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Categories of Donation After Cardiocirculatory Death

O. Detry, H. Le Dinh, T. Noterdaeme, A. De Roover, P. Honoré, J.-P. Squifflet, and M. Meurisse

ABSTRACT

The interest in donation after cardiocirculatory death (DCD) was renewed in the early1990s, as a means to partially overcome the shortage of donations after brain death. Insome European countries and in the United States, DCD has become an increasinglyfrequent procedure over the last decade. To improve the results of DCD transplantation,it is important to compare practices, experiences, and results of various teams involved inthis field. It is therefore crucial to accurately define the different types of DCD. However,in the literature, various DCD terminologies and classifications have been used, renderingit difficult to compare reported experiences. The authors have presented herein anoverview of the various DCD descriptions in the literature, and have proposed an adaptedDCD classification to better define the DCD processes, seeking to provide a better tool tocompare the results of published reports and to improve current practices. This modified

classification may be modified in the future according to ongoing experiences in this field.

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DECEASED DONOR organ transplantation utilizesgrafts procured from a deceased human being, the

so-called “cadaveric organ donor.” In the pioneering daysof organ transplantation, the first deceased donor organprocurements were performed after declaration of donordeath based on cardiocirculatory arrest criteria.1–4 In 1963,

rofessor Alexandre, from Brussels, Belgium, performedhe first donation after brain death (DBD) in a patienthose death was declared based on neurological criteria.5

The concept of brain death was confirmed in 1968 by TheAd Hoc Committee at The Harvard Medical School.6 Thewide acceptance of brain death in the Western world, andthe better of DBD results due to the absence of warmischemia (WI), led to the near complete abandonment ofdonation after cardiocirculatory death (DCD).

The interest in DCD was renewed in the early 1990s, asa means to partially overcome the shortage of DBD. Insome European countries and in the United States, DCDhas become an increasingly frequent procedure over thislast decade,7–10 including more than 40% of the deceaseddonor pool in the Netherlands in 2008.11 In Middle Easternountries and in Asia, where DBD is rarely performed foregal, cultural, and/or religious reasons,12,13 DCD is nearly

the only type of organ procurement.14 After several suc-essful experiences with DCD kidney transplanta-ion,11,15–19 these donors have recently provided other

organs, including liver,20–26 pancreas,27,28 and lung.29–35

Despite a first report of successful heart transplantation

after procurement from DCD donors,36 DCD heart trans-

© 2012 Published by Elsevier Inc.360 Park Avenue South, New York, NY 10010-1710

Transplantation Proceedings, 44, 1189–1195 (2012)

plantation has not reached (yet?) a significant clinicalapplication.

To improve the results of DCD transplantation, it isimportant to compare the practices, experiences, and re-sults of various teams involved in this field. It is thereforecrucial to accurately define the different types of DCD.However, in the literature, different terminologies andclassifications of DCD have been used, rendering compar-isons difficult among the reports. The authors have pre-sented herein an overview of the various DCD descriptionsin the literature and have proposed an adapted DCDclassification to better define the DCD processes, seeking toprovide a better tool to compare the results of publishedreports.

DEFINITION AND CLASSIFICATION OF DCD DONORS

Cardiocirculatory death is defined as the “irreversible ces-sation of circulatory and respiratory functions.”37 In DCD

onation, donor death is diagnosed by the cessation ofeartbeat and/or blood circulation, as assessed by electro-ardiography, monitoring of arterial pulses, or invasiverterial pressure. DCD donation does not exclude donorrain death. The term “non–heart-beating donation

From the Department of Abdominal Surgery and Transplanta-tion, CHU Liège, University of Liège, Belgium.

Address reprint requests to Pr Olivier Detry, Department ofAbdominal Surgery, University of Liège, CHU Liège, Sart Tilman

B35, B4000 Liège, Belgium. E-mail: oli.detry@chu.ulg.ac.be

0041-1345/–see front matterhttp://dx.doi.org/10.1016/j.transproceed.2012.05.001

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1190 DETRY, LE DINH, NOTERDAEME ET AL

(NHBD)” was often used in the past (and is still sometimesused), but DCD is now preferred, as it more clearly impliesdonor death and can be compared with DBD. Both DCDand DBD donations imply organ procurement from adeceased donor, in contrast to a living donation. The initials“DCD” sometimes refer to “donation after cardiac death”;however, as DCD may be used in the future for hearttransplantation,36 a declaration of donor death based onrreversible cardiocirculatory failure may more accuratelyefine the DCD process. Indeed it is difficult to understandr ethically justify the declaration of donor’s death byirreversible cardiac failure” if within minutes after theo-called “cardiac death,” the donor’s heart is procured forubsequent successful cardiac transplantation.38,39

The first DCD classification, proposed by the Rochestergroup in 1994, was based upon the possibility of planningdonor cardiocirculatory arrest and the DCD surgical pro-cedure.37 Uncontrolled DCD involves organ procurementfter unexpected cardiopulmonary arrest and/or unsuccess-ul resuscitation.37 In controlled DCD, the cardiocirculatory

arrest is the consequence of a planned medical act ofwithdrawal of ventilatory and organ-perfusion support thatcan be performed either in the intensive care unit (ICU) orin the operating room (OR). In controlled DCD, procure-ment WI is recorded and minimized, as the procurementteam is notified of the process and may be ready to start thesurgical organ procurement within a few minutes after thedeclaration of death. In addition, cold ischemia (CI) mayalso be minimized as the potential organ recipients may becalled into the hospital before the planned withdrawal ofdonor life support.

In addition, in 1995, after several years of extensiveresearch and clinical experience in DCD kidney transplan-tation, Pr Gauke Kootstra organized in Maastricht, Hol-land, an international meeting on NHBD. During thismeeting, he proposed a DCD classification of four catego-ries, which has been largely used over the last 15 years as

Table 1. Kootstra’s 1995 Maastricht Categories of DonationAfter Cardiocirculatory Death40

Category Description

1 Dead on arrival2 Unsuccessful resuscitation3 Awaiting cardiac arrest4 Cardiac arrest while brain dead

Fig 1. Process of controlledonation after cardiocirculatory

eath.

he NHBD Maastricht classification (Table 1).40 This classi-cation has the advantage of characterizing the DCDrocesses that may have their own particularities, includingthical or surgical aspects. This classification also has thedvantages of simplicity and usefulness, especially for kid-ey transplantation.

PROCUREMENT WI

Compared to DBD, DCD imposes an additional WI thatinduces a significant ischemic insult, increasing the risk ofearly posttransplant graft dysfunction. As a consequence ofthis procurement WI, DCD transplantation may be compli-cated by increased rates of primary nonfunction or chronicsecondary ischemic lesions, leading to recipient death orretransplantation when difficult and/or unstable conditionsyield the organ. Indeed, the length of the WI during DCDmay be variable according to the category of the DCDprocess, the longest being associated with the uncontrolledMaastricht category 1 DCD donation.

While WI during DCD is easily understood, its precisedefinition is difficult. At the cellular level, the WI insult tovarious organs is not identical, and does not start at thesame time.41 Particularly, the presence of air in the lungsmay avoid pulmonary tissue ischemia in the early periodafter cardiac arrest.42,43 The liver parenchyma, perfused inhe majority by hypoxic portal flow, is used to a low oxygenevel to some degree.44 In uncontrolled DCD, the futureonor undergoes resuscitation attempts that may provideome tissue oxygenation. However, these attempts are oftenot sufficiently efficient to avoid organ ischemia. Up to now,here has been no objective pre- or postharvesting param-ter that helps to determine whether a given donor orbdominal organ has suffered an irreversible WI insult thatould exclude the possibility of organ transplantation. Inncontrolled DCD, WI is usually defined as the timeetween the first cardiac arrest and the cold flush of thergans. Controlled DCD processes may be defined in twohases: the withdrawal phase, the period between supportithdrawal and cardiac arrest, and the acirculatory phase,efined as the period between cardiac arrest and aorticushing (Fig 1). The acirculatory phase is composed of ano-touch period,” which is variable according to the ethicalommittee or legal requirements in various countries. (It issually 2 to 10 minutes, but may be up to 20 minutes intaly.7,37,45) and the surgical period between declaration of

death and cold organ perfusion. The exact measure of the

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DCD CATEGORIES 1191

duration of the two phases is easily adjusted in controlledDCD. However, if the time determining the end of WI andthe beginning of CI is clear, the determination of themoment of the start of organ damage due to WI is difficult(or even impossible) since it is variable among organs. Thewithdrawal phase is often marked by a progressive drop ofoxygen saturation that is usually difficult to monitor as mostpulse oxymeters are not calibrated to measure saturationsbelow 90%. In addition, during the DCD process, the dropin arterial pressure is also not always progressive, withperiods of relative hypotension followed by pressure nor-malization. In 1995, Kootstra defined DCD WI as theperiod between cardiac arrest and organ flush.46 Thisdefinition is still used by the Eurotransplant organization in2011.47 For DCD kidney grafts, WI is now usually defineds the period between support withdrawal to aortic flush,eaning the whole DCD process.16,48 In DCD liver trans-

lantation, most reports define WI as the period betweenupport withdrawal and aortic cold perfusion,22,49–53 but

some authors have proposed to evaluate more precisely theperiod of real hepatic tissue WI. The American Society ofTransplant Surgeons defined total warm ischemia time ashe period between support withdrawal to aortic flush, andrue warm ischemia time as the time between the drop in the

ean arterial pressure below 60 mm Hg and the initiationf perfusion.37 But as shown in Table 2, many centers or

procurement organizations use other criteria, often mixing(mean or systolic) arterial pressure and oxygen saturationcriteria, to establish the beginning of “true” WI time in livertransplantation, without providing clear scientific evi-dence.54–59 The same issue has also been raised in DCDlung transplantation.29,34,60,61 There is clearly a need totandardize the nomenclature, but this problem is beyondhe scope of this article.

PROBLEMS OF THESE CLASSIFICATIONS AND THEMODIFICATIONS PROPOSED IN THE LITERATURE

The Maastricht classification and the “controlled/uncon-trolled” characterization of DCD are clearly current, usefulstandards. However, within the different types of DCD,clinical differences may lead to various posttransplant re-sults presented in the literature. In Maastricht DCD cate-gories 1 and 2, donor cardiovascular death is an unpredict-

Table 2. Definitions of Procurement “True” Warm Ischemia inControlled DCD Liver Transplantation

Centers/PO YearPressure(mm Hg) Oxygenation (%) Reference

ASTS 2010 MAP � 60 NA 37Philadelphia 2009 MAP � 50 �70 54

eattle 2005 MAP � 35 �25 55nited Kingdom 2005 SBP � 50 NA 20,56,57hicago 2009 SBP � 50 �70 58iami 2003 SBP � 35 �25 59

DCD, donation after cardiocirculatory death; PO: procurement organization;

ASTS: American Society of Transplant Surgeons; MAP: mean arterial pressure;SBP: systolic blood pressure; NA: not available.

ble event occurring outside or within the hospital,espectively. In these categories, DCD is, per definition, anncontrolled procedure with a prolonged period of DCDI, if defined as the period between the first cardiac arrest

o the flush of the potential grafts. Using one of the largestorld experiences in category 1 and 2 DCD in Spain,ondevila et al found it important to differentiate uncon-

rolled DCD with potential witnesses of the cardiac arrestnd rapid attempt of resuscitation versus those that occurithout any witness even in the hospital.62 Experienced

Spanish centers also have reported significantly worse re-sults in category 2 DCD donors hospitalized in the ICUcompared with those without an ICU stay.63 The worstesults of category 2 ICU DCD donors may be attributed toheir long hospitalizations and to the cerebral damages thatay be detrimental to donor organs due to significant

roinflammatory and procoagulant responses.64,65 In thisreport, the authors proposed to call these donors “category5,” despite the fact that they were clearly under theKoostra’s category 2 definition.63 Category 5 has subse-

uently been used by other authors.66–68 Recently anItalian group with limited experience in the field evenproposed a category 6 for DCD patients on extra-corporealmembrane oxygenation.45 In addition, some English groups

ave proposed to separate the Maastricht category 3 intoA for controlled DCD performed in hospital and 3B forontrolled DCD performed in hospice, due to worse resultsmong the latter group despite equivalent WI and CI.48,69

Moreover, in the literature there is also some misunder-standing in the characterization of Maastricht category 4 ascontrolled versus uncontrolled, as they can be both.48,70,71

In addition, in the recent years, a new type of DCD hasbeen performed in Belgium (ie, DCD after euthana-sia).72–74 There are now laws allowing physician-assistedsuicide in the Netherlands, Belgium, and Luxembourg,under strict medical and legal conditions requiring the clearwillingness of the patient with unbearable suffering to die ina humane condition. Other countries have ongoing activepolitical discussions on this subject. It is likely that in thefuture other countries will establish laws on this practice. Toour view, and to that of various Belgian university ethicalcommittees that have been questioned on the subject, thereis no ethical or legal objection to harvest organs afterphysician-assisted death following active, repeated requestsof the patient who has been granted euthanasia. This is aclear voluntary donation by conscious people willing to helpother human beings, despite the fact that their own medicalcondition may not be adequately palliated by modernmedicine. These particular DCD donors may be a source ofgood organs, as these DCD donors have no recent braindamage at the time of the highly controlled cardiocircula-tory arrest. The authors postulate that these DCD procure-ments after euthanasia may be more frequent in the future.Indeed, the Eurotransplant organization has officially rec-ognized these DCD donations in their computerized organdonor forms. Clearly, these DCD donations are not in-

cluded in the original Maastricht classification. Therefore,

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for all of these reasons, the authors consider the need toadapt the current classifications of DCD.

PROPOSITION FOR AN ADAPTED DCDMAASTRICHT CLASSIFICATION

Table 3 shows the adapted DCD classification proposedherein. The authors consider that Kootstra’s Maastrichtclassification should be conserved as the skeleton for fur-ther improvement, as it is simple and clear and classifieseasily the various DCD types for ethical issues and fornonmedical, nonspecialized readers interested in the field.Up to now, other attempts to improve the Maastrichtclassification have added new categories based on variousischemic insults, potentially altering transplant results, de-spite the fact that the DCD situation was already includedin the Maastricht classification. As an exemple, Sanchez-Fructuoso et al proposed to create category 5 for uncon-trolled DCD occurring in the ICU,63 despite the fact thatthese DCD donors are included in Kootstra’s category 2(unsuccessful resuscitation). Compared with Kootstra’s1995 Maastricht classification,40 we have proposed hereino conserve the categories 1 to 4 but to divide them into aeries of clinical situations. In addition, category 5 namely,CD after medically assisted death, is added, since this

ategory has clearly separate ethical and legal issues fromhose in categories 1 to 4.

As proposed by Fondevila et al,62 category 1 (dead onarrival) may be divided into subcategories; 1A if there wasno witness to the cardiovascular arrest versus 1B, if thecardiovascular arrest was witnessed and the potential DCDunderwent some kind of unsuccessful resuscitation.

Kootstra’s category 2 (unsuccessful resuscitation) in-cludes rapid but failed attempts of in-hospital resuscita-tion. As the Spanish experience has reported significantlyworse results in kidney transplantation from category 2DCD occurring in patients hospitalized in the ICU,63 we

ropose to divide the category into 2A (unexpectedardiocirculatory death in ICU) versus 2B (unexpectedardiocirculatory death in hospital including emergencyoom or ward).

Table 3. Modifi

Proposed AdaptedCategories Proposed

1A Cardiocirculatory death outside hospital wit1B Cardiocirculatory death outside hospital wit2A Unexpected cardiocirculatory death in ICU2B Unexpected cardiocirculatory death in hosp

resuscitation attempt3A Expected cardiocirculatory death in ICU3B Expected cardiocirculatory death in OR (wi3C Expected cardiocirculatory death in OR (wi4A Unexpected cardiocirculatory arrest in a br4B Expected cardiocirculatory arrest in a brain5A Medically assisted cardiocirculatory death i5B Medically assisted cardiocirculatory death i

DCD, donation after cardiocirculatory death; ICU, intensive care unit; ER, emergen

In Maastricht category 3 (awaiting cardiac arrest), DCDrocurement is a medically planned, controlled procedure

n an ICU patient with a dreadful neurological prognosis, inhom further medical treatment is deemed futile.75 WI and

CI are precisely monitored and minimized. Category 3represents a numerically significant source of transplantablekidneys, livers, pancreata, and lungs. Even cardiac procure-ment may be considered in this category 3.36 But allategories 3 are not comparable in terms of ischemic insultso various organs. The WI may vary considerably accordingo the place and way in which one performs the withdrawal.f it is performed in the ICU, even with a double-lumenatheter,76 the WI may be prolonged, as there is no efficient

cooling of the body or topical application to the abdominalorgans in most cases; furthermore, the donor must betransported to the OR for the DCD procedure. We proposeto name this category 3A (Table 3). When support with-drawal is performed in the OR among category 3 DCD, theprocurement is performed within minutes after the decla-ration of death, using a rapid laparotomy technique. How-ever, the period between support withdrawal and cardio-vascular arrest, the so-called “withdrawal phase” may varyconsiderably.77 Moreover, some category 3 DCD donorsdisplay rapid respiratory and cardiac arrest due to a lack ofspontaneous breathing due to destruction of the brain stemrespiratory center or to partial or total suppression of itsfunction by withdrawal of support.37,78 The authors proposeto separate these category 3 DCD OR donors into twogroups: category 3B in whom the withdrawal phase is longerthan 30 minutes versus category 3C in whom this phase inless than 30 minutes. It is possible that these categories 3C,highly controlled DCD donors may yield excellent liver,pancreas, or even heart grafts.

The Maastricht category 4 DCD of cardiac arrest whileawaiting brain death is different in Western and Easterncountries. In Western countries, most category 4 DCD donorsare brain-dead organ donors with unexpected and uncon-trolled cardiac arrest after unsuccessful resuscitation. Theymostly occurr in the ICU during the preparation for DBDorgan donation. Indeed the death of these donors is declared

CD Categories

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witness Totally uncontrollednesses and rapid resuscitation attempt Uncontrolled

UncontrolledR or ward), with witnesses and rapid Uncontrolled

Controlledal phase �30 min) Controlledal phase � 30 min) (Highly) controlledad donor (in ICU) Uncontrolleddonor (in OR or ICU) (Highly) controlledor ward Controlled

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DCD CATEGORIES 1193

because of brain death and not of cardiocirculatory failure.This category does not require a “stand-off period.” Thesedonors may be urgently transported to the OR for organprocurement but their WI is usually long. We propose toclassify these DCD donors as category 4A to differentiatethem from the Eastern countries category 4B DCD donors. InEastern countries, such as Japan.79 and many Muslim nations,he concept of brain death is not widely accepted for culturalnd/or religious reasons. Brain-dead donors may be trans-orted to the OR for organ procurement after controlledespiratory support withdrawal. These highly controlled DCDonors may might be a potential source of all transplantablergans. The category 4B DCD donation may also be (rarely)erformed in Western countries if the family does not rely onhe brain-death diagnosis and requests a controlled DCDonation.20

In addition to the four Maastricht categories defined in1995, we propose to add a fifth DCD category, correspondingto organ donation after medically assisted death or euthanasia.As explained above, euthanasia was legally approved in a fewcountries. In Belgium, some individuals who had euthanasiaexpressed their willingness to have their organs procured afterdeath. The authors propose to name these donations category5 (Table 3), as they cannot be included in the Maastricht 1995classification. Most patients who require euthanasia in Bel-gium and in the Netherlands are cancer patients who clearlyare not candidates for DCD donation. But a small proportionof these cases are patients with severe, stable neurologicaldeficits, whose medical affectation cannot be transmittedthrough organ donation. These patients are potential DCDdonors. Most euthanasias are performed at home by theregular family physician, but DCD donation after euthanasiarequires one to perform the euthanasia in an OR (or in apreparation room close to the OR to allow the presence of thefamily at the time of death), in an ICU or in the ward, ifrequested by the patient and/or the family. In this condition,

Table 4. Clinical Differences According to the Modified DCD CaThese DCD Organs i

Categories Proposed Definition

1A Cardiocirculatory death outside hospital with no wit1B Cardiocirculatory death outside hospital with witnes

and rapid resuscitation attempt2A Unexpected cardiocirculatory death in ICU2B Unexpected cardiocirculatory death in hospital (ER

ward), with witnesses and rapid resuscitation atte3A Expected cardiocirculatory death in ICU3B Expected cardiocirculatory death in OR with withdra

phase � 30 min3C Expected cardiocirculatory death in OR with withdra

phase � 30 min4A Unexpected cardiocirculatory arrest in a brain-dead4B Expected cardiocirculatory arrest in a brain-dead do5A Medically assisted cardiocirculatory death in ward5B Medically assisted cardiocirculatory death in OR

DCD, donation after cardiocirculatory death; ICU, intensive care unit; WI, warm iscroom.

he authors propose to consider category 5A as medicallyssisted cardiocirculatory death in the ICU or ward with theonor rapidly transported to the OR after the death diagnosis.f the euthanasia is performed in the OR, the authors proposeo name this DCD category 5B (Table 3).

CLINICAL INTERESTS OF THISADAPTED CLASSIFICATION

The original Kootstra 1995 Maastricht classification separatedDCD into four clear situations with common ethical and legalimplications. This classification is still useful; the authors haveherein added a category 5, which also has clearly differentethical and legal issues. However, as it is of primary impor-tance to more precisely analyze clinical DCD results in theliterature, the authors propose that the adaptation describedherein presents important clinical issues.

Table 4 shows categories 2A, 3 (3A, 3B, 3C), and 4 in whichthe donor subjects may have experienced severe cerebraldamage due to long ICU stays that may impair short- orlong-term graft function.11,16 In particular, this was the re-ported cause of inferior results of DCD kidney transplantationfrom category 2A donors.63 Table 4 presents possible WI to beexpected in various situations. Total WI is defined as theperiod between the first cardiac arrest and the organ flush foruncontrolled DCD, and from withdrawal of support to organflushing for controlled DCD. In controlled DCD (categories 3,4B, and 5), CI may be reduced by hospital admission and/orsurgical preparation of the recipient. CI may also be reducedin uncontrolled DCD situations by allocation of the DCD graftto a hospitalized potential recipient. All of these DCD cate-gories may lead to different clinical results of transplantation.

Although this classification is more complicated, it ismore complete than the 1995 Kootstra classification, whilemaintaining the same basic categories 1 to 4 (adding a fifth)that are now well-known and accepted criteria. Each cate-gory was divided into two or three subcategories: subcate-

ries, and Some Literature References Reporting Clinical Use ofical Transplantation

Brain Damage ICU Stay Total WI Kidney Liver

No No UnknownNo No Long 17 61

Variable Yes Long 63 23No No Long 63 23

Yes Yes �1 h 76 26Yes Yes �40 min

Yes Yes �40 min 19 9,21

r Yes Yes Long 22Yes Yes �40 min 19 20No No �40 minNo No �20 min 72,73 72,73

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1194 DETRY, LE DINH, NOTERDAEME ET AL

gory A is linked to longer WI (and worse results) thansubcategory B; and B versus C, respectively. In addition,subcategories A (2A, 3A, 4A, and 5A) are mostly linked toDCD processes occurring in the ICU, which helps tounderstand and memorize this classification (Table 3).Moreover, by keeping the original skeleton of the 1995classification, space is left to add new subcategories in thefuture, if deemed clinically relevant. For example, category1B (cardiocirculatory death outside hospital with witnessesand rapid resuscitation attempt) could one day be separatedinto 1B (resuscitation with human external massage andventilation) versus 1C (resuscitation with mechanical rean-imation as the cardiocompressor) versus 1D (resuscitationwith ECMO), if clinically required by groups with thelargest experience in this field.80,81

In conclusion, despite higher complication rates due toprocurement WI, DCD organ transplantation is increasing. Itwill expand even further in the future, as a partial means toovercome the donor shortage. The original DCD categorieswere efficient to expand this type of procurement, but a morecomplete categorization is now needed to define the varioussituations and to compare the clinical results encounteredamong different clinical groups and countries with active DCDprograms. We have presented modifications of the Maastrichtclassification that may be helpful in this matter and may befurther modified in the future according to ongoing experi-ences as this field continues to progress.

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