Alpha A. (Berry) Fowler, III, MD

William Taliaferro Thompson Professor of Medicine,
Division of Pulmonary Disease and Critical Care Medicine
Department of Internal Medicine
Virginia Commonwealth University School of Medicine, Richmond, VA

 image of Dr. Alpha Fowler
Abstract: The incidence of sepsis and sepsis-associated organ failure continues to rise in American Intensive Care Units. Over 1 million cases of sepsis (i.e., bacterial, fungal, viral) occur in the U.S. population each year. Some 375,000 patients will die from sepsis either primarily from septic shock or secondarily from organ failure. Sepsis Induced organ failure contributes cumulatively to patient mortality. Patients with severe sepsis suffer higher mortality rates compared to patients with organ failure but no sepsis. Despite over 15,000 patients studied and over 1 billion dollars in study costs, effective sepsis therapy remains elusive. Clinical trials that have targeted mediators of inflammation or coagulation such as rosuvastatin or activated protein C have not reduced septic mortality, suggesting that single-target therapy fails to meet the challenges of complex multicellular activation and interactions. Recent studies suggest that ascorbic acid may attenuate pathological responses in septic microvasculature. In preclinical studies, ascorbic acid improved capillary blood flow, microvascular barrier function, and arteriolar responsiveness to vasoconstrictors in septic animals. We showed that parenterally administered ascorbic acid attenuated vascular lung injury in septic mice. Subnormal plasma ascorbic acid concentrations in septic patients correlates inversely with multiple organ failure and directly with survival. We report in this presentation that intravenous Vitamin C is safe to administer to patients with severe sepsis, that it improves sepsis induced organ failure and that it attenuates biomarkers of systemic inflammation and vascular injury. We also report aspects of the ongoing NIH-sponsored trial: Vitamin C Infusion for TReatment In Sepsis Induced Acute Lung Injury (CITRIS-ALI).