Counteraction of early circulatory derangement by administration of low dose steroid treatment at the onset of established endotoxemic shock is not directly mediated by TNF-α and IL-6

摘要

Background: Once a septic condition is progressing, administration of steroids in the pro-inflammatory phase of septic shock ought to yield maximal effect on the subsequent, devastating inflammatory response. Recently, a retrospective study showed that early initiation of corticosteroid therapy improved survival in septic shock. We aimed to prospectively evaluate effects of early administrated hydrocortisone therapy on physiologic variables in a porcine model of septic shock. Experiment: Eight anesthetized pigs were given a continuous infusion of endotoxin during this 6 h prospective, randomized, parallel-grouped placebo-controlled experimental study. At the onset of endotoxemic shock, defined as the moment when the mean pulmonary arterial pressure reached the double baseline value, the pigs were either given a single intravenous dose of hydrocortisone (5 mg kg -1) or the corresponding volume of saline. Results: Mean arterial pressure and systemic vascular resistance index were significantly higher (both p 0.05), and heart rate was significantly lower (p 0.05), in the endotoxin + hydrocortisone group as compared to the endotoxin + saline group. Body temperature and blood hemoglobin levels increased significantly in the endotoxin + saline group (both p 0.05). Urinary hydrocortisone increased significantly in both groups (p 0.05). There were no significant differences in the plasma levels of TNF-alpha, IL-6 or nitriteitrate between the groups. Conclusion: Early treatment with hydrocortisone ameliorates some endotoxin mediated circulatory derangements, fever response and microvascular outflow. Our results suggest that these effects are not directly mediated by the pro-inflammatory cytokines TNF-alpha or IL-6, nor by NO.