Although short courses of high-dose glucocorticoids decreased survival during sepsis, a 5- to 7-day course of physiologic hydrocortisone doses with subsequent tapering increases survival rate and shock reversal in patients with vasopressor-dependent septic shock.

No abstract

Endotoxin, an LPS found in the outer membrane of Gram-negative bacteria, has been considered by many to be the principal toxin involved in the pathogenesis of Gram-negative septic shock (1). However, it is now clear that endotoxin may cause most (ifnot all) of its biological effects via the release of host factors (2-5) . Several studies have suggested that TNF, a cytokine produced by macrophages during septic shock, is one ofthe endogenous mediators that causes cardiovascular injury and death (2-5).Previous studies examining the effects of endotoxin and TNF in animal models have used a number of techniques to study cardiovascular function during the first 1-12 h after challenge. Most of these investigations have shown evidence of myocardial depression (2-11) . However, recent studies of human and animal septic shock have demonstrated that cardiovascular function continues to change over a period of several days. Typically, the left ventricular ejection fraction (LVEF)' falls to a nadir 2-3 d after the onset of hypotension. This progressive decrease in LVEF is associated with IV dilatation and maintenance of normal or increased cardiac output. In survivors, these cardiovascular changes return to normal in 7-10 d (12-20).The present study shows that dogs given a single intravenous bolus of TNF produce all the same complex cardiovascular changes over 7-10 d as those seen in septic shock over the same period . Furthermore, endotoxin without any other bacterial products can also produce the same serial changes in cardiovascular function seen in human septic shock.