November 1, 2016
Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis.
What was the research question?
Does the early use of hydrocortisone in severe sepsis (sepsis as per new definition) prevent the progression to septic shock?
How did they do it?
Double-blind, randomized clinical trial conducted in 34 centers in Germany.
380 adult patients with severe sepsis (but not in septic shock) were randomized to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190).
The primary outcome was development of septic shock within 14 days.
Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL.
What did they find?
353 patients were analyzed based on the intention-to-treat analysis (64.9% male; mean [SD] age, 65.0 [14.4] years).
Septic shock occurred in 21.2% in the hydrocortisone group compared to 22.9% in the placebo group (P = .70).
Mortality was not statistically different at 28 days, 90 days, 180 days, ICU discharge, or hospital discharge. All other secondary outcomes were not different.
In the hydrocortisone vs placebo groups, secondary infections occurred in 21.5% vs 16.9% (p=0.26), weaning failure in 8.6% vs 8.5% (p=0.96), muscle weakness in 30.7% vs 23.8% (p=0.18), and hyperglycemia in 90.9% vs 81.5% (p=0.009).
Are there any limitations?
The trial may have missed those patients who developed septic shock before obtaining the consent.
Mortality rate was lower than reported in other clinical trials, therefore, the study may have included less severe patients and there might be a benefit in more severe cases.
Sample size calculation may not be accurate as the actual rate of septic shock was lower than the estimated rate of 40% in the placebo group.
What does it mean?
Hydrocortisone did not reduce the risk of progression to septic shock within 14 days if used early in patients with severe sepsis.
These findings do not support the use of hydrocortisone in these patients.