Intravenous Ascorbic Acid in Septic Shock
Do not administer intravenous vitamin C to adults with septic shock, as the highest-quality evidence demonstrates it increases the risk of death or persistent organ dysfunction compared to placebo.
Evidence Against Vitamin C Use
The most recent and rigorous trial—the LOVIT study (2022)—enrolled 872 patients with septic shock requiring vasopressors and found that intravenous vitamin C (50 mg/kg every 6 hours for up to 96 hours) significantly increased the composite outcome of death or persistent organ dysfunction at 28 days (44.5% in vitamin C group vs 38.5% in placebo; risk ratio 1.21,95% CI 1.04–1.40; P=0.01) 1. This represents a 21% relative increase in harm with vitamin C therapy 1.
At 28 days, mortality was numerically higher in the vitamin C group (35.4% vs 31.6%), though this did not reach statistical significance 1. Importantly, vitamin C provided no benefit for any secondary outcome, including organ dysfunction scores, duration of mechanical ventilation, ICU length of stay, or acute kidney injury 1.
Guideline Recommendations
A 2023 international rapid practice guideline from 21 experts across 16 countries issued a conditional recommendation against using intravenous vitamin C in adult patients with sepsis, beyond standard nutritional supplementation 2. The panel judged that undesirable consequences probably outweigh desirable consequences 2.
The guideline found that at 90-day follow-up, intravenous vitamin C probably does not substantially impact mortality (relative risk 1.05,95% CI 0.94–1.17; 6 trials, n=2148, moderate certainty) 2. While vitamin C may slightly reduce duration of vasopressor support by approximately 19 hours, this effect is of low certainty and does not translate into meaningful clinical outcomes 2.
Why Earlier Enthusiasm Was Misplaced
Early observational studies and small single-center trials suggested potential benefit, but these findings have not been replicated in adequately powered randomized controlled trials 3, 4. The ViCTOR trial (2020) found no mortality benefit from the combination of vitamin C, thiamine, and hydrocortisone (57% mortality in HAT group vs 53% in routine care; p=0.4) 5.
The heterogeneity in dosing regimens, timing of initiation, and treatment duration across studies has contributed to inconsistent results 4. However, the most recent, largest, and highest-quality trial (LOVIT) definitively shows harm 1.
Safety Concerns
Vitamin C is not benign in this population. In the LOVIT trial, one patient experienced severe hypoglycemia and another had a serious anaphylaxis event attributed to vitamin C 1. These adverse events underscore that high-dose intravenous vitamin C carries real risks in critically ill patients 1.
What to Do Instead
Focus on evidence-based septic shock management 6, 7:
- Fluid resuscitation: Administer at least 30 mL/kg crystalloid within the first 3 hours 6, 7
- Vasopressor therapy: Use norepinephrine as first-line agent, targeting MAP ≥65 mmHg 6, 7
- Adjunctive hydrocortisone: Consider hydrocortisone 200 mg/day IV only if hypotension persists despite adequate fluids and vasopressors 6, 8
- Source control: Identify and treat the underlying infection 6
Common Pitfalls to Avoid
- Do not use vitamin C based on outdated observational data or mechanistic rationale—the definitive randomized trial shows harm 1
- Do not combine vitamin C with thiamine and hydrocortisone as a "cocktail"—this regimen has failed to show mortality benefit in randomized trials 5
- Do not be swayed by the theoretical benefits of vitamin C on endothelial function or inflammatory mediators—these mechanisms do not translate into improved clinical outcomes and may actually worsen them 2, 1
- Discourage small single-center trials on this topic, as the international guideline panel explicitly recommends 2