During conditions of imposed stress (e.g., infection, trauma and surgery), there is a release of “stress” hormones to maintain homeostasis. While the hormones that are released during this stress response include glucagon, epinephrine and growth hormone, cortisol is arguably the most important.

A current and widely held concept is that exogenously administered corticosteroids suppress the hypothalamus-pituitary-adrenal (HPA) axis, thereby inhibiting normal endogenous adrenal cortical function and subsequent release of cortisol. Furthermore, during conditions of stress, failure to increase plasma levels of cortisol can increase the risk of morbidity and/or mortality (i.e., inadequate or “failed” stress response). Although the potential consequences of a failed corticosteroid response are varied (Table 1), the most life-threatening includes refractory hypotension and shock states.

The concept of adrenal hyporesponsiveness during stress situations (i.e., failed stress response) appears to be based on several case reports, published in the 1950s, of intractable and...

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