Vitamin C Pharmacokinetics in Critically Ill Patients Author Q&A

with Harm-Jan de Grooth, MD, and Wai-Ping Manubulu–Choo, PharmD

June 12, 2018

1. What prompted this study to look into the optimal dose and infusion method of vitamin C use in critically ill patients?

There has been a large increase in research interest into high-dose intravenous vitamin C after three recent studies reported promising results in patients with septic shock. While exploring the possibilities of performing a multicenter randomized trial, we noticed a “translational gap” in vitamin C research. There is ample preclinical data on the concentration-function relationship, and there are several clinical studies using empiric high dosages, but no robust population-specific pharmacokinetic data were available to link dosage regimens to plasma concentrations.  

2. How would you overcome limitations of this study to move forward? What are some of the factors that could enhance this study further?

Our study was primarily designed to evaluate different dosing strategies for further clinical efficacy trials. We developed a generalizable pharmacokinetic model that can now be used to inform dosage decisions to attain high-normal to supranormal plasma concentrations in critically ill patients.

3. Are there any findings that you'd like to expand on in the future? And what results would you like to find?

First and foremost, the clinical efficacy of high-dose intravenous vitamin C in specific critically ill populations still has to be established. Despite the sound biological rationale and promising results from small randomized trials and well-controlled observational studies, the evidence base is still relatively narrow. In addition, we still need to learn more about the risk of increased oxalate excretion. In this study, we confirmed that high-dose vitamin C leads to increased oxalate in the urine. However, we don’t yet know to what extent increased urinary oxalate is due to in-vitro conversion and—as the formation of oxalate stones depends on many factors besides oxalate concentration—we don’t yet understand its clinical significance.

Several studies in patients with sepsis are underway, and this year we will start recruitment for a multicenter randomized trial to investigate the efficacy and safety of high-dose vitamin C in patients after cardiac arrest. We’re excited to see what the upcoming years of vitamin C research will bring.

Read their article from the June journal CHEST®, Vitamin C Pharmacokinetics in Critically Ill Patients: A Randomized Trial of Four IV Regimens.

Wai-Ping Manubulu-Choo, PharmD, is a hospital pharmacist at Westfriesgasthuis in Hoorn, The Netherlands. Harm-Jan de Grooth, MD, divides his time between research and clinical work at the departments of Anesthesiology and Intensive Care at the VU University Medical Center in Amsterdam, The Netherlands.