This proposal is part of a career development plan integrating didactics in the form of a Master's Degree in Clinical Investigation with direct, mentored experience in the design and conduct of randomized clinical trials. Expertise in these areas will provide the necessary components for a successful career in patient-oriented critical care research. The Center for Lung Research at Vanderbilt University has focused substantial efforts toward the understanding of fluid and solute exchange in the injured lung, both in the pre-clinical arena and in prospective, randomized clinical trials. The mentors and consulting faculty in this environment are well recognized, established senior investigators in critical care research with vast pre-clinical and clinical experience. ARDS is defined by acute impairment of oxygenation and radiographic infiltrates compatible with pulmonary edema without increased hydrostatic pressures. It affects approximately 15,0000 people per year in the United States, with mortality approaching 50% and a financial burden estimated to exceed $5 billion. Fluid overload, weight gain, and hyperproteinemia are associated with increased mortality in patients with ARDS. Reduced oncotic pressure gradients related to hypoproteinemia may contribute to generation and maintenance of pulmonary edema in this condition. Previous trials have demonstrated clinical benefits associated with albumin and diuretic therapy in patients with ARDS, through the mechanisms by which these improvements occur is unclear. It is hypothesized that these benefits occur through increases in the oncotic pressure gradient and reductions in extravascular lung water, through the exact mechanism is unknown. The purpose of this project is to elucidate the pulmonary and hemodynamic effects of colloid and diuretic therapy in patients with ARDS using recently developed technology, which permits simple and accurate measurement of systemic hemodynamics and extravascular lung water in critically ill patients. This investigational proposes a critical trial randomizing hypoproteinemic ARDS patients to albumin and furosemide or dual placebo with targeted goals of diuresis and weight loss. Therapeutic effects on respiratory function, extravascular lung water, oncotic pressure, alveolar fluid clearance, and systemic hemodynamics will be characterized. This trial could advance our understanding of factors affecting fluid balance in patients with ARDS and has the potential to change clinical practice standards.
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