Navigating Uncertainty: Characterizing Rebound Lactic Acidosis in Pediatric Normothermic Machine Perfusion

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Abstract
Background: Normothermic machine perfusion (NMP) is an emerging strategy for pediatric liver transplantation, but pediatric‐specific viability criteria remain undefined. Lactate clearance, extrapolated from adult protocols, is a central marker of allograft function. In our pediatric NMP (pNMP) experience, we observed a novel pattern: initial clearance followed by secondary rise, termed rebound lactic acidosis. Methods: We retrospectively reviewed pediatric liver allografts preserved on the TransMedics Organ Care System at two centers (January 2025 through June 2026). After excluding donors > 35 kg, 18 perfusions (17 transplants) were classified as rebound lactic acidosis (lactate rise > 0.5 mmol/L after initial clearance) or sustained clearance. Rebound cases were characterized by lactate kinetics, perfusion parameters, acid–base status, bile production, histology, and recipient outcomes. Results: Six allografts demonstrated rebound, with onset 1.0–6.6 h into perfusion. All sustained bile production throughout perfusion. Circuit alkalosis temporally correlated with rebound in three cases and improved with gas flow reduction. The first allograft was discarded; the remaining five were transplanted, including one perfused for 35.5 h. Recipients had elevated POD1 transaminases and INR that normalized by POD7; three are discharged home and two remain hospitalized, all with functioning allografts (follow‐up up to 312 days). Conclusions: Rebound lactic acidosis during pNMP may not indicate allograft nonviability and may be ameliorated by modifying circuit perfusion or pH. Lactate kinetics should be interpreted within a multiparametric viability framework incorporating perfusion adequacy, acid–base status, bile production, liver function, and histology. Pediatric‐specific criteria are needed to safely expand the donor pool.

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