Cortisol deficiency in metomidate anesthetized bacteremic pigs: results in circulatory failure — beneficial effect of cortisol substitution

Etomidate and the closely related metomidate are known to inhibit cortisol synthesis. We studied the influence of metomidate on hemodynamic performance and survival time of bacteremic pigs. Thirty pigs, 30.2 +/- 0.8 kg, were anesthetized with intravenous metomidate (2.5 mg.kg-1.h-1) plus ketamine (3.0 mg.kg-1.h-1), and were then mechanically ventilated. The animals were randomly allocated to three groups of 10 pigs each. Group A received an infusion of live Pseudomonas aeruginosa bacteria (2.5.10(9).kg-1.h-1 organisms until death), Group B additionally received a bolus of 1 mg.kg-1 cortisol (followed by an infusion of 0.1 mg.kg-1.h-1) starting 1 h prior to the bacterial infusion, and Group C served as anesthesia control without receiving bacteria or cortisol. The experiments in Group C were terminated after 10 h. In Group A the cortisol level was severely suppressed from the very beginning. The animals died of circulatory failure after 4.3 +/- 0.4 h. In contrast, Group B exhibited fairly stable hemodynamics, but the animals died due to pulmonary edema after 11.1 +/- 1.3 h. Cortisol deficiency in metomidate anesthetized pigs facilitates the development of circulatory failure in the course of Pseudomonas bacteremia, which does not occur if cortisol is infused to reconstitute a physiological level. However, this cortisol substitution did not prevent the development of pulmonary edema caused by Pseudomonas aeruginosa. Possible mechanisms of the deleterious effect of cortisol deficiency and implications in regard to the clinical use of metomidate/etomidate are discussed.