Thiamine, Ascorbic Acid, and Their Combination on MMP-9/TIMP-1 and Inflammatory Balance in Sepsis

The Effect of Thiamine, Ascorbic Acid, and Their Combination on Matrix Metalloproteinase-9 (MMP-9), Tissue Inhibitor of Metalloproteinase-1 (TIMP-1), and Inflammatory Balance (IL-6/IL-10) in Adult Sepsis Patients: A Two-Center Randomized Controlled Trial

This two-center, open-label randomized controlled trial evaluated the effect of adjunctive thiamine, ascorbic acid, and their combination compared with 0.9% saline on the extracellular matrix-remodeling axis (matrix metalloproteinase-9 [MMP-9] and tissue inhibitor of metalloproteinase-1 [TIMP-1]) and the inflammatory-balance axis (interleukin-6 [IL-6] and interleukin-10 [IL-10]) in adult patients with sepsis. Serum biomarkers were measured by ELISA at baseline and after 72 hours and related to organ dysfunction (SOFA score), acute kidney injury, and in-hospital mortality.

Forty adults admitted to the intensive care unit with sepsis (SOFA score >= 2 and arterial lactate >= 2 mmol/L) were randomized using a computer-generated sequence to four parallel arms: control (0.9% saline), thiamine 200 mg, ascorbic acid 50 mg/kg body weight, or the thiamine plus ascorbic acid combination. Study drugs were infused over 60 minutes every 12 hours for three days, in addition to the standard hour-1 sepsis bundle. MMP-9, TIMP-1, IL-6, and IL-10 were quantified by ELISA at baseline and 72 hours. Outcomes included the MMP-9/TIMP-1 ratio, the IL-6/IL-10 balance, SOFA score, acute kidney injury, and in-hospital mortality.

Inclusion Criteria:

• Adults aged 18 years or older
• Admitted to the intensive care unit with sepsis (Sepsis-3)
• SOFA score >= 2
• Arterial lactate >= 2 mmol/L

Exclusion Criteria:

* Known allergic reaction to thiamine or ascorbic acid