In this episode, I’ll discuss the use of vitamin C in critically ill patients.
Even before the combination of vitamin C with thiamine and hydrocortisone was published, researchers have been exploring the potential benefit of vitamin C use in critically ill patients.
The journal Critical Care Medicine has recently published a systematic review and meta-analysis on IV vitamin C use in critically ill patients to evaluate the effects of vitamin C alone or in combination on outcomes in the critically ill.
The authors of this review identified 15 studies with nearly 2500 patients. 6 of the studies looked at monotherapy with vitamin C, 8 studies looked at the combination of vitamin C, thiamine, and hydrocortisone, and one study looked at vitamin C with enteral alpha-tocopherol. The primary outcome was overall mortality. The authors did identify several subgroups a priori which included combination vs monotherapy, high dose vs low dose, and septic vs non-septic patients.
When all studies were considered, there was not a statistically significant benefit on mortality found with IV vitamin C use although there appeared to be a trend favoring IV vitamin C.
Looking at the pre-specified subgroups, there was no effect found on mortality in the studies of IV vitamin C in combination with thiamine and hydrocortisone but there was a statistically significant decrease in mortality in the monotherapy group as well as the high dose group.
In this analysis high dose IV vitamin C was defined as doses of 10 grams per day or more.
There were no adverse events identified by the meta-analysis as being more likely in the patients who received vitamin C whether high dose or in combination with thiamine and hydrocortisone. One trial did report higher rates of hypernatremia however this was not identified as an issue when all the studies were looked at in aggregate.
The authors concluded that further research into combination therapy with vitamin C, thiamine, and hydrocortisone seems unwarranted based on the lack of effect found by the review.
Although the review did identify a benefit on mortality for the monotherapy and high dose IV vitamin C groups, the authors did not give a recommendation to use vitamin C in critically ill patients because of this. They cite imprecise estimates of the actual treatment effects and a possible risk of bias in the studies as reasons why IV vitamin C monotherapy, especially when given in high doses of 10 grams per day or more, as the reasons why future study should be done to clearly identify the benefits of IV vitmain C in both septic and nonseptic patients.
As there are no studies of high dose IV vitamin C in critically ill patients currently underway according to clinicaltrials.gov, I would not anticipate high dose vitamin C becoming part of ICU or septic shock protocols anytime soon.
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