A Combination of Hydrocortisone, Ascorbic Acid, and Thiamine for Septic Shock: A Systematic Review of Randomized Controlled Trials Evaluating Mortality Outcomes
Vira Farhati, Joanna Hunter, Prenali Dwisthi Sattwika, Muhammad Fakhrur RoziAbstract
Background:
The Sepsis-3 definition highlighted the dysregulated immune response to infection. However, evidence supporting therapeutic strategies for this complex dysregulation has not yielded promising results. This systematic review aimed to evaluate the effectiveness of hydrocortisone as an anti-inflammatory drug combined with ascorbic acid and thiamine in reducing mortality among adult patients with septic shock.
Materials and Methods:
This review included randomized controlled trials (RCTs) assessing the effectiveness of combined hydrocortisone, ascorbic acid, and thiamine in reducing mortality among patients with septic shock. We systematically searched Ovid MEDLINE, EMBASE, CENTRAL, CINAHL, and ClinicalTrials.gov up to July 2024. We critically appraised the eligible studies and narratively synthesized the findings.
Results:
Of the 566 identified articles, 6 RCTs met the eligibility criteria. The intervention dosages were consistent across trials—hydrocortisone: 200 mg/day, ascorbic acid: 6 g/day, and thiamine: 400 mg/day. None of the included RCTs demonstrated a statistically significant reduction in mortality between the intervention and control groups. As quantitative pooling was not performed, no overall effect estimate was calculated. Shock resolution, as a secondary outcome, was inconsistently reported, with three studies demonstrating statistically significant improvement. The reported safety profile was variable, with blood glucose disturbances and hypernatremia identified as the most frequently reported adverse events in three studies.
Conclusions:
This review found that the combination of hydrocortisone, ascorbic acid, and thiamine did not reduce mortality among patients with septic shock. While some studies suggested potential benefits in shock resolution, these findings were inconsistent, based on low-certainty evidence, and safety reporting was variable. Therefore, current evidence remains insufficient to support its routine use.