Amelioration of respiratory and circulatory changes in established endotoxic shock by ketoprofen

In an intensive-care setting we studied the effects of ketoprofen, a dual inhibitor of cyclooxygenase and lipoxygenase, on circulatory and respiratory changes during established endotoxic shock in sheep. Two groups (n = 7 in each) were exposed to E. coli endotoxin, which caused a sharp increase in pulmonary artery pressure (200%; PAP), intrapulmonary shunt fraction (300%; QS/QT%), and oxygen extraction ratio (50%; VO2/DO2%). There was also a significant decrease in mean arterial pressure (25%; MAP), respiratory compliance (60%; CT), arterial oxygen tension (65%; PaO2), and oxygen delivery index (15%; DO2) in both groups. After 30 min of endotoxin infusion, group K received ketoprofen, 2.5 mg/kg b.w. i.v., while group E served as shock controls. After 4 h there had been a significant improvement in MAP, PaO2, DO2, QS/QT%, and CT in the ketoprofen-treated group compared with the controls (P < 0.01). In addition, the oxygen extraction ratio normalised in group K, but remained 70-100% increased in group E (P < 0.01). The wet-to-dry weight ratios of the lungs and the liver were significantly lower in the ketoprofen-treated group compared with the controls (P < 0.05). It was concluded that ketoprofen significantly ameliorated the respiratory and circulatory effects of established endotoxic shock in sheep.