Is Inappropriate Response to Cosyntropin Stimulation Test an Indication of Corticosteroid Resistance in Septic Shock?

We recently published a comparison of two hydrocortisone dosage regimens in patients with septic shock. We compare the results conferred by the two regimens as a function of the response to cosyntropin stimulation test (CST). Patients with septic shock were treated by one of two hydrocortisone regimens: either a 50-mg intravenous bolus every 6 h during 7 days (200 mg group; n = 49), or a 100-mg initial bolus followed by a continuous infusion of 300 mg daily for 5 days (300 mg group; n = 50). Nonresponders was defined as a CST response of 9 µg/dL or less. Nonresponders had more severe septic shock, greater fluid resuscitation needs, and greater vasopressor dependence than responders. When analyzed only as a function of CST results, there was no difference in survival between responders and nonresponders. However, analyses crossing CST results and the treatment regimens showed that patients who were responders and in the 300 mg group had significantly less intensive care unit mortality compared with responders in the 200 mg group (respective mortality of 24% vs. 55% [relative risk 0.43, 95% confidence interval, 0.20 to 0.94, P = 0.018]). Multivariate analysis identified baseline blood cortisol as an independent prognostic factor for 28-day mortality in all groups (hazard ratio 1.002, 95% confidence interval, 1.001 to 1.002, P ≤ 0.0001). The results suggest that in patients who respond to CST, hydrocortisone can provide a dose-dependent benefit. In contrast, nonresponse may indicate corticosteroid resistance. This heterogeneity of response to hydrocortisone may explain the difficulties encountered when trying to demonstrate its benefit in septic shock.

Effects of Increasing Hydrocortisone to 300 mg Per Day in the Treatment of Septic Shock: a Pilot Study.

PURPOSE: The Surviving Sepsis Campaign guidelines recommend hydrocortisone in septic shock only when fluid resuscitation and vasopressors fail to restore hemodynamic stability. Hydrocortisone administration modalities are supported only by low-grade recommendations. Our main objective here was to determine differences in 28-day mortality between two low-dose hydrocortisone regimens for the treatment of septic shock. METHODS: We performed a multicenter, prospective, randomized, double-blind, pilot study in four adult medical intensive care units. Patients presenting septic shock were rapidly administered one of two regimens of hydrocortisone, either a 50-mg intravenous bolus every 6 h during 7 days (200-mg group; n = 59) or a 100-mg initial bolus followed by a continuous infusion of 300 mg daily for 5 days (300-mg group; n = 63). Hydrocortisone was stopped abruptly at the end of treatment. RESULTS: There were no significant differences between the 200-mg and 300-mg groups as concerns 28-day mortality (respectively 52.5% vs. 44.4% [RR 0.84, 95% CI, 0.58-1.22, P = 0.47]), refractory shock incidence or delay from shock to vasopressor cessation. There were also no differences in adverse events between the groups. Shock relapse after hydrocortisone cessation was independent of hydrocortisone regimens, but it was associated with the persistence of infection and the use of etomidate. The resumption of hydrocortisone due to shock relapse was significantly more frequent in the 300-mg group. CONCLUSION: We found no differences in mortality or adverse events between the two hydrocortisone administration regimens. Shock relapse was significantly associated with the persistence of infection and the use of etomidate.