Clinical Pearls & Morning Reports
Glucocorticoids have been used as an adjuvant therapy for septic shock for more than 40 years. Nonetheless, uncertainty about their safety and efficacy remains. Venkatesh et al. conducted the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) trial to test the hypothesis that hydrocortisone results in lower mortality than placebo among patients with septic shock. Read the latest NEJM Original Article here.
Q: What are the current guidelines regarding the use of hydrocortisone in patients with septic shock?
A: Current clinical practice guidelines recommend the use of hydrocortisone in patients with septic shock if adequate fluid resuscitation and treatment with vasopressors have not restored hemodynamic stability; however, the guidelines classify the recommendation as weak, on the basis of the low quality of available evidence.
Q: Does the adjunctive use of glucocorticoids result in lower mortality than placebo among patients with septic shock?
A: In the trial by Venkatesh et al., the primary outcome was death from any cause at 90 days after randomization. The study found that the administration of hydrocortisone did not result in lower 90-day mortality than placebo among patients with septic shock. At 90 days after randomization, 511 of 1832 patients (27.9%) who had been assigned to receive hydrocortisone had died, as had 526 of 1826 (28.8%) who had been assigned to receive placebo (odds ratio, 0.95; 95% confidence interval [CI], 0.82 to 1.10; P=0.50).
A: The authors observed a more rapid resolution of shock and a lower incidence of blood transfusion among patients who received hydrocortisone than among those who received placebo. Patients who had been assigned to receive hydrocortisone had a shorter time to ICU discharge and earlier cessation of the initial episode of mechanical ventilation than did those who had been assigned to receive placebo. There were no significant between-group differences with respect to mortality at 28 days, the rate of recurrence of shock, the number of days alive and out of the ICU or hospital, the duration and rate of recurrence of mechanical ventilation, the rate of use of renal-replacement therapy, or the rate of new-onset bacteremia or fungemia. A total of 33 adverse events was reported in the trial population, with a higher percentage in the hydrocortisone group than in the placebo group (1.1% vs. 0.3%, P=0.009). There were 6 serious adverse events, with 4 occurring in the hydrocortisone group and 2 in the placebo group.
A: The trial differs from previously published trials in several respects. Hydrocortisone was administered by means of continuous infusion, because such a plan has been shown to attenuate the inflammatory response and reverse shock. Practice guidelines for septic shock suggest that infusions may minimize potentially harmful metabolic effects of glucocorticoids. A tapering strategy was not used for the discontinuation of glucocorticoids, because a beneficial effect of these agents on survival was previously reported without tapering. The authors did not perform corticotropin testing, because its interpretation in critically ill patients is controversial and such testing is not recommended in current clinical practice guidelines. Fludrocortisone was not administered, because it has been shown previously to be ineffective.