Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome

Fowler III, Alpha A; Kim, Christin; Lepler, Lawrence; Malhotra, Rajiv; Debesa, Orlando; Natarajan, Ramesh; Fisher, Bernard J; Syed, Aamer; DeWilde, Christine; Priday, Anna; Kasirajan, Vigneshwar

ive course as described by Burnham et al [12] . Karhu et al [13] and Choi et al [14] recently reported finding rhinovirus as the etiology of severe community acquired pneumonia and respiratory failure in mechanically ventilated adults who had a proven viral etiology of respiratory failure. We report here the first application of high dose intravenous vitamin C employed as an interventional drug treatment for virus-induced ARDS. Very few studies in critically ill patients with ARDS have reported the use of intravenous vitamin C. The use of vitamin C to treat lung injury is still investigational. Nathens et al [15] infused ascorbic acid at 1 g every 8 h combined with oral vitamin E for 28 d in 594 surgically critically ill patients and found a significantly lower incidence of acute lung injury and multiple organ failure. Tanaka et al [16] infused ascorbic acid continuously at 66 mg/kg per hour for the first 24 h in patients with greater than 50% surface area burns and showed significantly reduced burn capillary permeability. A single report (published as abstract only) of a clinical study of large intravenous doses of ascorbic acid, and other antioxidants (tocopherol, N-acetyl-cysteine, selenium), in patients with established ARDS showed reduction in mortality of 50% [17] . Clinical protocols currently in use for hospitalized septic patients fail to normalize ascorbic acid levels. Vitamin C dosages utilized in the treatment of the patient we describe in this case report arose from our previous human studies, infusing high dose intravenous vitamin C into critically ill patients with severe sepsis [18] and in our preclinical studies [19] [20] [21] . Our work thus far shows vitamin C to exert potent "pleotropic effects" when used as described in this report. We showed that septic patients receiving high dose intravenous vitamin C exhibit significant reduction in multiple organ injury and reduced inflammatory biomarker levels [18] . Our preclinical work in septic lunginjured animals shows that vitamin C down-regulates pro-inflammatory genes that are driven by transcription factor NF-κB. Furthermore, vitamin C significantly increases alveolar fluid clearance in septic lung-injured animals [21] . Finally, infused vitamin C's capability to downregulate liberated reactive oxygen and nitrogen species appears to be critical for attenuating lung injury [22] .