Clinical Outcomes of Various Hydrocortisone Dosing Regimens for Septic Shock

Introduction: Adjunctive use of IV hydrocortisone 200 mg daily is recommended by the SCCM Surviving Sepsis Guidelines for refractory septic shock. At our institution, this is administered as 50 mg every six hours (Q6H). During a national hydrocortisone shortage, alternative dosing strategies—100 mg every 8 (Q8H) or 12 hours (Q12H)—were proposed to conserve supply, as each 100 mg single-use vial supports only one dose and the standard regimen requires four vials per day with ample waste. Given hydrocortisone’s short half-life, we questioned whether reduced dosing frequency might impact clinical outcomes.


Methods: This retrospective cohort study evaluated adult patients with septic shock admitted to the medical intensive care unit (ICU) at University of Kentucky HealthCare between March 1, 2023, and February 29, 2024. Patients were included if they received hydrocortisone 50 mg Q6H, 100 mg Q8H, or 100 mg Q12H for at least 24 hours, with concomitant vasopressor use and antibiotic administration for suspected sepsis at steroid initiation. Patients were excluded if they died or switched to a different dosing regimen within 24 hours of starting hydrocortisone. The primary outcome was shock resolution by day 7, defined as vasopressor discontinuation without death. Secondary outcomes included time to vasopressor discontinuation, ICU and hospital length of stay, 28- and 90-day mortality, incidence of hyperglycemia, secondary infections, and bleeding events requiring transfusion.


Results: A total of 194 patients were included: 71.6% received hydrocortisone 50 mg Q6H, 5.7% received 100 mg Q8H, and 22.7% received 100 mg Q12H. Shock resolution by day 7 occurred in 69.8% patients in the Q6H group, 90.9% in the Q8H group, and 75.0% in the Q12H group (p = 0.312). There was a significant reduction in time to vasopressor discontinuation in the Q8H compared to Q12H (20.1 h vs 68.3 h; p=0.009), however increased in the Q6H to the Q12H cohort (45.5 h vs 68.3 h; p= 0.043).


Conclusions: Comparable outcomes support alternative hydrocortisone dosing strategies during shortages to reduce waste. However, findings should be interpreted with caution due to small sample sizes in the Q8H and Q12H groups and baseline differences. As hydrocortisone shortages persist, future inclusion of additional patients may help reduce type II error.