A randomized trial of ascorbic acid for the prevention of post-reperfusion syndrome during liver transplantation

Abstract

Background: Post-reperfusion syndrome (PRS) is a critical hemodynamic complication during liver transplantation, characterized by a significant drop in mean arterial pressure and associated with increased morbidity and mortality, systemic inflammation, and ischemia-reperfusion injury. Ascorbic acid (AA), with its antioxidant and anti-inflammatory properties, has been proposed as a potential therapeutic intervention.

Methods: A single-center, double-blind, randomized controlled trial was conducted at the Hospital Universitario Ramón y Cajal, Madrid. Patients undergoing liver transplantation were randomly assigned to receive either 1500 mg of intravenous AA during the anhepatic phase (vitamin C-treated group) or 0.9% saline as a placebo (control group). The primary endpoint was PRS incidence. The secondary outcomes included inflammatory cytokine levels, postoperative renal function, and patient/graft survival.

Results: Thirty-nine patients were randomized (20 controls and 19 AA-treated patients). The incidence of PRS was 30% in the control group and 10.5% in the AA group (p=0.235). Postoperative renal failure occurred more frequently in the AA group (68.4%) than in the control group (35%) (p=0.037). Four AA-treated patients (21.1%) required re-transplantation. No significant differences in cytokine levels were observed between the groups, although increases in IL-6, IL-8, and IL-10 levels were noted in patients with PRS, suggesting a stronger inflammatory response.

Conclusions: AA supplementation demonstrated a noticeable trend toward reducing PRS during liver transplantation, although this was not statistically significant. An increase in renal failure and the need for re-transplantation were observed in the AA-treated group. Although the study suggests potential benefits, its small sample size limits the conclusions, pointing to the need for larger multicenter trials to determine the optimal dosage and timing.

Keywords: acute kidney injury; cytokine response; hemodynamic instability; oxidative stress; vitamin C therapeutic use.

FIGURE 1

CONSORT (Consolidated Standards of Reporting Trials) flow diagram of study enrollment and randomization.