Both doses and duration of corticosteroid

Both doses and duration of corticosteroid selleck chem MG132 therapy vary significantly in published studies[6,28,39,40,102,103]. Thus, some used a daily dose of hydrocortisone (or equivalent) of 200-300 mg (��low-dose��, also called ��physiologic-dose�� or ��stress-dose��)[3,28,39,98,100-105] while others used a ��supra-physiologic�� dose (> 300 mg)[98,106-108]. None of the early studies using high doses of corticosteroids for short courses reported any benefit[98,106-108], while more recent studies using a ��physiologic-dose�� for longer durations have shown a significant reduction in vasopressor agents requirement and in intensive care unit length of stay, greater shock resolution, and decreased mortality[6,28,39,98,100,104,105,109-111].

A randomized, double-blind placebo controlled trial, CORTICUS (Corticosteroid Therapy of Septic Shock)[102] including 499 patients with septic shock randomized to hydrocortisone (50 mg intravenously every 6 h for 5 d, followed by 50 mg intravenously every 12 h for 3 d, and then by 50 mg daily for 3 d) or placebo, concluded that there was no benefit in terms of mortality, although steroid administration was associated with a greater shock reversal, but also with a higher incidence of episodes of new infections. On the other hand, Annane et al[28] in a randomized, double-blind controlled trial have found that the administration of hydrocortisone (50 mg intravenously every 6 h) and oral fludrocortisone (50 ��g once daily) in patients with refractory septic shock and AI (delta cortisol < 250 nmol/L) resulted in a 30% decrease in 28-d mortality.

It should be mentioned that consensus statements from an international task force[6] recommended corticosteroid therapy (intravenous hydrocortisone 200-300 mg/d in four divided doses for a week before tapering slowly) in patients with vasopressor-dependant septic shock. Like in patients with severe sepsis/septic shock with other causes than liver cirrhosis, as mentioned above, the effects of steroid therapy in cirrhotic patients with AI remain controversial, some studies reporting beneficial results[12-14] while a recent randomized control study[29] has shown no benefit (Table (Table33). Table 3 Published studies on corticosteroid therapy in patients with liver cirrhosis Harry et al[14] evaluated the effects of stress doses of hydrocortisone in a retrospective comparative study including 40 patients. Twenty patients received hydrocortisone (300 mg/d) for 4-5 d. In patients with acute-on-chronic liver failure requiring norepinephrine support, the results showed a reduction in vasopressor doses, but no Cilengitide survival benefit; moreover, corticosteroid therapy was associated with a significant increase in infections.

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