Dr. Teja’s Research

Fludrocortisone in acute respiratory failure with airspace disease

Abstract: Acute hypoxemic respiratory failure (AHRF) affects over 90 million people worldwide each year, with mortality rates up to 30-50%.  AHRF encompasses pneumosepsis and acute respiratory distress syndrome and is characterized by abnormal response to infection, trauma or other disease processes resulting in immune and endothelial dysregulation, pulmonary edema and life-threatening respiratory failure. Evidence suggests that steroids may be useful in AHRF, but the optimal choice of steroid in pulmonary critical care is controversial. The mineralocorticoid fludrocortisone has anti-inflammatory properties distinct from those induced by glucocorticoids, including modulation of inflammation in the lung, improved tissue perfusion, and alveolar fluid clearance by pulmonary epithelial cells. Despite accumulating evidence of efficacy in combination with hydrocortisone in sepsis, fludrocortisone has never been tested without hydrocortisone, and has never been examined in AHRF specifically. This study hypothesizes that fludrocortisone will improve outcomes in patients with AHRF and airspace disease. To provide sufficient power to demonstrate clinical effect, the PI will take an innovative approach and capitalize on established connections with critical care colleagues to enroll on three adaptive trial platforms simultaneously, with two primary aims: Aim 1 will conduct a pilot randomized controlled trial to test the feasibility of randomizing at several sites on three adaptive trial platforms simultaneously, and inform the design of a larger study on fludrocortisone in AHRF.  AIM 2 will gather feasibility data for patients with AHRF treated with fludrocortisone with which to apply for funding for a large definitive trial.  This novel study approach has application to trials in critical care beyond this research question. It will also guide development of new evidence-based guidelines for treatment of patients with AHRF, with the potential to save many thousands of lives in North America each year.