Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients

Prospective, randomized, double-blind, placebo-controlled, single-center trial in ICU patients with organ failure admitted for cardiac surgery, major trauma, or subarachnoid hemorrhage. 200 patients randomized after stratification by diagnosis: 102 to AOX and 98 to placebo. Mean age ~59 years; balanced sex distribution. Exclusion: no consent, participation in another study, liver cirrhosis or major burns, life expectancy <48 hours, or commitment to full aggressive care. Analysis by intention to treat.

Five-day intravenous antioxidant micronutrient regimen started within 24 hours of ICU admission, with a double-loading dose on days 1–2 and therapeutic doses on days 3–5; daily infusion for 10–12 hours. Selenium 540 mcg on days 1–2 and 270 mcg on days 3–5; Zinc 60 mg on days 1–2 and 30 mg on days 3–5; Vitamin C 2700 mg on days 1–2 and 1600 mg on days 3–5; Vitamin B1 305 mg on days 1–2 and 102.5 mg on days 3–5; Vitamin E IV 12.8 mg on days 1–2 and 6.4 mg on days 3–5; Vitamin E enteral 600 mg on days 1–2 and 300 mg on days 3–5. Infusions were intravenous for 10–12 hours daily; solutions prepared in separate bags. Standard ICU vitamins (thiamine 100 mg IV daily and vitamin C 500 mg IV daily) given to all patients.

AOX did not reduce early organ dysfunction (AKI/SOFA scores over the first 5 days). Inflammatory response decreased faster with AOX (lower CRP, P=0.039). Infectious complications and mortality did not differ. Overall hospital stay was shorter with AOX, driven by trauma patients; no clear benefit in brain-injured or cardiac patients. Authors conclude AOX reduces inflammation but does not improve early organ dysfunction; potential niche in highly inflammatory conditions, but optimal dosing and patient selection require further study.

Single-center, underpowered for subgroup analyses; 47 protocol violations (19 in placebo, 28 in AOX) and heterogeneity among diagnostic categories (notably trauma with brain injury); lack of post-ICU SOFA measurements; potential imbalance in baseline brain injury severity affecting mortality; nutritional confounders may have influenced outcomes.