CHEST Guidelines-Vitamin-C-Is-Not-Ready-for Prime-Time-in-Seps

Vitamin-C-Is-Not-Ready-for Prime-Time-in-Seps

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The letter to the editor critiques a study by Marik et al., which investigated the use of hydrocortisone, vitamin C, and thiamine for treating severe sepsis and septic shock. The authors, Andre C. Kalil and colleagues, from the University of Nebraska Medical Center, highlight significant methodological flaws in the study, such as its lack of blinding, randomization, control groups, and case-control propensity matching. The small sample size further increased the risk of bias and false benefits. Baseline imbalances, such as higher rates of pre-existing conditions and disease severity in the control group, suggest potential confounding biases. They also noted that vitamin C levels were measured in only the treatment group, which could lead to a major selection bias. Additionally, the administration of hydrocortisone, another element of the treatment, could introduce further confounding. The lack of data on timely antibiotic initiation, a crucial factor for survival, could skew the study’s findings. Concerns were also raised about the safety of vitamin C due to potential acute renal failure, with the study's sample size being too small to detect this side effect. The claimed 87% reduction in death odds appears extraordinary and questionable given the study's flaws. Kalil and colleagues assert there's no solid evidence to support the use of vitamin C outside clinical trials, advocating for a double-blind randomized controlled trial to ascertain its true effectiveness. They suggest an adaptive trial design, which could confirm or refute the findings more efficiently. Overall, they conclude that ethically and scientifically, vitamin C should not be used for sepsis treatment until more robust data is obtained.

Keywords

sepsis treatment

Marik study critique

hydrocortisone

vitamin C

thiamine

methodological flaws

University of Nebraska Medical Center

randomized controlled trial

confounding biases

adaptive trial design