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. 2020 Aug;20(8):2017-2025.
doi: 10.1111/ajt.15775. Epub 2020 Jan 27.

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

Alex Manara  1 , Sam D Shemie  2   3 , Stephen Large  4 , Andrew Healey  5   6 , Andrew Baker  7 , Mitesh Badiwala  8   9 , Marius Berman  4 , Andrew J Butler  10   11 , Prosanto Chaudhury  2   12 , John Dark  13 , John Forsythe  14 , Darren H Freed  15 , Dale Gardiner  16   17 , Dan Harvey  16   17 , Laura Hornby  3   18 , Janet MacLean  5 , Simon Messer  4 , Gabriel C Oniscu  19   20 , Christy Simpson  21 , Jeanne Teitelbaum  22 , Sylvia Torrance  3 , Lindsay C Wilson  3 , Christopher J E Watson  10   11
Affiliations

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

Alex Manara et al. Am J Transplant. 2020 Aug.

Abstract

There is international variability in the determination of death. Death in donation after circulatory death (DCD) can be defined by the permanent cessation of brain circulation. Post-mortem interventions that restore brain perfusion should be prohibited as they invalidate the diagnosis of death. Retrieval teams should develop protocols that ensure the continued absence of brain perfusion during DCD organ recovery. In situ normothermic regional perfusion (NRP) or restarting the heart in the donor's body may interrupt the permanent cessation of brain perfusion because, theoretically, collateral circulations may restore it. We propose refinements to current protocols to monitor and exclude brain reperfusion during in situ NRP. In abdominal NRP, complete occlusion of the descending aorta prevents brain perfusion in most cases. Inserting a cannula in the ascending aorta identifies inadequate occlusion of the descending aorta or any collateral flow and diverts flow away from the brain. In thoracoabdominal NRP opening the aortic arch vessels to atmosphere allows collateral flow to be diverted away from the brain, maintaining the permanence standard for death and respecting the dead donor rule. We propose that these hypotheses are correct when using techniques that simultaneously occlude the descending aorta and open the aortic arch vessels to atmosphere.

Keywords: donors and donation: donation after circulatory death (DCD); editorial/personal viewpoint; ethics; extracorporeal membrane oxygenation (ECMO); organ perfusion and preservation; organ procurement; organ procurement and allocation.

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Conflict of interest statement

The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Dr Healey reports a stipend income from Trillium Gift of Life Network as Chief Medical Officer‐Donation, outside the submitted work. Dr Large reports a patent Covering mOrgan2 organ perfuser. Dr Shemie reports being the Medical Advisor for deceased organ donation, Canadian Blood Services. Dr Messer reports proctoring fees from TransMedics, outside the submitted work. Dr Freed reports being founder and CSO for Tevosol, Inc, outside the submitted work. Dr Forsythe reports personal fees from NHS Blood and Transplant, during the conduct of the study. Ms Hornby reports personal fees from Canadian Blood Services, outside the submitted work. Dr Oniscu reports nonfinancial support from Maquet, grants from NHS Blood and Transplant, during the conduct of the study. The other authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
A, Potential collateral circulations A to D that could theoretically restore flow and/or perfusion to the brain. B, Proposed solution of flow diversion away from the brain by occluding the descending thoracic aorta and draining the aortic arch arteries to atmosphere either by inserting a large bore cannula into the ascending aorta or draining the arch arteries individually. Any potential collateral flow to the brain should be preferentially diverted to the low resistance large bore subclavian vessels open to atmospheric pressure
Figure 2
Figure 2
Proposed refinements to normothermic regional perfusion (NRP) techniques. A, Abdominal NRP. The procedure has been used in 12 donors with occlusion of the descending thoracic aorta and a large cannula in the ascending aorta. Delivery of oxygenated blood into the aorta rather than the iliac vessels excludes the possible collateral circulation between the inferior epigastric and internal thoracic arteries (collateral circulation B in Figure 1A). B, Direct (hypothermic) procurement and perfusion (DPP) with abdominal‐normothermic regional perfusion (A‐NRP). During the dissection, Stage 1, the descending thoracic aorta is occluded, a double lumen cannula inserted into the ascending aorta and left open to atmosphere, and A‐NRP commenced. In Stage 2 cardioplegia is administered rapidly before explantation of the heart by temporarily placing a clamp on the ascending aorta cephalad to double lumen cannula. After explantation of the heart, Stage 3, the ascending aortic clamp is repositioned proximal to the double lumen cannula to open the aortic arch vessels to atmosphere for the duration of A‐NRP. C, Thoraco‐abdominal NRP. The cephalad ends of each of the aortic arch vessels are cannulated and any drained blood returned to the venous reservoir for retransfusion
Figure 3
Figure 3
A, Abdominal normothermic regional perfusion (NRP). The descending aorta is clamped. Note the minimal pressure in the ascending aortic cannula that is open to atmosphere. (Image reproduced with the kind permission of the donor's family.) B, Double lumen cannula used in direct (hypothermic) procurement and perfusion (DPP) with abdominal‐normothermic regional perfusion (A‐NRP) to open the ascending aorta to atmosphere and allow the administration of cardioplegia before explantation of the heart. C, Intraoperative thoracoabdominal‐normothermic regional perfusion (TA‐NRP). 7Fr. cannula are inserted into the arch vessels and connected to hard‐shell reservoir during NRP. X ‐ brachiocephalic artery, Y – left carotid. Z – left subclavian artery arch vessels are ligated at origin, and second tie securing the cannula
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References

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