Chest
Original Research: Critical Care
Vitamin C Pharmacokinetics in Critically Ill Patients: A Randomized Trial of Four IV Regimens
Section snippets
Patients
This randomized factorial pharmacokinetic trial was performed between March 2015 and November 2016 in the mixed medical/surgical ICU of VU University Medical Center in Amsterdam, The Netherlands. The analysts determining the vitamin C and oxalate concentrations were blinded to treatment allocation. The trial protocol was registered at ClinicalTrials.gov before patient inclusion (identifier NCT02455180 ).
The study was approved by the medical ethics committee of VU University Medical Center
Results
Twenty patients (five per dosage regimen) were included and randomized (Fig 1). Baseline characteristics are shown in Table 1. All patients received the allocated study medications. No patients died during the 96-h study period.
Dose-Plasma Concentration Relationship
In this four-group randomized pharmacokinetic trial, 20 patients with multiple organ failure were randomized to receive either 2 or 10 g/d vitamin C administered as a twice daily 15-min bolus infusion or continuous infusion.
Two grams per day resulted in normal plasma concentrations, and 10 g/d resulted in supranormal concentrations. Bolus infusion caused higher 1-h concentrations but also caused trough concentrations that approached the hypovitaminosis cutoff in the 2 g/d dose group. Plasma
Conclusions
The present four-group randomized trial in patients with multiple organ dysfunction found that 2 g/d of IV vitamin C resulted in normal plasma concentrations, whereas supraphysiologic concentrations were achieved with 10 g/d. Although renal losses were substantial, high concentrations can be achieved with higher IV doses in a linear dose-concentration relationship. Sustained vitamin C administration is needed to prevent a decline to hypovitaminosis. Urine oxalate excretion was related to the
Acknowledgments
Author contributions: H.-J. G. and H. M. O.-S. take responsibility for the work as a whole, from inception to published article. H.-J. G., W.-P. M.-C., E. L. S., and H. M. O.-S. contributed to study conception and design. H.-J. G., W.-P. M.-C., A. M. E. S.-M., and H. M. O.-S. were responsible for the inclusion of patients, study procedures, and sample handling. W.-P. M.-C. and A. S. Z. performed the pharmacokinetic modeling. H.-J. G. performed the other analyses. A. R. G. and E. L. S. provided
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Cited by (0)
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Drs de Grooth and Manubulu-Choo contributed equally to this manuscript.
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FUNDING/SUPPORT: This study was performed on departmental funding.