Antemortem Heparin in Organ Donation After Circulatory Death Determination: A Systematic Review of the Literature

Abstract

Donation after circulatory death determination frequently involves antemortem heparin administration to mitigate peri-arrest microvascular thrombosis. We systematically reviewed the literature to: (1) describe heparin administration practices and (2) explore the effects on transplant outcomes. We searched MEDLINE and EMBASE for studies reporting donation after circulatory death determination heparin practices including use, dosage, and timing (objective 1). To explore associations between antemortem heparin and transplant outcomes (objective 2), we (1) summarized within-study comparisons and (2) used meta-regression analyses to examine associations between proportions of donors that received heparin and transplant outcomes. We assessed risk of bias using the Newcastle Ottawa Scale and applied the GRADE methodology to determine certainty in the evidence. For objective 1, among 55 eligible studies, 48 reported heparin administration to at least some donors (range: 15.8%-100%) at variable doses (up to 1000 units/kg) and times relative to withdrawal of life-sustaining therapy. For objective 2, 7 studies that directly compared liver transplants with and without antemortem heparin reported lower rates of primary nonfunction, hepatic artery thrombosis, graft failure at 5 y, or recipient mortality (low certainty of evidence). In contrast, meta-regression analysis of 32 liver transplant studies detected no associations between the proportion of donors that received heparin and rates of early allograft dysfunction, primary nonfunction, hepatic artery thrombosis, biliary ischemia, graft failure, retransplantation, or patient survival (very low certainty of evidence). In conclusion, antemortem heparin practices vary substantially with an uncertain effect on transplant outcomes. Given the controversies surrounding antemortem heparin, clinical trials may be warranted.

Better liver transplant outcomes by donor interventions?

“…Authors observed more primary nonfunction (PNF) and inferior graft survival among livers recovered without antemortem heparin. In contrast, in a meta-regression analysis of 32 studies, no associations were detected between antemortem heparin and transplant outcomes, including early allograft dysfunction, PNF, hepatic artery thrombosis (HAT), ischemic type biliary lesions (ITBL), and patient and graft survival [63].…”

Developing Guidance for Donor Intervention Randomized Controlled Trials: Initial Discussions From the Canada-United Kingdom 2022 Workshop

“…Given the lack of robust evidence, there is potentially unwarranted consensus in the transplant community that many interventions (eg, heparin) improve recipient outcomes. 22 It is therefore unclear if equipoise exists―that is, whether there is honest, professional disagreement in the community of expert practitioners as to the preferred intervention. 23 Moreover, the nature of harm-benefit analysis differs between organ donor and recipient.…”

Decision-making About Premortem Interventions for Donation: Navigating Legal and Ethical Complexities

“…Some interventions (eg, systematic heparization, elective ventilation, and femoral cannulation) may pose a small risk of significant harm to some patients such as prolongation of life in an undesired state. 5,7 They may also risk causing distress or other psychosocial burdens for the families of some potential donors, for example, if use of PMIs necessitates changes to the location and timing of end-of-life care and especially if donation is ultimately unsuccessful despite the use of PMIs. There are also ethical concerns that some interventions might exceptionally hasten death.…”

“…There are also ethical concerns that some interventions might exceptionally hasten death. 7 However, PMIs may also provide significant benefits in preserving opportunities for successful donation of organs for transplantation. 5,8 Limitations of evidence regarding the risks and potential benefits of many PMIs have led to calls for more research evaluating these.…”