atc pre-meeting symposia #3: nurse coordinator itns – natco – ishlt may 31 st 2008 track 1:...

ATC pre-meeting symposia #3: Nurse Coordinator ITNS – NATCO – ISHLT May 31st 2008

Track 1: Liver: Risk factors/Outcomes

of using

Expanded Criteria Donors (ECD): Post- operative complications

Frank E. L. van Gelder, RN, BSN, CETCFrank E. L. van Gelder, RN, BSN, CETC

Senior Transplant coordinator Senior Transplant coordinator

University Hospitals Leuven U.Z GasthuisbergUniversity Hospitals Leuven U.Z Gasthuisberg

AbdominaleTransplant surgeryAbdominaleTransplant surgery


Reality…. Victim of our own success

Better medical standardsBetter medical standards Aggressive therapy of Neuro surgical patientAggressive therapy of Neuro surgical patient Excellent survival rates of organ transplant recipientsExcellent survival rates of organ transplant recipients Elderly donor and recipient population….Elderly donor and recipient population….

leads toleads toIncreased demand– decreased offerIncreased demand– decreased offer

stimulates the intention to go more extended to meet stimulates the intention to go more extended to meet the demand and close the gapthe demand and close the gap


Donor Donor PoolPool

Where to optimize with calculated risks?


Definition of ECD liver donor

A donor whose characteristics may include general or A donor whose characteristics may include general or organ specific factors such as advanced donor age, organ specific factors such as advanced donor age,

prior infection with hepatitis B or hepatitis C, a history of prior infection with hepatitis B or hepatitis C, a history of hypertension or diabetes mellitus, abnormal donor hypertension or diabetes mellitus, abnormal donor

organ function, or non-heart-beating status of a organ function, or non-heart-beating status of a deceased donor. The term “expanded” is used because deceased donor. The term “expanded” is used because

an expansion of the donor pool is considered to an expansion of the donor pool is considered to increase transplantation and is preferred over the term increase transplantation and is preferred over the term

of marginal donor *. of marginal donor *.

(*) definition @ www.unos.org


SC Donor EC Donor

InvestigationInvestigation

ExperienceExperience

# Organs# Organs

Safety BalansSafety Balans

How to evaluate ECD?


Pushing limitsPushing limits……

Is this justifiedIs this justifiedMedically, ethically & economically? Medically, ethically & economically?


Definition ECD organs

DCD donorsDCD donors controlled/uncontrolledcontrolled/uncontrolled

Hemodynamically instable donorsHemodynamically instable donors

Co morbidityCo morbidity Age relatedAge related Disease relatedDisease related

Infected donorsInfected donors Bacterial of ViralBacterial of Viral

(Malignicies)(Malignicies)

PreservationPreservation (Surgically damaged organs)(Surgically damaged organs)


Definition of post-operative complications

Donor relatedDonor related

Recipient relatedRecipient related


Expanded Criteria DonorsExpanded Criteria Donors

What influences outcomes in transplantation

Transplant OutcomeTransplant Outcome

Donor side:Donor side: -HemodynamicsHemodynamics

- Organ quality (steatosis)Organ quality (steatosis)-Neuro-hormonal inbalanceNeuro-hormonal inbalance-Pro-inflammatory reactionsPro-inflammatory reactions

-Co-morbidityCo-morbidity-IschemiaIschemia

-Preservation Preservation -ReperfusionReperfusion

Transplant sideTransplant sideRecipient RelatedRecipient Related

-Co-morbidity-Co-morbidity-Immunology-Immunology

-Infection Risk-Infection Risk-CV disease-CV disease-Meld score-Meld score

- Retransplantation- Retransplantation


Recipient related date

Meld score > 30 is directly associated with a Meld score > 30 is directly associated with a higher patient moratlityhigher patient moratlity

Higher risk of mortality when sub-optimal grafts Higher risk of mortality when sub-optimal grafts transplanted in patients with increased risktransplanted in patients with increased risk(re-transplantation and higher MELD score)(re-transplantation and higher MELD score)

Optimal utiliztion of Donor Grafts with extended criteriaOptimal utiliztion of Donor Grafts with extended criteriaCameron M and R. Busutill Annals of Surgery: 243 (6), June 2006Cameron M and R. Busutill Annals of Surgery: 243 (6), June 2006


ECD Livers – type of post-operative complication

DCD donorsDCD donors

Hemodynamically instable HB donorsHemodynamically instable HB donors

Co morbidity – Age (graft quality)Co morbidity – Age (graft quality)

Infected donorsInfected donors

Preservation Preservation

PNF, DGF, Biliary complicationsPNF, DGF, Biliary complications

PNF, DGFPNF, DGF

PNF, DGF, Transmittable diseasePNF, DGF, Transmittable disease

Donor related infectionsDonor related infections

PNF, DGF, Biliary complications PNF, DGF, Biliary complications


1. Outcome of livers from DCD donors

DCD liver donors are exclusively Maastricht Cat III livers DCD liver donors are exclusively Maastricht Cat III livers (awaiting cardiac arrest)(awaiting cardiac arrest) Introduced as “the solution” for organ shortageIntroduced as “the solution” for organ shortage Pitfalls:Pitfalls:

Definition warm ischemiaDefinition warm ischemia SurgerySurgery Withdraw methodsWithdraw methods Minutes of “no-touch” periodMinutes of “no-touch” period

Warm ischemia as such:Warm ischemia as such: Unclear what the impact isUnclear what the impact is


DCD donors: a way-out to organ shortage?

Experimental model in large animal model shows cut-off Experimental model in large animal model shows cut-off @ 30 minutes for warm ischemia in controlled NHB @ 30 minutes for warm ischemia in controlled NHB (DCD) donors(DCD) donorsD. Monbaliu , J. Pirenne University Hopsitals Leuven, BelgiumD. Monbaliu , J. Pirenne University Hopsitals Leuven, Belgium

87% patient and 83% 1yr graft survival in controlled cat 87% patient and 83% 1yr graft survival in controlled cat III NHB (DCD)III NHB (DCD)Muiesan P. et al, Annals of Surgery 2005 November; 242 (5): 732-8Muiesan P. et al, Annals of Surgery 2005 November; 242 (5): 732-8

70% 1yr and 63% 3yr graft survival70% 1yr and 63% 3yr graft survivalAbt PL, Crawford MD et al, Annals of Surgery 2004 January; 239 (1): 87-92Abt PL, Crawford MD et al, Annals of Surgery 2004 January; 239 (1): 87-92


DCD Livers: the reality

Up to 50% graft loss within the first yearUp to 50% graft loss within the first year

70% one-year patient survival70% one-year patient survival

Morbidity dramatically increases due to unclear Morbidity dramatically increases due to unclear definitions, combined risk factors @ donor and definitions, combined risk factors @ donor and recipient siderecipient side


DCD livers: post-operative complications

Incidence of PNF doubles (12% versus 6%)Incidence of PNF doubles (12% versus 6%)

Incidence of DGF triples (30% versus 10%)Incidence of DGF triples (30% versus 10%)

Incidence of Biliairy complications quadruples Incidence of Biliairy complications quadruples

(48% versus 12%)(48% versus 12%)

Incidence of re-transplantation doubles (14% Incidence of re-transplantation doubles (14% versus 7%)versus 7%)


DCD donors : ideal approach to avoid post-op complications

No combination of risk-factorsNo combination of risk-factors Donor ageDonor age Recipient medical statusRecipient medical status Cold ischemia timeCold ischemia time Warm ischemia time (CLEAR DEFINITION!!!)Warm ischemia time (CLEAR DEFINITION!!!)

A controlled situationA controlled situation Abort use of graft when doubtAbort use of graft when doubt Optimize preservation techniquesOptimize preservation techniques

(pressurized, protaglandines, ECMO,…)(pressurized, protaglandines, ECMO,…)


2. Hemodynamically instable HB donors

BD results in a series of hemodynamic, neurohormonal BD results in a series of hemodynamic, neurohormonal and pro-inflammatory perturbations that could lead to and pro-inflammatory perturbations that could lead to donor organ delayed or non functiondonor organ delayed or non function

Hicks et al Methods of Molecular Biology, 2006; 333: 331-74Hicks et al Methods of Molecular Biology, 2006; 333: 331-74

Ischemic pre-conditioning versus Ischemic damageIschemic pre-conditioning versus Ischemic damage

Donor management is pivotal in early graft outcomeDonor management is pivotal in early graft outcomeThe effect of a protocol of aggressive donor management: implication for the national organ donor shortage Salim The effect of a protocol of aggressive donor management: implication for the national organ donor shortage Salim et al: The journal of trauma August 2006 Vol 61(429-35)et al: The journal of trauma August 2006 Vol 61(429-35)

Agressive pharmacologic donor management results in more transplanted organs Rosendale, Kauffman et al: Agressive pharmacologic donor management results in more transplanted organs Rosendale, Kauffman et al: Transplantation Vol 75 (4) February 2003Transplantation Vol 75 (4) February 2003

Influence of high donor serum sodium levels on early postoperative graft function in human liver transplantation: Influence of high donor serum sodium levels on early postoperative graft function in human liver transplantation: the effect of early correction of donor hypernatremia Totsuka et al Liver Transplantation Surgery 1999 the effect of early correction of donor hypernatremia Totsuka et al Liver Transplantation Surgery 1999 september; 5(5): 421-8september; 5(5): 421-8


Hemodynamically instable donors: post-operative complications

Primary non-function and delayed graft function:Primary non-function and delayed graft function: Long periods of hypotension in combination with Long periods of hypotension in combination with

extensive use of catecholamines lead to an increased extensive use of catecholamines lead to an increased risk of PNF and DGF because of induced severe risk of PNF and DGF because of induced severe ischemiaischemia

It directly influences the potential number of available It directly influences the potential number of available liver graftsliver grafts

Biliary complications could be associated with Biliary complications could be associated with induced long ischemia induced long ischemia


3. Donor organ quality: aged donors

What is the definition of “older” donorsWhat is the definition of “older” donors

Very limited literature supporting the “expanded older donor” theory Very limited literature supporting the “expanded older donor” theory of less good organ functionof less good organ function

The problem of using older donors is that other risk factors may The problem of using older donors is that other risk factors may increase:increase: Liver fibrosis and steatosisLiver fibrosis and steatosis Infection risksInfection risks Malignancy risksMalignancy risks

This in combination with high risk patients could seriously This in combination with high risk patients could seriously compromise early –on resultscompromise early –on results


Age distribution Effective Donors 1990 - 2007

Median age 2007 effective donors: 46,7 yrs ± 19,9


Donor age and outcomeDonor age and outcome


Casus

Patient ICB on ICUPatient ICB on ICU

83 yrs83 yrs Diabetes mellitus Type 2Diabetes mellitus Type 2 AoValve prothesis and Redo CBPS 2 yrs agoAoValve prothesis and Redo CBPS 2 yrs ago Abdominal infra-renal aneurysmAbdominal infra-renal aneurysm

Is this still a donor??Is this still a donor?? Normal liver functionNormal liver function


Don’t turn a donor down based on age or medical history only!! Go and have a look at the liver!

38yrs: a bit alcohol, obesity38yrs: a bit alcohol, obesity

83yrs: normal echo and liver values83yrs: normal echo and liver values


Liver Tx with “very old” livers: Results

Primary-Non-Function: nonePrimary-Non-Function: none Temporary graft dysfunction (peak Temporary graft dysfunction (peak

AST>3.000IU/L): 2AST>3.000IU/L): 2 Mean peak AST: 1.110.71±1.119IU/LMean peak AST: 1.110.71±1.119IU/L Median hospital stay: 17 days (12-107)Median hospital stay: 17 days (12-107) Patient/graft survival: 82% (Kaplan-Meier 1y Patient/graft survival: 82% (Kaplan-Meier 1y

survival is 80%)survival is 80%)

Pirenne et al, Transplant Proceedings 2005Pirenne et al, Transplant Proceedings 2005


How to judge old liver donors?

Avoid a combination of risk factors: Avoid a combination of risk factors: SteatosisSteatosis HypernatriemiaHypernatriemia

Short cold and warm ischemiaShort cold and warm ischemiaexperineced procurement teamsexperineced procurement teams

Centre driven selection criteriaCentre driven selection criteria Patient with best possible outcomePatient with best possible outcome


“Very old” donors

38 livers procured from donors 38 livers procured from donors >> 70 yo 70 yo and deemed suitable for LTx (1/5/2001 - and deemed suitable for LTx (1/5/2001 - 6/1/2007)6/1/2007)

Median age of these 38 donors: 78 yoMedian age of these 38 donors: 78 yo

Range: 70-87 yoRange: 70-87 yo

35%: >80 yo35%: >80 yo Cause of death: Cause of death:

Cerebro-Vascular Accident Cerebro-Vascular Accident (82%)(82%)

Trauma (18%)Trauma (18%)


4. Infected donors

Most common viral infections in Liver Donors that could Most common viral infections in Liver Donors that could impact patient outcomeimpact patient outcome Hepatitis C positive donorsHepatitis C positive donors Hepatitis B positive donorsHepatitis B positive donors

Bacterial infections:Bacterial infections: When transmitted can be a dreadful complicationWhen transmitted can be a dreadful complication Most common (Paredes et al Transplant proc 2007 Sep;39(7))Most common (Paredes et al Transplant proc 2007 Sep;39(7))

Coagulase negative Staphylococci (46%)Coagulase negative Staphylococci (46%) Stafylococcus Aureus (15%)Stafylococcus Aureus (15%) Streptococcus Viridans(9%), Enterobacter (9%), Streptococcus Viridans(9%), Enterobacter (9%),

Entercoccus Faecalis (8%)Entercoccus Faecalis (8%)


Risk estimation of bacterial and fungal infections in donors*

Up to 50% of all donors show post-donation one or more Up to 50% of all donors show post-donation one or more positive bacterial and/or fungal infectionspositive bacterial and/or fungal infections With bacteremia positive in 20%With bacteremia positive in 20% Significant older donors when pathogen transmission takes placeSignificant older donors when pathogen transmission takes place When pathogen transmission takes place, patient mortality significantly When pathogen transmission takes place, patient mortality significantly

increases (up to 40% @ 1yr)increases (up to 40% @ 1yr) Longer ICU stay (> 3 days)Longer ICU stay (> 3 days)

Complications that are related to bacteremia and post-Complications that are related to bacteremia and post-transplant related infectiontransplant related infection Mycotic aneurysm (very high patient mortality)Mycotic aneurysm (very high patient mortality) Secundary related infection with higher morbidity riskSecundary related infection with higher morbidity risk

(*) Cerutti et al : Bacterial and fungal positive cultures in organ donors: clinical impact in liver transplantation(*) Cerutti et al : Bacterial and fungal positive cultures in organ donors: clinical impact in liver transplantationLiver Transplantation 2006 Aug; 12(8): 1253-9Liver Transplantation 2006 Aug; 12(8): 1253-9


5. Preservation related post-opertave complications

Definition of “an optimal preserved” liver graftDefinition of “an optimal preserved” liver graft Cold ischemiaCold ischemia Warm ischemiaWarm ischemia

HypotensionHypotension DCDDCD CatecholaminesCatecholamines

Preservation solutionPreservation solution

Related complicationsRelated complications PNF with re-transplantationPNF with re-transplantation DGF with increased mortality and morbidityDGF with increased mortality and morbidity Biliary strictures with more morbidity and QoL impactBiliary strictures with more morbidity and QoL impact


Expanded Criteria donors and preservation

DCD is largest group of interest because warm DCD is largest group of interest because warm ischemia is the problem to tackleischemia is the problem to tackle ECMOECMO Warm preservationWarm preservation Organ preservation machinesOrgan preservation machines

Still a long way to go: may studies are started up Still a long way to go: may studies are started up in large animal models or perfusion of discarded in large animal models or perfusion of discarded human organs to identify key factors for optimal human organs to identify key factors for optimal preservationpreservation


Further use of marginal Livers will require: Further use of marginal Livers will require: better preservation technique& viability testing better preservation technique& viability testing methodsmethods

Monbaliu, Vekemans et alMonbaliu, Vekemans et al Organ Recovery SystemOrgan Recovery System


Non Heart Beating Donors

In a pig model, livers tolerate short periods of warm In a pig model, livers tolerate short periods of warm ischemiaischemia

Monbaliu et al, Transplantation 2005Monbaliu et al, Transplantation 2005

Clinical LTx from non heart beating donors started in Clinical LTx from non heart beating donors started in Leuven (6 cases / 1 reTx) and in Belgium (16 livers) Leuven (6 cases / 1 reTx) and in Belgium (16 livers) 2003-20052003-2005

Monbaliu et al, Transplant Proceedings, in pressMonbaliu et al, Transplant Proceedings, in press


Biliary strictures: “achilles heel” of liver TxBiliary strictures: “achilles heel” of liver Txtoxic, ischemic, technical, & immune factorstoxic, ischemic, technical, & immune factorsOnce centre experience (UZ Leuven, Belgium)Once centre experience (UZ Leuven, Belgium)

Type of StricturesN = 81 (20%) on 403LTx

• Type1: 59,7%• Type 2: 6,1%• Type 3: 3,7%• Type4: 19,5%• Comb 1&2: 4,9%• Diffuse: 6,1%


Variable 81 BS 322 no BS P-value

Donor Age (years) 41,9 ± 15,3 41,3 ± 17,8 ns

ICU stay (days) 3,9 ± 8,1 3,4 ± 4,3 ns

Cold Ischemia Time (min) 523,6 ± 128,9 502,2 ± 135,6 ns

Warm Ischemia period (donor) 92,32 ± 23,31 89,21 ± 21,45 ns

Anastomosis Time 56,8 ± 14 55,9 ± 16 ns

Peak GOT 1235 ± 1621 905 ± 868 0,003

Peak Bilirubine 8,16 ± 9,6 5,53 ± 4,9 0,0005

Peak APh 987 ± 749 743 ± 489 0,0001

Peak GGT 493 ± 356 401 ± 263 0,005

Univariate (T-test and Mann Whitney -U test)

403 LTX analyzed last 10 years403 LTX analyzed last 10 years

81 Biliary Strictures (BS) = 20,1%81 Biliary Strictures (BS) = 20,1%

Delayed graft Delayed graft function function

symptomssymptoms


Nominal variables Incidence of BS:If variable is present or not: what is % of BS

Variable Present Not present P-val

Flolane & pressurization 12% 28% 0,0001

Cardiac Arrest in Donor 10,2% 20% 0,01

Hypotension in Donor 14% 21% ns

Flushing of donor bile duct 17,8% 75% 0,00001

Cholecystectomy @ Procurement 24% 18% ns

Local versus Imported 18% 27% 0,03

Smiltuneous unclamping 18,1% 20,3% ns

Rejection 25% 17,3% 0,03

Positive Xmatch 23% 16,1% ns

CMV infection 17% 19% ns

Steroids 20,1% 20,4% ns

Anastomosis hepatico-ent 15% 20,4% ns

Univariate (Fisher exact and Chi ²)


“Tricks” to reduce biliary problems

Low viscosity preservation solution*

Pressurize UW + flolane**

Flush donor bile duct

Shorten ischemia time

Shorten donor bile duct

Large anastomosis

Spatulate small donor bile duct

Avoid diathermy

No T tube

No tensionPirenne, Van Gelder et al Liver Transplantation 2001Pirenne, Van Gelder et al Am J of Transplantation, 2001 (abstract)Welling, Heidt et al Liver Transplantation 2008


Scoring systems to calculate post-operative risks using ECD livers

Calculation of Expanded Liver Grafts Calculation of Expanded Liver Grafts (Busutill et al, Annals of Surgery Vol 243 June 2006)(Busutill et al, Annals of Surgery Vol 243 June 2006) Donor age > 55Donor age > 55 Donor hospital stay > 5 daysDonor hospital stay > 5 days Cold ischemia > 10 hrsCold ischemia > 10 hrs Warm ischemia > 40 minutesWarm ischemia > 40 minutes

Score: 0 is none of the above listed criteria, 3 is Score: 0 is none of the above listed criteria, 3 is maximum score (3 or more factors) and in relation with maximum score (3 or more factors) and in relation with recipient age >55 or in an urgent status on the listrecipient age >55 or in an urgent status on the list When DS was 3 there is a clear impact on patient and graft When DS was 3 there is a clear impact on patient and graft

survival independingly age and statussurvival independingly age and status


Scoring systems to calculate post-operative risks using ECD livers

Expanded criteria liver donors (ECD): effect of Expanded criteria liver donors (ECD): effect of cumulative riskcumulative risk(Fisher-Fröhlich et al, Annals of Transplant 2006; 11(3): 38-42)(Fisher-Fröhlich et al, Annals of Transplant 2006; 11(3): 38-42) Hep B or CHep B or C Acute hemodynamic detriorationAcute hemodynamic detrioration Donor age > 65yrsDonor age > 65yrs Donor BMI > 30 kg/m²Donor BMI > 30 kg/m² Bilirubine > 3mg/dlBilirubine > 3mg/dl AST and ALT trippledAST and ALT trippled Serum sodium > 165 mmol/LSerum sodium > 165 mmol/L ICU stay > 7daysICU stay > 7days Hepatic steatosis > 40%Hepatic steatosis > 40%


1 or 2 factors associated with no impact on 1 or 2 factors associated with no impact on patient outcomepatient outcome

3 factors lead to 15% less one year patient 3 factors lead to 15% less one year patient survivalsurvival

4 factors or more lead to 0% one year patient 4 factors or more lead to 0% one year patient survivalsurvival

Expanded criteria liver donors (ECD): effect of Expanded criteria liver donors (ECD): effect of cumulative risk (Fisher-Fröhlich et al, Annals of cumulative risk (Fisher-Fröhlich et al, Annals of Transplant 2006; 11(3): 38-42)Transplant 2006; 11(3): 38-42)


In summary

ECD can be a valuable sourceECD can be a valuable source Comparable outcomesComparable outcomes Comparable post-operative complicationsComparable post-operative complications

EnsureEnsure Maximal investigationMaximal investigation SafetySafety Experienced procurementExperienced procurement NO combination of multiple ECD factorsNO combination of multiple ECD factors

AGED donorsAGED donors Higher incidence of malignancy and infection Higher incidence of malignancy and infection


Take Home Message

Standard praktice for ECDStandard praktice for ECD Protocols Protocols Management Management PreservationPreservation Quality and risk assesment evaluation toolsQuality and risk assesment evaluation tools

(scores, MP, …)(scores, MP, …)

Experienced teams both sides Experienced teams both sides Quality and safetyQuality and safety Allocation policies should be focussed on ECD criteria to Allocation policies should be focussed on ECD criteria to

avoid post-operative complications avoid post-operative complications

atc pre-meeting symposia #3: nurse coordinator itns – natco – ishlt may 31 st 2008 track 1:...

Documents

atc premeeting symposia

deceased donor

donor pool

ecd donors

definition of ecd liver

advanced donor age

term of marginal donor

abnormal donor organ