Guidelines · Donor selection criteria 07 Role of donor transplant co-ordinator prior to death of...

Guidelines relating to solid organtransplants from non-heart beating donors

Guidelines relating to solid organ transplants from non-heart beating donors

Published by the British Transplantation Society

Triangle House, Broomhill Road, London SW18 4HX

Tel: 0870 833 2430 Fax: 0870 833 2434

Email: [email protected] Web: www.bts.org.uk

ISBN 0-9542221-7-2

Produced by Triangle Three Ltd

When Brigid McNamee's husband Johndied three people were given the chanceof life. Brigid says "as our son Sean growsup he will be able to understand moreabout his father's gift, something he canbe proud of." Reproduced courtesy of UKTransplant


British Transplantation Society

Guidelines

Contents

Process of writing 04

Introduction 05

Categorisation of non-heart beating donors 06

Donor selection criteria 07

Role of donor transplant co-ordinator prior to death of the donor 08For category 3 and some category 4 donorsFor Category 1, 2, 5 and some category 4 donors 09

Consent 10

Diagnosis of death 11

Immediate post-mortem management for renal or renal and liver donors 12

Process of organ retrieval 14

Preservation of organs following non heart beating organ donation 16

Viability testing 17

Recipient selection, laboratory protocol 19

Initial immunosuppression and care 20

Graft outcome after non-heart beating organ retrieval 21Outcome in renal transplantation 21Outcome in pancreas transplantation 22Outcome in liver transplantation 22Outcome in lung transplantation 23

Informing recipient population 24

Staffing implications 25

Author's potential conflict of interests 27

References 28

Apendix A 31

Appendix B 33

Appendix C 34

In the spring of 2002 the Council of theBritish Transplantation Society agreed thatthe Standards Committee (Chair: Dr C GNewstead, Consultant Renal Physician,Leeds Teaching Hospitals Trust) shouldprepare guidelines relating to this topic.Dr Newstead wrote the first draft inconjunction with Mr S Willis (TransplantCo ordinator, Leeds Teaching HospitalsTrust) drawing extensively on protocolsalready in existence at Newcastle,Leicester, North and South Thames.Subsequently revisions and originalcontributions were made by: Mr D Talbot,(Consultant Hepatobiliary and TransplantSurgeon, Freeman Hospital, Newcastle) MrN V Jamieson (Consultant TransplantSurgeon Addenbrooke's HospitalCambridge), Miss L Robson LeadTransplant Co-ordinator Freeman Hospital,Newcastle), Dr P Murphy and Dr D Bell(Neuro-ITU Leeds Teaching Hospitals Trust)

A preliminary draft was circulated at therequest of The Department of Health to agroup of coroners attending a workshopin late November 2002 to solicitcomments.

It was subsequently decided afterdiscussion with a number of interestedparties including The Council of the BTSthat the BTS guidelines would be alteredto cover the management of the processof donation after the diagnosis of death.It would in addition cover the areas ofdirect involvement of the "TransplantTeam" both of the donor and evaluationof the patient who has the potential tobecome a donor. Excluded from thisguidance therefore is the importantcontribution of other hospital staff forexample those working in Accident andEmergency, Intensive Care as well asCoroners.

Other authorities that include: TheIntensive Care Society, The Association ofAnaesthetists, The Academy of MedicalRoyal Colleges and Faculties inconjunction with the Department ofHealth are preparing guidance on themanagement of the patient who has thepotential to become a non-heart beatingorgan donor.

Authors reviewed contributions made byothers, in particular those published in theUnited States [1, 2].

The likelihood of early changes to Britishlegislation covering this area also led to areassessment of the document. Thischange of strategy led to significantediting the subsequent draft was againcirculated to the above named colleaguesfor comment.

After revision the draft was posted on theBTS website for two months from July2004 and the final version has taken intoaccount constructive comments receivedfrom a number of contributors.

In the body of the document key pointsare shown highlighted.

Process of writing

04



05


Introduction

The number of transplants performedin the United Kingdom has remainedvirtually static over the last ten years.During this interval the number ofdonors has decreased byapproximately 20%.

The causes for the reduction in heartbeating cadaveric donors aremultifactorial. There has been alaudable decrease both in fatalitiesfrom road traffic accidents in theUnited Kingdom as well as asignificant decrease in the number ofdeaths from intracranial haemorrhage.Changes in neuro-intensive caremanagement may have contributed.

Renal and other solid organs as well astissue retrieval from non-heart beatingdonors is not a new concept. Beforethe introduction of legislation definingbrain stem death in the 1970s allcadaveric kidneys were retrieved fromnon-heart beating donors.

In Maastricht (Netherlands), Japanand parts of the United States ofAmerica as well several units in theUnited Kingdom, in particular;Addenbrooke's Hospital (Cambridge),Guy's and St George's Hospitals(London), Leicester General Hospital,and Freeman Hospital (Newcastle)have longstanding programmesretrieving organs (principally kidneys)from non-heart beating donors.

As well as the important healthbenefit acquired by the recipientfollowing successful organtransplantation organ donation canprovide benefits to the donor family.Organ donation is usually a positiveexperience for bereaved families andmay be the most comforting aspect ofan otherwise tragic and sudden event.Non-heart beating donation in thesituation where a patient cannot bediagnosed as dead using brainstemcriteria offers the family the choice todonate organs which otherwise wouldnot have been available. It also allowshealthcare professionals to carry outthe wishes of the deceased when thatis known.

Renal and other solid organs as well astissue retrieval from non-heart beatingdonors is not a new concept

Organ donation is usually a positiveexperience for bereaved families

Non-heart beating donation in thesituation where a patient cannot bediagnosed as dead using brainstemcriteria offers the family the choice todonate organs which otherwise wouldnot have been available. It also allowshealthcare professionals to carry outthe wishes of the deceased when thatis known.


These donors can be dividedinto categories basedprincipally on work from theMaastricht group. This isimportant both for thelogistics of retrieval andoutcome followingtransplantation.

Category 1: dead on arrival athospitalFor these individuals to be potentialdonors the moment of suddendeath needs to have been witnessedand the time that it occurreddocumented as well as pre-admission resuscitation.

Category 2: unsuccessfulresuscitationThese are individuals in whomcardio-pulmonary resusitation iscommenced following collapse.These patients are usually in anAccident and EmergencyDepartment, in which the interval ofresuscitation and the efficiency ofresuscitation has been welldocumented.

Category 3: awaiting cardiacarrestThese are a group of patients forwhom death is inevitable but theydo not fulfil brainstem dead criteria.These patients are cared for in manyareas within hospitals but mostcommonly are identified inNeurosurgical Intensive Care Units,General Intensive Care Units,Coronary Care Units, Accident andEmergency Departments andMedical Wards.

Category 4: cardiac arrest in abrainstem dead cadaverThis is an individual in whom deathhas been diagnosed by brainstemcriteria who then suffers anunexpected cardiac arrest. On someoccasions these cases will beawaiting the arrival of an organretrieval team.

Category 5: unexpectedcardiac arrest in patient in anITU/ or critical care unitThis has recently been suggested asan addition to the other fourcategories [3]

Categorisation of non-heart beating donors

06



07



Donor selection criteria

To streamline the process it is helpfulfor each retrieval team to adoptselection criteria that are known to ITUand A&E as well as donor transplantco-ordinator staff.

For renal or renal and liver donors The arbitrary cut off point forsomething that changes gradually suchas age is not logically defensible andreferring staff encouraged to discuss allpotential donors with donor transplantco-ordinators.

Guide selection criteria:

1. Age<65 years (renal), age <70 years (liver)2. Warm ischaemic time less than or equal to 20

minutes for the liver and less than or equal to40 minutes for the kidneys. This time can bedefined as starting when there is hypotensionbelow a systolic BP of 55 mmHg and is measured up to the point of the coldperfusion of the organ.

3. No history of renal impairment.4. No uncontrolled hypertension or complicated

insulin dependent diabetes.5. No uncontrolled systemic sepsis or malignancy

using the same criteria as for potential donorswho are declared death after brain stemtesting.

The "Guidance on the MicrobiologicalSafety of Human Organs, Tissues andCells used in Transplantation" issuedby the Advisory Committee on theMicrobiological Safety of Blood andTissues for Transplantation August2000 will be followed [4].

For lung donorsGuide selection criteria:

Aged < 55 yearsP02 / Fi02 > 30Kpa

No gross abnormality on chest x-ray in past 24hours. Unilateral changes do not preclude theretrieval of one lung.Time for the cardiothoracic retrieval team to be present at the withdrawal of treatment.

Contraindications Previous chest surgery (presence of achest drain does not precludedonation).Asthma requiring systemic steroids.Smoking history, length of ventilationand positive gram stain of airwaysecretions are not absolutecontra-indications.

The Cardiothoracic retrieval team willbring all the equipment they requireand transport to and from the hospitalis organised by the CardiothoracicRecipient Transplant Coordinator. Theteam consists of 2 surgeons, a scrubnurse and a perfusionist. The team willnot require any assistance with thebronchoscopy procedure or theretrieval.

To streamline the process it is helpfulfor each retrieval team to adoptselection criteria that are known toIntensive Care Units and Accident andEmergency as well as donor transplantco-ordinator staff.

8



Role of the donor transplant co-ordinatorprior to death of the donor

For category 3 and some category 4donorsWhen a Donor transplant co-ordinator attendsthe Intensive Care Unit it will be to assess thepatients suitability for non-heart beating organdonation. The assessment will be initially frommedical notes and ITU charts and will involvereview of:

. Height, weight, ABO blood group,biochemistry

. Ventilation and Oxygenation

. Haemodynamics, ECG, inotropicrequirements, urine output, fluid balance

. Medical History

. Social History

. Arterial blood gases (particularly forpotential lung donors)

This information will be discussed with aConsultant in Transplantation for their opinionregarding suitability for organ donation. The potential for tissue donation should beexplored with competent authorities.

Although the method of treatment withdrawalis dictated by unit policy, the donor transplantco-ordinator must have knowledge of thisprior to the next of kin interview.

If the next of kin agree to consider organdonation a Donor transplant co-ordinator willdiscuss the following issues:

. What happens when death occurs and theneed to go to theatre promptly followingthe certification of death.

. Or the immediate cold preservation ofabdominal organs via in-situ perfusion where this is agreed local practice.

. Or circumstances where treatmentwithdrawal and certification of death takesplace in the operating theatre.

. If the time between treatment withdrawaland death is prolonged a point may bereached when organ donation is notpossible.

. Medical and social history includingcompletion of UK Transplant's Donor assessment documentation and GeneralPractitioner Questionnaire.

. A lack of objection for blood sampling for either immediate or later testing forvirology and other infections, blood groupand HLA type.

. The potential to administer ante mortum agents to maintain the function of anorgan where that is either local policy or in a particular case thought desirable.

. The procedure following donation and the follow up by the Donor Transplant co-ordinator.

At this point lack of objection to organ andtissue donation will be documented.

If the family retract lack of objection at anypoint the organ donation team will standdown.

The Donor Transplant co-ordinator will arrangethe surgical team and operating theatre andensure arrangements to transfer the patient totheatre are in place.

For lung donation it is helpful to knowwhether the planned withdrawal of treatmentincludes extubation, as equipment for re-intubation and bronchoscopy will be requiredonce death has been certified.

Next of kin and family support will be offeredaccording to the Critical Care Unit guidelinesand UK Transplant Donor Family Care Policy.

A Donor transplant co-ordinator will reviewthe families understanding of the situationand discuss the process of retrieval, ante-mortem blood sampling, testing of blood samples, ante-mortem treatmentsdesigned to maintain the performance oforgans and the post-mortem cold preservation where appropriate will bediscussed.


9



For Category 1, 2, 5 and some category 4donorsIn this situation the co-ordinator as well as thesurgical retrieval team are required to attendvery promptly, most usually the Accident andEmergency department and less often-otherdepartments in a hospital.

In this situation there is often very little time toacquire information. The co-ordinatorsassessment will be initially from Casualty staffand Paramedic records and medical history ofparticular relevance at this stage is previousmalignancy, diabetes, hypertension and thedocumentation relating to the failed cardio-pulmonary resuscitation. An estimate of thelikely warm ischaemia time is extremelyimportant.

The national donor register will be checked tosee if the potential donor was registered.

This information will be discussed with aConsultant in Transplantation for their opinionregarding suitability for organ donation. Thepotential for tissue donation should beexplored with competant authorities.

If next of kin or family are present a verballack of objection will be obtained prior tocannula insertion and perfusion. If familymembers are not present cannulation can stillbe initiated while efforts are made to locatethe next of kin. In this situation approval forthe in-situ cooling process will have to beobtained from the Coroners Office by prioragreement or on a case-by-case basis. It isanticipated that the Human Tissue Act willclarify this area.

As soon as is practicable the co-ordinator willinterview relatives. If they agree to considerorgan donation a Donor transplant co-ordinator will discuss:

. Medical and social history, includingcompletionof UK Transplant's Donor assessmentdocumentation and General PractitionerQuestionnaire.

. Ensuring that families are aware that somekidneys may be found unsuitable fortransplantation post retrieval.

. The procedure following donation and the follow up by the Donor transplant co-ordinator.

At this point lack of objection to organ andtissue donation will be documented.

If the family retract lack of objection at anypoint the organ donation team will standdown and the cannula used to administer thecooling perfusate removed.

The Donor transplant co-ordinator will arrangethe surgical team and operating theatre andwill be responsible for the arrangements totransfer the patient to the operating theatre.

The next of kin and other family members willbe offered support according to theDepartment guidelines and the UK TransplantDonor Family Care Policy.

The Donor Co-ordinators prime purpose willbe to gather information to allow clinicians toassess suitability the for non-heart beatingorgan donation.

Usually most critical is the potential donorspast medical history as well as thedocumentation relating to the failed cardio-pulmonary resuscitation. An accurateestimate of the likely warm ischaemia time isextremely important

In the situation where approval of the in-situcooling process has been obtained from theCoroners office and other competentauthorities the team will initiate this.


Role of the donor transplant co-ordinatorprior to death of the donor

Consent



For in-situ organ perfusionIt is not clear at the present time thatconsent is required for in-situ organperfusion but it is certainly preferablycommenced only after written consentbeing first obtained from next of kin. Theforthcoming Human Tissue Act it isanticipated will clarify this area from alegal standpoint. The relatives are told thatthe purpose of the in-situ perfusiontechnique is to cool the organs within thebody so that it may be possible to removethem later and use them fortransplantation. This will give the next ofkin more time to consider whether theywish to consent to organ donation.

Placing cannula for in situ-renal perfusionin the situation where there are norelatives available and the deceased's priorwishes are not known is possible and hasbeen practised in some areas in UnitedKingdom for many years. In this situationconsent for organ retrieval from thedeceased is discussed with relatives whencontacted as in the paragraph above. Ifconsent is not obtained the process isstood down.

As discussed above it is probable that theforthcoming Human Tissue Bill will clarifythe legal situation and if the final Bill weresimilar to the draft legislation it is likelywould encourage the expansion of thisopportunity to become an organ donor.

For Organ retrievalCommencement of retrieval will onlyproceed when the following conditionshave been met:

Next of kinAs a general guide, the legal next of kin ofthe deceased person, as defined by theTreasury Solicitor, are:

‘Whilst for the purposes of this policycertain persons, including common lawspouses, are not regarded as next of kin,wherever it is apparent that a closerelationship existed with the deceased, it isalways advisable in these circumstances toconsult with them. If there is the potentialfor significant family dispute regardingconsent the procedure is often abandoned.

Placing cannula for in situ-renal perfusionin the situation where there are norelatives available and the deceased's priorwishes are not known is possible and hasbeen practised in some areas in UnitedKingdom for many years. In this situationconsent for organ retrieval from relatives isdiscussed when they can be contacted. Iflack of objection is not obtained theprocess is stood down.

10

Lack of objection is indicated by thenext of kin.

Where appropriate the Coroner, orDeputy has given permission to proceed with organ retrieval.

Where appropriate the Coroner's Pathologist has given permission fororgan retrieval and names the specificorgans that can be removed.

1)

2)

3)

The legally married partner or close blood relative; son, daughter, mother,father, grandchild, brother, sister.

A legally adopted child has the same rights as if he or she had been borninto the adoptive family.

A separated wife or husband has the same entitlement as existed before theseparation, even if there has been a'Deed of Separation'. Entitlementceases, however, if there has been a'Deed of Judicial Separation' as this hasthe same power as a Decree Absoluteof divorce. However, for the purposes ofthis guidance, where spouses areseparated, but not judicially, then consent shall not be obtained from thespouse. A divorced spouse has no entitlement.

Confusion may arise with anyrelationships involving 'step'relationships, including in lawrelationships, common-law, or samegender relationships and second-cousinrelationships. Such a person cannot bedefined as 'legal next of kin'. The DraftHuman tissue Bill in Part 2 section 24 (4)gives a new list of "qualifyingrelationships" [5].

1)

2)

3)

4)



11

A fundamental principle of organdonation is retrieval from a patientwho has died. There is no statutorydefinition of death in English andWelsh Law. It is welcomed that theplanned Human Tissue Bill [5] basedon the consultation document HumanBodies Human Choices [6] is likely toprovide a definition.

The Department of Health revisedcode of practice published in 1998defined death as "the irreversible lossof the capacity for consciousnesscombined with irreversible loss of thecapacity to breathe".

It seems logical that the keyrequirement is for the cliniciancertifying death to be confident thatan interval has elapsed without cardiacoutput that is long enough to ensurethat hypoxic injury to the cerebralcortex and brain stem has occurred.This must be such that the patient hassuffered the irreversible loss of boththe capacity for consciousness and tobreathe.

As is the case when the diagnosis ofdeath is made based on the absenceof brain stem reflexes the clinicianmaking the diagnosis will not be partof the organ retrieval team. Howeverthe retrieving surgeon needs to beconfident that a competent clinicianhas established the diagnosis.

In the United States of America theCommittee on Non-Heart-BeatingTransplantation II in their publicationNon-Heart-Beating Transplantation [1]"found that the interval of fiveminutes between the cessation ofcardiopulmonary function and thedeclaration of death providedadequate assurance of the irreversiblecessation of cardiopulmonary function,and satisfied the requirements of theUniversal Determination of DeathAct".

In hospital clinical practice innormothermic conditions and withoutthe presence of agents that have beenshown to offer a degree of cerebralprotection there is rarely difficultyestablishing the diagnosis.

It seems logical that the keyrequirement is for the cliniciancertifying death to be confident thatan interval has elapsed withoutcardiac output that is long enoughto ensure that hypoxic injury to thecerebral cortex and brain stem hasoccurred such that the patient hassuffered the irreversible loss of boththe capacity for consciousness andto breathe

An interval of a minimum of fiveminutes is recommended.

Diagnosis of death

12



For Category 1, 2 and 5 donorsMuch the largest proportion of thesedonors will be from within theAccident and Emergency departments.Referrals to the transplant team will bemade after the attending medicalteam has pronounced death. It will bethe responsibility of the attendingmedical team to explain to therelatives that the patient has died. Thetime and date of the pronouncementof death will be recorded in thepatient's notes.

External cardiac massage andventilation with 100% oxygen canthen be re-established where this hasbeen agreed as the local protocol.

Non heart beating donor kidneys maybe perfused and cooled in-situ using adouble balloon, triple lumen intra-aortic catheter. The femoral artery andvein on one side is approachedthrough a short groin incision and thedouble balloon perfusion catheterintroduced into the aorta via a femoralarteriotomy. 100 mls of blood aretaken for viral serology, biochemistry,tissue typing and toxicology. Theballoons inflated and perfusioncommenced. Some units prefer toinstil radiographic contrast medium inthe balloons in order to check that thecatheter is correctly positioned forselected perfusion of the renal arteries.The system is vented by placing a foleycatheter into the femoral vein at thegroin. The kidneys are perfused with atotal of 10-20 litres of hyperosmolarcitrate solution cooled to 4 C. Eachlitre of perfusate has 5000units ofheparin added. Some units additionallyuse a bolus of 1.5 mega units ofstreptokinase which at the outset of

perfusion. Some units utilise coolingdevices require additional ports to beinserted into the abdomen in additionto perfusion cannula

In Spain and parts of the USA, but notUK, cooling of the whole of theabdominal viscera of the cadaver ispracticed when after failed cardio-pulmonary resuscitation large borecannulae are inserted into majorarteries and veins in the groin andconnected to an extracorporealcooling and oxygenation circuit. In thissituation this allows family members tobe contacted and informed of eventsand subsequently approach toconsider organ donation. In Spainlegislation also requires judicialapproval to proceed.

The Draft Human Tissue Bill which it isintended will replace The HumanTissue Act of 1961 allows for personshaving control of the management ofthe institution where the body is lyingto take the minimum steps using theleast invasive procedure necessary forpreserving the body for use intransplantation. This authority wouldcease if it became established thatconsent for removal of a part fortransplantation has not been, and willnot be, given. If this act is passed inthis form it will at the least clarify thelegal situation.

For some category five donors it maybe realistic to move to immediateorgan retrieval and as for Category 3donors the logistics of this will dependupon the availability of surgical staffand operating theatres as well as theneed for relatives to be informed andregister lack of objection.

Immediate post mortem management forrenal or renal and liver donors

13



Immediate post mortem management forrenal or renal and liver donors

For Category 3 donorsThe timing of retrieval after thediagnosis of death due to cardiacarrest is somewhat vexed. AllTransplant authorities haverecommended an interval to ensurebrain stem death as well as cardiacstandstill. In Pittsburgh an interval oftwo minutes has been adopted. Theoriginal Maastricht protocol had a tenminute interval however a period offive minutes is now accepted inprimary legislation in the Netherlands.

This five minute period is in excess ofthe time the brain stem can survive ina situation of warm hypoxia and is theinterval recommended by theseguidelines.

For Category 4 donorsInterventions to optimise organviability in these individuals, who arelegally dead and awaiting retrieval, donot differ at first principle fromcontinuing artificial support whilstawaiting that retrieval, particularly if'lack of objection' for donation hasbeen recorded. Resuscitationmanoeuvres, immediate transfer to theoperating theatre and cannulation forcold perfusion could beaccommodated without the need forany further legislation or guidelines. Itwould be mandatory however to keepthe family informed and ensure theirsupport for this course of action.

Category 1, 2 and 5 donorsReferrals to the transplant team will bemade after the attending medicalteam has pronounced death. It will bethe responsibility of the attendingmedical team to explain to therelatives that the patient has died.There will be no interventions for aperiod of five minutes.External cardiac massage andventilation with 100% oxygen canthen be re-established.Organs may be perfused and cooledin-situ

For Category 3 and 4 donorsThere will be no interventions for aperiod of five minutesUsually after that interval rapidretrieval is initiated, if this needs bedelayed in-situ organ cooling can beconsidered

For all donorsRelatives need to be fully informed asearly as is practicable and invited toregister a lack of objection. Organ ortissue donation may be possible withconsent to some but not all of theprocedures.

14



For abdominal organsIf asystole does not occur within 2hours the liver retrieval maybeabandoned, although kidney retrievalmaybe still possible after an interval ofseveral hours.

Two approaches to achieve coldperfusion are used. Firstly to perform a femoral cut down and in situperfusion with a short while latertransfer to the operating theatre. Thesecond approach is to combine thecannulation with the laparotomy. Thelatter approach is commonly used iflivers and pancreas are retrieved, asportal perfusion is then possible. Withthe femoral cut down approach thedonor is moved to theatre andretrieval performed within two hours.

A standard abdominal incision isperformed and the abdominal cavitycooled with ice slush as soon aspossible. For a kidney only retrievalthese are removed and perfused. Thekidneys are partially prepared to assessthe quality of perfusion and back tableperfusion continued until the effluentform the renal vein is clear and thekidneys appear uniformly perfused.Some practitioners advocate the use of streptokinase during the retrieval oforgans from category one, two, three,four and five donors. In a small-randomised controlled study animprovement in viability characteristicof procured kidneys was demonstratedif a streptokinase pre-flush was used[7].

If the surgeon is retrieving liver andpancreas this should be done in theusual way after aortic and portalperfusion have been established. Thefirst bag of low viscosity kidneypreservation solution and the first bagof UW solution for the portal veinshould contain heparin (20.000 IU).Care must be taken to avoid damageto variants in the vasculature as theseaberrant vessels are more difficult toidentify and easier to damage whenpulse less. Probably this is best firstperformed with in situ perfusion ofthe kidneys continuing while the liverand pancreas are mobilised. To reduceliver congestion it may be useful todrain the IVC before aortic cannulationand some units utilise a fibrinolytic preflush.

The conflict between the desirability ofrapid surgical retrieving to minimiseischaemia time and the need to keepto a minimum the manipulation ofpancreas for whole organ transplantsproposes significant technicalchallenges.

The abdomen is closed and theoperator tabulates the procedure andthe organs removed in the patientsnotes for the Coroners pathologist.

For lungsIf the withdrawal of treatment andcannulation and perfusion of theabdominal organs is to occur in theIntensive Care Unit the followingprocedure for non heart-beating lungdonation will be followed and iscarried out simultaneously with thecannulation and perfusion of theabdominal organs.

Process of organ retrieval

15



Process of organ retrieval

1) The Cardiothoracic retrieval team must be on site when treatment is withdrawn

2) Treatment is withdrawn3) If asystole does not occur within

1 hour the lung retrieval will be abandoned

4) Asystole5) Death certified by local medical

staff6) Stand off time as per local

protocol7) Rigid bronchoscopy is performed8) Size 16-Foley catheter is inserted

into the distal trachea9) Patient is reintubated with 6mm

ET tube 10) The lungs are inflated, the ET tub

is removed and the foley catheter is placed in the larynx

11) The family can return once this and the cannulation and perfusion of the abdominal organs arecompleted. The foley catheter isnot visible.

12) The patient is transferred to the operating theatre

13) Time between asystole and cold flush of the lungs in theatre should be less than 90 minutes and ideally less than 60 minutes

14) Sternotomy performed 15) Assessment of lungs16) Pulmonary artery opened and clot

removed17) Lungs are flushed18) Heart lung block is removed. If

there is no consent for heart valve donation the heart will be put back into the body

19) Retrograde flush of the lungs on the back table and packed fortransportation

20) Time from sternotomy to the endof the retrieval will beapproximately 1 hour

There is more than one possibleapproach to achieve cold perfusion of abdominal organs.

Some practitioners advocate the use of streptokinase during the retrieval oforgans from category one, two, fourand five donors

If the surgeon is retrieving liver andpancreas this should be done in theusual way. Probably this is best firstperformed with in situ perfusion ofthe kidneys continuing while the liverand pancreas are mobilised. To reduceliver congestion it may be useful todrain the IVC before aortic cannulationand some units utilise a fibrinolytic preflush.

The conflict between the desirability of rapid surgical retrieving to minimiseischaemia time and the need to keepto a minimum the manipulation ofpancreas for whole organ transplantsproposes significant technicalchallenges

The procedure for non heart-beatinglung donation is carried outsimultaneously with the cannulationand perfusion of the abdominalorgans.

16



The Organ Preservation,Ischaemia/Reperfusion Discussion Forumof the BTS will be producing guidelines forpreservation in the future and so detailedrecommendations may well change. In the section of the BritishTransplantation Society's website relatingto this forum are collected recent keyreferences to research in this area.

Two types of hypothermic preservationsolutions are commonly used. A normothermic haemoglobin basedsolution is in development.

The donor is initially perfused with largevolumes of hypothermic flush.EuroCollins, Marshalls or HTK solution canbe used in this situation, as they are allrelatively inexpensive. After retrieval thekidneys, which have already beendamaged by warm ischaemia, should beflushed and stored either in University ofWisconsin (UW) machine preservation, orHTK solution. Some debate exists as tothe merits of high viscosity solutions andcosts too have been raised as a concern,however compared to the consequencesof transplanting a non-viable kidney the cost is justified.

The potential contribution of machineperfusion of kidneys retrieved from non-heart beating organ donors is not clear[8]. It does allow the possibility ofmeasuring a number of markers that maycorrelate with function. Whether theprocess itself allows an extension of theacceptable cold ischaemia time orimproves initial function is not yetestablished. A report on the value ofmachine perfusion in kidneytransplantation, has been commissionedby the Department of Health [9]. Thisconcludes that the short-term cost/benefitof machine perfusion did not justify itsuse, but that there may be sufficientcost/benefit if long-term outcomes areconsidered - but the evidence base isincomplete. This meta-analysis modelledthe effects of machine perfusion on renal

graft survival in non-heart beating andheart-beating donors groups. Theypredicted a 20% reduction in the instanceof delayed graft function, and a 2-3%improvement in 10-year graft survivalcould be gained through machineperfusion. Their analysis of cost/benefit ofmachine pulsatile perfusion was extendedfrom time of transplant to 10 year survivaland concluded where delayed graftfunction has a higher incidence, such as inkidneys retrieved from non-heart beatingdonors, the combined benefit of reduceddelayed graft function and improvementsin 10 year survival rates may well makemachine perfusion a cost effective optionin the long term. The authors concludedthat more research is necessary todetermine whether machine perfusion canproduce significant clinical and economicbenefit to organ preservation.

As in heart beating organ retrieval thestandard solution used for liver andpancreas cold preservation is UW solutionthough low viscosity solutions such asHTK have been proposed as being moreappropriate.

There is ongoing research activity to try tominimise the degree of ischaemic injury[10, 11,12]. There is substantial researchinterest in the possibility thatnormothermic preservation may result inless injury to livers [13]. This is particularlyimportant in the setting of non-heartbeating donation.

Kidneys which have already beendamaged by warm ischaemia should notbe stored in Marshalls or EuroCollinssolution

The potential contribution of machineperfusion of kidneys retrieved from non-heart beating organ donors is not yet clear

There is substantial research interest in thepossibility that normothermic preservationmay result in less injury to livers.

Preservation of organs following non heartbeating organ donation



Viability testing

A major limiting factor to thewidespread adoption of a non-heartbeating organ donation andtransplantation is the uncertaintyregarding the function of the graftonce transplanted. Delayed function,rejection and extended hospital stayare all a concern with non-heartbeating organ donation but primarynon-function has more significantconsequences. Primary non-function isespecially important for the recipientof a life-sustaining organ such as aliver or lung. The need to minimise thecold ischaemia time reduces the timeavailable for viability testing.

The principal purpose of viabilitytesting is to reduce primary non-function. Non-heart beatingdonor kidneys are prone to acutetubular necrosis. Viability testingshould therefore focus upondetermining the severity of injury tothe tubules and supportingmicrocirculation. Evidence alsosuggests that the damage the kidneyssustain is not necessarity bilateral,therefore one could not assume that ifone kidney presents as being viablethe other also falls into this category.

Risk factors for renal primarynon-functionDonor factors: Age >60; SerumCreatinine >150, Warm Ischaemic time>45 minutes, Cold Ischaemic time >22hours (ice storage). The efficacy ofcooling and rate of cooling have allbeen shown to be associated withhigher rates of primary non-function.

Recipient factors: Sensitised or re-transplanted patients, early rejectionepisodes and early expose tonephrotoxic agents, includingcyclosporin and tacrolimus.

At present time though there is noconclusive evidence as to the bestviability tests to use. There areadvocators of visual inspection,perfusion characteristics on machineperfusion and enzyme levels in theperfusate [14, 15]. Whatever methodis used by the centre careful audit isrequired to maintain good results andif the primary non-function is greaterthan 5% the measures used fortesting viability must be modified.

continued on page 18

Viability Criteria (Newcastle 2001)

Flow > 23ml/100g

GST < 200 IU/100g

Temperature (°C) < 14 (surface temperature) (five time points)

Wt increase (%) 10-25 % (relative contraindication)

Index (ml/min/100g/mmHg) >0.4 (most important)

Perfusion pressure (mmHg) <60 mmHg

Perfusion fluid Belzer UW with 1000u heparin per litre

Donor pre-treatment Heparin and Streptokinase

17

Viability testing

18



Additional points:

1) Younger donors with shorter warmischemic times have better outcomes independent of theabove variables.

2) Retrieval should be within ninety minutes of perfusion.

3) Cold ischemic time must not exceed 24 hours.

4) The position of the catheter balloons should be checked at retrieval.

Objective assessment of texture,colour, consistency and perfusioneffluent on the back table areimportant parts of the assessment.

Primary non-function has significantadverse consequences. These areespecially severe for the recipient of a life-sustaining organ such as a liver or lung

The principal purpose of viabilitytesting is to reduce primary non-function

At present time though there is noconclusive evidence as to the bestviability tests to use

19



Given the possibility of an inferior (initial)performance of kidneys retrieved fromnon-heart beating donors some arguethat these organs should be reserved forcandidates for whom the consequences ofprolonged delayed graft function are notespecially serious or who do not benefitparticularly from a large nephron mass.

For recipients of other organs in partbecause of the lack of other options theallocation to any particular recipient isusually governed by local clinicalimperatives.

Kidneys (and other organs from non-heartbeating donors) are currently in the UKallocated within the pool of potentialrecipients registered with the retrievingcentre, in part to minimise the length ofcold ischaemia time. In the future it maybe appropriate to allocate within a renalsharing alliance waiting list. This willdepend at least in part on localgeographical considerations. Units atpresent in general either allocate theorgans using the same criteria as organsretrieved from heart beating donors oralter the allocation rules to favourcandidates who are less likely to receivean offer via the national matchingscheme.

Organs retrieved from non-heart beatingdonors are at risk of warm ischaemicinjury during the interval from withdrawalof full support and cardiac arrest forcategory 3 donors and duringunsuccessful resuscitation attempts forother categories of donors. Organsretrieved from heart beating donors donot experience this initial warm ischaemicinjury.

Cold ischaemic injury that occurs in theinterval between retrieval and re-implantation and is usually measured inseveral hours is likely to be particularlydeleterious to the function of organsretrieved from non-heart beating donors.

In order to try to minimize the duration ofthis interval it may be appropriate toorganize a "fast-track" method ofhandling recipients. Potential ways toreduce the interval include pre-retrievalHLA typing, for organs where that is partof the allocation algorithm. The selectionof recipients who are unlikely to besensitised to mismatched donor antigensand hence demonstrate a positive currentcross match (where that is performed) orcalling up potential recipients as reserveswhere the first choice is at high risk ofprior donor specific sensitisation. Thesestrategies will require access to efficientand high quality HLA typing by the mostaccurate methods.

One algorithm and management protocolfor allocation of kidneys that is similar tothe national scheme is included asappendix A. Another approach is toallocate one kidney from a donor by rulessimilar to the national allocation rules, butthe other kidney by rules designed tofavour candidates who havedemonstrated by spending by a longperiod on the waiting list that they areless likely to receive a kidney from thenational pool [16]. An example of such ascheme is shown in appendix B.

Units are likely to adopt strategies andallocation rules that are different to takeinto account local geography andestablished practice.

Renal units in general either allocate thekidneys using the same criteria as organsretrieved from heart beating donors oralter the allocation rules to favourcandidates who are less likely to receivean offer via the national matchingschemes.

For recipients of livers and lungs in partbecause of the lack of other options theallocation to any particular recipient isusually governed by local clinicalimperatives.

Recipient selection and laboratoryprotocol

20



Initial immunosuppression and care

Renal transplant recipientsThe Health Technology Appraisalpublished in 2004 by The NationalInstitute of Clinical Excellence onImmunosuppressive Therapy post RenalTransplantation did not consider recipientsof non-heart beating organs and in ourview the recommendations should not beapplied to this group.

These organs are likely to haveexperienced an increased length of warmischaemia compared to organs retrievedfrom heart beating donors. The length ofwarm ischaemia influences the likelihoodof delayed graft (and primary non)function. It is logical to try to minimisefurther nephrotoxic injury to the graft. Todelay the introduction of nephrotoxicimmunosuppression until the transplant isfunctioning or to avoid nephrotoxicimmunosuppression is practiced my manycentres. There are limited published resultsto guide practice.

In a small-randomised trial of 29 patientsmicro emulsion ciclosporin was comparedto tacrolimus in recipients of renaltransplants from non-heart beatingdonors [17]. Unfortunately despiterandomisation the degree of DR mismatchwas uneven as was the proportion ofcontrolled and uncontrolled donors. Therewere no clinically critical differences inoutcome. The majority of the recipients ofnon-heart beating kidneys reported in theliterature have received ciclosporin. Theoptimal immunosuppressive strategyremains to be established.

Initial treatment with IL-2 receptorblockers, prednisolone andmycophenolate mofetil with the delayedintroduction of a calcineurin inhibitorwhen there is either graft function with acreatinine below an arbitrary level of say350 micromol/l or there is evidence ofrejection is practiced by some units.

Systemic heparinisation is sometimesemployed particularly if there is noimmediate graft function or the donorwas category one, two, four or five.When the donor was from one of thesecategories protracted prophylacticantibiotic cover including for anaerobesfor three days post surgery isrecommended.

It is not clear whether recipients ofkidneys from non-heart beating donorsexperience a significant excess ofrejection. It is certainly more difficult todiagnose if there is delayed graft function.Weekly biopsy in the presence of delayedgraft function is recommended.Histological appearances of the graftparticularly of the blood vessels are oftenatypical. Vascular changes that can mimic"vascular rejection" are not thatuncommon.

For recipients of other solidorgansThe world wide experience in recipients ofliver, lung and pancreas transplants is stillsmall. It is not yet clear if there are anycomplications that are peculiar torecipients of organs from this source.Neither is it clear what is the frequency ofcomplications compared to that seen inrecipients of organs from heart beatingdonors.

Clearly primary non-function in recipientsof liver or lung transplants is extremelyserious, as would be an increasedincidence of certain other complicationssuch as late hepatic artery thrombosis.

It is logical to try to minimise furthernephrotoxic injury to the renal transplant.

There is limited experience in recipients ofliver, lung and pancreas transplants. It isnot clear if there are any complicationsthat are peculiar to recipients of organsfrom this source.

21



Renal transplants

Summarising the predicted outcomefollowing kidney transplantation withkidneys retrieved from non-beating donorsis not straightforward. The series haveusually been reported from single centresand involve relatively small numbers ofpatients. The results may not be easilyreproduced in another service. Inevitablythe series with the longest follow up arefrom grafts performed some while ago.During the interval immunosuppressivestrategies have changed, the accuracy ofHLA matching and HLA specific antibodyscreening improved and patient co-morbidity better defined. Patients willhave been managed with a higher dose ofdialysis, with improved correction ofanaemia and hyperparathyroidism all ofwhich may be expected to improveoutcome. In contrast the average age ofpatients starting dialysis's has increasedsignificantly with inevitable effects on co-morbidity and predicted longevity.

The outcome of 122 recipients of kidneysfrom non-heart beating donors werecompared the same number of recipientsof kidneys from heart beating donors withup to 15 years follow up [18]. The rate ofdelayed graft function was higher at 48percent in the first compared to 24percent in the latter group. The rate ofprimary non-function was not significantlydifferent at 5.7 and 4.9 percent. Graftsurvival counting recipient death as graftfailure was 74 and 76 percent at five yearsand 64 and 61 percent at 10 years. Thepaper summarises the results of thelargest comparable reports and table 1 isprincipally adapted from this publication.

United Kingdom transplant havepublished a comparison of the outcomeof first cadaveric kidney only transplantsretrieved from non-heart beating andheart beating donors encompassing the

Studies of Kidney Transplantation From Donors Without a Heartbeat

Reference No of Transplantations From Donors Without a Heartbeat

First Year of Program

Duration of Study

Matched Patients

Graft Survival

Time After Transplan-tation

Donors With a Heartbeat

Donors Without a Heartbeat

yr yr Percent

Wijnen et al [19] 57 1980 12 Yes 5 55 54

Gonzalez Segura et al [20]† 52 1985 10 No 5 77 68

9 66 50

Pacholczyk et al [21] 76 1986 9 Yes 1 90 82

Balupuri et al [22] 47 1988 10 No 5 83 88

Sanchez-Fructuoso et al [23] 95 1989 10 No 5 84 83

Cho et al [24] 229 1994 2 No 1 86 83

Sanchez-Fructuosa et al [25] 188 1995 7 Yes 7 87 93

† The survival rates were estimated by Kaplan-Meier analysis.

Graft outcome after non-heartbeating organ retrieval

continue overleaf

Table 1

22



period 1994 to 2000 [26]. Although thenumber of kidneys retrieved from non-heart beating donors is small at 172compared to 8046 in the other group thedata show an increased early graft loss inthe non-heart beating group then parallelrates of graft was over the first year. One-year transplant survival was notsignificantly different at 82 versus 85percent where there was a non-heartbeating versus heart beating donor.

Pancreas transplants

In one series of 18 simultaneous kidneypancreas transplants performed between1993 to 1999 when pancreata wereretrieved from category 3 non-heartbeating donors were compared in a singlecentre study to 339 recipients of organsfor heart beating donors. There was ahigher rate of enteric conversion (32%versus 13% p < 0.01) for recipients ofpancreas from non-heart beating versusheart beating donors. No difference inpatient (100% versus 95.4%) or pancreas(87.4% versus 86.5%) survival was seen[27].

Non-heart beating donors may prove tobe a particularly valuable source of cellsfor isolated islet transplantation.

Liver transplants

The donor organ shortage of end-stageliver disease is a particular serious problemgiven the lack of efficacy of anyalternatives. However re-perfusionsyndrome and primary non-function in thetransplant recipient is extremely seriousand in the latter situation unless areplacement graft can be found promptlyis invariably fatal. In addition the biliarytree is especially at risk of ischaemic injuryresulting in both early and latecomplications.

At present the only donors that can beused for liver transplantation are thosethat have minimal warm ischaemia andtherefore are from the Maastrichtcategories three and four.

In an ITU setting eight livers wereretrieved from non-heart beating donorswhere cardiac arrest occurred after a shortinterval, 3 to 27 minutes after ceasingartificial ventilation. Patient and graftsurvival are 100 percent at a mean of 18months follow up [28]. The results of 144recipients of livers from non-heart beatingdonors performed between 1993 and2001 were compared to thecontemporaneous 26856 liver transplantsfrom heart beating organ donorsregistered on the United Network ofOrgan Sharing database in the USA. One-year graft survival was 63.3% and 80.4%(non-heart beating versus heart beatingdonors p= 0.003). Three-year graftsurvival was also poorer in recipients oforgans from non-heart beating donors at63.3% and 72.1% (p= 0.012). Recipientsof a non-heart beating graft had a greaterincidence of primary nonfunction (11.8%versus 6.4%, p= 0.008) andretransplantation (13.9% versus 8.3%,p=0.04) compared to recipients of liversfrom heart beating donors [29].

In a single centre study biliarycomplication occurred in five out of 15(33%) recipients of liver transplants fromnon-heart beating donors and in 19.2%of recipients of livers from heart beatingdonors (n=221,p<0.01) [30]. It is ofconcern that half of these biliarycomplications were ischaemiccholangiopathies that are likely to lead tosecondary biliary cirrhosis and may requireregrafting.

Many groups are actively exploring thisdonor source at present and it may makea significant contribution to the donorpool in the future [31].

Graft outcome after non-heartbeating organ retrieval

23



Graft outcome after non-heartbeating organ retrievalLung Transplantation

Lung transplantation is a lifesavingtherapy for selected patients with endstage lung disease, but its application isseverely constrained by suitable donors.Within the UK only 20-30% of heartbeating organ donors are suitable for lungdonation, this is in stark contrast to theretrieval rate for abdominal organs.

The lung may be the ideal organ for non-heart beating organ donation becauseunlike other solid organs, the lung doesnot rely on perfusion for parenchymalcellular respiration to occur. Tissue levelsof high-energy nucleotide phosphateshave been demonstrated to remain nearnormal up to four hours after thecessation of circulation provided the lungsremain inflated with oxygen.

The technique for the retrieval of lungsfrom a non-heart beating organ donorwas developed in the animal model. Itssuccess relies upon rapid bilateral chestcavity flushing or topical cooling to inducehypothermic conditions postcardiorespiratory arrest, the use of heparinand intravascular flush via a pulmonaryartery catheter. This technique hasprotected the function and morphology ofcadaver lungs, which are then suitable fortransplantation.

The agonal period in humans is never ascontrolled as in a laboratory model andorgan viability is often compromised to adegree that is difficult to determine. Workis therefore continuing in to develop aventilation and perfusion assessmenttechnique for non-heart beating donorlungs, which could differentiate betweenthose lungs with good and poor functionpost-transplantation.

Other work in the animal model hasdemonstrated lungs from non-heartbeating organ donors can provideadequate pulmonary function with carefulmanipulation of the recipient upon re-perfusion.

Using similar technique that describedabove a Swedish group has recentlydescribed lung retrieval from a non-heart-beating donor. The donor died after failedcardiopulmonary resuscitation followingan acute myocardial infarction in a cardiacintensive care unit. Three hours post deathand initial cooling the heart lung blockwas removed. The right lung wastransplanted and has demonstrated goodfunction at five months follow up [32].

As many retrieval units are in the processare developing non-heart beatingprotocols, the potential for lung donationshould not be overlooked [33].

Summarising the predicted outcomefollowing kidney transplantation withkidneys retrieved from non-beatingdonors is not straightforward. It isanticipated that the risks of primary non-function, delayed graft function areincreased and there is a reduced graftsurvival.

In the UK there is an increased early renalgraft loss in the non-heart beating groupthen parallel rates of graft was over thefirst year. One-year transplant survival wasnot significantly different at 82 versus 85percent where there was a non-heartbeating versus heart beating donor.

The experience of recipients of other solidorgans is presently small and it is difficultto draw meaningful comparisons.

Given the shortage of solid organs fortransplantation the most appropriatecomparison may be with the experienceof patients who do not receive an organrather than with that seen after receivingan organ from a heart beating cadavericdonor.

As the shortfall between the number ofindividuals placed on organ transplantwaiting lists and the number of cadavericorgan donors grows there has been aprogressive interest in attempting toretrieve organs from so-called marginal orextended donors. These are donors whoin the recent past would have beenconsidered unsuitable for organ donationbecause of medical co-morbidity. The fieldis changing rapidly but there isinformation allowing some predictions tobe made about the likely difference inoutcome between an "ideal" cadavericdonor and less than ideal donors.

By most criteria non-heart beating donorswould be considered non-ideal. Onaverage deceased organ donors are lessideal than a live donor where that is anoption. Even among live donors there isclearly a graduation from what may beconsidered the perfect donor such as anidentical twin, an option available only toa very small number of people.

Many clinicians and patient groups feelthat as the outcome following non-heartbeating donation is on average poorercompared with that seen with the averagedeceased brain dead donor, the non heartbeating origin of the kidney transplantshould be discussed with the intendedrecipient. This is in the setting where thereare other options for life sustainingtherapy such as dialysis. These discussionsare far from strait-forward, as for anyindividual there is a need to quantify thedegree of "risk" associated with eachcourse of action, in a situation where suchquantification is almost impossible.

Where the organ is the only life sustainingtreatment then the patient's and medicalteam's options are clearly greatlyconstrained.

Given that admission for such a procedureis always an emergency and that oftenthis occurs at unsocial hours to inform thepatient group in good time about thepotential for receiving an organ from anon-heart beating donor is good practice.To have a separate list of individuals forwhom medical staff and the patientagrees that receiving a non-heart beatingkidney would be a good option is alsogood practice. In Appendix C is one suchpatient information leaflet for potentialrenal recipients that may be used as atemplate to guide local practice.

Many clinicians and patient groups feelthat the outcome following non-heartbeating donation is significantly poorercompared with the average cadavericbrain dead donor and that the origin ofthe kidney transplant should be discussedfully with the intended recipient.Informing this discussion will be the"Maastrich" category of the donor.

Where the organ is the only life sustainingtreatment then the patient's and medicalteam's options are clearly greatlyconstrained.

Informing the Recipient Population

24



25



Staffing implications

Donor transplant co-ordinators

In order to facilitate non-heart beatingorgan donation Donor transplant co-ordinator teams must ensure they can beresponsive to the needs of the Accident &Emergency Department or Critical CareUnit.

In programs offering in-situ perfusion co-ordinators are often required to attendthe Accident and Emergency departmentswithin 15-20 minutes of being contacted.

Strategies that are currently in place tofacilitate non-heart beating organ include;in-house Co-ordinators based in Accident& Emergency departments or specifichospitals, as well as a second on CallService for Non Heart Beating Organdonation.

In some centres, two donor transplant co-ordinators attend a referral. One co-ordinator's responsibility is to support andinform the family and staff within criticalcare unit and one to organise thelogistical aspects of organ retrieval.

Intensive care departments

The process of organ retrieval ought notimpinge on clinical care or significantlyaffect staff numbers. The time devoted tostaff development and education as wellas counselling is however significant andconsideration should be given to staffexpansion of a nominated trainedindividual to carry out this role. This maywell be an individual from an intensivecare nursing or a transplant co-ordinatorbackground.

Transplant surgical staff

On call surgical teams for organ retrievalfrom non-heart beating donors may needto attend Accident and Emergencydepartments at short notice in order toplace perfusion cannula. Similar to the co-ordinators availability within 30 minutestravel in time to the main Accident andEmergency source may be necessary.Again similar to the co-ordinators retrievalfrom patients on intensive care units maydemand long periods in attendance at thehospital site during the agonal interval.For logistic reasons it may be sensible todeclare an upper time limit for such await.

The successful retrieval from a non-heartbeating donor may pose a significantlogistic challenge if two kidneys, the liverand possibly other solid organs areretrieved in order to ensure adequate staffto implant recipients in a timely fashion.

Operating theatre personnel

Rapid access to operating facilities ismandatory to allow the prosecution of asuccessful non-heart beating donorprogram. This is true both for organretrieval and implantation. The retrievalfrom a cadaver without a heartbeat whois not ventilated is different to retrievalfrom a heart-beating donor. Support andeducation to operating theatre personnelshould be available, probably bestdelivered by the transplant coordinators.

26



For laboratory

No single Histocompatibility andImmunology staff member should attemptto investigate an import/local donor andan asystolic donor at the same time.Experience has shown that the workloadin this situation is just manageable buttime is fully committed and has to betightly managed. This is not appropriate tothe situation, which requires focusedeffort for the production of highconfidence and timely results. The primaryperson on-call should have a back up.

Inpatient ward areas

Kidneys retrieved from non-heart beatingdonor's have an increased likelihood ofprimary non and delayed graft function.Recipients will be expected to have anincreased need for dialysis support andlonger in patient stays that will have to be met from the acute transplant wardresources.

It is much less easy to plan retrieval fromnon-heart beating donors in an activeprogramme a back up retrieval team maybe required.

In a program offering in-situ organperfusion following unexpected cardiacarrest there are considerable burdensplaced on the retrieval team who need to attend a short notice.

Rapid access to operate facilities ismandatory to allow the prosecution of a successful non-heart beating donorprogram.

No single Histocompatibility andImmunology staff member should attemptto investigate an import/local heartbeating donor and a non-heart beatingdonor at the same time. The primaryperson on-call should have a back up.

Staffing implications

27



Dr C G Newstead has received multiplehonoria for lectures and teaching as wellas expenses for travel andaccommodation to attend scientificmeetings principally from Fujisawa,Novartis, Roche and Wyeth. He hasreceived Honoria for contributions toadvisory boards for Roche and Wyeth, butnon-since appointed chair BritishTransplantation Society StandardsCommittee. Research and that ofcollaborators has been in part sponsoredby the above named companies as well asthe Yorkshire Kidney Research Fund,Medical Research Council, IpsenInternational, Jensen-Cilag, Alpha BloodProducts, Baxter Healthcare and BiotrinInternational

Dr D Bell none declared.

Mr N V Jamieson has received honoriafor lectures and expenses for travel andaccommodation to attend scientificmeetings from Fujisawa, Novartis,Sangstat, Johnson and Johnson andWyeth and has received Honoria forcontributions to advisory boards forWyeth.

Mr D Talbot: has received multiplehonorary for lectures and teaching. Hehas also received travel tickets andaccommodation to attend variousmeetings principally from Fujisawa,Novartis, Roche and Wyeth. Researchsponsorship has come from the NorthernCounties Kidney Research fund, theSpecial trustees of the Newcastle HospitalsNHS Trust, Fujisawa, Roche and Novartis.

Dr P Murphy none declared.

Miss L Robson none declared.

Mr S Willis none declared.

Author's potential conflicts ofinterest

References

28



1) Non-Heart-beating Organ Transplantation. Practice and Protocols. Pub Institute of Medicine National Academic Press, Washington DC ISBN 0-309-06641-7, full text version available at: http://www.nap.edu/books/0309066417/html/

2) Mandell MS, Taylor GJ, D'Alessandro A, McGaw LJ, Cohen EIntraoperative Advisory Council on Donation After Cardiac Death of the United Network for Organ Sharing. Executive summary from the Intraoperative Advisory Council on Donation After Cardiac Death of the United Network for Organ Sharing: practice guidelinesLiver Transpl 2003; 9(10): 1120-1123

3) Sanchez-Fructuosa AI, Prats D, Torrente J et alRenal transplantation from non-heart beating donors: a promising alternative to enlarge the donor poolJ Am Soc Nephrol 2000; 11: 350-358

4) Guidance on the Microbiological Safety of Human Organs, Tissues and Cells used in Transplantation. Available from: www.doh.gov.uk/msbt

5) Draft Human Tissue Billwww.dh.gov.uk/assetRoot/04/07/10/12/04071012.pdf

6) Human Bodies Human Choices The Law on Human Organs and Tissue in England and Wales A consultation Reportwww.dh.gov.uk/assetRoot/04/08/15/82/04081582.pdf

7) Gok MA, Shenton BK, Buckley PE, Peaston R, Cornell C, Soomro N, Jaques BC, Manas DM, Talbot DHow to improve the quality of kidneys from non-heart-beating donors: a randomised controlled trial of thrombolysis in non-heart-beating donors

Transplantation 2003, 76, 1714-1719

8) Matsuno N, Sakurai E, Tamaki I, Uchiyama M, Kozaki K, Kozaki MThe effect of machine perfusion preservation verses cold storage on the function of kidneys from non-heart beating donorsTransplantation 1994; 57(2): 293-294

9) Wight J, Chilcott J, Holmes M, Brewer NThe clinical and cost-effectiveness of pulsatile machine perfusion versus cold storage of kidneys for transplantation retrieved from heart-beating and non-heart-beating donorsHealth Technology Assessment 2003; 7: No 25

10) St Peter SD, Imber CJ, Lopez I, Hughes D, Friend PJExtended preservation of non-heart-beating donor livers with normothermic machine perfusionBr J Surg 2002; 89(5): 609-616

11) St Peter SD, Imber CJ, Friend PJLiver and kidney preservation by perfusionLancet 2002; 359(9306): 604-613

12) Barros-Schelotto P, Net M, Valero R, Ruiz A,Almenara R, Capdevila L, Sugranes G, Suarez-Crivaro F, Lopez-Boado MA, Pellegrino A, Deulofeu R, Miquel R, Taura P, Manyalich M, Garcia-Valdecasas JCReduced reperfusion injury by glycine in a porcine liver transplantation model with non-heart-beating donorsTransplant Proc 2002; 34(4): 1114-1117

13) Reddy SP, Bhattacharjya S, Maniakin N, Greenwood J, Guerreiro D, Hughes D, ImberCJ, Pigott DW, Fuggle S, Taylor R, Friend PJPreservation of porcine non-heart-beating donor livers by sequential cold storage andwarm perfusionTransplantation 2004; 77(9):1328-1332

29



14) Kievit JK, Nederstigt AP, Oomen AP, Janssen MA, Schoot L, Kootstra GRelease of alpha-glutathione S-transferase(alpha GST) an pi-glutathione S-transferase (pi-GST) from ischaemic damaged kidneys into the machine perfusate- relevance to viability assessmentTrans Proc 1997; 29: 3591-3593.

15) Balupuri S, Buckley P, Snowden C,Mohammed M, Sen B, Griffiths P, Hannon M,Manas D, Kirby J, Talbot DThe trouble with kidneys derived from thenon-heart-beating donor: a single center 10-year experienceTransplantation 2000; 69: 842-846

16) Dr C Dudley Personal communication on behalf of Richard Bright Renal Unit, Southmead Hospital, Bristol

17) Williams ST, Knight AL, White SA, Doughman TM, Nicholson MLPreliminary Analysis of a Randomised TrialComparing Microemulsion Cyclosporin and Tacrolimus for Recipients of Renal Transplants From Non-Heart-Beating DonorsTransplant Proceedings 2000. 32; 196

18) Weber M, Dindo, D, Demartines N, AmbühlPM, Clavein PAKidney transplantation from donors withouta heartbeatN Engl J Med 2002; 347(4): 348-255

19) Wijnen RMH, Booster MH, Stubenitski BM,de Boer J, Heineman E, Kootstra GOutcome of transplantation of non-heartbeating donor kidneysLancet 1995; 345: 1067-1070

20) Gonzalez Segura C, Castelao AM, Torras J et alLong-term follow-up of transplanted non-heart-beating donor kidneysTransplant Proc 1995; 27: 2948-2950

21) Pacholczyk MJ, Lagiewska B, Szostek M et alTransplantation of kidneys harvested fromnon-heart-beating donors: early and longterm resultsTranspl Int 1996; 9(suppl 1): S81-S83

22) Balpuri S, Buckley P, Snowden C et alThe trouble with kidneys derived from thenon heart-beating donor: a single centre 10-year experienceTransplantation 2000; 69: 842-946

23) Sanchez-Fructuoso AI, Prats D, Torrente J et alRenal transplantation from non-heart beating donors: a promising alternative to enlarge the donor poolJ Am Soc Nephrol 2000: 11: 350-358

24) Cho YW, Terasaki PI, Cecka JM, Gjertson DWTransplantation of kidneys from donorswhose hearts have stopped beatingN Engl J Med 1998; 338: 221-225

25) Sanchez-Fructuoso AI, de Miguel MarquesM, Prats D, Barrientos ANon-heart-beating donors: experience fromthe Hospital Clinico of MadridJ Nephrol 2003; 16(3): 387-392.

26) UK Transplant, UK Transplant Activity Report2001. ISSN 1477-8505: 23

27) D'Alessandro AM, Odorico JS, Knechtle SJ,Becker YT, Hoffmann RM, Kalayoglu M,Sollinger HWSimultaneous pancreas-kidney (SPK)transplantation from controlled non-heart-beating donors (NHBDs).Successful extrarenal transplantation from non-heartbeating donorsCell Transplant 2000; 9(6): 889-893

30



28) Reich DJ, Munoz SJ, Rothstein KD, Nathan HM, Edwards JM, Hasz RD, Manzarbeitia CYControlled non-heart-beating donor livertransplantation: a successful single centerexperience, with topic updateTransplantation 2000; 70(8): 1159-1166

29) Abt PL, Desai NM, Crawford MD, FormanLM, Markmann JW, Olthoff KM, Markmann JFSurvival following liver transplantation fromnon-heart-beating donorsAnn Surg 2004; 239(1): 87-92

30) Abt P, Crawford M, Desai N, Markmann J, Olthoff K, Shaked ALiver transplantation from controlled non-heart beating donors: an increased incidence of biliary complicationsTransplantation 2003; 75(10): 1659-1663

31) Muiesan PCan controlled non-heart-beating donorsprovide a solution to the organ shortage?Transplantation 2003; 75(10): 1627-1628

32) Steen S, Sjoberg T, Pierre L, Liao Q, Eriksson L, Algotsson LTransplantation of lungs from a non-heartbeating donorLancet 2001; 357(9259): 925-829

33) Egan, TMNon heart beating lung donors: yes or noAnnals of Thoracic Surgery 2000; 70:14511452

31



Appendix ARecipients listed at UKT for NHBD donors must:

1) Have a well-documented clinical history

2) Have been screened for HLA specific sensitisationin accord with BTS guidelines (one sample every3 months)

3) Must be either unsensitised or have a residualreaction frequency of <10%

4) Adult patients registered on Local Centre waitinglist (non-heart beating donor kidneys are rarelyallocated to recipients outside of the retrievalcentre).

5) Known to have indicated that willing to acceptnon-heart beating donor kidney (to be actioned after an interval to allow people to organize mailshot and replies to be collated)

Step 1

Donor HLA typed on peripheral blood after consentfrom relatives (virology testing, ABO group et cetera)(4-4.5h)

Step 2

Matching run performed by UKT using the followingeligibility criteria and sort order (after appropriateimplementation and testing):

1) Adult patients registered on Local Centre waitinglist

2) Known to have indicated that willing to acceptnon-heart beating donor kidney

3) No donor relevant HLA antibodies known

4) 000 HLA A, B and DR mismatch grade

5) MinimumRecipient age donors age minus ten years (pointssystem to tie break)

6) Usual matching rules for other mismatch grades(e.g., homozygotes first, HLA mismatch grade,points system to tie break)

7) MinimumRecipient age donors age minus five years

8) Recipients all ages

Step 3

Sort order notified by UKT to transplant team on call(note this may be prior to organ retrieval).

If top two candidates are registered as unsensitised.

For top two potential recipients transplant team liaisewith relevant renal medicine staff about currentsuitability for transplantation. Check made at this timethat no known sensitising events since last antibodyscreen.

If one or more of top two candidates' medicallyunsuitable move to candidate three and so on.

Decision made whether appropriate to call inrecipients prior to retrieval made. This will dependupon how likely it is predicted that the retrieval maybe unsatisfactory.

Otherwise call in candidates when organs retrieved.

When patients contacted check made at this time thatno known sensitising events since last antibody screen.

If one of or more of top two candidates does notmeet criteria of no known sensitising event, serumscreen negative or if serum screen positive but andknown more than 0% residual PRA then a back upcandidate is nominated from sort list in order up to amaximum of four total potential candidates for twokidneys.

For back up recipients transplant team liaise withrelevant renal medicine staff about up to datesuitability for transplantation. Check made at this timethat no known sensitising events since last bloodsample.

If one or more back up candidates unsuitable move tonext candidate and so on.

32



Decision made whether appropriate to call inrecipients prior to retrieval made.

This will depend upon how likely it is predicted thatthe retrieval may be unsatisfactory. Otherwise call incandidates (and back ups) when organs retrieved

When patients contacted check made at this time thatno known sensitising events since last blood sample.

Step 4

From results of step 3 perform crossmatches withselected recipients and back ups where nominatedusing according to locally agreed practices (2- 3h).Note crossmatch can take place prior to organretrieval.

If historic peak or current positive cross match,recipients eliminated from consideration.

Step 5

Call in selected crossmatch negative recipients andrepeat crossmatches with current sera (2-2.5h)

Or if decision made to call in prior to retrieval or priorto result of historic and current sera cross matchknown run cross match versus time of transplant serawhen available. (2-2.5h)

Estimated total laboratory time ~ 8-10h

33



Appendix B

All blood group compatible patients to be considered

Exclude patients whose recorded unacceptableantigens are shared by the donor.

Length of time on waiting list (latest listing excludingsuspensions of > 6 months)

4) Age

5. Matchability score

The kidney is allocated to the recipient with thehighest score. In the event of a tie subtract one pointfor each mismatched HLA antigen.

Age Points

< 40 10

41-60 5

> 60 0

Matchability score Points

9-10 10

7-8 8

5-6 5

3-4 3

1-2 0

Days Points

1100-1500 5

1501-2000 10

2001-2400 15

2401-2774 20

>2775 25

1) Previous transplant?

a. Yes 0

b. No 5

34



Appendix C

Important Information for Patients Awaiting aKidney Transplant

Non Heart Beating (NHB) Organ Donation

As you know the demand for kidney transplantationin the UK is greater than the current supply of organsavailable. The Department of Health is implementingseveral initiatives to improve this situation.

These include:

. Making more direct appeals for people to carrydonor cards and use the organ donor register.

. Increasing the number of transplants from livedonors.

. Increasing the number of 'non-heart beatingorgan donation programmes'.

What is a Non Heart Beating Organ Donationprogramme?

They are three methods of kidney donation within theUnited Kingdom.

Living-donor organ donation. In this situation ablood relative or someone who is emotionally relatedto the recipient volunteers to be a kidney donor.

Organ donation after brain death. This is often asa result of a head injury or stroke causing damage tothe brain. If injury occurs to a vital area of the braincalled the 'brain stem'; that patient can never regainconsciousness or breath again and within hours theirheart will stop beating. If tests conclude that deathhas occurred consent for organ donation is discussedwith the family.

Non-heart beating organ donation. When non-heart beating organ donation takes place the donorhas been declared dead following the absence ofbreathing and a heartbeat.

Several Transplant Units in the United Kingdom aredeveloping a Non-heart beating Organ Donationprogramme. Although this will be a new developmentit is not a new idea. This method of organ donationhas been used successfully in North America, Japan,Europe and three centres within the UK for manyyears.

Receiving any kidney transplant carries certainrisks. These include those due to the actual operation,the possibility of the transfer of infection from donorto recipient and the anti-rejection medication. Allkidneys offered for transplantation also experiencesome degree of damage. This is due to events prior todonation, the operation to remove the kidney, and thelength of time the kidney is stored before it can betransplanted.

Special risks with non-heart beating organs. Themajor difference between kidneys donated from non-heart beating organ donors and other organ donors isthe function of the kidney in the early days after thetransplant. Usually these kidneys do not work straightaway. This delay in function can last for days or weeksafter the transplant operation. The recipient is requiredto continue with dialysis for a while aftertransplantation. Unfortunately it is difficult to predictthe speed of recovery of the kidney.

Rarely the kidney never regains function. This canoccur with any transplanted organ. The consequenceof this is the disappointment of having undergone anoperation that has been unsuccessful and thepotential for your body to produce antibodies, whichcan make finding another transplant more difficult.

35



Approximate Summary of Expected Results

As you can see the kidneys donated from non-heartbeating organ donors have a small increased risk ofnever functioning and a distinct increased risk ofdelayed function compared to kidneys donated frombrain dead organ donors. The long-term results aresimilar.

The purpose of this document is to provide you withinformation so you can discuss with your relatives andthe renal team whether you would consider having anon-heart beating Kidney transplant.

This development will not change your chances ofreceiving a kidney from the usual National AllocationSystem. But it will increase the chances of youreceiving a kidney transplant sooner. This is because atpresent Kidneys donated from non-heart beatingdonors within the local region will only be used forpatients on the local waiting list.

In order to keep the time between removing thekidney and transplantation to a minimum it is helpfulif the Renal Transplant Unit are aware of thosepatients who would and those who would not accepta kidney from a non-heart beating organ donor.

If you would accept a kidney from a non-heart beating organ donor could you please return the enclosed authorisation slip,which also asks for up to date contact details.

If you do not return the authorisation slip wewill assume you do not want to be consideredfor this type of transplant.

Approximate Summary of Expected Results

Percentage Never functioning

Percentage with delayed Function

Percentage Graft survival 1 year

Percentage Graft Survival 5 year

Live related

0 1 98 85

Organ donation after brain death.

2 20 90 75

Non-Heart beating

3 80 85 70

Published by the British Transplantation Society

Triangle House, Broomhill Road, London SW18 4HX

Tel: 0870 833 2430 Fax: 0870 833 2434

Email: [email protected] Web: www.bts.org.uk

ISBN 0-9542221-7-2

Produced by Triangle Three Ltd

Guidelines · Donor selection criteria 07 Role of donor transplant co-ordinator prior to death of...

Documents

Transcript of Guidelines · Donor selection criteria 07 Role of donor transplant co-ordinator prior to death of...