BACKGROUND: In patients with sepsis the production of arachidonic acid metabolites by cyclooxygenase increases, but the pathophysiologic role of these prostaglandins is unclear. In animal models, inhibition of cyclooxygenase by treatment with ibuprofen before the onset of sepsis reduces physiologic abnormalities and improves survival. In pilot studies of patients with sepsis, treatment with ibuprofen led to improvements in gas exchange and airway mechanics. METHODS: From October 1989 to March 1995, we conducted a randomized, double-blind, placebo-controlled trial of intravenous ibuprofen (10 mg per kilogram of body weight [maximal dose, 800 mg], given every six hours for eight doses) in 455 patients who had sepsis, defined as fever, tachycardia, tachypnea, and acute failure of at least one organ system. RESULTS: In the ibuprofen group, but not the placebo group, there were significant declines in urinary levels of prostacyclin and thromboxane, temperature, heart rate, oxygen consumption, and lactic acidosis. With ibuprofen therapy there was no increased incidence of renal dysfunction, gastrointestinal bleeding, or other adverse events. However, treatment with ibuprofen did not reduce the incidence or duration of shock or the acute respiratory distress syndrome and did not significantly improve the rate of survival at 30 days (mortality, 37 percent with ibuprofen vs 40 percent with placebo). CONCLUSIONS: In patients with sepsis, treatment with ibuprofen reduces levels of prostacyclin and thromboxane and decreases fever, tachycardia, oxygen consumption, and lactic acidosis, but it does not prevent the development of shock or the acute respiratory distress syndrome and does not improve survival.
RCT Entities:
BACKGROUND: In patients with sepsis the production of arachidonic acid metabolites by cyclooxygenase increases, but the pathophysiologic role of these prostaglandins is unclear. In animal models, inhibition of cyclooxygenase by treatment with ibuprofen before the onset of sepsis reduces physiologic abnormalities and improves survival. In pilot studies of patients with sepsis, treatment with ibuprofen led to improvements in gas exchange and airway mechanics. METHODS: From October 1989 to March 1995, we conducted a randomized, double-blind, placebo-controlled trial of intravenous ibuprofen (10 mg per kilogram of body weight [maximal dose, 800 mg], given every six hours for eight doses) in 455 patients who had sepsis, defined as fever, tachycardia, tachypnea, and acute failure of at least one organ system. RESULTS: In the ibuprofen group, but not the placebo group, there were significant declines in urinary levels of prostacyclin and thromboxane, temperature, heart rate, oxygen consumption, and lactic acidosis. With ibuprofen therapy there was no increased incidence of renal dysfunction, gastrointestinal bleeding, or other adverse events. However, treatment with ibuprofen did not reduce the incidence or duration of shock or the acute respiratory distress syndrome and did not significantly improve the rate of survival at 30 days (mortality, 37 percent with ibuprofen vs 40 percent with placebo). CONCLUSIONS: In patients with sepsis, treatment with ibuprofen reduces levels of prostacyclin and thromboxane and decreases fever, tachycardia, oxygen consumption, and lactic acidosis, but it does not prevent the development of shock or the acute respiratory distress syndrome and does not improve survival.
Authors: Anne B Lipke; Gustavo Matute-Bello; Raquel Herrero; Venus A Wong; Stephen M Mongovin; Thomas R Martin Journal: Am J Physiol Lung Cell Mol Physiol Date: 2011-04-22 Impact factor: 5.464
Authors: Paul Jeffrey Young; Manoj Saxena; Richard Beasley; Rinaldo Bellomo; Michael Bailey; David Pilcher; Simon Finfer; David Harrison; John Myburgh; Kathryn Rowan Journal: Intensive Care Med Date: 2012-01-31 Impact factor: 17.440
Authors: Laura E Fredenburgh; Margarita M Suárez Velandia; Jun Ma; Torsten Olszak; Manuela Cernadas; Joshua A Englert; Su Wol Chung; Xiaoli Liu; Cynthia Begay; Robert F Padera; Richard S Blumberg; Stephen R Walsh; Rebecca M Baron; Mark A Perrella Journal: J Immunol Date: 2011-10-03 Impact factor: 5.422
Authors: Andrew J Paris; Yuhong Liu; Junjie Mei; Ning Dai; Lei Guo; Lynn A Spruce; Kristin M Hudock; Jacob S Brenner; William J Zacharias; Hankun D Mei; April R Slamowitz; Kartik Bhamidipati; Michael F Beers; Steven H Seeholzer; Edward E Morrisey; G Scott Worthen Journal: Am J Physiol Lung Cell Mol Physiol Date: 2016-09-30 Impact factor: 5.464