IV ASCORBATE REDUCTION OF ARDS MORTALITY IS CONTINGENT AND DOSE-DEPENDENT WITH THE DEGREE OF HYPEROXIC SUPPORT

Abstract

TYPE: Late Breaking Abstract TOPIC: Critical Care PURPOSE: Several randomized trials have failed to demonstrate a mortality benefit of high-dose intravenous ascorbate (vitamin C) in patients with sepsis. Recent ex-vivo human lung experiments have revealed that ascorbate acts directly on lung endothelium in hyperoxic conditions. We hypothesized that similar effects may have occurred in CITRIS-ALI trial patients, a double-blind randomized controlled trial of high-dose intravenous vitamin C in patients with ARDS. METHODS: CITRIS-ALI patients were classified, post-hoc, into three groups: Low, moderate, and severe hyperoxia based upon FiO2 < 50%, 50-80%, and ≥ 80% respectively. Logistic regression analysis was applied to evaluate the statistical interactions between hyperoxic groups and 28-day mortality and marginal analysis was performed. RESULTS: Severe hyperoxia support significantly interacted with vitamin C administration instead of placebo (p<0.001). Patients with mild hyperoxia had mortality 30% (95% CI 13.6–46.4%) and 42.4% (95% CI 25.6–59.3) for placebo and vitamin C arms respectively, p=0.3. Moderate hyperoxia groups exhibited mortality of 41.4% (95% CI 23.5 – 59.3%) and 26.7% (95% CI10.8–42.5) for placebo and vitamin C arms, p=0.2. The highest degree of hyperoxia group had mortality 74% (95% CI 56–92%) and 14.3% (95% CI 0–29.3%) for placebo and vitamin C arms, p<0.001. CONCLUSIONS: These findings suggest that high-dose intravenous vitamin C reduction of ARDS mortality is significantly linked to the degree of hyperoxia required for support, being most significant in patients who require the highest levels of hyperoxia. CLINICAL IMPLICATIONS: These findings explain the heterogeneity of outcomes in vitamin C sepsis trials in contrast to CITRIS-ALI and could guide the design of future clinical trials. DISCLOSURE: Nothing to declare. KEYWORD: Hyperoxia