CORTICUS: Hydrocortisone Therapy for Patients with Septic Shock
In adult patients with severe septic shock, does hydrocortisone versus placebo reduce mortality at 28 days?
Type of Trial: RCT
Blinding: double blinded
Setting: 52 participating ICUs fro March 2002-Nov 2005
499 adults with severe sepsis with clinical evidence of infection, systemic response to inflammation, shock (SBP 90 mmHg despite 1 hr fluid resuscitation OR need for vasopressors) and organ dysfunction attributable to shock
Chronic steroids for 7 mo; acute steroids within 4 weeks; immunosupression; less than 24h survival expectation
Hydrocortisone given as 50 mg in 6-hourly boluses. Tapering regime from day 6. Stopped on day 12
Identical placebo prepared and administered in an identical way to intervention
Primary outcome: no difference in 28-day mortality in short corticotropin non-responders (i.e. the sub-group that were more likely to benefit from exogenous corticosteroids)
39.2% in hydrocortisone group vs. 36.1% in placebo group
Absolute difference 3.1% (95% C.I. -9.5% to 15.7%) favouring placebo.
No difference in 28-day mortality in short corticotropin responders (i.e. the sub-group that were less likely to benefit from exogenous corticosteroids)
28.8% vs. 28.7%, P=1.0
No difference in 28-day mortality in all patients
34.3% vs. 31.5%, P=0.51
Statistically significant reduction in the time to reversal of shock favouring the hydrocortisone group (seen in responders, non-responders and all patient groups).
median time until reversal of shock, in all patients, was 3.3 days (95% C.I. 2.9-3.9) in the hydrocortisone group vs. 5.8 days (95% C.I. 5.2-6.9) in the placebo group
Non-significant increase in rate of superinfections in hydrocortisone vs. placebo group
33% vs. 26%, RR 1.27 (95% C.I. 0.96-1.68)
The use of hydrocortisone did not decrease mortality in a general population of patients with septic shock, even though the drug hastened reversal of shock.
Excellent randomization and blinding methodology
Sensible primary outcome, and useful secondary outcomes
Fair commentary of problems by authors in ‘Discussion’ section of paper
Despite 52 ICUs, this study failed to recruit required numbers (average of less than 10 patients per ICU over 3 years) despite common incidence of severe sepsis.
Actually mortality (~38%) was much lower than estimated mortality used for power calculation (50%)
Steroids may lead to harm from superinfection but it does lead to reversal of shock quicker than placebo
Should not be given routinely but can be worth considering once all else has failed