Fluid therapy is one of the most common daily interventions in the ICU. Competing fluid goals are common in critically ill patients, and optimal fluid management may not only improve physiology but also improve relevant clinical outcomes. Greg Martin, MD and collaborators at Vanderbilt University and Wake Forest University have conducted three seminal clinical studies in this area: one observational cohort study and two interventional clinical trials. These studies have suggested significant benefits for improving oxygenation and potentially for shortening the duration of mechanical ventilation for hypo-oncotic patients with acute lung injury (ALI). The results may be summarized as follows:
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In a retrospective cohort study of 455 severe sepsis patients at risk for ALI, reductions in oncotic pressure were highly and independently predictive of the development of ALI and subsequent adverse clinical outcomes (prolonged mechanical ventilation, greater mortality).
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In a randomized, controlled clinical trial of 37 hypo-oncotic patients with ALI, treatment with a combination of albumin and furosemide improved oxygenation and hemodynamic stability compared to dual placebo.
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In a randomized, controlled clinical trial of 40 hypo-oncotic patients with ALI, treatment with a combination of albumin and furosemide improved oxygenation and hemodynamic stability compared to placebo plus furosemide (diuretic monotherapy).
Further analyses from these studies reveal two important findings. The first is that changes in oxygenation were not well predicted by clinical measures of oncotic pressure or fluid balance (i.e. diuretic effects), but they were statistically associated with albumin dosage. Second, additional laboratory studies confirmed an important biological effect of albumin as a thiol donor that altered systemic antioxidant balance in critically ill patients with ALI.
To further understand the role of colloids in optimally managing fluid balance in ALI patients, we have a current trial, Phase III Study Comparing Albumin and Hetastarch Therapy in Acute Lung Injury (also known as “Cardiopulmonary Evaluation of Albumin and Starch Effects in ALI” and as NCT00796419 in ClinicalTrials.gov) that is currently enrolling hypo-oncotic patients with ALI to determine: (1) the comparative effect on oxygenation of albumin vs. hetastarch treatment, (2) the physiological effects on pulmonary edema (“extravascular lung water”) of treatment with albumin vs. hetastarch, (3) the pulmonary and systemic antioxidant effects of albumin and hetastarch therapy and their associations with clinical outcomes, and (4) relevant clinical outcomes comparing albumin and hetastarch therapy, including ventilator-free days, ICU length of stay and 30 day and 180 day subject survival.