CORTICUS: Hydrocortisone Therapy for Patients with Septic Shock

Clinical Question

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

PICO

  • Population:

    • 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

      • Excluded if:

        • Chronic steroids for 7 mo; acute steroids within 4 weeks; immunosupression; less than 24h survival expectation

  • Intervention:

    • Hydrocortisone given as 50 mg in 6-hourly boluses. Tapering regime from day 6. Stopped on day 12

  • Control:

    • Identical placebo prepared and administered in an identical way to intervention

  • Outcome:

    • 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.

      • p=0.69

    • Secondary outcome:

      • 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)

Conclusions

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.

Strengths

  • Excellent randomization and blinding methodology

  • Sensible primary outcome, and useful secondary outcomes

  • Fair commentary of problems by authors in ‘Discussion’ section of paper

Weaknesses

  • 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%)

Take Note

  • 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

Sources:

https://www.thebottomline.org.uk

Rachel FComment