Optimization of Perioperative Conditions to Prevent Ischemic Cholangiopathy in Donation After Circulatory Death Donor Liver Transplantation

Kubal, Chandrashekhar A.; Mangus, Richard S.; Fridell, Jonathan A.; Saxena, Romil; Rush, Natalia; Wingler, Matthew; Ekser, Burçin; Tector, Joseph

doi:10.1097/tp.0000000000001204

Cited by 53 publications

(67 citation statements)

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“…Also, the Indiana University Group compared cDCD livers treated with TPA added to the aortic flush and subsequently directly injected into the hepatic artery (n = 30) with a historic group of controls from an earlier era (n = 61). They claimed the use of TPA significantly reduced the rates of both anastomotic and nonanastomotic biliary strictures, though donor age was greater and the warm and cold ischemia times significantly longer in non‐TPA grafts . In contrast, a study from Leiden compared recipients of livers treated with urokinase during back‐table surgery (n = 63: 46 DBD and 17 cDCD) with a group of controls from an earlier era (n = 122: 94 DBD and 28 cDCD).…”

Section: Discussionmentioning

confidence: 99%

“…An additional theory holds that microthrombi deposition in peribiliary arterioles during the low‐flow/no‐flow period following ventilator withdrawal or cardiorespiratory arrest in controlled/expected donation after circulatory death (cDCD) and uncontrolled/unexpected donation after circulatory death (uDCD) donors, respectively, may also play a role. On the basis of this theory, different authors have suggested that the viability of organs arising from DCD donors may be improved through the application of fibrinolytic therapy …”

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confidence: 99%

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Heparin but not tissue plasminogen activator improves outcomes in donation after circulatory death liver transplantation in a porcine model

et al. 2018

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Ischemic-type biliary lesions (ITBLs) arise most frequently after donation after circulatory death (DCD) liver transplantation and result in high morbidity and graft loss. Many DCD grafts are discarded out of fear for this complication. In theory, microvascular thrombi deposited during donor warm ischemia might be implicated in ITBL pathogenesis. Herein, we aim to evaluate the effects of the administration of either heparin or the fibrinolytic drug tissue plasminogen activator (TPA) as means to improve DCD liver graft quality and potentially avoid ITBL. Donor pigs were subjected to 1 hour of cardiac arrest (CA) and divided among 3 groups: no pre-arrest heparinization nor TPA during postmortem regional perfusion; no pre-arrest heparinization but TPA given during regional perfusion; and pre-arrest heparinization but no TPA during regional perfusion. In liver tissue sampled 1 hour after CA, fibrin deposition was not detected, even when heparin was not given prior to arrest. Although it was not useful to prevent microvascular clot formation, pre-arrest heparin did offer cytoprotective effects during CA and beyond, reflected in improved flows during regional perfusion and better biochemical, functional, and histological parameters during posttransplantation follow-up. In conclusion, this study demonstrates the lack of impact of TPA use in porcine DCD liver transplantation and adds to the controversy over whether the use of TPA in human DCD liver transplantation really offers any protective effect. On the other hand, when it is administered prior to CA, heparin does offer anti-inflammatory and other cytoprotective effects that help improve DCD liver graft quality. Liver Transplantation 24 665-676 2018 AASLD.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Heparin but not tissue plasminogen activator improves outcomes in donation after circulatory death liver transplantation in a porcine model

et al. 2018

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“…Successful outcomes have been reported from single centers, with short warm ischemia times, but most US single centers, meta‐analyses, and UNOS data reports demonstrate inferior results with DCD donors, including lower survival and a significant incidence of ischemic cholangiopathy . Although evidence from retrospective series suggests that DCD donor OLT is associated with either equivalent or inferior short‐term and longterm outcomes, recent reports suggest improving outcomes . Khorsandi et al from the UK Institute of Liver Studies, King's College Hospital evaluated survival in patients with HCC undergoing DCD donor or DBD grafts.…”

Section: Dcd Liver Transplantationmentioning

confidence: 99%

“…In particular, the area under the systolic blood pressure curve and slope of the systolic blood pressure regressed from the time of extubation, calculated with the values in the first 10 minutes after extubation, were associated with better outcomes, possibly due to a favorable blood pressure trajectory during the agonal phase. Additionally, once procured, a fibrinolytic preflush such as tissue plasminogen activator (tPA) can be employed to decrease ischemic‐type biliary lesions, which is hypothesized to function by reducing peribiliary microvasculature microthrombi . In an analysis of organ procurement in the Netherlands, it was found that both higher BMI and procurement from a DCD donor were risk factors for increased procurement injury, further suggesting the need for experienced transplant surgeons .…”

Section: Recent Improvements In Dcd Liversmentioning

confidence: 99%

Donation after cardiac death in the hepatocellular carcinoma patient: Same indication?

Vining¹,

Ecker²,

Abt³

et al. 2017

Liver Transpl

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“…While our institution, 2,6 King's, 7 and others 8,9 report outcomes in DCD LT comparable to Donation after Brain Death (DBD), DCD LT is still not perfect. In our report, the incidence of IC and hepatic artery thrombosis in late DCD group was significant high than in DBD group (3 vs. 0.5%, P < .05).…”

Section: Response To "Minimization Of Ischemic Cholangiopathy In Donamentioning

confidence: 99%

Response to “Minimization of Ischemic Cholangiopathy in Donation After Cardiac Death Liver Transplantation: Is it Thrombolytic Therapy or Warm Ischemic Time Stringency and Donor Bile Duct Flush?”

Bohórquez

Loss

2018

American Journal of Transplantation

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We thank Giorgakis and colleagues for their interest in our recent published article.1,2 Since the etiology of ischemic cholangiopathy (IC) in Donation after Cardiac Death (DCD) for Liver Transplantation (LT) is not well defined, hypotheses include ischemia-reperfusion injury, microvascular thrombosis, cytotoxic injury, and impaired biliary epithelial regeneration, 3-5 adopting a multifaceted protocol to optimize perioperative conditions is essential. We concur with their observation that fast organ recovery with rapid decompression, in-situ aortic and portal flushing, biliary tree flushing-and in our institution, retrograde venous flushing-keep short ischemic times, careful donorrecipient selection, and pristine technical implantation are imperative to good outcomes.As we mentioned in our paper, we acknowledge the limitations of our retrospective non-randomized study. In the setting of multiple simultaneous changes in our protocol, we cannot, and we do not assume that our graft and patient survival rates are exclusively related to the use of tPA. However, our report shows the safety of tPA utilization after portal reperfusion with no adverse events and no increase in transfusion requirements. Additionally, the early success of this DCD protocol led us to liberalize our thresholds for DCD donor age, hepatic steatosis, and ischemia times with >60% of our last 100 DCD livers originated outside our donor service area and 10% received a donor with functional warm ischemia time (fWIT) >30 minutes.As Giorgakis et al comment, short ischemia times are important in DCD LT and fWIT seem to play an essential role. In our late DCD group, only one patient with fWIT >30 minutes, fWIT of 45 minutes, developed IC indicating that not all factors are mitigated by our protocol. It is worth mentioning that although concept of fWIT is clear to the transplant community, there is a lack of consensus on the level of oxygen saturation and/or systolic blood pressure used to define its beginning.While our institution, 2,6 King's, 7 and others 8,9 report outcomes in DCD LT comparable to Donation after Brain Death (DBD), DCD LT is still not perfect. In our report, the incidence of IC and hepatic artery thrombosis in late DCD group was significant high than in DBD group (3 vs. 0.5%, P < .05). Therefore, efforts should continue to investigate and improve DCD LT outcomes.We look forward to learning more from our colleagues across the Atlantic and propose a faculty exchange to variations in technique. DISCLOSUREThe authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. Keywordsclinical research/practice, donors and donation: donation after circulatory death (DCD), liver allograft function/dysfunction, liver transplantation/hepatology, organ procurement

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Optimization of Perioperative Conditions to Prevent Ischemic Cholangiopathy in Donation After Circulatory Death Donor Liver Transplantation

Abstract: Optimizing peritransplant conditions, such as shortening ischemic times with the use of thrombolytic donor flush, may prevent IC after DCD LT. With this approach, the DCD donor pool may be expanded.

Cited by 53 publications

References 31 publications

Heparin but not tissue plasminogen activator improves outcomes in donation after circulatory death liver transplantation in a porcine model

Heparin but not tissue plasminogen activator improves outcomes in donation after circulatory death liver transplantation in a porcine model

Donation after cardiac death in the hepatocellular carcinoma patient: Same indication?

Response to “Minimization of Ischemic Cholangiopathy in Donation After Cardiac Death Liver Transplantation: Is it Thrombolytic Therapy or Warm Ischemic Time Stringency and Donor Bile Duct Flush?”

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