Corticosteroids in severe sepsis and septic shock

Critical illness related corticosteroid insufficiency (CIRCI) is a well documented entity. Yet, controversy surrounds the question of when and when not to give steroids in critically ill patients, particularly septic patients. CORTICUS, the highest level study to date to address the issue, found no benefit from steroid therapy in patients with hypotension persisting after fluid resuscitation whether their cortrosyn stimulation test was normal or showed “relative” adrenal insufficiency. The Surviving Sepsis guidelines downgraded their steroid recommendation to patients refractory to pressors, and did not recommend adrenal testing.

More recently, this systematic review suggests benefit from low dose steroids (defined as 300 mg hydrocortisone or its equivalent/day) in a broader range of patients:

Corticosteroid therapy has been used in varied doses for sepsis and related syndromes for more than 50 years, with no clear benefit on mortality. Since 1998, studies have consistently used prolonged low-dose corticosteroid therapy, and analysis of this subgroup suggests a beneficial drug effect on short-term mortality.

Some, but not all of the studies in that review based steroid treatment on the cortrosyn stimulation test.

Not surprisingly, some studies showed increased hyperglycemia attributable to steroids, as well as hypernatremia, the latter particularly associated with hydrocortisone, which among corticosteroids has stronger mineralocorticoid effects.

This study adds to our uncertainty, as pointed out by the accompanying editorial:

The authors report that there have now been 12 randomized trials testing the more recent strategy of low-dose steroids for a week or more and suggest an impressive overall reduction in mortality (risk ratio, 0.84; 95% confidence interval, 0.72-0.97; P=.02), even when accounting for the CORTICUS study. They conclude that steroids are indicated for all patients in septic shock, despite the findings of this trial, and in contrast with the position articulated in the SSC guidelines.

So it seems that clinicians treating patients with sepsis have 3 choices regarding steroids: no use, limited use, or broad use. Steroid use could be abandoned if the largest and latest trial, CORTICUS, is thought to effectively trump all prior studies. Steroids could be used in a limited set of patients and initiated only after it has been demonstrated that these patients are not responding to conventional measures, based on the SSC guidelines. Or steroids could be used broadly in septic shock, and possibly even in all severe sepsis (ie, any infection complicated by acute organ dysfunction), based on the results of the meta-analysis by Annane et al.4

Putting it mildly, this is a messy situation.

The answer? Again, from the editorial:

...the major difference between the SSC guidelines and the current meta-analysis seems to be a difference of judgment and opinion in the face of inconclusive evidence. That means that the final decision rests squarely on those at the bedside.