2026 Southeastern Residency Conference

Title: Hydrocortisone vs. Methylprednisolone for the Treatment of Refractory Septic Shock 
Authors: Erin Weippert, Sydney Kisala, Van Bui, Sarah Jung, Marina Rabinovich  
Background: The 2024 Society of Critical Care Medicine Guidelines on the Use of Corticosteroids in Sepsis recommend the use of corticosteroids in patients with septic shock. The recommended regimen is hydrocortisone 200 – 300 mg intravenously (IV) per day in divided doses or as a continuous infusion. Due to an ongoing IV hydrocortisone shortage, IV methylprednisolone is increasingly used as an alternative, though evidence for its safety and efficacy in septic shock is limited. The purpose of this study was to compare the effectiveness and safety of methylprednisolone to hydrocortisone in the management of refractory septic shock. 
Methods: This was a single-center, retrospective, cohort study conducted at a safety net hospital in Atlanta, GA. Patients with septic shock who received methylprednisolone during the primary and secondary IV hydrocortisone shortage periods (February 2023 - February 2024 and May - August 2025) were compared with patients who received hydrocortisone (February 2024 - February 2025). Eligible patients were at least 18 years old, admitted to an intensive care unit (ICU), diagnosed with septic shock requiring at least two vasopressors, and received at least 48 hours of either IV methylprednisolone or IV hydrocortisone. Patients were excluded if they were pregnant, received corticosteroids for an alternative indication, or received both hydrocortisone and methylprednisolone. Variables collected include patient demographics, highest serum lactate level, initial Sequential Organ Failure Assessment (SOFA) score, type and number of vasopressors received, source of infection, steroid duration, and time from shock onset to steroid initiation. The primary outcome was time to shock resolution, defined as the attainment of a goal mean arterial pressure (MAP) ≥ 65 mmHg without vasopressor support for at least 24 hours. Secondary outcomes included the incidence of shock recurrence, time to achieving lactate of < 2 mmol/L, receipt of vasopressors and corticosteroids beyond 7 days, hospital mortality at 28 days, ICU length of stay, and duration of corticosteroid therapy. Safety outcomes included the incidence of hyperglycemia, hypernatremia, and gastrointestinal bleeding. Descriptive statistics were used for analysis and categorical variables were compared using a chi-square or Fisher’s exact test while continuous variables were compared using the Mann-Whitney U test. A p-value of 0.05 was considered statistically significant. 
Results: A total of 191 patients were included for analysis with 116 included in the hydrocortisone group and 75 in the methylprednisolone group. Baseline characteristics were similar between groups with the majority of patients being male, of Black or African American race, median age of 60 years, and admitted to the medical ICU. However, patients in the methylprednisolone group had a greater need for renal replacement therapy (50.6% vs. 35.3%, p=0.036). 85 patients (73.3%) in the hydrocortisone group and 50 patients (67%) in the methylprednisolone group achieved shock resolution (p=0.327). The primary outcome of time to shock resolution was similar in the two groups (4 days vs. 3.9 days, p=0.479). For secondary outcomes, there were no significant differences between the groups for recurrence of shock, time to achieving lactate of < 2 mmol/L, or ICU length of stay. More patients in the hydrocortisone group received vasopressors and corticosteroids beyond seven days (25.9% vs. 9.3%, p=0.005), while the methylprednisolone group exhibited a higher 28-day hospital mortality (56% vs. 38.8%, p=0.02). There were no significant differences in safety outcomes between the groups. 
Conclusions: The results of this study demonstrated no difference in time to shock resolution between hydrocortisone and methylprednisolone in critically ill patients with septic shock. These results suggest that methylprednisolone may be a reasonable alternative to hydrocortisone in this patient population, although larger prospective studies are needed to confirm these findings and evaluate long-term outcomes.