Extracorporeal membrane oxygenation support of donor abdominal organs in non-heart-beating donors

Both family consent and legal consent were required for organ/tissue donation from non-heart-beating donors (NHBD) in Taiwan. A district attorney had to come to the bedside to confirm the donor's asystole, confirm the family consent, and complete some legal documents before a legal consent was issued for organ donation. The resultant warm ischemic time would be unpredictably long and in fact precluded the organ donation from NHBD in Taiwan. We developed a method of using extracorporeal membrane oxygenation (ECMO) to maintain NHBD for a longer time and prevent warm ischemic injury of the donor abdominal organs. After ventilator disconnection in NHBD, phentolamine and heparin were injected and mannitol infusion was given. After the donor's asystole was confirmed by the electrocardiogram (EKG) strip recording, the ECMO support was set up through the right femoral veno-arterial route, an occlusion balloon catheter was inserted through the left femoral artery to occlude the thoracic aorta, and bilateral femoral arteries were ligated. Usually, the ECMO could begin within 10 min after the donor's asystole. The ECMO, combined with a cooler, provided cold oxygenated blood to the abdominal visceral organs, and prevented their warm ischemic injuries. Under the ECMO support (range: 45-70 min), eight renal grafts were procured from 4 NHBD. With the exception of the first two renal grafts with delayed function, all others had immediate function postoperatively and dialysis was no longer needed. In conclusion, by our ECMO technique, NHBD could be maintained for a longer time and the renal grafts had better immediate postoperative function than those reported by other methods.     

Liver transplantation from Maastricht category 2 non-heart-beating donors

BACKGROUND: The demand for liver transplantation has increasingly exceeded the supply of cadaver donor organs. Non-heart-beating donors (NHBDs) may be an alternative to increase the cadaver donor pool. METHODS: The outcome of 20 liver transplants from Maastricht category 2 NHBDs is compared with 40 liver transplants from heart-beating donors (HBDs). After unsuccessful cardiopulmonary resuscitation (CPR), cardiopulmonary support (CPS) with simultaneous application of chest and abdominal compression (n=6), and cardiopulmonary bypass (CPB; n=14), which was hypothermic (n=7) or normothermic (n=7), were used to preserve the organs from NHBDs. Factors that may influence the outcome of livers from Maastricht category 2 NHBDs were also investigated. RESULTS: With a minimum follow-up of 2 years, actuarial patient and graft survivals with livers from Maastricht category 2 NHBDs were 80% and 55%, respectively. Transplantation of organs from these donors was associated with a significantly higher incidence of primary nonfunction, biliary complications, and more severe initial liver dysfunction compared with livers from HBDs. Graft survival was 83% in livers from NHBDs preserved with CPS and 42% in those maintained with CPB. No graft failed if the duration of warm ischemia did not exceed 130 min with CPR or CPS, and if the period of CPB did not surpass 150 min when this method was used after CPR, regardless if it was hypothermic or normothermic. CONCLUSION: Livers from Maastricht type 2 NHBDs may be used for transplantation if the period of warm ischemia during CPR or CPS does not exceed 130 min. Hypothermic or normothermic CPB after CPR preserves liver viability for an additional 150 min.     

Expanding the donor pool: use of renal transplants from non-heart-beating donors supported with extracorporeal membrane oxygenation

Abstract:  In response to organ shortage, we used the renal grafts from non-heart-beating donors (NHBDs). Extracorporeal membrane oxygenation (ECMO) was used to maintain NHBDs before organ procurement. We compared the results of renal transplantation from different donors, including heart-beating donors (HBDs), living-related donors (LDs), and NHBDs supported with ECMO. From February 1998 to June 2003, we recruited 219 patients receiving renal transplantation at National Taiwan University Hospital. Among them, 31 received kidneys from NHBDs supported with ECMO, 120 from HBDs, and 68 from LDs. Multiple organ transplant recipients were not included in this study. We compared the graft survival, serum creatinine levels, and estimated glomerular filtration rates of the three groups. The rate of delayed graft function was higher in NHBD recipients (41.9%) than in HBD recipients (27.0%) and LD recipients (10.9%) (p = 0.003). In the NHBD group, the recipients of grafts with delayed function had significantly longer ECMO runs (63.1 ± 3.0 min) than those without delayed function (53.7 ± 2.5 min) (p = 0.024). Estimated glomerular filtration rate (p = 0.472) and mean serum creatinine level (p = 0.286) were not significantly different between the three groups using a longitudinal approach. The 5-yr graft survival rates for NHBD (88.4%, 95% CI: 0.680–0.962), HBD (83.2%, 95% CI: 0.728–0.899), and LD transplant recipients (89.3%, 95% CI: 0.619–0.974) were not significantly different (p = 0.239). The 5-yr patient survival rates for NHBD, HBD, and LD transplant recipients were 100, 93.0 (95% CI: 0.859–0.966) and 100% respectively. The long-term allograft survival and function of kidneys from NHBDs supported by ECMO, HBD, and LD did not differ significantly. Long ECMO running time tended to delay graft function.     

Pancreatic islet cell transplantation using non-heart-beating donors (NHBDs)

Recent dramatic improvements in clinical islet cell transplantation demonstrated by the Edmonton group have increased the demand for this treatment, and donor shortage could become a major problem. Utilization of marginal donors could alleviate the donor shortage, and non-heart-beating donors (NHBDs) might be good resources. The University of Pennsylvania group demonstrated that it was possible to isolate islets from NHBDs, and the group actually transplanted islets from NHBDs, for the first time. The patient became insulin-independent; however, there had been no more cases using NHBDs until our group initiated islet transplantations from NHBDs in Japan. In order to utilize NHBDs effectively, we modified the standard islet isolation method. These modifications included minimizing the warm ischemic time, the use of trypsin inhibition during isolation, carrying out density measurement before purification and the use of a less toxic islet purification solution. With these modifications we were able to transplant nine of ten islet preparations from ten NHBDs (90%), into five type-1 diabetic patients. The first transplantation was performed on April 7, 2004 (the first time in Japan), and this patient became insulin-independent after the second islet transplantation (first time in Japan). All patients showed improved glycemic control and reduced insulin requirements, without hypoglycemic events. We also performed living-donor islet transplantation, with our modified islet isolation protocol, on January 19, 2005. The improved islet isolation protocol enabled us to perform effective islet transplantations from NHBDs, and it also enabled us to perform the living-donor islet transplantation.     

The long-term outcome of tacrolimus in cadaveric kidney transplantation from non-heart beating donors

Tacrolimus (Tac), developed in 1990, has been applied as an immunosuppressive agent for liver, heart, and kidney transplantation and is known to have more powerful immunosuppressive effects than cyclosporine (CyA). To evaluate the efficacy of Tac in cadaveric kidney transplants from non-heart beating donors, we present the long-term outcome of patients receiving kidneys with ischemic damage, and compared it with that of CyA. Between July 1990 and December 2000, 55 patients with end-stage renal disease received kidneys from non-heart beating donors (Maastrichy category 3) and were treated with Tac and steroid immunosuppressive therapy. During the same period, we also performed 137 non-heart beating cadaveric renal transplants treated with CyA-based immunosuppressive therapy. The patient survival rate was 98% at 1 yr and 96% at 3-10 yr in the Tac group, and 97% at 1-3 yr, 93% at 5 yr and 85% at 10 yr in the CyA group. The graft survival rate was 91% at 1 yr, 80% at 3 yr, 63% at 5 yr and 34% at 10 yr in the Tac group, and 88% at 1 yr, 75% at 3 yr, 63% at 5 yr and 49% at 10 yr in the CyA group. There was no significant difference in either patient or graft survival rates between the two groups. Acute early rejection in the Tac group was less than that in the CyA group but acute tubular necrosis was the same in both groups. This indicates that Tac is available for cadaveric kidney transplants from non-heart beating donors. In conclusion, Tac is available as an immunosuppressive agent even for kidney transplants from non-heart beating donors.     

大鼠两种不同供肝对原位肝移植术中和术后影响的比较

目的　比较正常 (HB)和心跳停搏 (NHB)供肝对大鼠原位肝移植术中和术后的影响。方法　雄性SD大鼠随机分成HB和NHB两组 ;NHB组又分别设心跳停搏 30min(HNB - 30 )和 4 5min(NHB - 4 5 )两组。每组各行原位肝移植 5 0、30和 30次。结果　HB和NHB组冷缺血、无肝期、肝下下腔静脉 (IVC)阻断、受体手术时间分别为 (6 9.76± 1.5 2 )min和 (70 .32± 1.5 3)min、(16 .4 6± 0 .96 )min和(16 .4 0± 0 .73)min、(2 2 .5 6± 1.73)min和 (2 2 .75± 1.16 )min、(89.38± 3.75 )min和 (90 .5 8± 3.76 )min ;术后受体苏醒和主动饮水时间分别为 (5 .4 3± 3.88)min和 (5 4 .0 6± 5 .99)min、(43.0 4± 10 .19)min和(12 6 .79± 15 .0 2 )min ;受体术后鼻粘膜出血率分别为 4 .17%和 92 .6 8% ;受体第 1周体重下降幅度分别为 (6 .15± 1.92 ) %和 (9.6 2± 1.80 ) % ;第 2周体重增加幅度分别为 (7.4 4± 2 .5 9) %和 (3.16± 1.0 4 ) %。HB组近期死因分别为原发性移植肝无功能 (PGF)、麻醉过深、肺部感染和肝上下腔静脉 (SVC)吻合口漏 ;而NHB组分别为PNF、麻醉过深、无肝期较长 (>17min)和再灌注后供肝渗血 ;HB和NHB - 30、NHB - 4 5组术后 1周存活率分别为 90 %、5 0 %和 30 %。结论　NHB较HB术中操作更复杂 ,更需     

Effect of machine perfusion preservation on delayed graft function in non-heart-beating donor kidneys – early results

The functioning of non-heart-beating (NHB) donor kidneys upon transplantation is often delayed. To evaluate the effect of preservation by machine perfusion (MP) on early post-transplant function, 37 NHB donor kidneys were compared to 74 matched heart-beating (HB) donor kidneys preserved by cold storage (CS). The NHB donor kidneys were subject to 49 ± 34 min of warm ischemia. Delayed function (DF) and primary nonfunction (PNF) rates were significantly higher for NHB than for HB donor kidneys (49 % and 19 % vs 34 % and 7 %, respectively). Consequently, renal function was impaired but recovered within 6 months. MP could not eliminate the differences in DF rate between NHB and HB donor kidneys. However, NHB donor kidneys preserved by MP showed less DF than that reported in kidneys preserved by CS. This suggests that MP has a beneficial effect on ischemically damaged kidneys. The similar results observed with category 2 and category 3 NHB donors also suggest this effect. The high PNF rate emphasizes the need for viability tests that prevent the transplantation of nonviable organs. We conclude that MP alone is not sufficient to reduce DF and PNF rates in NHB donor kidneys. Received: 16 January 1997 Received after revision: 7 April 1997 Accepted: 11 April 1997     

脑死亡来源供肝肝移植9例临床分析

目的总结使用脑死亡来源供肝肝移植的临床经验,初步分析脑死亡来源供肝应用于临床的安全性。方法2006年1月至2007年12月我院器官移植科共实施9例脑死亡来源供肝肝移植。供体年龄16～43岁,死于颅脑外伤7例,死于脑血管意外2例,器官切取前平均动脉压(105±5.2)mmHg(1mmHg=1.333kPa)(6例需使用升压药物),肝功能检测丙氨酸转氨酶(175±40)U/L,天冬氨酸转氨酶(180±46)U/L,总胆红素(40±8.6)mmol/L。受者年龄(48.6±10.1)岁,男性8例,女性1例;术前诊断为肝硬化5例,肝癌4例,术前MELD评分(27.6±6.7)分。结果供肝冷缺血时间为(7.4±2.8)h,所有患者手术顺利。1例于术后7天死于肾功能衰竭。8例受者康复出院并随访6～24个月,1例于术后24个月死于肿瘤复发,其他并发症发生包括急性排斥反应2例,胆道狭窄并感染1例,胆道缺血1例,肺部感染1例。结论按照我们选择脑死亡供肝的原则,肝移植受者术后近期及中期预后良好,具有临床应用前景。     

Lung transplantation from donation after cardiac death (non-heart-beating) donors

Although lung transplantation is a well-accepted treatment for advanced lung diseases, donor shortage remains a significant limiting factor resulting in an increasing number of deaths of people on waiting lists. Recently, some transplant centers have begun to use lungs retrieved from donors after circulatory arrest. This review outlines the relevant published experimental data and clinical experiences with lung transplantation from donation after cardiac-death donors (DCDs) or non-heart-beating donors (NHBDs). Techniques for lung preservation and ex vivo lung assessment of DCD (NHBD) lungs are reviewed, and aspects of primary graft dysfunction after DCD (NHBD) lung transplantation are discussed. This review was submitted at the invitation of the editorial committee.     

Transplantation of kidneys harvested from non-heart-beating donors: early and long-term results

Abstract  The purpose of this retrospective study was to evaluate results of non-heart-beating donor (NHBD) kidney transplantation. Between Jan 1986 and Dec 1994,80 out of 582 cadaveric kidneys were harvested from NHBD (31.9 min ± 24 after cardiac arrest). The results in the NHBD group (76 recipients) were compared with those obtained after transplantation of kidneys harvested from heart-beating donors (HBD) with respect to early graft function, and the graft and recipient's survival. Both groups were matched for sex, age, PRA level, number of HLA mismatches, and cold ischemia time. Triple immunosuppression therapy was used in both groups. Acute tubular necrosis (ATN) was observed significantly more frequently in the NHBD group (50 of 76 recipients vs 33 of 100 in the HBD group). The striking finding of this study was that the occurrence of primary non-function was the same in both groups and that the main cause of it was acute rejection. The 1-year patient and graft survival rates were 98.7 % and 81.6 % for the NHBD group and 99 % and 90 % for the HBD group, respectively. There was also no statistical difference in the serum creat-inine concentration in both groups. We concluded that despite an increased incidence of ATN in the NHBD kidney recipients, the long-term results are good and comparable with those in the HBD group.     

Advantages of Celsior solution in graft preservation from non-heart-beating donors in a canine liver transplantation model.

BACKGROUND: The optimal method for preserving livers from non-heart-beating donors (NHBD) is still unknown. We compared the Celsior solution, a new extracellular-type, low-potassium, low-viscosity preservation solution, with the University of Wisconsin (UW) solution in a canine orthotopic liver transplantation from NHBD. MATERIALS AND METHODS: Fourteen adult mongrel dogs, weighing 9 to 17 kg, were divided into two groups: the Celsior or the UW group (n = 7 each). The thoracic descending aorta and supradiaphragmatic inferior vena cava were cross-clamped for 20 min to induce warm ischemia as a NHBD model. The liver was flushed with the respective cold preservation solution and then stored at 4 degrees C for 4 h. The grafts were transplanted using the piggy-back technique under portal decompression by leaving the native right lobe as a temporary shunt. RESULTS: The duration of liver flushing out (min) was shorter (P < 0.05), and the serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactate dehydrogenase, lactate, and alpha-glutathione S-transferase concentrations 2 and 6 h after reperfusion of the graft (RPF) were lower (P < 0.05) in the Celsior group than in the UW group. Hepatic tissue blood flow (HTBF) did not deteriorate as much (P < 0.05) in the Celsior group. The serum endothelin-1 level was lower (P < 0.05) in the Celsior group 2 h after RPF. Histopathology of liver specimens revealed portal congestion and hepatocyte necrosis with neutrophil infiltration in the UW group, while these findings were mild in the Celsior group. CONCLUSIONS: The Celsior solution improves vascular endothelial injury in livers from NHBDs and may have advantages in graft flush and preservation of grafts from NHBDs.     

Successful liver transplantation from agonal non-heart-beating donors in pigs

An effective way to overcome shortage of donors in liver transplantation (LTx) is to consider such from non-heart-beating donors (NHBDs). We investigated how a liver graft should be treated before and/or after procurement for successful LTx from an NHBD. Porcine LTx was performed with FR167653 (FR), a dual inhibitor of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and/or prostaglandin E(1) (PG). Animals were allocated to an FR group (n=4, donors and recipients were treated with FR), a PG group (n=4, donors and recipients were treated with PG), or an FRPG group (n=4, donors and recipients were treated with both FR and PG). No recipients in the FR group and only two of four recipients in the PG group survived, whereas all recipients in the FRPG group survived. Suppression of TNF-alpha and IL-1beta and maintenance of microcirculation are the key to successful transplantation from NHBDs.     

Outcome of renal allografts from non-heart-beating donors with delayed graft function

Delayed graft function (DGF) in renal transplantation using non-heart-beating donors (NHBDs) usually exceeds 80%. There is debate whether DGF in this subgroup is associated with poor long-term outcome. Between 1 January 1988 and 31 January 2000, 130 of 158 (82.3%) NHBD graft recipients with functioning grafts transplanted within our regional NHBD programme developed DGF. Overall graft survival and graft survival censored for recipient death was 113/130 (86.9%) versus 113/121 (93.4%) at year 1, 55/84 (65.5%) versus 55/64 (85.9%) at year 5 and 18/40 (45.0%) versus 18/28 (64.3%) at year 10 after transplantation. Seventeen grafts (13.1%) were lost due to rejection or graft nephropathy. Nine of these kidneys failed during the 1st year. Twenty-seven patients (20.8%) died with functioning grafts, eight within the 1st year after transplantation. In those patients who survived, DGF was associated with excellent long-term outcome in this study. The number of grafts lost due to recipient death exceeded those lost due to rejection or graft nephropathy.     

Long-term outcome of kidney transplant using non-heart-beating donor: multicenter analysis of factors affecting graft survival

This multicenter study was retrospectively evaluated for the predictive factors affecting the long-term graft survival of a kidney transplant from a non-heart-beating donor (NHBD). PATIENTS AND METHOD: A total of 706 patients received transplants from NHBD in 11 centers between 1986 and 2000 and the results were entered into the analysis. The patients were treated with cyclosporine- or tacrolimus-based immunosuppressive therapy. Graft survival was calculated by the Kaplan-Meier method. Factors selected for univariate analysis were donor age, and acute early and acute late rejection. Hypertension (HT), hyperlipidemia (HL), and diabetes mellitus were also analyzed in 638 recipients whose graft survived for more than 1 yr. RESULTS: In the cases using NHBD, graft survival for 1, 5, and 10 yr was 87, 69, and 53%, respectively. Donor age of over 55 yr, acute early and late rejection, post-transplant HT and diabetes at the first post-operative year were shown to be significantly harmful on long-term graft survival. For longer graft survival in NHBD kidney transplantations, reducing acute rejection, and controlling blood pressure and sugar are crucial.     

Simultaneous pancreas-kidney (SPK) transplantation from controlled non-heart-beating donors (NHBDs)

From January 1993 through June 1999, 18 simultaneous pancreas-kidney transplants (SPKs) were performed from controlled non-heart-beating donors (NHBDs) and 339 SPKs were performed from heart-beating donors (HBDs). No difference in donor characteristics was noted except for warm ischemic time, which was 14.8 min (range 4-46 min) for NHBDs. Following transplantation, no difference in pancreatic function was noted; however, a higher rate of enteric conversions was seen in pancreas transplants from NHBDs (32% vs. 13%; p < 0.01). Hemodialysis for acute tubular necrosis (ATN) was higher in kidney transplants from NHBDs (22.2% vs. 4.1%; p = 0.009) as was discharge serum creatinine (1.7 mg/dl vs. 1.5 mg/dl; p < 0.05). Also, the number of patients remaining rejection free was lower for NHBDs and approached significance (33.3% vs. 50.1%; p = 0.07). However, no difference in patient survival (100% vs. 95.4%) or pancreatic (87.4% vs. 86.5%) and renal (86.3% vs. 86.3%) allograft survival was noted during the study period. Our results indicate that SPK transplantation from controlled NHBDs is a viable method for increasing the number of pancreas and kidney transplants available for transplantation.     

Impact of cold ischemia time on renal allograft outcome using kidneys from young donors

Prolonged cold ischemia time (CIT) is associated with delayed graft function and worse kidney transplant (KT) outcome, but the effect of CIT on long‐term allograft survival in KT from younger donors has not been well established. We investigated the predictive value of CIT exposure on long‐term death‐censored graft loss in 829 KT recipients from younger donors (<50 years) that were performed in our center between 1991 and 2005. Overall death‐censored graft failure rate was significantly higher in CIT≥19 h group versus CIT<19 h group (26 vs. 16.5%; P = 0.002). Significant differences were also observed when patients with primary nonfunctioning graft were excluded (21 vs. 14%; P = 0.020) and in patients who received tacrolimus plus mycophenolate mofetil (12 vs. 4%; P = 0.05). By multivariate Cox analysis, CIT was found to be independently associated with death‐censored graft loss with a 20% increase for every 5 h of CIT [relative risk (RR) 1.04; 95% Confidence Interval (CI): 1.01–1.1; P = 0.021]. Likewise, graft loss risk significantly increased in CIT≥19 h group versus CIT<19 h group (RR 1.5; 95%CI: 1.1–2.1; P = 0.023). Prolonged CIT is an independent predictor of graft survival in KT from younger donors. Efforts at minimizing CIT (<19 h) should improve transplant outcome significantly in this population.