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Answering the Question? IV Vitamin C for the Critically Ill

April 6, 2022

Written by Jonathan Brewer

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IV Vitamin C (IVVC) administration appeared to be safe and reduced overall mortality in this meta-analysis of critically ill patients, when given in higher doses and as monotherapy.

Why does this matter?
Inflammation, oxidative stress, and subsequent organ dysfunction are the cornerstones of critical illness. IVVC has been found in early animal and human studies to be associated with reduced oxidative stress. Individual studies have had mixed results: CITRUS ALI, HYVCTTSSS, VITAMINS, VITAMINS for kids, ORANGES, and ACT. Does this theoretical effect translate to our clinical patients?

“A vitamin a day keeps the doctor away”
This was a systematic review and meta-analysis of 15 trials (12 regarding sepsis and 3 regarding non-sepsis related illnesses) involving 2,490 patients. When compared with placebo, inclusion of both high and low-dose IVVC reduced overall mortality, though not statistically significantly (RR 0.87, 95%CI, 0.75-1.00; p = 0.06). However, high-dose IVVC (≥ 10,000 mg/d) was statistically significant and resulted in lower overall mortality (RR 0.70; 95%CI, 0.52-0.96; p = 0.03) when compared to low-dose IVVC.

Some individual studies did not demonstrate a benefit with IVVC (such as the VITAMINS trial – that combined IVVC with thiamine and hydrocortisone), which may have contributed to the lack of effect. When IVVC was given as monotherapy, there was a significant reduction in overall mortality (RR 0.64, 95%CI, 0.49-0.83; p = 0.006). No trial reported an increase in adverse events related to IVVC.

What I take from this is that IVVC may be yet another tool to consider for treatment of our critically ill patients. However, more trials are needed to determine which critically ill population this may benefit the most.

Editor’s note: We need to approach trials about vitamin C – specifically hydrocortisone + ascorbate + thiamine (HAT) – very carefully. The primary author of the paper that sparked the “metabolic resuscitation” craze resigned. This meta-analysis is interesting, but most of the RCTs are small. It’s encouraging, but let’s be cautious. ~Clay Smith

IV Vitamin C in Critically Ill Patients: A Systematic Review and Meta-Analysis. Crit Care Med. 2022 Mar 1;50(3):e304-e312. doi: 10.1097/CCM.0000000000005320.

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