Thiamine, Ascorbic Acid, and Hydrocortisone As a Metabolic Resuscitation Cocktail in Sepsis: A Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 34582409 · doi:10.1097/CCM.0000000000005262
What was done
Authors conducted a systematic review and meta-analysis searching PubMed, Embase, and Cochrane databases through March 2021. They included randomized controlled trials evaluating a combination of thiamine, ascorbic acid, and hydrocortisone versus standard care or placebo in adult ICU patients with sepsis or septic shock. The primary endpoint was change in Sequential Organ Failure Assessment (SOFA) score within 72 hours. Secondary outcomes included vasopressor duration, ICU mortality, and a composite renal endpoint (KDIGO stage 3 acute kidney injury or need for renal replacement therapy).
What was found
Eight randomized controlled trials with 1,335 patients were analyzed. For the 72-hour SOFA score change (8 RCTs, n = 1,253), the median of mean improvement was -3.2 in the intervention group compared to -1.8 in controls, yielding a weighted mean difference of -0.82 points (95% CI, -1.15 to -0.48). Vasopressor duration was significantly reduced in the intervention group across 6 RCTs (exact values not reported in abstract). There was no significant difference in ICU mortality or the renal composite outcome across 7 RCTs.
Why it matters
Early observational studies suggested dramatic benefits from this metabolic cocktail, but this pooled RCT evidence demonstrates that the small physiological improvements do not translate into clinical survival or renal benefits in sepsis.
Limits
The abstract does not provide exact effect estimates, confidence intervals, or p-values for mortality, vasopressor duration, or renal failure. The overall pooled sample size across 8 trials is relatively modest (1,335 patients), and the clinical significance of a 0.82-point SOFA reduction is minimal.
Cited by
- context A study of 47 sepsis patients treated with IV vitamin C (6 g/day), hydrocortisone, and thiamine reported an 8% mortality rate compared to roughly 40% in historical controls receiving standard of care.