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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZHL1-CSR-F (O1))
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Colombini-Hatch, Sandra
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Emory University
Internal Medicine/Medicine
Schools of Medicine
United States
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Martin, Greg S (2014) State-of-the-art fluid management in critically ill patients. Curr Opin Crit Care 20:359
Polito, C; Martin, G S (2013) Albumin: physiologic and clinical effects on lung function. Minerva Anestesiol 79:1180-6
Park, Youngja; Jones, Dean P; Ziegler, Thomas R et al. (2011) Metabolic effects of albumin therapy in acute lung injury measured by proton nuclear magnetic resonance spectroscopy of plasma: a pilot study. Crit Care Med 39:2308-13
Berkowitz, David M; Danai, Pajman A; Eaton, Stephanie et al. (2009) Alcohol abuse enhances pulmonary edema in acute respiratory distress syndrome. Alcohol Clin Exp Res 33:1690-6
Esper, Annette M; Moss, Marc; Martin, Greg S (2009) The effect of diabetes mellitus on organ dysfunction with sepsis: an epidemiological study. Crit Care 13:R18
Berkowitz, David M; Danai, Pajman A; Eaton, Stephanie et al. (2008) Accurate characterization of extravascular lung water in acute respiratory distress syndrome. Crit Care Med 36:1803-9
Danai, Pajman A; Sinha, Sumita; Moss, Marc et al. (2007) Seasonal variation in the epidemiology of sepsis. Crit Care Med 35:410-5
Esper, Annette M; Moss, Marc; Lewis, Charmaine A et al. (2006) The role of infection and comorbidity: Factors that influence disparities in sepsis. Crit Care Med 34:2576-82
Martin, Greg S; Mannino, David M; Moss, Marc (2006) The effect of age on the development and outcome of adult sepsis. Crit Care Med 34:15-21
Slynkova, Katarina; Mannino, David M; Martin, Greg S et al. (2006) The role of body mass index and diabetes in the development of acute organ failure and subsequent mortality in an observational cohort. Crit Care 10:R137

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