Ibuprofen reduces the progression of permeability edema in an animal model of hyperdynamic sepsis

Since severity of acute lung injury (ALI) is reduced by pretreatment with non-steroidal agents, we hypothesized that ibuprofen would ameliorate ALI when administered after the onset of septic lung injury. Twenty-four hours after cecal ligation and perforation (CLP) in 23 sheep during a 4 h study period (period S), pulmonary lymph flow (QL) increased 16.2 +/- 12.1 ml/min (P less than 0.01) from base line, whereas lymph-to-plasma total protein concentration ratios (L/P]TP) remained unchanged. During the subsequent 24 h of study (period D), 10 sheep received parenteral ibuprofen, 12.5 mg/kg every 6 h, and 13 sheep served as untreated septic controls. Throughout period D, a progressive increase in QL (16.2 +/- 16.3 ml/60 min) from period S was greater in the untreated than in the ibuprofen (2.5 +/- 9.0 ml/60 min, P less than 0.02) group. Between base line and period D, increase in lung wet-to-dry weight ratios was greater in the untreated group than in the ibuprofen group (P less than 0.05). Concurrently mean pulmonary arterial pressure increased 4.7 +/- 7.3 mmHg in the untreated group (P less than 0.05) during period D vs. 0.0 +/- 5.2 mmHg in the ibuprofen group (NS). When administered after septic ALI had been established by CLP, ibuprofen reduced an otherwise progressive increase in both fluid flux and extravascular lung water.