Systemic steroids for severe sepsis and septic shock (Review, AJRCCM)

Despite more than 5 decades of study and debate, the role of corticosteroid treatment in patients with severe sepsis and septic shock remains controversial…

… we await more definitive guidance from future multicenter, prospective, randomized, controlled trials designed to better answer these important therapeutic questions.

When the review article’s opening paragraph starts and finishes like this, you can breathe easy; you haven’t missed anything since the last time you read about the topic. The authors review the conflicting evidence and rather than telling us what to do, elucidate the multiple areas of confusion and controversy:

• Although adrenal suppression is common in sepsis, it is still unclear how to assess adrenal function, or whether it should be done at all. The sensitivity and specificity of the cosyntropin (ACTH) stimulation test are unknown, and its utility uncertain. There is no good evidence base even to define what adrenal suppression is (in terms of lab cut-off values) in people with severe sepsis. Nevertheless, the Society of Critical Care Medicine continues to recommend we call it “corticosteroid insufficiency” and define it in the old way (a cortisol increase of <9 mcg/dL after a 250 mcg ACTH stimulation test, or a random cortisol < 10), without advising it be routinely checked.
• Annane’s practice-changing study published in 2002 showed that among 300 septic shock patients, those with a negative cosyntropin stimulation test (“non-responders”) randomized to 50 mg hydrocortisone IV q 6 hours had significantly improved 28-day mortality compared to placebo (53% vs. 68%). The trial was criticized for changing enrollment criteria mid-study and use of adrenal-suppressing etomidate for intubation on most patients, leading to a 72% rate of adrenal suppression/non-responders.
• CORTICUS then swung the pendulum back by showing no 28-day mortality benefit of steroids in 499 septic shock patients (39% vs. 36%) who were non-responders to cosyntropin. Steroids did reduce the time spent in shock (3.3 vs. 5.8 days), but steroid-treated patients had more superinfections and new episodes of sepsis. CORTICUS was likewise criticized for changing enrollment criteria mid-study, not meeting its enrollment targets, and its low mortality rate compared to prior studies.
• Summing up, corticosteroids do improve blood pressure, but any beneficial effects on survival from septic shock remain hotly debated.

…But you already knew all that.

 

Clinical Takeaway: The Surviving Sepsis Guidelines are unchanged from 2008, and continue to recommend:

• Hydrocortisone 300 mg / day or less in patients with septic shock “only after it has been confirmed that their blood pressure is poorly responsive to fluid resuscitation and vasopressor therapy.” (Grade 2C: weak recommendation, low quality evidence). What does “poorly responsive” to vasopressor therapy mean? Dear Reader, that’s always been up to you to decide.
• No benefit of continuous vs. bolus infusions has been demonstrated (continuous produces less hyperglycemia, but more of a rebound effect after discontinuation).
• Adding fludrocortisone to hydrocortisone is not supported by the COIITS trial, in which it was associated with a higher infection rate, and shouldn’t be necessary as hydrocortisone has mineralocorticoid activity. Surviving Sepsis calls fludrocortisone an optional adjunctive treatment to hydrocortisone.
• Give hydrocortisone for 7 days, then wean it to prevent rebound hypotension and blood glucose lability.
• Stick with the 300 mg / day dose: giving high-dose corticosteroids to people in septic shock is known to be harmful.

Patel GP, Balk RA. Systemic Steroids in Severe Sepsis and Septic Shock. Am J Respir Crit Care Med 2012;185:133-139.