What study data is available on the use of corticosteroid therapy to treat sepsis/septic shock?

Updated: Oct 07, 2020
  • Author: Andre Kalil, MD, MPH; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, FAPS, MCCM  more...
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Some trials have documented positive results from stress-dose administration of corticosteroids in patients with severe and refractory shock. [99] Although further confirmatory studies are awaited, stress-dose steroid coverage should be provided to patients who have the possibility of adrenal suppression.

Other studies have shown that lower-dose steroids may be beneficial for patients with relative adrenal insufficiency. In a study by Annane et al that included 299 patients with septic shock who were randomly assigned to receive low-dose steroids (hydrocortisone, 50 mg q6hr, and fludrocortisone, 50 µg/day) or placebo, 77% were nonresponders; for nonresponders who received steroids, there was a 10% absolute benefit with respect to mortality (63% vs 53%). [100]

In this study, all patients had been intubated, had been persistently hypotensive despite crystalloid resuscitation and vasopressor administration, and had had evidence of end-organ failure. [100] Nonresponders were defined as those whose cortisol level increased by less than 10 µg/dL in a cortisol stimulation test and thus were considered adrenally insufficient. This test involves measuring cortisol levels before and 30 minutes after IV administration of 0.25 mg of cosyntropin (ie, adrenocorticotropic hormone [ACTH]).

Although performing the cortisol stimulation test in the ED setting may not be practical, given time and resource constraints, it is worth noting that more than 75% of patients with vasopressor-refractory hypotension were adrenally insufficient. [100] This finding suggested that the majority of patients with vasopressor-refractory shock would benefit from steroid administration, regardless of the results of the cortisol stimulation test. A common choice is hydrocortisone 100 mg IV; a good alternative is dexamethasone 10 mg IV.

In a subsequent study, Annane et al published a systematic review of corticosteroid use for severe sepsis and septic shock, the pooled results of which showed that the subgroup of studies using prolonged, low-dose corticosteroid therapy demonstrated a beneficial effect on short-term mortality. [101] However, no clear benefit was shown with the use of high-dose corticosteroids for severe sepsis or septic shock. [101]

In the CORTICUS (Corticosteroid Therapy of Septic Shock) study, a large randomized trial of hydrocortisone versus placebo in patients with septic shock, no difference in mortality was noted between the groups, even though the patients who received steroids had a more rapid resolution of shock, as measured by a shorter duration of vasopressor therapy [102] and a faster improvement in Sequential Organ Failure Assessment (SOFA) scores. [103] However, the incidence of superinfection and recurrent sepsis was higher in those who received steroids.

Additionally, the result of the cortisol stimulation test had no bearing on outcome in the CORTICUS trial, [102] which raises questions about the value of this test in determining who will benefit from steroid treatment. However, the CORTICUS study enrolled all patients with septic shock, regardless of vasopressor response. Consequently, patients in this study had a lower mortality than those in the Annane study.


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