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 F

Rachel is a physician assistant who has been holding down the ICU since 2016. She joined the Pulmcast podcast in 2017 and has been hooked on FOAMed ever since. Rachel has a passion for teaching using technology with a special focus on preserving dignity in the ICU. When she's not at work, you’ll find her playing with her golden retriever, hunting for thrift store treasures, and soaking up time with her husband and son.

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