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Hydrocortisone ineffective for septic shock prevention
Hydrocortisone therapy did not reduce the risk for septic shock among adults with sepsis, researchers in Germany found.
“Assuming that severe sepsis and septic shock reflect a disease continuum, it was hypothesized that early hydrocortisone administration might prevent shock development owing to the attenuation of an exaggerated inflammatory response,” Didier Keh, MD, of the department of anesthesiology and intensive care medicine, Charité-Universitätsmedizin Berlin, and colleagues wrote.
In the double blind, randomized controlled Hydrocortisone for Prevention of Septic Shock (HYPRESS) trial, patients were assigned to a continuous infusion of hydrocortisone 200 mg for 5 days followed by tapered doses until day 11 (n = 190), or placebo (n = 190). The primary outcome was septic shock within 14 days; secondary outcomes included time to septic shock, mortality in the ICU or hospital, survival to 180 days and examination of secondary infections, weaning failure, muscle weakness and hyperglycemia.
In the intention-to-treat population of 353 patients, 64.9% were male and the mean age was 65 years.
Thirty-six (21.2%) patients assigned to hydrocortisone and 39 (22.9%) patients in the placebo group experienced septic shock, Keh and colleagues reported. They found no significant difference between the two groups in time to septic shock, mortality in the ICU or hospital, or mortality at 28, 90 or 180 days.
The 28-day mortality was 8.8% in the hydrocortisone group vs. 8.2% in the placebo group (95% CI, –5.6% to 6.7%). At 90 days, mortality was 19.9% in the hydrocortisone group vs. 16.7% in the placebo group (95% CI, –5.1% to 11.4%), and at 180 days mortality was 26.8% in the hydrocortisone group vs. 22.2% in the placebo group (95% CI, –4.6% to 13.7%).
Secondary infections occurred among 21.5% of patients in the hydrocortisone group compared with 16.9% in the placebo group, while 8.6% of those who received hydrocortisone and 8.5% of the placebo group experienced weaning failure. Muscle weakness occurred in 30.7% of the hydrocortisone group vs. 23.8% of the placebo group. Most patients in both groups had hyperglycemia: 90.9% of the hydrocortisone group and 81.5% of the placebo group.
In an accompanying editorial, Sachin Yende, MD, MS, of the department of critical care medicine at the University of Pittsburgh, and B. Taylor Thompson, MD, of the division of pulmonary and critical care medicine at Massachusetts General Hospital, Boston, wrote that “research has failed to demonstrate unequivocal efficacy [of glucocorticoids] for patients with sepsis, and larger trials should help address outstanding questions.
“However, if past is prologue, it may be time to change direction and consider alternative trial designs to identify glucocorticoid-response subtypes and enable greater precision in current ICU practice,” Yende and Thompson wrote. – by Andy Polhamus
Disclosure: Keh reports no relevant financial disclosures. Yende reports receiving grants from Bristol-Myers Squibb, the National Institute of General Medical Sciences and the NIH. Please see the full study for a complete list of all authors’ relevant financial disclosures.