inadequate intracellular glucocorticoid activity , referred to as critical illness - related corticosteroid insufficiency , typically results in an exaggerated proinflammatory response . while there are large geographic variations in the prescription of glucocorticoids for sepsis , up to 50% of intensive care unit patients receive such therapy . despite over 30 years of investigation and over 20 meta - analyses , the use of glucocorticoids in patients with sepsis remains extremely controversial and recommendations are conflicting . the most important recent studies are that of annane and colleagues   and the corticosteroid therapy of septic shock ( corticus ) study . both of these studies have important limitations : 24% patients received etomidate in the study by annane and colleagues , whereas 19% received etomidate in the corticus study . the benefit of steroids in the study by annane and colleagues may have been restricted largely to those patients who received etomidate . furthermore , only patients with ' refractory septic shock ' were enrolled in the annane study whereas , as a result of an overwhelming selection bias , only approximately 5% of eligible patients were enrolled in the corticus study . a more recent study found no benefit from a 7-day course of 40 mg of prednisolone in patients hospitalized with community - acquired pneumonia . in the study by annane and colleagues , patients received 50 mg of hydrocortisone intravenously every 6 hours for 7 days , whereas in the corticus study , patients received this dose for 5 days , followed by a tapering off over a further 5 days . recently , two longitudinal studies in patients with severe community - acquired pneumonia found high levels of circulating inflammatory cytokines 3 weeks after clinical resolution of sepsis . these data suggest that patients with severe sepsis may have prolonged immune dysregulation ( even after clinical recovery ) and that a longer course of corticosteroids may be required . the use of a continuous infusion of hydrocortisone has been reported to result in better glycemic control with less variability of blood glucose concentration . this may be clinically relevant as it has been demonstrated that an oscillating blood glucose level is associated with greater oxidative injury than sustained hyperglycemia . indeed , a number of reports indicate that glucose variability may be an independent predictor of outcome in critically ill patients . a continuous infusion of glucocorticoid may , however , result in greater suppression of the hpa axis . furthermore , the preferred glucocorticoid and the optimal dosing strategy in patients with septic shock remain to be determined . evidence - based medicine is defined as the use of the best current scientific evidence in making decisions about the care of individual patients . owing to the dearth of high - level evidence , it is not possible to make strong evidence - based recommendations on the use of glucocorticoids in patients with sepsis . therefore , at this juncture , it is useful to summarize what we know , what we think we know , and what we do not know in order to lay the foundation for future scientific exploration ; this information is summarized in table 1 . current knowledge concerning glucocorticoids in sepsis in summary , the risk / benefit ratio of glucocorticoids should be determined in each patient . a course ( 7 to 10 days ) of low - dose hydrocortisone ( 200 mg / day ) should be considered in vasopressor - dependent patients ( dosage of norepinephrine or equivalent of greater than 0.1 g / kg per minute ) within 12 hours of the onset of shock . steroids should be stopped in patients whose vasopressor dependency has not improved with 2 days of glucocorticoids . while the outcome benefit of low - dose glucocorticoids remains to be determined , such a strategy decreases vasopressor dependency and appears to be safe ( no excess mortality , superinfections , or acute myopathy ) . infection surveillance is critical in patients treated with corticosteroids , and to prevent the rebound phenomenon , the drug should be weaned slowly . at this time , glucocorticoids appear to have a limited role in patients who have sepsis or severe sepsis and who are at a low risk of dying . corticus : corticosteroid therapy of septic shock ; hpa : hypothalamic - pituitary - adrenal .
an intact hypothalamic - pituitary - adrenal ( hpa ) axis with effective intracellular glucocorticoid anti - inflammatory activity is essential for host survival following exposure to an infectious agent . 
 glucocorticoids play a major role in regulating the activity of nuclear factorkappa- b , which has a crucial and generalized role in inducing cytokine gene transcription after exposure to an invading pathogen . 
 severe sepsis is , however , associated with complex alterations of the hpa axis , which may result in decreased production of cortisol as well as glucocorticoid tissue resistance .