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Liver Transplant Donation After Cardiac Death: Experience at the University of Liege
Liver Transplant Donation After Cardiac Death: Experience at the University of Liege O. Detry, B. Seydel, M.-H. Delbouille, J. Monard, M.-F. Hans, A. De Roover, C. Coimbra, S. Lauwick, J. Joris, A. Kaba, P. Damas, F. Damas, A. Lamproye, J. Delwaide, J.-P. Squifflet, M. Meurisse, and P. Honoré ABSTRACT Objective. Donation after cardiac death (DCD) has been proposed to overcome in part the organ donor shortage. In liver transplantation, the additional warm ischemia time associated with DCD procurement may promote higher rates of primary nonfunction and ischemic biliary lesions. We reviewed the results of liver transplantation from DCD. Patients and Methods. From 2003 to 2007, we consecutively performed 13 controlled DCD liver transplantations. The medical records of all donors and recipients were retrospectively reviewed, evaluating in particular the outcome and occurrence of biliary complications. Mean follow-up was 25 months. Results. Mean donor age was 51 years, and mean intensive care unit stay was 5.4 days. Mean time between ventilation arrest and cardiac arrest was 9.3 minutes. Mean time between cardiac arrest and arterial flushing was 7.7 minutes. No-touch period was 2 to 5 minutes. Mean graft cold ischemia time was 295 minutes, and mean suture warm ischemia time was 38 minutes. Postoperatively, there was no primary nonfunction. Mean peak transaminase level was 2546 UI/mL. Patient and graft survival was 100% at 1 year. Two of 13 patients (15%) developed main bile duct stenosis and underwent endoscopic management of the graft. No patient developed symptomatic intrahepatic bile duct strictures or needed a second transplantation. Conclusions. Our experience confirms that controlled DCD donors may be a valuable source of transplantable liver grafts in cases of short warm ischemia at procurement and minimal cold ischemia time.
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ADAVERIC ORGAN DONOR shortage produces long waiting lists of candidates for organ transplantation with significant waiting list mortality. Organ donation after cardiac death (DCD) has been proposed to increase the potential pool of organs despite initial warm ischemia time that can be deleterious.1 In particular, transplantation of liver harvested from DCD donors may lead to a greater incidence of primary nonfunction, ischemic biliary lesions, and repeat transplantations.2–5 We retrospectively reviewed our experience with liver transplantation (OLT) using grafts procured from DCD donors.
PATIENTS AND METHODS From 2003 to December 2007, we procured 21 DCD donor livers (Maastricht category III)6 with weaning from ventilation performed in the operating room in all cases. These donors provided 0041-1345/09/$–see front matter doi:10.1016/j.transproceed.2009.01.001 582
15 liver and 37 kidney grafts. Four livers were sent to other Belgian centers, and 11 were transplanted locally. We accepted and transplanted 2 DCD liver grafts from other Belgian centers, for a total of 13 DCD OLTs in 5 years. We retrospectively reviewed the outcome of these procedures. In particular, we evaluated the causes of DCD donor brain damage and duration of DCD warm ischemia. The early and late results of DCD OLT were evaluated From the Departments of Abdominal Surgery and Transplantation (O.D., B.S., M.-H.D., J.M., M.-F.H., A.D.R., C.C., J.-P.S., M.M., P.H.), Anaethesia and Intensive Care (S.L., J.J., A.K., P.D., F.D.), and Hepatogastroenterology (A.L., J.D.), University of Liege, Liege, Belgium. Address reprint requests to Oliver Detry, MD, PhD, Department of Abdominal Surgery and Transplantation, CHU de Liège, University of Liège, Sart Tilman B35, B4000 Liège, Belgium. E-mail: [email protected] © 2009 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 41, 582–584 (2009)
LIVER DONATION AFTER CARDIAC DEATH
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for immediate graft function, postoperative transaminase levels, and Quick levels, and biliary complications as well as graft and patient survival. Follow-up was complete for all patients as of June 30, 2008; no patients were lost to follow-up. Mean (range) follow-up was 25 (9 – 65) months.
RESULTS Donors
Mean (range) age of the DCD donors (8 men and 5 women) was 51 (25–71) years. Causes of brain damage were brain ischemia due to reversed cardiac arrest (n ⫽ 6), spontaneous intracranial bleeding (n ⫽ 4), and trauma (n ⫽ 3). Mean donor intensive care unit stay was 5.4 (2– 8) days. Mean time between ventilation arrest and cardiac arrest was 9.3 (4 –14) minutes. Mean period between cardiac arrest and arterial flush was 7.7 (4 –15) minutes. No-touch period was 2 to 5 minutes. According to surgeon preference, HTK (histidine-tryptophan-ketoglutarate) solution was used as the preservation solution in 8 procedures, and University of Wiseonsin solution in 5 procedures. Recipients
Mean (range) age of the recipients (12 men and one women) was 55 (50 –70) years. The indications were hepatocarcinoma (n ⫽ 9), postalcoholic cirrhosis (n ⫽ 2), hepatitis C virus-associated cirrhosis (n ⫽ 1), and neuroendocrine hepatic metastases (n ⫽ 1). Their mean MELD (Model for End-Stage Liver Disease) score at transplantation was 14.2 (8 –25). The technique of OLT was piggyback with side-to-side cavocavoplasty in all cases. Mean cold ischemia time was 295 (105– 462) minutes. Mean suture warm ischemia time was 38 (25– 48) minutes. No primary nonfunction was observed in this series. Mean peak transaminase level was 2546 (92–10, 504) UI/ mL. Quick level at day 2 was 70% (39%–96%) and 92% (62%–100%) at day 7. Recipient intensive care unit stay was 3.5 (2–7) days, and total posttransplantation stay was 20 (10 – 40) days. Patient and graft survival was 100% at 1 year. One patient died after 14 months of donor- derived sarcoma.7 Two patients developed hepatocarcinoma recurrence; one died at 17 months and the other underwent resection of pulmonary metastases with curative intent. Two of 13 patients (15%) developed graft main bile duct stenosis and underwent endoscopic management with dilation and stenting, in one patient because of an anastomotic stricture and in the other because of main bile duct stenosis. No patient developed symptomatic intrahepatic bile duct strictures. No patient needed a second transplantation during follow-up. Patient and graft survival rates were 100% and 78.5% at 1and 2- year follow-up, respectively (Fig 1).
Fig 1.
Graft and patient survival rates (Kaplan-Meier method).
cholangiopathy in the mid and long terms. Thus, DCD OLT is still a hazardous procedure with greater risk of recipient graft failure and death. These potential hazards have been confirmed in the literature. Most single-center reports describe higher incidences of biliary complications that may induce graft failure and necessitate a second transplantation.3,4 Results from the United Network for Organ Sharing showed lower graft and patient survival after DCD OLT compared with donation after brain death.8 A greater complication rate was not observed in this series. Despite elevated transminase levels posttransplantation in some cases (⬎10,000 UI/mL in one case), no primary nonfunction was observed. Moreover, at follow-up, only 2 of 13 patients (15%) developed symptomatic biliary stenosis, which has been successfully managed to date using endoscopy. No graft was lost due to the particular donation. This single-center experience is, therefore, somehow different from that described in the literature, which may be related to the short duration of warm ischemia in this series of controlled DCD donors. The withdrawal of respiratory support was performed in the operating room, and the time between withdrawal and abdominal organ cold flushing was less than 30 minutes in all cases. The cold ischemia time was also short (mean, ⬍5 hours; no more than 8 hours in any case). Moreover, most DCD grafts were transplanted in stable patients with hepatocarcinoma or with a low MELD score, which may be the key to good results in DCD OLT. In conclusion, these preliminary results showed that DCD OLT demonstrates good outcome in terms of graft and patient survival. Keeping cold ischemia time short and selecting candidates with low MELD scores may be two keys to further development of OLT with DCD liver grafts.
DISCUSSION
REFERENCES
DCD has been proposed as a potential, but partial, answer to the cadaveric donor shortage. In OLT, DCD imposes additional warm ischemic trauma to the liver graft, with risk of primary nonfunction in the short term and ischemic
1. Kootstra G: The asystolic, or non-heartbeating, donor. Transplantation 63:917, 1997 2. Reddy S, Zilvetti M, Brockmann J, et al: Liver transplantation from non-heart-beating donors: current status and future prospects. Liver Transpl 10:1223, 2004
584 3. Abt P, Crawford M, Desai N, et al: Liver transplantation from controlled non– heart-beating donors: an increased incidence of biliary complications. Transplantation 75:1659, 2003 4. Muiesan P, Girlanda R, Jassem W, et al: Single-center experience with liver transplantation from controlled non-heartbeating donors: a viable source of grafts. Ann Surg 242:732, 2005 5. Abt PL, Desai NM, Crawford MD, et al: Survival following liver transplantation from non– heart-beating donors. Ann Surg 239:87, 2004
DETRY, SEYDEL, DELBOUILLE ET AL 6. Kootstra G, Daemen JH, Oomen AP: Categories of non– heart-beating donors. Transplant Proc 27:2893, 1995 7. Detry O, De Roover A, de Leval L, et al: Transmission of an undiagnosed sarcoma to recipients of kidney and liver grafts procured in a non– heart-beating donor. Liver Transpl 11:696, 2005 8. Mateo R, Cho C, Singh G, et al: Risk factors for graft survival after liver transplantation from donation after cardiac death donors: an analysis of OPTN/UNOS data. Am J Transplant 6:791, 2006
C
ADAVERIC ORGAN DONOR shortage produces long waiting lists of candidates for organ transplantation with significant waiting list mortality. Organ donation after cardiac death (DCD) has been proposed to increase the potential pool of organs despite initial warm ischemia time that can be deleterious.1 In particular, transplantation of liver harvested from DCD donors may lead to a greater incidence of primary nonfunction, ischemic biliary lesions, and repeat transplantations.2–5 We retrospectively reviewed our experience with liver transplantation (OLT) using grafts procured from DCD donors.
PATIENTS AND METHODS From 2003 to December 2007, we procured 21 DCD donor livers (Maastricht category III)6 with weaning from ventilation performed in the operating room in all cases. These donors provided 0041-1345/09/$–see front matter doi:10.1016/j.transproceed.2009.01.001 582
15 liver and 37 kidney grafts. Four livers were sent to other Belgian centers, and 11 were transplanted locally. We accepted and transplanted 2 DCD liver grafts from other Belgian centers, for a total of 13 DCD OLTs in 5 years. We retrospectively reviewed the outcome of these procedures. In particular, we evaluated the causes of DCD donor brain damage and duration of DCD warm ischemia. The early and late results of DCD OLT were evaluated From the Departments of Abdominal Surgery and Transplantation (O.D., B.S., M.-H.D., J.M., M.-F.H., A.D.R., C.C., J.-P.S., M.M., P.H.), Anaethesia and Intensive Care (S.L., J.J., A.K., P.D., F.D.), and Hepatogastroenterology (A.L., J.D.), University of Liege, Liege, Belgium. Address reprint requests to Oliver Detry, MD, PhD, Department of Abdominal Surgery and Transplantation, CHU de Liège, University of Liège, Sart Tilman B35, B4000 Liège, Belgium. E-mail: [email protected] © 2009 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 41, 582–584 (2009)
LIVER DONATION AFTER CARDIAC DEATH
583
for immediate graft function, postoperative transaminase levels, and Quick levels, and biliary complications as well as graft and patient survival. Follow-up was complete for all patients as of June 30, 2008; no patients were lost to follow-up. Mean (range) follow-up was 25 (9 – 65) months.
RESULTS Donors
Mean (range) age of the DCD donors (8 men and 5 women) was 51 (25–71) years. Causes of brain damage were brain ischemia due to reversed cardiac arrest (n ⫽ 6), spontaneous intracranial bleeding (n ⫽ 4), and trauma (n ⫽ 3). Mean donor intensive care unit stay was 5.4 (2– 8) days. Mean time between ventilation arrest and cardiac arrest was 9.3 (4 –14) minutes. Mean period between cardiac arrest and arterial flush was 7.7 (4 –15) minutes. No-touch period was 2 to 5 minutes. According to surgeon preference, HTK (histidine-tryptophan-ketoglutarate) solution was used as the preservation solution in 8 procedures, and University of Wiseonsin solution in 5 procedures. Recipients
Mean (range) age of the recipients (12 men and one women) was 55 (50 –70) years. The indications were hepatocarcinoma (n ⫽ 9), postalcoholic cirrhosis (n ⫽ 2), hepatitis C virus-associated cirrhosis (n ⫽ 1), and neuroendocrine hepatic metastases (n ⫽ 1). Their mean MELD (Model for End-Stage Liver Disease) score at transplantation was 14.2 (8 –25). The technique of OLT was piggyback with side-to-side cavocavoplasty in all cases. Mean cold ischemia time was 295 (105– 462) minutes. Mean suture warm ischemia time was 38 (25– 48) minutes. No primary nonfunction was observed in this series. Mean peak transaminase level was 2546 (92–10, 504) UI/ mL. Quick level at day 2 was 70% (39%–96%) and 92% (62%–100%) at day 7. Recipient intensive care unit stay was 3.5 (2–7) days, and total posttransplantation stay was 20 (10 – 40) days. Patient and graft survival was 100% at 1 year. One patient died after 14 months of donor- derived sarcoma.7 Two patients developed hepatocarcinoma recurrence; one died at 17 months and the other underwent resection of pulmonary metastases with curative intent. Two of 13 patients (15%) developed graft main bile duct stenosis and underwent endoscopic management with dilation and stenting, in one patient because of an anastomotic stricture and in the other because of main bile duct stenosis. No patient developed symptomatic intrahepatic bile duct strictures. No patient needed a second transplantation during follow-up. Patient and graft survival rates were 100% and 78.5% at 1and 2- year follow-up, respectively (Fig 1).
Fig 1.
Graft and patient survival rates (Kaplan-Meier method).
cholangiopathy in the mid and long terms. Thus, DCD OLT is still a hazardous procedure with greater risk of recipient graft failure and death. These potential hazards have been confirmed in the literature. Most single-center reports describe higher incidences of biliary complications that may induce graft failure and necessitate a second transplantation.3,4 Results from the United Network for Organ Sharing showed lower graft and patient survival after DCD OLT compared with donation after brain death.8 A greater complication rate was not observed in this series. Despite elevated transminase levels posttransplantation in some cases (⬎10,000 UI/mL in one case), no primary nonfunction was observed. Moreover, at follow-up, only 2 of 13 patients (15%) developed symptomatic biliary stenosis, which has been successfully managed to date using endoscopy. No graft was lost due to the particular donation. This single-center experience is, therefore, somehow different from that described in the literature, which may be related to the short duration of warm ischemia in this series of controlled DCD donors. The withdrawal of respiratory support was performed in the operating room, and the time between withdrawal and abdominal organ cold flushing was less than 30 minutes in all cases. The cold ischemia time was also short (mean, ⬍5 hours; no more than 8 hours in any case). Moreover, most DCD grafts were transplanted in stable patients with hepatocarcinoma or with a low MELD score, which may be the key to good results in DCD OLT. In conclusion, these preliminary results showed that DCD OLT demonstrates good outcome in terms of graft and patient survival. Keeping cold ischemia time short and selecting candidates with low MELD scores may be two keys to further development of OLT with DCD liver grafts.
DISCUSSION
REFERENCES
DCD has been proposed as a potential, but partial, answer to the cadaveric donor shortage. In OLT, DCD imposes additional warm ischemic trauma to the liver graft, with risk of primary nonfunction in the short term and ischemic
1. Kootstra G: The asystolic, or non-heartbeating, donor. Transplantation 63:917, 1997 2. Reddy S, Zilvetti M, Brockmann J, et al: Liver transplantation from non-heart-beating donors: current status and future prospects. Liver Transpl 10:1223, 2004
584 3. Abt P, Crawford M, Desai N, et al: Liver transplantation from controlled non– heart-beating donors: an increased incidence of biliary complications. Transplantation 75:1659, 2003 4. Muiesan P, Girlanda R, Jassem W, et al: Single-center experience with liver transplantation from controlled non-heartbeating donors: a viable source of grafts. Ann Surg 242:732, 2005 5. Abt PL, Desai NM, Crawford MD, et al: Survival following liver transplantation from non– heart-beating donors. Ann Surg 239:87, 2004
DETRY, SEYDEL, DELBOUILLE ET AL 6. Kootstra G, Daemen JH, Oomen AP: Categories of non– heart-beating donors. Transplant Proc 27:2893, 1995 7. Detry O, De Roover A, de Leval L, et al: Transmission of an undiagnosed sarcoma to recipients of kidney and liver grafts procured in a non– heart-beating donor. Liver Transpl 11:696, 2005 8. Mateo R, Cho C, Singh G, et al: Risk factors for graft survival after liver transplantation from donation after cardiac death donors: an analysis of OPTN/UNOS data. Am J Transplant 6:791, 2006