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The Effect of Vitamin C on Clinical Outcome in Critically Ill Patients: A Systematic Review With Meta-Analysis of Randomized Controlled Trials*

Putzu, Alessandro MD1; Daems, Anne-Marie MD1; Lopez-Delgado, Juan Carlos MD, PhD2,3; Giordano, Vito Federico MD4; Landoni, Giovanni MD4,5

doi: 10.1097/CCM.0000000000003700
Clinical Investigations

Objectives: The effects of vitamin C administration on clinical outcome in critically ill patients remain controversial.

Data Sources: Online databases were searched up to October 1, 2018.

Study Selection: We included randomized controlled trials on the use of vitamin C (any regimen) in adult critically ill patients versus placebo or no therapy.

Data Extraction: Risk ratio for dichotomous outcome and standardized mean difference for continuous outcome with 95% CI were calculated using random-effects model meta-analysis.

Data Synthesis: Forty-four randomized studies, 16 performed in ICU setting (2,857 patients) and 28 in cardiac surgery (3,598 patients), published between 1995 and 2018, were included in the analysis. In ICU patients, vitamin C administration was not associated with a difference in mortality (risk ratio, 0.90; 95% CI, 0.74–1.10; p = 0.31), acute kidney injury, ICU or hospital length of stay compared with control. In cardiac surgery, vitamin C was associated to a reduction in postoperative atrial fibrillation (risk ratio, 0.64; 95% CI, 0.52–0.78; p < 0.0001), ICU stay (standardized mean difference, –0.28 d; 95% CI, –0.43 to –0.13 d; p = 0.0003), and hospital stay (standardized mean difference, –0.30 d; 95% CI, –0.49 to –0.10 d; p = 0.002). Furthermore, no differences in postoperative mortality, acute kidney injury, stroke, and ventricular arrhythmia were found.

Conclusions: In a mixed population of ICU patients, vitamin C administration is associated with no significant effect on survival, length of ICU or hospital stay. In cardiac surgery, beneficial effects on postoperative atrial fibrillation, ICU or hospital length of stay remain unclear. However, the quality and quantity of evidence is still insufficient to draw firm conclusions, not supporting neither discouraging the systematic administration of vitamin C in these populations. Vitamin C remains an attractive intervention for future investigations aimed to improve clinical outcome.

1Division of Anesthesiology, Department of Anesthesiology, Pharmacology & Intensive Care Medicine, Geneva University Hospitals, Geneva, Switzerland.

2Intensive Care Department, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain.

3Institut d’Investigació Biomèdica Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain.

4Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.

5Vita-Salute San Raffaele University, Milan, Italy.

*See also p. 867.

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The authors have disclosed that they do not have any potential conflicts of interest.

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