IV Vitamin C in Critically Ill Patients: A Systematic Review and Meta-Analysis

Abstract

To conduct a systematic review and meta-analysis to evaluate the impact of IV vitamin C on outcomes in critically ill patients. DATA SOURCES: Systematic search of MEDLINE, EMBASE, CINAHL, and the Cochrane Register of Controlled Trials. STUDY SELECTION: Randomized controlled trials testing IV vitamin C in critically ill patients. DATA ABSTRACTION: Two independent reviewers abstracted patient characteristics, treatment details, and clinical outcomes.DATA SYNTHESIS: Fifteen studies involving 2,490 patients were identified. Compared with placebo, IV vitamin C administration is associated with a trend toward reduced overall mortality (relative risk, 0.87; 95% CI, 0.75-1.00; p = 0.06; test for heterogeneity I 2 = 6%). High-dose IV vitamin C was associated with a significant reduction in overall mortality (relative risk, 0.70; 95% CI, 0.52-0.96; p = 0.03), whereas low-dose IV vitamin C had no effect (relative risk, 0.94; 95% CI, 0.79-1.07; p = 0.46; test for subgroup differences, p = 0.14). IV vitamin C monotherapy was associated with a significant reduction in overall mortality (relative risk, 0.64; 95% CI, 0.49-0.83; p = 0.006), whereas there was no effect with IV vitamin C combined therapy. No trial reported an increase in adverse events related to IV vitamin C. CONCLUSIONS:IV vitamin C administration appears safe and may be associated with a trend toward reduction in overall mortality. High-dose IV vitamin C monotherapy may be associated with improved overall mortality, and further randomized controlled trials are warranted.

IV Vitamin C in Sepsis: A Latest Systematic Review and Meta-Analysis

“…Te meta-regression and subgroup analysis showed that the quality of studies (P � 0.04; I 2 � 77.3%) could be the primary source of the heterogeneity, while the protocol (P � 0.13; I 2 � 56.1%) and the publication year (P � 0.03; I 2 � 66.7%) could also contribute to the heterogeneity. Consistent with Patel et al [38], our subgroup analysis suggested that compared with the combination treatment group, vitamin C monotherapy showed a decreasing trend in overall mortality. However, it difered from the result of a high-quality randomized controlled study published in 2022 by Lamontagne et al [13].…”

“…Te primary outcome analysis showed that IV vitamin C tended to reduce overall mortality in patients with sepsis compared with the control group. However, the diference between the two groups was not statistically signifcant (Figure 3), which is consistent with the result of Patel et al [38]. Te heterogeneity among the included studies was signifcant.…”

Impact of intravenous vitamin C as a monotherapy on mortality risk in critically ill patients: A meta-analysis of randomized controlled trials with trial sequential analysis

“…Judicious interpretation of the findings of the current meta-analysis is required because of its limitations. First, the heterogeneity from our inclusion of patients with and without sepsis/septic shock as well as our definition of critically ill individuals as those whose mortality rate was higher than 5% in the control group based on a previous study (16) may bias our findings. Nevertheless, the heterogeneity was low in our mortality rate, indicating a low risk of bias.…”

“…Our subgroup analysis focusing on dosage suggested a favorable outcome associated with a low dosage of vitamin C, highlighting a 10.3389/fnut.2023.1094757 need for further research on this issue. Third, we did not investigate the efficacy of vitamin C-based combination therapy as several meta-analyses have addressed this issue (16). Finally, despite the demonstration of a gender difference in the beneficial impact of vitamin C on disease severity (i.e., acute respiratory tract infections) (46), we are unable to analyze gender-related outcomes because of a lack of relevant data.…”

“…Several metaanalyses reported no beneficial effect of vitamin C on the risk of mortality in cardiac surgical patients and those with COVID-19 infection (14,15). For patients with sepsis/septic shock or critical illnesses, the association between mortality and the use of vitamin C was also controversial (16)(17)(18)(19)(20)(21)(22). Such conflicting findings may be attributed to the variations among individual studies including study design (i.e., prospective or retrospective), the choice of study population (e.g., critical vs. non-critical), the use of vitamin C as monotherapy or part of a combined regimen, as well as the selected dosage and route of administration.…”