Hydrocortisone Does Not Reduce Risk of Septic Shock in Severe Sepsis

Researchers did not observe a significant improvement with hydrocortisone over placebo for time until septic shock or mortality.

Hydrocortisone appeared to have no significant effect in patients with severe sepsis, according to research published in JAMA.1

Based on data from the HYPRESS (Hydrocortisone for Prevention of Septic Shock; ClinicalTrials.gov Identifier: NCT00670254) double-blind, randomized controlled trial, researchers found that hydrocortisone did not reduce the risk of septic shock occurring within 14 days, the study’s primary end point, compared with placebo (see Table at end of article).

“Low-dose hydrocortisone did not prevent the evolution from severe sepsis to septic shock. There were no significant differences between treatment groups with regard to mortality or length of stay in the ICU or hospital, or mortality up to 180 days,” Didier Keh, MD, from the Department of Anesthesiology and Intensive Care Medicine, Charité–Universitätsmedizin in Berlin, Germany, and colleagues wrote. “These findings do not support the use of hydrocortisone in these patients.”

Dr Keh and colleagues also found no significant differences in mortality at 28, 90, or 180 days; ICU mortality; or hospital all-cause mortality in the intention-to-treat population. Analysis of the per-protocol population also revealed no significant differences for secondary end points between the treatment arms.

Post hoc analysis of 54 patients with community-acquired pneumonia did not reveal significant differences for the primary or secondary end points between the treatment (n=24) or placebo groups (n=30).

From January 2009 to August 2013, researchers screened 9953 adult patients with severe sepsis or septic shock at 34 university or community hospitals in Germany. Inclusion criteria included the following: informed consent; evidence of infection; evidence of a systemic response to infection (defined as at least 2 systemic inflammatory response syndrome criteria); and evidence of organ dysfunction present for not longer than 48 hours. The main exclusion criterion was septic shock.

A total of 380 patients were included in the study and randomly assigned 1:1 to hydrocortisone or placebo. Medication was delivered by continuous infusion through day 11.

Bharat K. Awsare, MD, medical director of the 25-bed MICU at Thomas Jefferson University Hospital in Philadelphia, Pennsylvania, reviewed the results for Infectious Disease Advisor. While these findings showed that steroids did not prevent the progression of severe sepsis to septic shock, he advised that the conclusions should be interpreted with caution because the study may have been underpowered since the rate of actual development of septic shock was half of what investigators expected.

“Based on this study, we should not use steroids in all patients with severe sepsis to prevent development of septic shock. However, there may be instances where steroids may still be helpful. There likely is a subset of these patients who truly do benefit from steroids,” he said. “This has been shown in other trials. For example, a recent study in community-acquired pneumonia showed a benefit including mitigating the development of septic shock.2 There also may be modest benefit in those with septic shock and acute respiratory distress syndrome.”

Dr Awsare added that the current standard of care (identifying patients with sepsis early often before admission to the ICU, early antibiotics and fluids, and prompt source control) could have reduced the risk for development of septic shock in this study.

“I don’t think this study will end the debate on steroids in sepsis in general,” he said. “The challenge for future investigators will be to identify patient subsets who may potentially benefit from steroids. In the future, therapy may be tailored to the individual patient with the assistance of biomarkers and genotypes.”

Table 1. Percentage of patients receiving either hydrocortisone or placebo presenting with septic shock within 14 days of initial presentation of severe sepsis

Hydrocortisone, % Placebo, % P value
Intention-to-treat population (n=190) 21.2 22.9 .7
Per-protocol population (n=190) 18.7 21.2 .59

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  1. Keh D, Trips E, Marx G, et al; for the SepNet-Critical Care Trials Group. Effect of hydrocortisone on development of shock among patients with severe sepsis: The HYPRESS Randomized Clinical Trial. JAMA. 2016; Oct 3. doi: 10.1001/jama.2016.14799. [Epub ahead of print]
  2. Torres A, Sibila O, Ferrer M, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response. JAMA. 2015;313:677-686. doi: 10.1001/jama.2015.88.