article186

ADRENAL

"Hydrocortisone for Patients with Septic Shock on Mechanical Ventilation".The New England Journal of Medicine. 2018.

Clinical Question

Does the administration of hydrocortisone reduce 90-day mortality in patients with septic shock undergoing mechanical ventilation?

Bottom Line

Among patients with septic shock who were undergoing mechanical ventilation, hydrocortisone did not result in significantly lower 90-day mortality compared to placebo.

Major Points

Guidelines

As of the last update for this topic, no guidelines had been published reflecting the results of this trial.

Design

- Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial
- N=3,800 patients with septic shock
- Hydrocortisone (n=1,898) vs. Placebo (n=1,902)
- Setting: 69 ICUs in Australia, UK, New Zealand, Saudi Arabia, Denmark
- Enrollment: 2013-2017
- Analysis: Intention-to-treat
- Primary outcome: Death from any cause at 90 days after randomization

Population

Inclusion Criteria:
- Adults (≥18 years) undergoing mechanical ventilation
- Documented or clinically suspected infection, two or more systemic inflammatory response syndrome criteria
- Treated with vasopressors/inotropes for ≥4 hours at randomization

Exclusion Criteria:
- Likely need for systemic glucocorticoids for another indication
- Receipt of etomidate
- Likelihood of death within 90 days due to preexisting disease
- Treatment limitations in place
- Inclusion criteria met for more than 24 hours

Baseline Characteristics
- Mean age: 62.5 years
- Male: 61%
- Median APACHE II score: 23.5
- Primary site of infection: mainly pulmonary in medical admissions, abdominal in surgical
- Median time from randomization to trial regimen: 0.8 hours

Interventions

- Hydrocortisone infusion at 200 mg per day or matching placebo
- Administered over 24 hours for up to 7 days or until ICU discharge or death, whichever came first

Outcomes

Primary Outcome:
- Death at 90 days: 27.9% in the hydrocortisone group vs. 28.8% in the placebo group (OR 0.95; 95% CI 0.82 to 1.10; P=0.50)

Secondary Outcomes:
- Faster resolution of shock in hydrocortisone group
- Shorter duration of initial mechanical ventilation in hydrocortisone group
- No significant differences in recurrence of shock, ICU or hospital stay, recurrence of mechanical ventilation, renal-replacement therapy, or new-onset bacteremia/fungemia
- Fewer blood transfusions in hydrocortisone group
- No difference in mortality at 28 days

Criticisms

- Only adverse events judged to be related to the trial regimen were reported, which may limit inferences about adverse events.
- No adjudication of the appropriateness of antibiotic therapy was performed.
- Data on secondary infections were not collected, except bacteremia and fungemia.

Funding

Supported by grants from the National Health and Medical Research Council of Australia, Health Research Council of New Zealand, indirect funding from the National Institute of Health Research in the UK, and Practitioner Fellowships from the National Health and Medical Research Council of Australia.