Effects of ketoprofen on respiratory and circulatory changes in endotoxic shock

To study the effects of ketoprofen, a dual inhibitor of the arachidonic acid metabolism, on hemodynamic and respiratory changes during endotoxic shock.

Prospective, randomised, controlled study using an established intact animal model of endotoxic shock in sheep.

An animal laboratory in a university hospital.

4 groups were studied (n = 7 in each). Group K received ketoprofen and group A received aspirin 30 min before start of endotoxin infusion. Group E received endotoxin, but no drug treatment. Group C received neither endotoxin nor drug treatment. All the animals were anaesthetised with ketamine, had controlled ventilation with FiO2 = 0.5 and received Ringer's lactate at an infusion rate that would keep the pulmonary capillary wedge pressure constant.

Both ketoprofen and aspirin prevented the early rise in pulmonary arterial pressure that occurred in group E a few minutes after start of i.v. infusion of endotoxin. Furthermore, ketoprofen prevented any significant changes in arterial blood pressure, arterial oxygen tension, oxygen delivery index, oxygen extraction ratio, respiratory compliance, intrapulmonary shunt fraction, and platelet counts that occurred in group E. Aspirin, on the other hand, provided only partial and time limited (1-2 h) protection against these changes. Wet-to-dry weight ratios of the lungs were significantly lower in the ketoprofen treated than in the untreated shock controls and the aspirin treated animals.

Ketoprofen completely prevented the changes in hemodynamics and respiratory function observed in control-endotoxin-treated animals.