Crit Care Resusc
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The concept of relative adrenal insufficiency in patients with severe sepsis continues to be controversial. This arises in part from the lack of an accepted "gold standard" for the diagnosis of adrenal insufficiency in the critically ill. Historically, assessment of adrenal function in this population has relied on measurement of plasma total cortisol level, in a blood sample taken either at random or as part of a corticotropin stimulation test. ⋯ We review the mechanisms known to affect tissue glucocorticoid activity and examine how they may be modified by critical illness. These include both free and interstitial cortisol concentrations, intracellular cortisol generation, and glucocorticoid-receptor activity and density. Changes in these factors are not reflected in plasma total cortisol concentrations, and more sophisticated techniques, including genetic transcriptional surveys, may be required to reveal the role of glucocorticoid insufficiency in critical illness.
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There is now significant evidence that initial use of the correct antibiotic saves more lives than virtually all other intensive care therapy. This means covering all possible causative organisms with the initial empirical choice. For nosocomial sepsis, broad-spectrum antibiotics must be started as soon as the relevant samples have been taken for culture, with de-escalation of therapy targeted to the causative organisms when results and susceptibilities are available. ⋯ We have shown that some patients with normal serum creatinine levels have very high creatinine clearance rates; in ICU patients with sepsis, blood pressure and tissue perfusion are maintained with large fluid loads and inotropic agents, thereby raising creatinine clearance. High clearances produce low trough concentrations of antibiotic, with important implications for underdosing and the development of antibiotic resistance. The new paradigm for treating sepsis, particularly nosocomial sepsis, is: get it right the first time, hit hard up front, and use large doses of broad-spectrum antibiotics for a short period.