Hypoproteinemia predicts acute respiratory distress syndrome development, weight gain, and death in patients with sepsis

Objective: Starling's equation indicates that reduced oncotic pressure grad ients will favor edema formation, and the current consensus definition of a cute respiratory distress syndrome (ARDS) excludes only the hydrostatic pre ssure contribution. We hypothesized that low serum total protein levels mig ht correlate with the likelihood of ARDS in at-risk patients because serum total protein is the chief determinant of oncotic pressure in humans. Design: Regression analysis to compare outcomes in patients with low serum total protein levels with outcomes in patients with normal serum total prot ein levels with respect to weight change, development of ARDS, and mortalit y. Setting: Intensive care units (ICUs) of seven clinical centers in North Ame rica. Patients: A total of 455 ICU patients who met consensus criteria for severe sepsis (178 of whom developed ARDS) from a recently completed prospective clinical trial. Intervention: None. Measurements and Main Results:We found that 92% of the patients developing ARDS had low or borderline serum total protein levels (<6 g/dL). Logistic a nd multiple regression analyses confirmed that of 18 clinical variables, in itial serum total protein level and protein change over time were the most statistically significant predictors of weight gain, prolonged mechanical v entilation, ARDS development, and mortality in the study population. This c orrelation remained significant after adjustment for the other major predic tors of outcome present at baseline tie, Acute Physiology and Chronic Healt h Evaluation II score). Conclusions: Hypoproteinemia is significantly correlated with fluid retenti on and weight gain, development of ARDS and poor respiratory outcome, and m ortality in patients with sepsis, Prospective, randomized trials of serum p rotein manipulation are needed to establish whether there is a cause-effect relationship to this association.