The immune response: targets for the treatment of severe sepsis.

Given the challenges of measuring cortisol levels and the finding that the Annane trial showed an overall trend toward benefit of steroid therapy, regardless of ACTH responsiveness, the 2008 Surviving Sepsis Guidelines recommended that the ACTH stimulation test not to be used as a tool to guide the use of steroid therapy [ 4 ].

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However, when the 15 observational studies were adjusted for publication bias the association failed to reach statistical significance [ 34 ].

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It showed a nonsignificant trend towards improved survival in those treated with afelimomab [ 27 ].

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These studies failed to show benefit and even showed a trend towards harm including increased mortality due to secondary infections in those treated with steroids, thus, causing steroid therapy use to decrease in the early 1990s [ 2 , 17 ].

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