Donor

Report
Expanding the Donor Pool:
ECD and DCD Practice
Carl-Ludwig Fischer-Fröhlich, Stuttgart, Germany
Expanded criteria donors (ECD)
• frequent co-morbidities in donors
• donor derived diseases  transmission  Mortality / Morbiditiy 
• pitfalls
infection
malignancy
gene defect
poisoning
 acute – chronic – latent – cured – recurrence free ?
 global or local problem ?
 treatment in the recipient possible ?
 benefit for the individual recipient ?
Example: 52 yrs, SAH (admitted 10 h after event)
180
Temp. °C
160
Brain death and
Inflammation:
HR /min
Bsyst mmHg
140
Bdiast mmHG
120
Infection parameters:
= become unreliable
100
80
60
-
brain injury
-
brainstem coning
-
overlay of infection ??
40
20
0
17
23
5
11
17
23
5
11
17
23
5
Time
Leuco.
25
17
18
18
G/l
CRP
29
86
181
223
mg/l
Platelets
267
271
211
211
G/l
Fibrinogen
2,6
3,8
4,9
7,4
mg/l
NA
135
135
149
146
mmol/l
Infections (1)
Critical Symptoms
Previous mental or neurological changes
(skin / fever / diarrhea / pain / body examination):
• poisoning? malignancy? exotic virus – fungus – bacteria – parasite - zoonosis?
Living conditions / social situation / „antecedents“:
• chance for collecting infectious pathogens
• traveling, working, living, pets, animals, sanitary condition, CDC-risk
Diagnostic tests may fail !
• serology, cultures, PCR etc.: specific / sensitive? false pos./neg. ?
Minimum screening (serology +/-PCR if indicated in high risk population):
• HIV, Hepatitis B & C, CMV, EBV, Toxoplasmosis
• Further pathogens according to regional prevalence (WMV, Dengue, Malaria…)
Council of Europe: Guide to the safety and quality of organs in transplantation of organs (5 th ed., 2013)
Infections (2)
Bacteria, Virus, Fungus, Parasites et al.:
• systematic spread / blood
latent / locally restricted
properly treated infection
= transmission
= different patterns of transmission (e.g. CMV)
= no exclusion (e.g. 48h antibiotics in bacteria)
• communicate all in coming results / data to recipient centers
• reassess with recipient CMV-, PCP-, antibiotic-prophylaxis et al.
Absolute Contraindication:
• Encephalitis or Meningitis of unknown origin
• Un-treated true Sepsis or tuberculosis
Council of Europe: Guide to the safety and quality of organs in transplantation of organs (5 th ed., 2013)
Malignancy
transmission risk assessment:
• staging TNM – histology – therapy – recurrence free – kind of follow up
• brain tumor vs. other solid tumors vs. haematopoetic disorders
• tumor markers: not reliable
Transplant Registries (e.g. UNOS / IPTTR), case reports:
 low rate of transmission if donor was properly screened
 lethal adverse events if overseen in donor
current practice:
~ non cerebral: some T1N0M0, if recurrence free survival > * years
~ cerebral:
WHO Grade + duration + therapy
 Final decision depends on recipient’s needs
 …but never forget to screen for malignancy in a potential donor
Council of Europe: Guide to the safety and quality of organs in transplantation of organs (5 th ed., 2013)
Gene Defect or rare diseases
Glycogenosis
• Donor 73 yr., cerebral stroke -> bleeding
• Glycogenosis Type 5 (Mc Ardle):
- gene 11q13 defect for muscle-myophosphorylase
- isoenzyme for liver and brain coded by other gene
- risk for rhabdomyolysis after severe exercise
• www.orphanet.net
Council of Europe: Guide to the safety and quality of organs in transplantation of organs (5 th ed., 2013)
Poisoning
CO and / or Cyanide (smoke)
• Check for detoxication and recovery from poisoning
Council of Europe: Guide to the safety and quality of organs in transplantation of organs (5 th ed., 2013)
Preservation of organ function before recovery…
- 100 kg, 170cm, ICB, untreated hypertension, smoker, alcohol,
- ICU-Nurse: “Hi, needs volume and MAP >75 for diuresis, Crea. normal”
 prevention of acute kidney injury (with assumed chronic damage)
 liver-fibrosis, 3 vessel-CAD, arteriosclerosis
 both kidneys had primary function
 Donor maintenance improves marginal organs !
…pitfalls at recovery
 Final check in thorax and abdomen !
Is it safe to use this liver for transplantation?
67 years SAH
• ICU = 17 days
• ALAT = 91 IU/l
• BMI = 35 kg/m²
• paO2/FIO2= 134
•
•
•
•
Diabetes Typ II
Hypertension
Tetanus as child
anti-HBc +, HBsAg -
5% macrovesiuclar steatosis,
slight choelstasis, slight cholangitis
Consensus: Qualified examination at recovery + biopsy + care for HBV-transmission
Liver: Interaction donor & ECD & recipient
Multiple Cox Regression
Graft failure (n=2175)
Donor
Risk
Ratio
95%-CI
p-value
Age (yrs.)
1.011
[1.005-1.017]
<0.001
Organquality (reduced)
1.243
[1.001-1.545]
0.049
Recipient
Risk
Ratio
95%-CI
p-value
Age(yrs.)
1.014
[1.006-1.022]
0.001
High Urgent
1.809
[1.398-2.342]
<0.001
Creatinine (mg/dl)
1.205
[1.136-1.278]
<0.001
Bilirubine (mg/dl)
1.023
[1.016-1.030]
<0.001
Donor:
Age
Recipient:
Co-Morbidity (age) + actual status (Bili, Crea, HU)
 EDC are not relevant after proper donor selection
Frühauf NR, Fischer-Fröhlich CL, Kutschmann M, Schmidtmann I, Kirste G. Transplantation, 2011 ; 92: 1378-1384
Kidney: donor age = ECD ?
(Germany 2009-2012, n=7309, courtesy DSO/Aqua)
Graft survival rate (p <
Death censored graft survival rate (p
0,0001):
Donor age
0-17 yrs.
n
244
0-17 yrs.
n
244
18-54 yrs.
3372
18-54 yrs.
3372
55-64 yrs.
1517
55-64 yrs.
1517
65-74 yrs.
1625
65-74 yrs.
1625
75-84 yrs.
513
75-84 yrs.
513
≥ 85 yrs.
38
≥ 85 yrs.
38
Donor age
Days after transplantation
Days after transplantation
 Donor age explaining variable in all COX regressions in German popula
The Brain - Heart Connection:
Donor chatecholamine support  heart transplantion
*1- if  (after SAH/ICB)  primary graft failure 
*2- if  (at vasoplegia)  no effect on graft function
Poor cardiac output mitigated by
inotropic support (dobutamine)
after stress cardiomyopathy
Peripheral vasoconstriction after
brain death (norepinephrine)
*3 Experiment: explosive ICP 
~ irreversible myocard damage
~ contraction band necrosis
*5 SAH  cardiac failure
~ cardiac function workup
*4 Stress related cardiomyopathy:
…acute stress , severe illness or
…”sudden intracranial disease”
~ explosive catecholamine release
at nerve ends of myocard
~ arrythmia, akinesia, LVF…
*7 after brain stem coning
~ donor resucitation protocol
(covers other pathologies)
*1 Santise, Interact Cardiovasc Surg 2009, 9, 476-479
*2 Silva, Intens Care Med, 2002, 28, Suppl. 66
*3 Shivalkar, Circulation 1993, 87, 230-239
*4 Bybee, Prasa, Circulation 2008, 118, 397-409
*6 avoid at brain stem coning
~ by Esmolol or Urapidil
*5 Lee Neuro Crti Care 2006,5, 243-249
*6 Mertens, Organs Tissues Cells 2007, 10, 159-165
*7 Zaroff, Ciruclation 2002, 106, 836-841
Donors after circulatory death (DCD)
DCD categories:
FIRST INTERNATIONAL MEETING OF DCD
(MAASTRICHT - criteria 1995)
uncontrolled DCD MAASTRICHT I (dead on arrival)
MAASTRICHT II (CPR not succeeded)
controlled DCD
MAASTRICHT III (waiting for cardiac arrest)
MAASTRICHT IV (cardiac arrest after BD)
Kootstra G, Daemen JH, Oomen AP. 1995. Categories of non-heart-beating donors.
Transplantation Proceedings 27(5):2893–2894.
DCD: some basics
• How do you confirm death after the terminal cessation of heart function ?
• Does this DCD concept fit your legislation about brain death diagnostics ?
• How complies your no-touch period with the ”Donor Dead Rule“ ?
• Is DCD accepted within your health care system ?
• You must have a convinced team with all partners in the hospital integrated !
• You must have an effective protocol for all steps in your hospital !
Example Germany:
 in every donor death & irreversible cessation of all brain functions must be
confirmed before an organ can be recovered for transplantation after consent.
 any no-touch-period does not confirm this as safe sign of death……
Controlled DCD
•Severe cerebral lesion (Anoxia, ICB et al.) /
• No severe cerebral lesion (e.g. terminal
neurodegenerative or cardio-pulmoinary disease)
• No brain death criteria
If all ok: apply your protocol (e.g.)
•
prepare recovery
•
prepare WLST
•
Consider farewell
•
Perform WLST
•
In case of cardiac arrest
<120’ proceed with recovery
after appropriate no-touch period for
assuring irreversible cardiac arrest
otherwise stop procedure
•
Keep ischemia times low
•
Select appropriate recipients
•
Compensate side effects of prolonged warm ischemia by proper
organ preservation
•
Results might be equivalent to
DBD when performed properly.
• Previous consent to withdrawl life sustaining
therapy (WLST)
• Organ donation acceptance
• consent for canulation & medication pre-mortem
• Predictive Score of Cardiac arrest <120’
• Clinical evaluaiton
uncontrolled DCD
Apply protocol consented with all partners in your healthcare system:
• CPR failed, usually otherwise healthy persons (outside/inside hospital)
• Rapid arrangements in your hospital (unexpected event)
• Death certification by team independent from recovery or transplantation
• Appropriate family approach (time constraints)
• If consent farewell & recovery (see controlled DCD) or otherwise stop
Critical issue:
• Some maneuvers mandatory pre-consent & CPR continued until… et al.
Expanding the donor pool: ECD and DCD practice
Conclusion: Case wise decision
• Expanded donor criteria
~ risk for compromised grafts 
• Restricted donor criteria
~ dead on waiting list anyway
• Personal alert:
- “I may oversee a donor”
- fit recipient to donor
- update protocols (research)
 Thank you

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