Association of peri-reperfusion oxygen exposure and early allograft dysfunction after deceased donor orthotopic liver transplantation: a retrospective cohort study

Abstract

Hepatic insufficiency within a week of orthotopic liver transplantation (OLT), termed early allograft dysfunction (EAD), occurs in 20–25% of deceased donor OLT recipients and carries substantial morbidity and mortality. Ischemia reperfusion injury, in which reperfusion after ischemia provokes oxidative stress and inflammation, underlies EAD. We hypothesized higher peri-reperfusion oxygen exposure is associated with EAD. We conducted a retrospective single-center cohort study of 963 primary adult deceased-donor static cold storage OLT recipients, January 2014 to May 2022. The primary outcome was EAD (serum bilirubin, international normalized ratio, and aminotransferases). Peri-reperfusion oxygen exposure was assessed by median partial pressure of arterial oxygen (PaO 2 ) from 30 min before to 2 h after reperfusion. PaO 2 was examined continuously, and a data-derived dichotomized cutpoint was sought. Associations were evaluated by logistic regression adjusted for donor age, total ischemia time, recipient body mass index, alcohol-associated liver disease, and metabolic dysfunction-associated steatohepatitis, with missing data handled by multiple imputation. Sensitivity analyses addressed exposure timing, anesthesiologist inspired-oxygen preference, and early lactate clearance. EAD occurred in 199 of 963 recipients (21%). Modeled continuously, higher PaO 2 was associated with EAD after adjustment (adjusted OR 1.16 per 50 mmHg [95% CI 1.01–1.34]). The complete-case estimate was nearly identical but less precise (1.14 [95% CI 0.97–1.34]), with no detected departure from linearity ( p = 0.28, multiple imputation). The association could not be localized to the pre- or post-reperfusion window. The estimate changed little after adjusting for early lactate clearance, and the association remained evident within the low-inspired-oxygen stratum; the high-inspired-oxygen stratum was uninformative owing to limited exposure contrast. No cutpoint could be identified across the 205 candidate thresholds searched (complete cases; global p = 0.18). Higher peri-reperfusion PaO 2 was associated with EAD after adjustment; the association could not be statistically localized to the pre- or post-reperfusion window. Whether this reflects a modifiable causal factor, a marker of early graft dysfunction, or both remains uncertain. External validation and prospective trials are needed to determine whether conservative oxygen management reduces EAD risk.