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Mixed results from studies of steroids for septic shock (APROCCHSS, ADRENAL)
Clinical Question
Does the use of steroids in critically ill patients reduce mortality?
Bottom line
In the Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trial done exclusively in France, administration of 7 days of hydrocortisone plus fludrocortisone to patients with septic shock led to fewer deaths and faster time to weaning from mechanical ventilation and vasopressors without increasing the number of serious adverse events. You would have to treat 17 patients with this combination of steroids to prevent one death. A second multinational trial of hydrocortisone alone (Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock [ADRENAL]) did not show a mortality benefit but also resulted in faster resolution of shock and quicker cessation of mechanical ventilation. The ADRENAL trial did not have as high a mortality rate as the APROSCCHSS study, suggesting a lower severity of illness overall. Given the differences in patient populations, drugs administered, and individual outcomes in these 2 randomized studies, it is difficult to draw strong conclusions. However, both trials show some beneficial effects of the use of steroids in septic shock. 1b
Reference
Study design: Randomized controlled trial (double-blinded)
Funding: Government
Setting: Inpatient (ICU only)
Synopsis
In the APROCCHSS study, 1241 patients with septic shock for less than 24 hours were randomized to receive either hydrocortisone plus fludrocortisone or placebo for 7 days. A previous arm of this trial also evaluated drotrecogin alfa (activated) until this drug was taken off the market in 2011. Hydrocortisone or matching placebo were administered intravenously at 50 mg every 6 hours; fludrocortisone or matching placebo were given via nasogastric tube at 50 mcg each morning. The 2 groups were similar at baseline: two-thirds were men, average age was 66 years, 80% were admitted to the intensive care unit (ICU) from a medical ward, and the most common site of infection was the lung. For the primary outcome of 90-day mortality, there were fewer deaths in the hydrocortisone plus fludrocortisone group (43.1% vs 49.1%; relative risk [RR] 0.88; 95% CI 0.78 - 0.99; P = .03). Further, this group had significantly fewer deaths at ICU discharge, hospital discharge, and day 180; had a shorter time to weaning from mechanical ventilation and vasopressor therapy; and had more vasopressor-free days and organ failure–free days. There were no differences in the 2 groups in the number of serious adverse events, including gastrointestinal bleeding, secondary infection, or neurologic events, but the hydrocortisone plus fludrocortisone group had a higher risk of hyperglycemia (RR 1.07; 1.03 - 1.12; P = .002). A second study of 3658 patients with septic shock (ADRENAL) evaluated the efficacy of continuous intravenous infusion with hydrocortisone alone at 200 mg per day for 7 days compared with matching placebo. In this trial, no significant mortality difference was found (27.9% in hydrocortisone group vs 28.8% in placebo group), but patients in the steroid group had faster resolution of shock and shorter duration of initial mechanical ventilation. Differences in the patient populations of the 2 studies may account for the lack of mortality effect seen in the ADRENAL study. The patients in the ADRENAL trial may have been less sick (as evidenced by the lower mortality rates). They also had higher rates of surgical admissions and abdominal infections and lower rates of pulmonary and genitourinary infections.
Reviewer
Nita Shrikant Kulkarni, MD
Assistant Professor in Hospital Medicine
Northwestern University
Chicago, IL
Comments
Good poem
J'en conclus que l'administration de stéroîdes dans le choc septique est bénéfique.
In my present practice as semiretired neurosurgical consultant this may not be related to my present practice but certainly in my old practice corticosteroids use in septic conditions and intracranial conditions remained controversial , gradually we stopped using corticosteroids in trauma intracranial bleeding, and stroke and septic condition was rare but infectious specialist never used it.
This has been debated since I was a resident over 30 years ago and it may just be one of those things that will never be resolved.
The evidence on steroids with sepsis seems to change every week.
pt died anyway!