Surgical and logistical concerns for ex vivo–based perfusion strategies for “donation after circulatory death” multiorgan recovery

Central MessageExpanding multiorgan recovery from donation after circulatory death to include the heart presents logistical and technical challenges. Optimal collaboration among recovery teams is crucial.See Commentary on page 57. Expanding multiorgan recovery from donation after circulatory death to include the heart presents logistical and technical challenges. Optimal collaboration among recovery teams is crucial. See Commentary on page 57. Organ recovery following donation after circulatory death (DCD) has been successfully developed and refined over the past 2 decades to expand the donor pool of kidneys, livers, and lungs.1Nguyen J.H. A technique for rapid control of distal aorta in donation after cardiac death procurements.Transpl Int. 2008; 21: 186-188PubMed Google Scholar,2Saxena P. Zimmet A.D. Snell G. Levvey B. Marasco S.F. McGiffin D.C. Techniques for lung procurement for transplantation following donation after circulatory death.Oper Tech Thorac Cardiovasc Surg. 2014; 19: 380-393Abstract Full Text Full Text PDF Scopus (3) Google Scholar Compared with donation after brain death (DBD), DCD organs are exposed to additional warm ischemia. However, aided by emerging ex vivo organ perfusion technology, encouraging results have recently been reported for DCD livers, lungs, and kidneys.3Paterno F. Guarrera J.V. Wima K. Diwan T. Cuffy M.C. Anwar N. et al.Clinical implications of donor warm and cold ischemia time in donor after circulatory death liver transplantation.Liver Transpl. 2019; 25: 1342-1352Crossref PubMed Scopus (28) Google Scholar, 4Summers D.M. Watson C.J.E. Pettigrew G.J. Johnson R.J. Collett D Neuberger J.M. et al.Kidney donation after circulatory death (DCD): state of the art.Kidney Int. 2015; 88: 241-249Abstract Full Text Full Text PDF PubMed Scopus (196) Google Scholar, 5Villavicencio M.A. Axtell A.L. Spencer P.J. Heng E.E. Kilmarx S. Dalpozzal N. et al.Lung transplantation from donation after circulatory death: United States and single-center experience.Ann Thorac Surg. 2018; 106: 1619-1627Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 6Schlegel A. Kalisvaart M. Scalera I. Laing R.W. Mergental H. Mirza D.F. et al.The UK DCD risk score: a new proposal to define futility in donation-after-circulatory-death liver transplantation.J Hepatol. 2018; 68: 456-464Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar This technology has recently been adopted by pioneering DCD heart transplant programs, first in Australia7Dhital K.K. Iyer A. Connellan M. Chew H.C. Gao L. Doyle A. et al.Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death: a case series.Lancet. 2015; 385: 2585-2591Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar and then validated in the United Kingdom.8Messer S. Page A. Axell R. Berman M. Hernández-Sánchez J. Colah S. et al.Outcome after heart transplantation from donation after circulatory-determined death donors.J Heart Lung Transplant. 2017; 36: 1311-1318Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar Although greater rates of primary graft dysfunction (PGD) requiring extracorporeal membrane oxygenation have been reported, early outcomes in patient survival among DCD heart transplants have been comparable with those of DBD heart transplants.9Chew H.C. Iyer A. Connellan M. Scheuer S. Villanueva J. Gao L. et al.Outcomes of donation after circulatory death heart transplantation in Australia.J Am Coll Cardiol. 2019; 73: 1447-1459Crossref PubMed Scopus (102) Google Scholar Two general approaches to DCD donor heart recovery have been adopted.7Dhital K.K. Iyer A. Connellan M. Chew H.C. Gao L. Doyle A. et al.Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death: a case series.Lancet. 2015; 385: 2585-2591Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar,8Messer S. Page A. Axell R. Berman M. Hernández-Sánchez J. Colah S. et al.Outcome after heart transplantation from donation after circulatory-determined death donors.J Heart Lung Transplant. 2017; 36: 1311-1318Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar,10Tchana-Sato V. Ledoux D. Detry O. Hans G. Ancion A. D’Orio V. et al.Successful clinical transplantation of hearts donated after circulatory death using normothermic regional perfusion.J Heart Lung Transplant. 2019; 38: 593-598Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar, 11Connellan M. Dhital K. Donor heart procurement from the donation after circulatory death pathway.Oper Tech Thorac Cardiovasc Surg. 2017; 22: 58-67Abstract Full Text Full Text PDF Scopus (8) Google Scholar, 12Oniscu G.C. Randle L.V. Muiesan P. Butler A.J. Currie I.S. Perera M.T.P.R. et al.In situ normothermic regional perfusion for controlled donation after circulatory death—the United Kingdom experience.Am J Transplant. 2014; 14: 2846-2854Crossref PubMed Scopus (186) Google Scholar, 13Manara A. Shemie S.D. Large S. Healey A. Baker A. Badiwala M. et al.Maintaining the permanence principle for death during in situ normothermic regional perfusion for donation after circulatory death organ recovery: a United Kingdom and Canadian proposal.Am J Transplant. 2020; 20: 2017-2025Crossref PubMed Scopus (39) Google Scholar The normothermic regional perfusion (NRP) technique involves restoring circulation to the entire donor but surgically excluding the brain by clamping the aortic arch blood vessels. NRP allows the teams an ability to resuscitate and assess the donor's organs in a fully loaded and working state. Organ recovery is then performed in a manner otherwise identical to standard DBD procurement, using traditional cold storage. In contrast, direct procurement with ex vivo perfusion (DPEP) for the heart requires a rapid collection of donor blood, a step specific to DCD heart procurement. This is followed by an in situ cold preservation flush and a mildly hypothermic (34°C) ex vivo perfusion strategy similar to those most commonly deployed for abdominal organs and lungs using the Organ Care System device (OCS; Transmedics, Andover, Mass).11Connellan M. Dhital K. Donor heart procurement from the donation after circulatory death pathway.Oper Tech Thorac Cardiovasc Surg. 2017; 22: 58-67Abstract Full Text Full Text PDF Scopus (8) Google Scholar DCD heart recovery using OCS Heart System was developed for DBD donors and has received approval from the Food and Drug Administration for this indication.14Chew H.C. Macdonald P.S. Dhital K.K. The donor heart and organ perfusion technology.J Thorac Dis. 2019; 11: 938-945Crossref Scopus (22) Google Scholar While there are ongoing legal, ethical, and regional controversies regarding the NRP approach,15Parent B. Moazami N. Wall S. Kon Z. Smith D. Walsh B.C. et al.Ethical and logistical concerns for establishing NRP-cDCD heart transplantation in the United States.Am J Transplant. 2020; 20: 1508-1512Crossref PubMed Scopus (18) Google Scholar DPEP using OCS for DCD heart transplantation avoids these. The device was investigated in Australia and the United Kingdom and has been examined in a clinical trial in the United States since 2019. Herein, we share our current practices in terms of effective communication, procedural tips, and handling DCD-related regional policies and events for DPEP DCD heart recovery based on our experience in the United States. There is no clear, nor uniform definition of the warm ischemic time (WIT). One of the criteria used in the selection of DCD donors is the time of withdrawal of life-sustaining treatment (WLST) to antegrade flush (“total” donor warm ischemic time: tDWIT). Currently, many transplant centers moved to focus on the “functional” donor warm ischemic time (fDWIT), which defines the time from the onset of organ ischemia (an arterial blood pressure or peripheral blood oxygen saturation below a certain value) to antegrade flush. This allows for the evaluation of additional organs and is considered a better predictor of clinical outcomes after DCD transplantation. Iyer and colleagues16Iyer A. Gao L. Doyle A. Rao P. Jayewardene D. Wan B. et al.Increasing the tolerance of DCD hearts to warm ischemia by pharmacological postconditioning.Am J Transplant. 2014; 14: 1744-1752Crossref PubMed Scopus (77) Google Scholar reported in their animal study that impaired functional, biochemical, and metabolic recovery was seen following resuscitation of DCD porcine hearts exposed to WITs of greater than 20 minutes. Pharmacologic postconditioning using Celsior solution (Waters Medical Systems, Rochester, Minn) extends the tolerance of DCD hearts to warm ischemia by approximately 10 minutes, allowing complete functional recovery of hearts up to 30 minutes of WITs in porcine hearts. The OCS DCD Heart trial sets the fWIT threshold as 70% of peripheral blood oxygen saturation or 50 mm Hg of systolic blood pressure and a time limit of 30 minutes before the heart would be excluded from the trial, so this threshold has gained general acceptance across centers for DPEP. For liver transplantation, acceptable limits and definitions for organ ischemia vary among centers; however, the majority of liver programs in the United States consider an allowable tDWIT or fDWIT of up to 30 minutes.3Paterno F. Guarrera J.V. Wima K. Diwan T. Cuffy M.C. Anwar N. et al.Clinical implications of donor warm and cold ischemia time in donor after circulatory death liver transplantation.Liver Transpl. 2019; 25: 1342-1352Crossref PubMed Scopus (28) Google Scholar Lungs and kidneys exhibit a clinically acceptable PGD rate after relatively longer tDWITs. Accordingly, some programs will accept organs after a 90- or even 120-minute tDWIT.2Saxena P. Zimmet A.D. Snell G. Levvey B. Marasco S.F. McGiffin D.C. Techniques for lung procurement for transplantation following donation after circulatory death.Oper Tech Thorac Cardiovasc Surg. 2014; 19: 380-393Abstract Full Text Full Text PDF Scopus (3) Google Scholar,4Summers D.M. Watson C.J.E. Pettigrew G.J. Johnson R.J. Collett D Neuberger J.M. et al.Kidney donation after circulatory death (DCD): state of the art.Kidney Int. 2015; 88: 241-249Abstract Full Text Full Text PDF PubMed Scopus (196) Google Scholar,17Scalea J.R. Redfield R.R. Arpali E. Leverson G.E. Bennett R.J. Anderson M.E. et al.Does DCD donor time-to-death affect recipient outcomes? Implications of time-to-death at a high-volume center in the United States.Am J Transplant. 2017; 17: 191-200Crossref PubMed Scopus (23) Google Scholar The definition of WIT and allowable WIT for each organ should be discussed beforehand and agreed upon by all organ recovery teams. The donor's hospital policy with respect to tDWIT limits and definition circulatory death also needs to be confirmed in advance. The first step in considering any DCD heart offer is assessing the likelihood of progression to organ recovery. Although there is no established evidence-based, algorithm for predicting cardiac death within less than 30 minutes of fDWIT, certain parameters may be useful. Munshi and colleagues18Munshi L. Dhanani S. Shemie S.D. Hornby L. Gore G. Shahin J. Predicting time to death after withdrawal of life-sustaining therapy.Intensive Care Med. 2015; 41: 1014-1028Crossref PubMed Scopus (13) Google Scholar reviewed 15 studies associated with time to death after WLST. Across the 7 prediction tools proposed, only a few were validated in a separate cohort, and most had only moderate sensitivity and primarily focused on time to death within 60 minutes. The parameters most consistently associated with more rapid progression to cardiac death across a variety of different populations were Glasgow Coma Scale score ≤4; spontaneous breathing rate below ventilator settings and absence of other brain stem reflexes; severe lung dysfunction (high oxygen or positive end-respiratory pressure requirement); and hemodynamic instability (high-dose vasopressor or inotrope requirement).18Munshi L. Dhanani S. Shemie S.D. Hornby L. Gore G. Shahin J. Predicting time to death after withdrawal of life-sustaining therapy.Intensive Care Med. 2015; 41: 1014-1028Crossref PubMed Scopus (13) Google Scholar, 19He X. Xu G. Liang W. Liu B. Xu Y. Luan Z. et al.Nomogram for predicting time to death after withdrawal of life-sustaining treatment in patients with devastating neurological injury.Am J Transplant. 2015; 15: 2136-2142Crossref PubMed Scopus (14) Google Scholar, 20Brieva J. Coleman N. Lacey J. Harrigan P. Lewin T.J. Carter G.L. Prediction of death in less than 60 minutes after withdrawal of cardiorespiratory support in potential organ donors after circulatory death.Transplantation. 2014; 98: 1112-1118Crossref PubMed Scopus (17) Google Scholar, 21DeVita M.A. Brooks M.M. Zawistowski C. Rudich S. Daly B. Chaitin E. Donors after cardiac death: validation of identification criteria (DVIC) study for predictors of rapid death.Am J Transplant. 2008; 8: 432-441Crossref PubMed Scopus (70) Google Scholar Brieva and colleagues20Brieva J. Coleman N. Lacey J. Harrigan P. Lewin T.J. Carter G.L. Prediction of death in less than 60 minutes after withdrawal of cardiorespiratory support in potential organ donors after circulatory death.Transplantation. 2014; 98: 1112-1118Crossref PubMed Scopus (17) Google Scholar reported that the clinical opinion of intensive care unit specialists was one of the strongest independent predictors.20Brieva J. Coleman N. Lacey J. Harrigan P. Lewin T.J. Carter G.L. Prediction of death in less than 60 minutes after withdrawal of cardiorespiratory support in potential organ donors after circulatory death.Transplantation. 2014; 98: 1112-1118Crossref PubMed Scopus (17) Google Scholar Existing models apply broadly to DCD donors, but the DCD heart donors are a more specific subset so these studies have to be interpreted carefully. We screen DCD heart offers to ascertain the existence/degree of spontaneous breathing and remaining brain reflexes on the donors. In our experience, if the respiratory drive and other brainstem functions are mostly preserved, the donor is less likely to progress to circulatory arrest within 30 minutes of heart ischemia. Although distance from the organ recovery site and consequences associated with prolonged travel time are neutralized by use of the OCS technology, related logistical barriers, such as transportation costs as well as donor organ quality (metabolic condition, inotrope requirements, echocardiographic findings), and recipient factors (listing status/urgency, degree of sensitization, and other competing factors for organ offer, such as blood type or size) influence the initial decision to accept or reject a distant DCD organ offer. In our experience, most hospitals permit donor extubation in the operating room (OR). However, in some cases, hospital practice or policy or family request dictates that the donor is extubated outside of the OR. Sterile preparation and draping of the surgical field may be performed even if the donor will be extubated outside of the OR. All tubing, including suction tubing, lines for preservation solutions, and the blood collection line for OCS are assembled and positioned ahead of time. Organ-recovery teams should accommodate requests from the the organ procurement or the to a time of death to have one the exposed for the of the donor's family if be for WLST. an additional is then over the entire surgical and the at the be the field For the for and on the intensive care unit should be considered as donor policy the time for transportation to the preparation and and for and preservation solution will to be for in the allowable the WIT may be by the donor to the during the before death and flush be up ahead of time using on with suction and to to the of heart before extubation is for DCD heart recovery. the among all teams all for step is on a or that is to the heart In to the a separate for OCS and is also the of to the heart to the OCS device is is within 30 minutes of in DCD organ recovery with ex vivo perfusion needs to be in of WIT for each tDWIT donor is for and to and and of to be of of among time to abdominal of aortic abdominal heart and liver teams on the liver will be to antegrade flush for blood to and of tDWIT of fDWIT or mm Hg for of time of WIT of antegrade of in the first minutes of or needs to be consistently below 70% and 50 mm Hg in the first minutes of heart fDWIT, one those to from ischemic donor warm ischemic fDWIT, functional donor warm ischemic organ procurement withdrawal of life-sustaining peripheral oxygen systolic blood in a new for DCD heart or as to for or blood collection to and an during and and for or or to for suction at 2 to suction for and abdominal aortic in a new ischemic donor warm ischemic fDWIT, functional donor warm ischemic organ procurement withdrawal of life-sustaining peripheral oxygen systolic blood aortic are in the extubation of is to the donor a before the first by the that the donor's circulation has a is to the absence of spontaneous recovery of respiratory or cardiac The from 2 to minutes to hospital policy less is by organ procurement D.C. A. et practice for controlled donation after cardiac death organ procurement and J Transplant. PubMed Scopus Google Scholar of on an arterial is a for onset of circulatory and a of by hospital policy dictates this is considered with respect to the time at which death is that minutes is for each time and additional time is following to these minutes to be from the allowable this that the initial of circulatory arrest within 20 minutes of ischemia onset to 30 minutes of and abdominal antegrade flush should be within to minutes after the of the Heart procurement are with the standard abdominal DCD as J.H. A technique for rapid control of distal aorta in donation after cardiac death procurements.Transpl Int. 2008; 21: 186-188PubMed Google J.H. D.M. A of liver transplantation at in Transpl. 2008; Google Scholar The for the heart procurement, by Connellan and M. Dhital K. Donor heart procurement from the donation after circulatory death pathway.Oper Tech Thorac Cardiovasc Surg. 2017; 22: 58-67Abstract Full Text Full Text PDF Scopus (8) Google Scholar are in for DCD heart to from to in with and from the to below the or of donor blood by heart if in in antegrade in a new DCD heart procurement technical that from abdominal DCD organ recovery antegrade flush be heart donor blood collection is to a in the OCS perfusion blood collection minutes from the abdominal may abdominal antegrade flush the abdominal aorta the heart a The of blood collection be and of which will be discussed the abdominal aorta or aorta is of abdominal antegrade flush the aorta and some antegrade flush to heart since the aorta is the is and the aorta is an additional aortic may be to the aorta the if by the abdominal with care to the lungs are also additional should be The donor is during and with be after the of This be before as a cardiac is by a in the to as this is a primary of PGD in lungs after the lungs are is most by the flush the is after has and is this has an site for is on the distal perfusion on OCS requires a in the of the of for this is the lung also to use use a of the aorta to a to for and antegrade the heart is with to that have been before in a DBD recovery but in this most the from the of the aorta and perfusion of the heart on OCS on the collection of blood before any organ antegrade flush the M. Dhital K. Donor heart procurement from the donation after circulatory death pathway.Oper Tech Thorac Cardiovasc Surg. 2017; 22: 58-67Abstract Full Text Full Text PDF Scopus (8) Google D. P. Y. B. J. et preservation of during ex vivo heart perfusion.J Heart Lung Transplant. 2015; Full Text Full Text PDF PubMed Scopus Google Scholar This is the most of DCD heart recovery using DPEP. on the of the abdominal may be based on a study using the United for Organ which that there was no in outcomes DCD liver transplants from donors with tDWIT minutes and tDWIT 30 and minutes.3Paterno F. Guarrera J.V. Wima K. Diwan T. Cuffy M.C. Anwar N. et al.Clinical implications of donor warm and cold ischemia time in donor after circulatory death liver transplantation.Liver Transpl. 2019; 25: 1342-1352Crossref PubMed Scopus (28) Google Scholar the WIT and liver the abdominal should be to antegrade flush to the abdominal is to complete blood collection before of any antegrade flush to the in blood of heart on the OCS which affect and heart recovery. an also be as even recently blood have and are and the used to in blood and as a 2 of be in in case of blood are to donor blood should be by to This be by heart recovery in or at donor hospitals if an blood recovery is G. M. H. A. M. of blood by using an device PubMed Google Scholar blood is should be to the in the as will likely be The and surgical on specific the the from the and if to and the collection The the suction and line as well the The abdominal will be to their organ antegrade flush within minutes of the for the abdominal the heart should to blood within after and to within minutes. The and this is if using However, the liver the to the liver WIT approaches 30 A. Kalisvaart M. Scalera I. Laing R.W. Mergental H. Mirza D.F. et al.The UK DCD risk score: a new proposal to define futility in donation-after-circulatory-death liver transplantation.J Hepatol. 2018; 68: 456-464Abstract Full Text Full Text PDF PubMed Scopus (117) Google D. R. W. J. W. H. et models of donor arrest and graft in liver transplantation from donors after circulatory death.Am J Transplant. PubMed Scopus Google Scholar the liver WIT minutes at the time of our will the liver to with the abdominal antegrade flush are In this we clamping the in the before the abdominal flush. This allows the heart to with the blood A prolonged blood collection however, should be to or in the OCS which from and the heart the the abdominal should the abdominal during blood collection by the heart since this will with donor blood However, if the is in the be in the by the abdominal procurement A is by the Andover, for blood a be however, a be a if is with direct heart using a blood for OCS device and the heart and abdominal before the abdominal the antegrade flush. While also be we use as our standard which the potential of and to Heart and liver WIT be by a of the organ recovery and the teams antegrade are The heart and liver teams should on a specific time for blood collection after which the abdominal will be to their antegrade flush. 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