IV Vitamin C in Adults With Sepsis: A Bayesian Reanalysis of a Randomized Controlled Trial.

Federico Angriman, Fiona Muttalib, François Lamontagne, Neill K J Adhikari

Journal: Critical care medicine 2023;51(8):e152-e156

PMID: 37026849

Abstract

OBJECTIVES

The Lessening Organ Dysfunction with Vitamin C trial showed a harmful effect of vitamin C on 28-day death or persistent organ dysfunction. To maximize interpretation, we present a post hoc Bayesian reanalysis.

DESIGN

Bayesian reanalysis of a randomized placebo-controlled trial.

SETTING

Thirty-five ICUs.

PATIENTS

Adults with proven or suspected infection, vasopressor support, and no more than 24 hours of ICU admission.

INTERVENTIONS

Patients were allocated to receive either vitamin C (50 mg/kg of body weight) or placebo every 6 hours for up to 96 hours.

MEASUREMENTS AND MAIN RESULTS

The primary outcome was the composite of death or persistent organ dysfunction (i.e., vasopressor use, invasive mechanical ventilation, or new renal replacement therapy) at 28 days. We used Bayesian log-binomial models with random effects for hospital site and varying informative prior beliefs for the effect of vitamin C to estimate risk ratios (RRs) with 95% credible intervals (Crls) in the intention to treat population (vitamin C, 435 patients; placebo, 437 patients). Using weakly neutral priors, patients allocated to vitamin C had a higher risk of death or persistent organ dysfunction at 28 days (RR, 1.20; 95% Crl, 1.04-1.39; probability of harm, 99%). This effect was consistent when using optimistic (RR, 1.14; 95% Crl, 1.00-1.31; probability of harm, 98%) and empiric (RR, 1.09; 95% Crl, 0.97-1.22; probability of harm, 92%) priors. Patients allocated to vitamin C also had a higher risk of death at 28 days under weakly neutral (RR, 1.17; 95% Crl, 0.98-1.40; probability of harm, 96%), optimistic (RR, 1.10; 95% Crl, 0.94-1.30; probability of harm, 88%), and empiric (RR, 1.05; 95% Crl, 0.92-1.19; probability of harm, 76%) priors.

CONCLUSIONS

The use of vitamin C in adult patients with proven or suspected infection and vasopressor support is associated with high probability of harm.

Address: Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.; Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.; Division of Pediatric Critical Care Medicine, Department of Pediatrics, BC Children's Hospital, Vancouver, BC, Canada.; Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada.; Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.; Division of Pediatric Critical Care Medicine, Department of Pediatrics, BC Children's Hospital, Vancouver, BC, Canada.; Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada.

DOI: 10.1097/CCM.0000000000005871

Link outs

Free resources

Medical:

https://medlineplus.gov/sepsis.html

Subscription / membership required

Full Text Sources:

MeSH Terms: Humans, Adult, Vitamins, Ascorbic Acid, Multiple Organ Failure, Bayes Theorem, Sepsis