Stress-dose corticosteroid therapy for sepsis and acute lung injury or acute respiratory distress syndrome in critically ill adults

Abstract

Sepsis and acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) are associated with high mortality rates despite recent therapeutic advances. Both disease states involve uncontrolled host defense responses that lead to inflammation, endothelial damage, enhanced coagulation, diminished fibrinolysis and fibroproliferation to produce microthrombi, and relative adrenal insufficiency. Corticosteroids inhibit the host defense response and may offer an inexpensive therapeutic option. Results of several randomized, double-blind studies demonstrated no survival benefit and higher secondary infection rates when supraphysiologic doses of corticosteroids were administered for less than 24 hours. Recently, the emphasis of research for corticosteroid therapy has involved adrenocortical replacement dosage regimens administered for several days to weeks, with doses corresponding to the stress level of the disease. Stress-dose therapy with hydrocortisone in patients with septic shock who require vasopressor support, especially if adrenal insufficiency is present, accelerates hemodynamic stability and reduces mortality. The frequency of gastrointestinal hemorrhage was higher with corticosteroid therapy than with placebo, but the occurrence of secondary infections was similar to that of placebo. The only randomized, double-blind study that evaluated stress-dose methylprednisolone therapy for ARDS was terminated early after only 24 patients were enrolled because therapy with methylprednisolone was associated with enhanced survival despite higher secondary infection rates. A multicenter study investigating stress-dose methylprednisolone for ARDS is under way and should provide valuable information. Sufficient data support stress-dose hydrocortisone therapy for vasopressor-dependent septic shock. Stress-dose methylprednisolone therapy for ALI-ARDS requires further study but may be warranted in cases of refractory infection-induced ARDS when impending mortality is likely.