The Case

A 70-year-old man with a history of hypertension and type 2 diabetes presents to the emergency department from home with fever, cough, and shortness of breath for two days. He is a nonsmoker and was immunized against influenza in the fall. Vitals at triage are temperature 102.7°F, blood pressure 105/61 mmHg, heart rate 118 bpm, respiratory rate 22 bpm, and oxygen saturation 89% on room air. The chest X-ray confirms pneumonia. The nurses have already established two intravenous (IV) lines of normal saline and provided supplemental oxygen via nasal cannula that corrects his hypoxia. He is also receiving appropriate antibiotics. His blood pressure begins to drop but responds to IV fluids. You wonder if IV hydrocortisone would provide any additional benefit.

Background

The Surviving Sepsis Campaign recently published its 2016 guidelines. It continues to give a weak recommendation for the use of intravenous hydrocortisone at a dose of 200 mg per day in patients with refractory septic shock (ie, inadequate response to fluid resuscitation and vasopressor therapy); this is based on low-quality evidence. As stated by the campaign:

We suggest against using IV hydrocortisone to treat septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability. If this is not achievable, we suggest IV hydrocortisone at a dose of 200 mg per day (weak recommendation, low quality of evidence).

Clinical Question

In adult patients with severe sepsis, does the use of IV hydrocortisone prevent the development of septic shock?

Reference

Keh D, Trips E, Marx G, et al. Effect of hydrocortisone on development of shock among patients with severe sepsis: the HYPRESS randomized clinical trial. JAMA. 2016;316(17):1775-1785.

• Population: Adult patients in intermediate care units or intensive care units.
  • Inclusion: Evidence of infection, at least two SIRS criteria, and organ dysfunction present for not longer than 48 hours.
  • Exclusion: Septic shock, younger than 18 years of age, hypersensitivity to hydrocortisone or mannitol, history of regularly on glucocorticoids, pregnant, breastfeeding, moribund, or had a do-not-resuscitate order.
• Intervention: 50 mg IV bolus of hydrocortisone, followed by a continuous infusion of 200 mg/24 hours for five days followed by dose tapering until day 11.
• Comparison: Placebo (mannitol).

• Outcome:
  • Primary: Development of septic shock (defined as hypotensive despite adequate fluid resuscitation or needing vasopressors for more than four hours) within 14 days.
  • Secondary: Time until septic shock or death (whichever came first); mortality in the ICU and hospital; mortality at 28, 90, and 180 days; duration of stay in the ICU and hospital; Sequential Organ Failure Assessment score; duration of mechanical ventilation; renal replacement therapy; and frequency of delirium.
  • Adverse Events: Development of secondary infections, weaning failure, muscle weakness, gastrointestinal bleeding, and hyperglycemia.

Authors’ Conclusions

“Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients.”

Key Results

In the study, 380 adult patients were randomized to receive hydrocortisone (n = 190) or placebo (n = 190). The mean age was 65 years, with 65 percent being male.