Vitamin C Can Shorten the Length of Stay in the ICU: A Meta-Analysis

Abstract

A number of controlled trials have previously found that in some contexts, vitamin C can have beneficial effects on blood pressure, infections, bronchoconstriction, atrial fibrillation, and acute kidney injury. However, the practical significance of these effects is not clear. The purpose of this meta-analysis was to evaluate whether vitamin C has an effect on the practical outcomes: length of stay in the intensive care unit (ICU) and duration of mechanical ventilation. We identified 18 relevant controlled trials with a total of 2004 patients, 13 of which investigated patients undergoing elective cardiac surgery. We carried out the meta-analysis using the inverse variance, fixed effect options, using the ratio of means scale. In 12 trials with 1766 patients, vitamin C reduced the length of ICU stay on average by 7.8% (95% CI: 4.2% to 11.2%; p = 0.00003). In six trials, orally administered vitamin C in doses of 1⁻3 g/day (weighted mean 2.0 g/day) reduced the length of ICU stay by 8.6% (p = 0.003). In three trials in which patients needed mechanical ventilation for over 24 hours, vitamin C shortened the duration of mechanical ventilation by 18.2% (95% CI 7.7% to 27%; p = 0.001). Given the insignificant cost of vitamin C, even an 8% reduction in ICU stay is worth exploring. The effects of vitamin C on ICU patients should be investigated in more detail.

Keywords: antioxidants; artificial respiration; burns; cardiac surgical procedures; cardiovascular system; critical care; dietary supplements; oxidative stress; sepsis; systematic review.

Figure 1

Flow diagram of the searches. The search terms and the number of identified records are shown in this figure. One of the identified trials recruited 500 participants, but reported only 290 participants [123]. This is such a great violation of the intention-to-treat (ITT) principle that we excluded that study from our analyses. One publication reported two separate trials [122]. This leads to the 18 included trials from the 18 identified publications.

Figure 2

Risk of bias summary. Review authors’ judgments about each risk of bias item for each included trial. A plus mark (+) indicates that there is no substantial concern for bias in the particular quality item. A question mark (?) indicates that conclusions are unable to be drawn regarding potential bias. A minus sign (−) indicates that there is concern regarding bias. The Dingchao [106], Ebade [114], and Alshafey [118] trials were particularly poorly reported; see Table S1 in Supplementary file S1. We tried unsuccessfully to contact Dr. Alshafey and Dr. Ebade to ask for details of their methods. We did not try to contact Dr. Dingchao, since the study is old. The reference numbers to the trials are shown in Table 1.

Figure 3

The effect of vitamin C supplementation on the length of ICU stay. This meta-analysis is termed final meta-analysis in Table 2. Subgroups of this set of 12 trials are shown in Table 2. The horizontal lines indicate the 95% CI for the vitamin C effect and the squares in the middle of the horizontal lines indicate the point estimates of the effect in the particular trial. The diamond shape indicates the pooled effect and its 95% CI. When the squares and diamonds are on the left-hand side of the vertical control level, they indicate that vitamin C is better than control. The reference numbers to the trials are shown in Table 1. Abbreviations: RoM, ratio of means; TE, logarithm of RoM; seTE, the standard error of TE; see ref. [127].

Figure 4

The effect of vitamin C supplementation on the length of mechanical ventilation. The two subgroups are formed by the duration of mechanical ventilation in the control group, see Table 1. The modification of vitamin C effect on the duration of mechanical ventilation was also analyzed by meta-regression over the control group duration of ventilation, and significant modification was found (p = 0.0013), see Supplementary file S1. The horizontal lines indicate the 95% CI for the vitamin C effect and the squares in the middle of the horizontal lines indicate the point estimate of the effect in the particular trial. The diamond shape indicates the pooled effect and its 95% CI. The reference numbers to the trials are shown in Table 1. Abbreviations: RoM, ratio of means; TE, logarithm of RoM; seTE, the standard error of TE; see ref. [127].