No Mortality Benefit of Methylprednisolone Over Hydrocortisone in Septic Shock, reveals study

Septic shock, a critical condition needing intensive care, has high mortality rates. Corticosteroids are frequently used to treat the inflammatory response, and hydrocortisone is the recommended medication. Clinicians, however, may give methylprednisolone instead, which makes it unclear if it is effective. A retrospective cohort study was performed using the MIMIC-IV v3.0 database, comparing outcomes in patients treated with either medication.

The research involved 1,607 septic shock patients. To control confounders, researchers conducted 1:1 propensity score matching (PSM) and got 376 matched pairs of patients—one receiving methylprednisolone and the other hydrocortisone. The primary outcome was death during 30 days, and subgroup and sensitivity analyses were carried out to check the robustness of the results. Other factors like the length of stay in ICU, blood glucose, and vasopressor requirement were also checked.

Key Findings

• The total 30-day mortality rate among the study population was 42.1%.

• Following propensity score matching, 37.5% (141 patients) of the methylprednisolone group and 34.8% (131 patients) of the hydrocortisone group died within 30 days (HR = 1.105, 95% CI: 0.871–1.402, P = 0.410).

• Subgroup analyses according to age, sex, blood culture result, pneumonia status, and invasive mechanical ventilation (IMV) yielded similar results, with no significant difference in mortality between groups.

• Sensitivity analyses excluding missing values supported the primary findings.

• But patients in the methylprednisolone group had longer ICU stays, greater blood glucose levels, and shorter vasopressin maintenance duration than those in the hydrocortisone group.

Despite guidelines favoring hydrocortisone, the study suggests that methylprednisolone is still commonly used, possibly due to clinician preference or drug availability. The lack of significant mortality differences indicates that both corticosteroids may have similar effectiveness in septic shock management.

In adults with septic shock, no difference in 30-day mortality was seen between patients who received methylprednisolone and those who received hydrocortisone. Methylprednisolone was, however, associated with increased length of stay in the ICU and with increased blood glucose levels. These results indicate that both corticosteroids could be useful treatments but that additional randomized trials are required to establish their relative efficacy and safety.

Reference:

Xu, J., Cai, H. & Zheng, X. Effect of methylprednisolone vs hydrocortisone on 30-day mortality in critically ill adults with septic shock: an analysis of the MIMIC-IV database. BMC Infect Dis 25, 328 (2025).https://doi.org/10.1186/s12879-025-10731-x