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Randomized Controlled Trial
. 2022 Dec;15(12):2918-2927.
doi: 10.1111/cts.13409. Epub 2022 Oct 17.

Controlled oxygenated rewarming as novel end-ischemic therapy for cold stored liver grafts. A randomized controlled trial

Thomas Minor  1 , Charlotte von Horn  1 , Hristo Zlatev  1 , Fuat Saner  2 , Melanie Grawe  1 , Bastian Lüer  1 , Eva-Maria Huessler  3 , Nils Kuklik  3   4 , Andreas Paul  2
Affiliations
Randomized Controlled Trial

Controlled oxygenated rewarming as novel end-ischemic therapy for cold stored liver grafts. A randomized controlled trial

Thomas Minor et al. Clin Transl Sci. 2022 Dec.

Abstract

Abrupt return to normothermia has been shown a genuine factor contributing to graft dysfunction after transplantation. This study tested the concept to mitigate reperfusion injury of liver grafts by gentle warming-up using ex vivo machine perfusion prior to reperfusion. In a single center randomized controlled study, livers were assigned to conventional static cold storage (SCS) alone or to SCS followed by 90 min of ex vivo machine perfusion including controlled oxygenated rewarming (COR) by gentle and protracted elevation of the perfusate temperature from 10°C to 20°C. Primary outcome mean peak aspartate aminotransferase (AST) was 1371 U/L (SD 2871) after SCS versus 767 U/L (SD 1157) after COR (p = 0.273). Liver function test (LiMAx) on postoperative day 1 yielded 187 μg/kg/h (SD 121) after SCS, but rose to 294 μg/kg/h (SD 106) after COR (p = 0.006). Likewise, hepatic synthesis of coagulation factor V was significantly accelerated in the COR group immediately after transplantation (103% [SD 34] vs. 66% [SD 26]; p = 0.001). Fewer severe complications (Clavien-Dindo grade ≥3b) were reported in the COR group (8) than in the SCS group (15). Rewarming/reperfusion injury of liver grafts can be safely and effectively mitigated by controlling of the rewarming kinetics prior to blood reperfusion using end-ischemic ex vivo machine perfusion after cold storage.

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Conflict of interest statement

The authors declared no competing interests for this work.

Figures

FIGURE 1
FIGURE 1
Consolidated Standards of Reporting Trials (CONSORT) diagram illustrating the study enrollment. COR, controlled oxygenated rewarming; SCS, static cold storage
FIGURE 2
FIGURE 2
Time courses of temperature (solid line) and total liver flow during controlled oxygenated rewarming perfusion prior to transplantation
FIGURE 3
FIGURE 3
Postoperative recovery liver function after controlled oxygenated rewarming (COR) and after static cold storage (SCS). Left: Liver function test (LiMAx) on postoperative day 1 (*: p < 0.05 Mann–Whitney U test). Right: Recovery of serum activity of coagulation factor V during the first 3 days after transplantation *: p < 0.05 (area under the curve [AUC] Mann–Whitney U test). Tx, transplantation
See this image and copyright information in PMC

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