Key Takeaway
Meta-analysis of 11 RCTs (1,737 patients) found high-dose IV vitamin C in sepsis was not associated with lower short-term mortality but significantly shortened vasopressor duration.
Summary
Systematic review and meta-analysis of randomized controlled trials examining whether intravenous high-dose vitamin C improves outcomes in sepsis patients. The study was registered at UMIN000040528 and searched EMBASE, Cochrane Central Register, and MEDLINE.
Eleven RCTs encompassing 1,737 patients met inclusion criteria. Using random-effects models, the primary outcome of short-term mortality showed no significant reduction with high-dose IV vitamin C (risk ratio 0.88, 95% CI 0.73-1.06, p = 0.18, I-squared = 29%). However, secondary outcomes were more promising: vitamin C was associated with significantly shorter vasopressor duration and greater Sequential Organ Failure Assessment (SOFA) score decline at 72-96 hours.
The findings suggest that while high-dose IV vitamin C may not reduce mortality on its own in sepsis, it appears to improve organ function markers and hemodynamic stability. Adverse effects were rare, with one study reporting hypernatremia. The results contributed to the ongoing debate about vitamin C as an adjunctive therapy in critical care.
Methods
- Systematic review and meta-analysis of RCTs
- Searched EMBASE, Cochrane Central Register, MEDLINE
- 11 RCTs with 1,737 patients included
- Random-effects models for pooled analysis
- Two independent reviewers for data extraction
- Primary outcome: short-term mortality
Key Results
- No significant mortality reduction (RR 0.88, 95% CI 0.73-1.06, p = 0.18)
- Low heterogeneity for mortality (I-squared = 29%)
- Significantly shorter vasopressor duration (SMD -0.35)
- Greater SOFA score decline at 72-96 hours
- Rare adverse effects (one study reported hypernatremia)
Limitations
- Mortality outcome may be underpowered
- Heterogeneity in vitamin C dosing protocols across trials
- Variable definitions of sepsis across studies
- Cannot determine optimal dose, timing, or duration
- Most included trials were relatively small