Sepsis syndrome occurs in 250,000 to 500,000 patients per year with approximately 1/3 of these patients developing Adult Respiratory Distress Syndrome (ARDS) and other organ failures. ARDS is a multifactorial disorder, and is the most common organ failure occurring secondary to sepsis syndrome. Extensive studies utilizing the sheep endotoxin model of ARDS as well as data from human pilot studies suggests that cyclooxygenase inhibitors (ibuprofen, in particular) would be useful in the prevention and reversal of many of the pathophysiological abnormalities related to sepsis. Animal studies in which ibuprofen treatment is given prior to endotoxin have shown that ibuprofen can improve the pathologic alterations in oxygenation, pulmonary and systemic hemodynamics, airway mechanics, and lung lymph flow. Importantly, animal studies have also shown that established airway mechanics abnormalities, pulmonary hypertension, and shock can be reversed by ibuprofen even when given several hours after endotoxin is administered, a time frame consistent with the realities of clinical research and medical therapy. Pilot studies of ibuprofen in patients with sepsis syndrome show that temperature, heart rate and lung mechanics are significantly improved, and suggest that shock is reversed. The physiologic abnormalities are temporally related to changes in prostaglandin concentrations in urine and plasma. We propose to conduct a multicenter randomized prospective double-blind trial of ibuprofen in patients with sepsis syndrome to determine the effect on mortality, shock development and reversal, ARDS development and reversal, gas exchange, airway mechanics, and pulmonary and systemic hemodynamics.
Showing the most recent 10 out of 19 publications
