SGEM#268: Vitamin C Not Ready for Graduation to Routine Use

Date: September 11th, 2019 Reference: Putzu et al. The Effect of Vitamin C on Clinical Outcome in Critically Ill Patients: A Systematic Review with Meta-Analysis of Randomized Controlled Trials. Critical Care Medicine. June 2019. Guest Skeptics: Dr. Erin Willard is a PGY-3 Emergency Medicine Resident, Department of Emergency Medicine, University of Arkansas for Medical Sciences. Dr. Carly Eastin is an Associate Professor, Division of Research and Evidence Based Medicine, Department of Emergency Medicine, University of Arkansas for Medical Sciences. Case: A 45-year-old female in the emergency department is being admitted to the intensive care unit (ICU) for septic shock secondary to urinary tract infection (UTI). She has been given fluids, antibiotics, and is currently maintaining adequate mean arterial pressure (MAP) on low-dose vasopressors. You are ready to call the ICU and get her admitted. But you remember seeing in the news there was a study claiming vitamin C could cure sepsis. You wonder if giving vitamin C will affect her outcome? Background: There was a huge buzz in the media a few years ago about a vitamin C cocktail (vitamin C, hydrocortisone and thiamine) as a possible cure for sepsis. This was because of a well-known critical care physician Dr. Paul Marik. Dr. Paul Marik Dr. Marik published a retrospective before and after study that included a vitamin C cocktail reporting an impressive number needed to treat of 3 to prevent one death due to sepsis. For the scientific rationale why vitamin C therapy may help septic patients check out Dr. Josh Farkas’ post on PulmCrit. We reviewed Dr. Marik’s observational study on SGEM#174. A dozen skeptics commented about the validity of the study including my EBM mentor Dr. Andrew Worster who started BEEM and Legend of Emergency Medicine Dr. Jerome Hoffman. The SGEM Bottom Line was that Vitamin C, hydrocortisone and thiamine was associated with lower mortality in severe septic and septic shock patients in this one small, single centred retrospective before-after study but causation has yet to be demonstrated. A number of clinical trials are currently underway in an attempt to replicated Dr. Marik’s findings. The existing evidence to support vitamin C use in patients with septic shock is weak and has been summarized in a systematic review meta-analysis.  Clinical Question: Does the administration of vitamin C to an adult critically ill ICU patient or cardiac surgery patients decrease mortality? Reference: Putzu et al. The Effect of Vitamin C on Clinical Outcome in Critically Ill Patients: A Systematic Review with Meta-Analysis of Randomized Controlled Trials. Critical Care Medicine. June 2019. Population: Randomized trials examining critically ill adult ICU or cardiac surgery patients Exclusions: Inappropriate setting (cardiac or ICU) or study design (RCT), pediatrics, non-critically ill Intervention: Any type of vitamin C formulation or regimen Comparison: Placebo or no therapy Outcome: Primary outcome: Mortality at the longest follow-up available Secondary outcomes: Acute kidney injury, supraventricular tachycardia, ventricular arrhythmia, stroke, ICU and hospital length of stay. Authors’ 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.” Quality Checklist for Therapeutic Systematic Reviews: The clinical question is sensible and answerable. Yes