For patients treated for vasoconstriction in the ICU, the end point of death or persistent organ dysfunction on day 28 was more common in those who were randomized to IV treatment with vitamin C instead of placebo (44.5% vs. 38, 5%, risk ratio [RR] 1.21, 95% CI 1.04-1.40), according to Francois Lamontagne, MD, of the Université de Sherbrooke in Quebec and colleagues, writing in the New England Journal of Medicine. The individual results of mortality (35.4% vs. 31.6%, respectively) and persistent organ dysfunction (9.1% vs. 6.9%) had an adverse trend for the vitamin C group, but were not significantly different:
Mortality: RR 1.17 (95% CI 0.98-1.40) Persistent organ dysfunction: RR 1.30 (95% CI 0.83-2.05)
And a secondary analysis of the primary outcome adjusted for predefined baseline characteristics was also not significant (RR 1.15, 95% CI 0.90-1.47). In addition, vitamin C recipients were not at greater risk for tissue dyskinesia, inflammation or endothelial injury, leaving researchers unable to determine the mechanism for possible vitamin C damage, the team said. The study findings were also presented at the 2022 Critical Care Reviews meeting. The researchers acknowledged that there was confusion in the study, given the lack of information on specific pathogens, antimicrobial therapy and the presence of acute respiratory distress syndrome in the study participants. More data are expected from ongoing vitamin C tests. These include REMAP-CAP in pneumonia, LOVIT-COVID in COVID-19 patients, and a European study on sepsis complicated by acute respiratory distress syndrome. Interest in vitamin IV as a possible treatment for sepsis is based on the belief that its antioxidant properties can reduce tissue damage caused by oxidative stress. However, evidence for the effectiveness of vitamin C in sepsis was not strong, as shown by a recent meta-analysis. The 2017 document that sparked interest in vitamin C in this context has been criticized as potentially “too good to be true” and the underlying data has also been challenged. Sepsis, meanwhile, remains a common cause of death even if treated early. It is responsible for more than a third of all hospital deaths and kills 11 million people worldwide each year, the Lamontagne team said. The Phase III LOVIT test was conducted in France, Canada and New Zealand. The eligible patients were adults with sepsis treated with vasopressor and kept in the ICU for no more than 24 hours. All had proven or suspected infections as the primary diagnosis. Patients with contraindications for vitamin C treatment, those receiving open vitamin C, and those with discontinuation or death within 48 hours were excluded. From November 2018 to July 2021, the researchers randomized 872 patients 1: 1 on vitamin C or placebo. The experimental group received a dose of vitamin C bolus, while the controls received a corresponding dextrose or saline. The prescribed treatments were administered over a period of 30 to 60 minutes every 6 hours for up to 96 hours. All other treatments were performed at the discretion of the treatment team. The mean age was 65 years and less than 40% of patients were women. The key features were similar between the vitamin C and placebo groups, as was the use of co-occurrences and life-saving therapies during their stay in the ICU. Lamontagne and his colleagues warned that their study was conducted in high-income countries and therefore may not be generalizable in lower-income countries where the rate of sepsis may be much higher.
James Lopilato is a personal writer for Medpage Today. It covers a variety of topics explored in current medical science.
Revelations The study was funded by the Lotte and John Hecht Memorial Foundation and Nova Biomedical Canada provided material for the study. Lamontagne received an institutional grant from the Lotte and John Hecht Memorial Foundation. He is also involved in other vitamin C tests. The authors cite links with the Lotte and John Hecht Memorial Foundation, and with Bayer, Baxter Healthcare Corporation, Bristol Myers Squibb, Fisher and Paykel Healthcare NZ, the French Ministry of Health, Leadiant Biosciences, Pfizer and Roche Diagnostics.
