Expanding the Donor Pool:ECD and DCD Practice

Carl-Ludwig Fischer-Fröhlich, Stuttgart, Germany

• 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 ?

Expanded criteria donors (ECD)

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17 23 5 11 17 23 5 11 17 23 5 Time

Temp. °CHR /minBsyst mmHgBdiast mmHG

Example: 52 yrs, SAH (admitted 10 h after event)

Infection parameters: = become unreliable- brain injury - brainstem coning - overlay of infection ??

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

Brain death andInflammation:

Infections (1)

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…)

Critical Symptoms

Council of Europe: Guide to the safety and quality of organs in transplantation of organs (5 th ed., 2013)

Infections (2)

• systematic spread / blood = transmission latent / locally restricted = different patterns of transmission (e.g. CMV) properly treated infection = 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

Bacteria, Virus, Fungus, Parasites et al.:

Council of Europe: Guide to the safety and quality of organs in transplantation of organs (5 th ed., 2013)

Malignancy

• staging TNM – histology – therapy – recurrence free – kind of follow up• brain tumor vs. other solid tumors vs. haematopoetic disorders• tumor markers: not reliable

transmission risk assessment:

Final decision depends on recipient’s needs

Transplant Registries (e.g. UNOS / IPTTR), case reports: low rate of transmission if donor was properly screened lethal adverse events if overseen in donorcurrent practice:~ non cerebral: some T1N0M0, if recurrence free survival > * years~ cerebral: WHO Grade + duration + therapy

Council of Europe: Guide to the safety and quality of organs in transplantation of organs (5 th ed., 2013)

…but never forget to screen for malignancy in a potential donor

Gene Defect or rare diseases

• 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

Glycogenosis

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)

Council of Europe: Guide to the safety and quality of organs in transplantation of organs (5 th ed., 2013)

• Check for detoxication and recovery from poisoning

- 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

Preservation of organ function before recovery…

Donor maintenance improves marginal organs !

…pitfalls at recovery

Final check in thorax and abdomen !

67 years SAH• ICU = 17 days• ALAT = 91 IU/l• BMI = 35 kg/m²• paO2/FIO2= 134

Is it safe to use this liver for transplantation?

• Diabetes Typ II• Hypertension• Tetanus as child• anti-HBc +, HBsAg -

Consensus: Qualified examination at recovery + biopsy + care for HBV-transmission

5% macrovesiuclar steatosis,slight choelstasis, slight cholangitis

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

Liver: Interaction donor & ECD & recipient

Death censored graft survival rate (p < 0,0001):Graft survival rate (p < 0,0001):

 Donor age n 0-17 yrs. 244

18-54 yrs. 3372

55-64 yrs. 1517

65-74 yrs. 1625

75-84 yrs. 513

≥ 85 yrs. 38

Days after transplantation Days after transplantation

Kidney: donor age = ECD ?(Germany 2009-2012, n=7309, courtesy DSO/Aqua)

 Donor age n 0-17 yrs. 244

18-54 yrs. 3372

55-64 yrs. 1517

65-74 yrs. 1625

75-84 yrs. 513

≥ 85 yrs. 38

Donor age explaining variable in all COX regressions in German population

*3 Experiment: explosive ICP ~ irreversible myocard damage~ contraction band necrosis

Donor chatecholamine support heart transplantion

*1- if (after SAH/ICB) primary graft failure

*2- if (at vasoplegia) no effect on graft function

*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

*4 Stress related cardiomyopathy:…acute stress , severe illness or…”sudden intracranial disease”~ explosive catecholamine release at nerve ends of myocard~ arrythmia, akinesia, LVF…

The Brain - Heart Connection:

*5 SAH cardiac failure~ cardiac function workup

*6 avoid at brain stem coning~ by Esmolol or Urapidil

*7 after brain stem coning~ donor resucitation protocol (covers other pathologies)

*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

Poor cardiac output mitigated byinotropic support (dobutamine)after stress cardiomyopathy

Peripheral vasoconstriction afterbrain death (norepinephrine)

Donors after circulatory death (DCD)

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)

DCD categories:

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

• 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

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 forassuring irreversible cardiac arrest otherwise stop procedure

• Keep ischemia times low

• Select appropriate recipients

• Compensate side effects of pro-longed warm ischemia by proper organ preservation

• Results might be equivalent to DBD when performed properly.

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.

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

Expanding the donor pool: ECD and DCD practice