CITRIS-ALI - Vitamin C for Sepsis-ARDS?

Written by Clay Smith

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High-dose vitamin C made no impact on short-term SOFA score or in lowering inflammatory markers in patients with sepsis and ARDS. There may have been a 28-day mortality reduction in the vitamin C group.

Why does this matter?
Not long ago, a sepsis cocktail using thiamine, vitamin C, and steroids was published and showed promising results. However, it was just a large case series. A subsequent meta-analysis of vitamin C in a mixed ICU population was underwhelming. What would a more rigorous approach with vitamin C show?

Sepsis/ARDS wonder drug?
This was a multicenter RCT with 167 patients with both sepsis and ARDS in the first 24 hours of illness, who were randomized to either high-dose vitamin C (50mg/kg in D5) or placebo Q6h for 96 hours. There was no difference in the primary outcome of both change in SOFA score at 96 hours and CRP or thrombomodulin levels at 168 hours. Both the vitamin C and placebo groups had a SOFA score of about 10 that dropped to about 7, with a difference of -0.10 (95% CI, -1.23 to 1.03). CRP levels increased at 168 hours in the vitamin C vs placebo groups, although not statistically significantly: 54.1 vs 46.1 μg/mL, respectively; difference, 7.94 μg/mL; 95% CI, -8.2 to 24.11) as did thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2). They gathered 45 additional secondary outcomes, one of which was 28-day mortality, and found it was lower in the vitamin C vs placebo groups: 29.8% (25/84) vs 46.3% (38/82), respectively; difference 16.58%, 95%CI 2% to 31.1%). Keep in mind, there was no statistical adjustment for multiple comparisons. The potential mortality benefit is interesting but is only hypothesis generating at this point.

Source
Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial. JAMA. 2019 Oct 1;322(13):1261-1270. doi: 10.1001/jama.2019.11825.

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