Lung
  • clinical assessment
  • Bronchoscopy
  • BAL

Potential Lung Donors (39)
Accepted (14)
Excluded by clinical (25)
Current selection criteria are poor
discriminators of pulmonary injury and infection
and lead to exclusion of potentially usable donor
lungs
Fischer Thorax 2004 59434-437
76
Predictive Value and Inter-Observer Variability
Donor CXR Interpretation
Overall (6)
Pulmonologist (3)
Surgeons (3)
Kappa statistics 0.510 0.149
0.336 (Moderate)
(Slight) (Fair)
  • Accept/reject decision concurred actual clinical
    64
  • Positive predictive value accept 78.3
  • Negative predictive value reject 36.3
  • Conclusion eval of CXR highly subjective-limited
    role

Bolton Eurp J CT Surg 2003 23484-487
77
Management of Respiratory Function in the
Potential Organ Donor
  • Goals of mechanical ventilation
  • Fraction of inspired oxygen, 0.40
  • Partial pressure of arterial oxygen, gt100 mmHg
    or oxygen saturation, lt95
  • Partial pressure of arterial carbon dioxide,
    35-40 mmHg
  • Arterial pH, 7.35-7.45
  • Tidal volume, 8-10 ml/kg of predicted body
    weight
  • Pressure end-expiratory pressure, 5 cm of water
  • Recruitment maneuver q 2 hrs ( ? )
  • Goals of bronchoscopy
  • Evaluate anatomy
  • Assess for foreign body and assist in removal
  • Define and locate aspirated material,
    secretions, or apparent infection
  • Clearance of secretions
  • Goals of pulmonary hygiene
  • Prevent atelectasis with the use of suction,
    percussion, postural drainage, and lung-expansion
    techniques
  • Use of anti-infective therapy
  • Use of antibiotic agents on the basis of
    results of Grams staining of aspirated secretions

78
Acute Lung Injury Before Ventilation
  • Consequences
  • V/Q mismatch
  • Alveolar-capillary injury
  • Inflammation
  • Hypertension
  • Barotrauma
  • Consequences
  • Atelectasis
  • Hypoxemia
  • Hypercapnia
  • Inflammation

79
Lung Protective Ventilation
Add PEEP
V o l u m e
Limit Distending Pressure
Pressure
80
Potential Lung Donor
Unacceptable Lungs
Marginal Lungs
Ideal Lungs
  • PaO2/FiO2 gt 300
  • PEEP 5cmH2O
  • Clear chest x-ray
  • Age lt 55
  • Tobacco lt 20 pk/yr
  • Absence of trauma, surgery, aspiration,
    secretions, malignancy purulent secretions

Baseline Status
Acquired reversible
Alveolar Flooding
Aspiration
Atelactasis
81
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83
Potential Organ Donor ManagementMaximizing
Utilization for Lung Transplant
  • Ideal criteria not utilized by marginal donors
  • PaO2/FiO2 ? 300 31
  • Abnormal CXR 61
  • Infection 38
  • Tobacco gt 20 Pk-yrs. 8
  • Age gt 55 6
  • Similar outcomes ideal and marginal
  • Post operative gas exchange
  • ICU length of stay
  • Short or medium term mortality

Gabby Am J Respir Crit Care Med 1999 160265-271
84
Marginal vs Ideal Donor Lung Studies
ICU Complications
Outcome 6 months
OR Complications
A-a 24 hrs
PFT 1 yr
Outcome early
Outcome 1 year
ICU LOS
Hosp LOS
Post-op vent
A-a post op
Outcome 2 years
85
Acute Respiratory Distress Syndrome
Pathophysiology of Pulmonary Edema
EVLW Kf (Pmv - Ppmv) - ? (?mr - ?pmv) - Lymph
flow
Kf filtration coefficient H2O ? vascular
permeability protein 1 ? 0
lt
Endothelium 0.5 - 0.8 Epithelium 1.0
  • Forces responsible for pulmonary edema
  • Increases Decreases
  • Kf Ppmv
  • Pmv ?
  • ?pmv ?mv

86
Donor Lung Extravascular Lung Water
  • Wet/Dry
  • Weight

Pc COP
Pc COP mmHg
Qflow-out K(PC PI) - s (?C - ?I) Qflow-out
PC ?C where PC PCWP 0.4 (Pa-PCWP)
Q Flow rate transudated fluid s
reflection coefficient K Hydraulic
conductance ?C Oncotic pressure capillary PC
Pressure capillary ?I Oncotic pressure
interstitium PI Pressure interstitium
87
Lung Donor Fluid Resuscitation
Fluid load CVP ? 6 mmHg
CVP 4-6 mmHg
CVP 8-10 mmHg
  • 3.7 liters crystalloid 90 min.
  • ? A-a 146 ?168
  • ?CVP ?A-a 239 ?211
  • PCWP 3.5 mmHg gt CVP
  • 600 cc crystalloid 90 min.
  • ?A-a 151 ? 142

Pennefather Transplantation 1993 561418-22.
  • greatest reason for lung non-suitability (31)
  • significant positive fluid balance 7000 cc vs.
    300 cc

Progressive pulmonary dysfxn
Reilly CHEST 1996 110222S
88
Aggressive Lung Resuscitation
Didactic curriculum
  • Educational changes

Procurement
Management Protocols
Cummings J Txp Coord 1995 5103-106
89
Reasons for Lung Refusal
Unaffected by Donor Management
1993
1992
Affected by Donor Management
45
63
Cummings J Txp Coord 1995 5103-106
90
Multidisciplinary Management
  • Initiation of local lung txp program/multi-discipl
    inary
  • Management strategies to optimize lung
  • Donor lung procurement 1.2 ? 28
  • Organs procured per donor 2.7 ? 3.7

Follette Txp Proced 1999 31169-70
91
Multidisciplinary Management Lung Donors
  • consensus standardized orders OPO txp
  • early bronchoscopy
  • early ventilator management
  • early hemodynamic monitoring
  • early corticosteroids, thyroxine
  • emphasis upon colloid
  • judicious use vasoactive support
  • early and continuous access to transplant
    pulmonologist

Management Strategies
Follette Txp Proced 1999 31169-70
92
Marginal Lung Studies-Aggressive OPO Management
13 Unacceptable PaO2/FiO2 150
  • Management
  • Invasive monitoring PaO2 / FiO2 103
    463
  • Methylpred FiO2 86 100
  • Fluid restriction CVP 11.3 mmHg 6.7
    mmHg
  • Titrated inotropes Net Fluid 4.1 L
    - 1.7 L
  • Bronchoscopy Dopamine 15 ?g/kg/min
    5.2 ?g/kg/min
  • Diuresis Abnormal 77 0

Pre-OPO
Procurement
Straznicka J Thorac CV Surg 2002 124250-58
93
Unilateral Donor Lung Dysfxn
22
  • CXR/Bronchoscopy clearly unilateral
  • Selective ventilation/pulm art clamp PaO2 499.5

PaO2 246
Puskas J Thorac CV Surg 1992 1031015-18
Other Procurement Team
  • 146 150 142
  • Days vent 7.4 6.5 4.6
  • ICU LOS 8.1 7.4 5.1
  • Hosp LOS 29 26 21
  • Death ? 30 days 2.9 4.3 6.8
  • 1 yr survival 81 87 89
  • marginal 43 41 41

Distant - P
Distant - O
Local - P
359
329
327
post-op
  • A-a

24 hrs
Shiraishi Ann Thorac Surg 1997 64203-6
94
Pulmonary Vein Gas Analysis for Assessing Donor
lung Function
Group A PaO2 gt 300 mmHg PvO2 gt 300 mmHg
Group B PaO2 lt 300 mmHg PvO2 gt 300 mmHg
During this study period we have increased the
procurement rate for lung retrieval to an average
of 65 of our multiple organ donors whose lungs
have been retrieved and successfully used for
transplantation
Aziz Ann Thorac Surg 2002 731599-1605
95
Non-heart Beating (DCD) Lung Donation
  • Timing of lung death and lung failure
  • Lung may be more amenable to non-heart beating
    donation than kidney ? parenchyma cells
    immediately adjacent to alveolar spaces and O2
    source1
  • Tissue high energy nucleotide phosphates normal 4
    hours2
  • Pre-arrest hypoxia limited effect on pulmonary
    fxn3
  • Successful animal models4
  • Successful early human experience5

1. Corris Thorax 2002 57(suppl 11)ii53-ii56 2.
DArmini J Surg Res 1995 59468-474 3. Mauney
Ann Thoracic Surg 1996 6254-61 4. Egan J Heart
Lung Txp 2004 233-10 5. Steen Lancet 2001
357825-829
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