PURPOSE: A blunted response to exogenous corticotrophin (ACTH) on admission is associated with increased mortality in patients with septic shock, and low dose corticosteroid (CS) replacement attenuates this risk. The recommended duration of steroid therapy is 7 days, but the response to repeat ACTH stimulation after this treatment is unknown. We repeated ACTH stimulation after 7 days of therapy to determine how many patients had a persistently abnormal response.
METHODS: We conducted a prospective observational study of patients with septic shock requiring at least one vasopressor agent to maintain MAP>65. Patients received 250mg of corticotrophin with total cortisol levels obtained at baseline, and 30 and 60 minutes after ACTH (T0, T30, T60). Nonresponders (NR) were defined as a change in cortisol ≤; 9ng/dl at T30 and T60 after ACTH. After 7 days of steroid therapy plus a 24 hour steroid washout period, ACTH stimulation test was repeated.
RESULTS: 196 patients met inclusion criteria and received ACTH stimulation. 70 were NR and of these, 20 were enrolled. Of these 20, 8 (40%, 95% CI 22–62%) died before repeat stimulation, 1 was lost to follow up, and 3 were maintained on CS (1 with persistent shock and 2 postoperative) beyond 7 days of therapy. Of the remaining 8 patients, none required vasopressors at day 7, yet 5 (62%, 95% CI 30–86%) remained NR after 7 days of steroid replacement. No Day 1 criteria predicted NR on Day 8.
CONCLUSION: Duration of therapy in relative adrenal insufficiency remains poorly defined. Our study suggests that among patients who no longer meet criteria for septic shock and survive beyond day 7, blunted response to ACTH may be common.
CLINICAL IMPLICATIONS: In patients with septic shock with blunted cortisol response to ACTH completing a 7 day course of corticosteroid treatment, mortality remains high. 30–86% of these non-responders may still have blunted responses after 7 days of steroid replacement. The implications of this and potential treatment indications are not known but further study is warranted.
DISCLOSURE: Lonny Yarmus, No Financial Disclosure Information; No Product/Research Disclosure Information