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Stress-dose corticosteroids appear safe and generally beneficial in patients with septic shock undergoing mechanical ventilation, without improving survival. That's the takeaway from the ADRENAL trial recently published in the New England Journal of Medicine.
Investigators (led by the famed ANZICS collaborative) randomized 3,800 patients with septic shock requiring mechanical ventilation in 69 medical-surgical ICUs around the developed world to receive either hydrocortisone (200 mg/day) or placebo for 7 days for as long as they were in the ICU. Patients were 2/3 medical, 1/3 surgical.
There was no difference in 90-day mortality (the primary outcome): about 28% in each group. Lots of press reaction focused on this; it was a negative trial.
However, patients receiving steroids had resolution of shock 1 day sooner overall (median 3 vs. 4 days). They also were liberated from the ventilator faster (6 vs. 7 days) and had a median of two fewer ICU days during their hospitalizations.
This came at an expected cost of more hyperglycemia, which was virtually always manageable.
Serious adverse events were adjudged to be 4 in the steroid group, and 2 in the placebo group: about 0.3% in each, not statistically significant.
There was no increased rate of infections observed in the steroid group.
Pfizer supplied the hydrocortisone but reportedly had no input into study design or manuscript preparation.
The simultaneously published APROCHHSS trial (n=1,800) found improved mortality among patients who received stress-dose hydrocortisone along with fludrocortisone 50 μg for severe septic shock, compared to placebo.
The findings rhymed with CORTICUS, a much smaller trial, in showing accelerated resolution of shock with steroids.
They also add wind to the sails of the concept of "metabolic resuscitation," in which vitamin C for septic shock is given along with hydrocortisone and thiamine. This cocktail was associated with impressive observed survival in a non-randomized case series. Vitamin C alone improved survival from septic shock in a small randomized trial. The treatment is still considered unproven and controversial.
The ADRENAL study's results could shift clinical practice away from a general reluctance among physicians to give steroids (reserving them only for patients with septic shock refractory to vasopressors) to a more liberal approach. Encouraged by the risk/benefit balance in ADRENAL, many intensivists will likely provide stress-dose IV hydrocortisone (which equates to a mere 50 mg/day of prednisone) to patients with septic shock on any dose of vasopressor, earlier in their clinical course, in the hopes of resolving shock and respiratory failure faster. Some may choose to add a dose of 50 μg fludrocortisone, for good measure.