Comment of Nutrients 2019, 11(9), 2103.
Vitamin C for Cardiac Surgery Patients: Several Errors in a Published Meta-Analysis. Comment on “Effects of Vitamin C on Organ Function in Cardiac Surgery Patients: A Systematic Review and Meta-Analysis. Nutrients 2019, 11, 2103”
Department of Public Health, University of Helsinki, POB 41, FI-00014 Helsinki, Finland
School of Public Health, University of Sydney, Sydney 2006, Australia
Author to whom correspondence should be addressed.
Nutrients 2020, 12(2), 586; https://doi.org/10.3390/nu12020586
Received: 2 December 2019 / Revised: 21 December 2019 / Accepted: 31 December 2019 / Published: 24 February 2020
(This article belongs to the Section Clinical Nutrition)
We recently published a meta-analysis on vitamin C and the length of intensive care unit [ICU] stay  and so were interested to read Hill et al.’s meta-analysis on randomized trials of vitamin C for cardiac surgery patients published in Nutrients in September 2019 . However, we have some methodological concerns.
The abstract states that “vitamin C significantly decreased … ventilation time (p < 0.00001)” . We believe that this conclusion is incorrect based on the evidence presented. This particularly small p-value from Figure 6  is associated with the test of heterogeneity, not with the test of overall effect (p = 0.02, Z = 2.27). In the abstract, this same error occurs for ICU length of stay and hospital length of stay in that the reported p-values are from the heterogeneity tests, not from the tests of overall effect.
Furthermore, Hill states in Figure 6 that the ventilation time in the Safaei trial  was 15.1 h with 1.0 h standard deviation (SD) in the vitamin C group and 22.9 h (SD 3.8 h) in the control group. These dispersion estimates were published by Safaei, however, as standard errors (SE) and not SDs: “All continuous variables are expressed as mean ± standard error of mean”  (p. 47) and “Values are mean ± SEM”  (Table 2). Thus, the use of SE in Figure 6 led to an erroneous p-value for the vitamin C effect . Hill made the same error (using SE from the Safaei trial) in their meta-analysis on ICU length of stay. This same error (using SE instead of SD) was repeated in Figures 6, 8, 12, 14, 18, and 20 . Consequently, they are incorrect.
Hill states that “Analyses were carried out on an intention-to-treat [ITT] basis for all outcomes, as far as possible”  (p. 3). The ITT principle means that investigators include in the analysis all participants who underwent randomization in the groups to which they were originally allocated [4,5,6]. However, Hill’s Figure 6 includes the Sadeghpour trial , which recruited 500 participants, but reported only 113 vitamin C participants and 177 placebo participants  (p. 3). The 42% dropout rate was very high and there were significant differences in the dropout rates between the treatment groups. Therefore, the Sadeghpour trial  should not be included in a meta-analysis that intends to follow the ITT principle.
Excluding the Sadeghpour trial  and using the SD values for the Safaei trial  (calculated from the published SE values), the p-value for the overall effect of vitamin C on ventilation time remained at 0.02; however, the heterogeneity disappeared (from p < 0.00001 to p = 0.39), see Figure S3 in the supplementary file. Several other concerns with the Hill meta-analysis  are described in the supplementary file.
This research received no external funding.
Conflicts of Interest
The authors declare no conflicts of interest.
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