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Low-Dose Hydrocortisone Infusion in Patients With Severe Sepsis Associated With Increased Mortality: Presented at CHEST 2009

By Betty S. Riggs

SAN DIEGO -- November 6, 2009 -- Treatment with low-dose hydrocortisone infusion was associated with worse survival in patients with severe sepsis, according to a study presented here at CHEST 2009, the annual meeting of the American College of Chest Physicians.

Gianfranco U. Meduri, MD, University of Tennessee Health Sciences Center, Memphis, Tennessee, and colleagues reported their findings on November 3.

For the study, researchers enrolled patients who had severe sepsis for <48 hours prior to admission to the intensive care unit (ICU). Patients were stratified into group A (without shock and multiple organ dysfunction syndrome score [MODS] <2) and group B (with shock or MODS >3).

Patients were then randomised to receive intravenous hydrocortisone (HC) 300 mg, followed by a hydrocortisone infusion (10 mg/hour) for 7 days, without tapering. The primary endpoint was improvement in MODS at day 7 for group A and resolution of shock at day 7 for group B.

There were 80 patients in the intention-to-treat (ITT) group, 48 of whom were randomised to HC (17 without shock and 31 with shock), and 32 of whom were randomised to placebo (13 without shock and 19 with shock).

The percentage of patients requiring mechanical ventilation was higher in the HC group compared with the placebo group (79% vs 60%, respectively; P = .06).

In the ITT analysis, MODS at day 7 was 0.93 +-1.25 in the HC group and 1.19 +-1.27 in the placebo group (P = .44).

Day 7 mortality was 12/48 (25%) in the HC group compared with 2/32 (6%) in the placebo group (P = .03). Day 28 mortality was also higher in the HC group than in the placebo group (46% vs 19%; P = .002).

According to Dr. Meduri, there are a number of possible explanations for the mortality findings. There was a higher severity of illness in the patients randomised to HC, as evidenced by the Acute Physiology, Age, Chronic Health Evaluation (APACHE III) scores and the need for mechanical ventilation. There was an unusually low mortality in the control group, which was lower than in most previously reported studies. The duration of treatment with HC may have been too short, resulting in rebound inflammation. Sudden cardiac death in patients with a history of atherosclerotic cardiovascular disease was associated with dysregulated inflammation. Underlying comorbid conditions were the most common cause of death in patients who died after the resolution of sepsis.

The limitations of the study include a small sample size, significant baseline imbalances, and an unusually low mortality in the placebo group.

[Presentation title: Prospective Double-Blind Randomized Clinical Trial on the Effects of Low-Dose Hydrocortisone Infusion in Patients With Severe Sepsis]

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