Septic Shock, Insulin, and Steroids

Intensive insulin therapy did not lower in-hospital mortality in septic shock patients who received hydrocortisone.

In a study published in 2002, patients with septic shock and impaired adrenal reserve appeared to benefit from 7-day courses of hydrocortisone (50 mg every 6 hours) plus the mineralocorticoid fludrocortisone (JW Gen Med Aug 30 2002). In contrast, hydrocortisone alone was not beneficial in the 2008 CORTICUS trial (JW Gen Med Jan 9 2008). Because patients in the 2002 trial were sicker and were treated earlier than those in CORTICUS, some experts still recommend low-dose hydrocortisone for patients with severe sepsis and refractory hypotension.
That hydrocortisone invariably induces hyperglycemia raises another question: Is intensive insulin therapy appropriate for hydrocortisone-treated patients with septic shock? To answer this question, researchers in France randomized 509 such patients to receive either intensive insulin therapy (target glucose level, 80–110 mg/dL) or usual care (target glucose level, around 150 mg/dL). In addition, to examine whether mineralocorticoid therapy is beneficial, the researchers randomized the same patients to receive or not to receive fludrocortisone in a 2x2 factorial design. The outcome: Overall in-hospital mortality was 44%; neither intensive insulin nor fludrocortisone lowered mortality or any of numerous secondary endpoints.

Comment:
In this multicenter study of hydrocortisone-treated patients with septic shock, intensive insulin therapy did not improve outcomes. An editorialist notes that (1) mean glucose levels in intensively treated patients fell short of the intended target, reaching only about 120 mg/dL, which was not markedly different from the mean glucose level (about 150 mg/dL) of the control group; and (2) the trial was underpowered to identify small differences in mortality. Thus, she calls for a much larger trial. My own sense, however, is that intensive glycemic control is not the magic bullet that will improve outcomes in septic shock patients and that research should be directed toward other pathophysiologic mechanisms.

—
Allan S. Brett, MD
Published in Journal Watch General Medicine February 4, 2010

Citation(s):
The COIITSS Study Investigators. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: A randomized controlled trial. JAMA 2010 Jan 27; 303:341.
Van den Berghe G. Should glucocorticoid-induced hyperglycemia be treated in patients with septic shock? JAMA 2010 Jan 27; 303:365.