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

Crit Care Med. 2022 Mar 1;50(3):e304-e312. doi: 10.1097/CCM.0000000000005320.


Objectives: 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 I2 = 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.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antioxidants / therapeutic use*
  • Ascorbic Acid / therapeutic use*
  • Critical Illness / therapy*
  • Dose-Response Relationship, Drug
  • Humans
  • Sepsis / drug therapy*
  • Sepsis / mortality
  • Treatment Outcome


  • Antioxidants
  • Ascorbic Acid