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evident
Original paper
2008NEJMPulmonary/Critical Care

CORTICUS

Hydrocortisone therapy for patients with septic shock

RCTSeptic shock

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Overview

Hydrocortisone did not improve 28-day survival or overall shock reversal in septic shock, though it hastened reversal in patients whose shock resolved.

Clinical takeaway

CORTICUS is the septic-shock steroid caution trial, best interpreted with APROCCHSS and ADRENAL when deciding steroid use for persistent vasopressor-dependent shock.

Key result

28-day mortality in corticotropin nonresponders was 39.2% with hydrocortisone vs 36.1% with placebo (p=0.69); overall 34.3% vs 31.5% (p=0.51).

Practice impact

Steroids are for selected refractory septic shock, not routine sepsis treatment.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial.

Enrollment

499

Follow-up

28 days for primary outcome.

Geography

Multinational

Clinical question

Does hydrocortisone improve survival in septic shock, and does response depend on corticotropin testing?

Population

  • Adults with septic shock; 233 of 499 (46.7%) did not respond to corticotropin.

Intervention

Hydrocortisone 50 mg IV every 6 hours for 5 days, then tapered over 6 days.

Comparator

Placebo.

Primary outcome

28-day mortality among patients without a response to corticotropin.

Hydrocortisone did not significantly reduce 28-day mortality in corticotropin nonresponders (39.2% vs 36.1%; p=0.69) or overall (34.3% vs 31.5%; p=0.51).

Between-group comparison / p=0.69

Key results

  • 28-day mortality in corticotropin nonresponders: 39.2% with hydrocortisone vs 36.1% with placebo (p=0.69).
  • 28-day mortality in corticotropin responders: 28.8% vs 28.7% (p=1.00); overall: 86 of 251 (34.3%) vs 78 of 248 (31.5%) (p=0.51).
  • Shock was reversed more quickly with hydrocortisone among patients whose shock reversed, but overall shock reversal was not improved.
  • Superinfection, including new sepsis and septic shock, was more frequent with hydrocortisone.

Harms

  • Hyperglycemia, hypernatremia, and superinfection are practical steroid harms.

Clinical Use

Practice impact

  • Helped move practice away from routine corticotropin testing to guide septic-shock steroids.

Applicability

  • Septic shock patients where steroid use is being considered for persistent vasopressor need.

Limitations

  • Underpowered after early stopping and enrolled less-severe shock than some other steroid trials.
  • Does not exclude hemodynamic benefit.

Common misinterpretations

  • Do not cite CORTICUS as proof steroids never help; shock reversal improved and later trials add nuance.

Related evidence

APROCCHSS - Contrasting ResultADRENAL - Later TrialProCESS - Context

Citation

Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008;358(2):111-124. doi:10.1056/NEJMoa071366

At 28 days, there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin (39.2% in the hydrocortisone group and 36.1% in the placebo group, P=0.69) or between those who had a response to corticotropin (28.8% in the hydrocortisone group and 28.7% in the placebo group, P=1.00).