Pharmacokinetics of Two Different High-dose Regimens of Intravenous Vitamin C in Critically Ill Patients

Pharmacokinetics of Two Different High-dose Regimens of Intravenous Vitamin C in Critically Ill Patients

Pharmacokinetics of Two Different High-dose Regimens of Intravenous Vitamin C in Critically Ill Patients

The purpose of this study is to determine the pharmacokinetic properties of two different dosage regimens of intravenous vitamin C in patients admitted to the Intensive Care Unit with life-threatening illness.

Rationale: Critically ill patients with trauma or sepsis exhibit a high degree of vitamin C deficiency at ICU admission and vitamin C plasma concentrations decrease even more during the first three days of admission. Vitamin C is a natural anti-oxidant and crucial for endothelial and organ protection Objective: To determine the pharmacokinetics of two high dose regimens of intravenous vitamin C in critically ill patients, in particular the attained plasma concentration and the fraction retained in the body and excreted in urine. Study design: Prospective randomized controlled pharmacokinetic intervention study Study population: Adult critically ill patients admitted to the ICU of the VU University Medical Center, Amsterdam, with sepsis or SIRS after major surgery or trauma with a non-neurological sequential organ failure (SOFA) score >6 and an expected length of ICU stay of >96 hours. Intervention (if applicable): Patients will receive either 2 or 10 gram/day vitamin C intravenously twice daily for two days in bolus or continuous infusion.

1 gram of intravenous Vitamin C (ascorbic acid) is given 4 times at 12 hour intervals (total dose 4 grams).

5 grams of intravenous Vitamin C (ascorbic acid) is given 4 times at 12 hour intervals (total dose 20 grams).

Patients receive vitamin C 4 times in either high (5g) or moderate (1g) dose. Vitamin C will be administered intravenously (ascorbinezuur CF 100 mg/ml, Centrafarm BV, Etten Leur, Netherlands) in 50ml of NaCl 0.9%, infused over 30 minutes.

Baseline (before intervention), thereafter at 1, 2, 4, 8, 12, 24, 36, 48, 72, 96 hours after first intervention

Inclusion Criteria: Sepsis or Systemic Inflammatory Response Syndrome (SIRS) after major surgery or trauma; Non-neurological sequential organ failure assessment (SOFA) score >6; Expected length of ICU stay > 96 hours; Written proxy consent by legal representative. Exclusion Criteria: Admission after out of hospital cardiac arrest Prior use of supplemental vitamin C in the week before Major bleeding Pre-existent renal insufficiency defined as an eGFR of < 30 ml/min/1.73 m2 (stadium 4-5) Expected need for renal replacement therapy within 48 hours Known glucose 6-phosphate dehydrogenase deficiency History of urolithiasis or oxalate nephropathy Previous use of prolonged high dose vitamin C supplements Hemochromatosis

de Grooth HJ, Manubulu-Choo WP, Zandvliet AS, Spoelstra-de Man AME, Girbes AR, Swart EL, Oudemans-van Straaten HM. Vitamin C Pharmacokinetics in Critically Ill Patients: A Randomized Trial of Four IV Regimens. Chest. 2018 Jun;153(6):1368-1377. doi: 10.1016/j.chest.2018.02.025. Epub 2018 Mar 6.