Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine · 2019
Pharmacokinetic data support 6-hourly dosing of intravenous vitamin C to critically ill patients with septic shock.
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Hudson Elizabeth P, Collie Jake Tb, Fujii Tomoko, Luethi Nora, Udy Andrew A, Doherty Sarah, Eastwood Glenn, Yanase Fumitaka, Naorungroj Thummaporn, Bitker Laurent, Abdelhamid Yasmine Ali, Greaves Ronda F, Deane Adam M, Bellomo Rinaldo
Аннотация
OBJECTIVES: To study vitamin C pharmacokinetics in septic shock.
DESIGN: Prospective pharmacokinetic study.
SETTING: Two intensive care units.
PARTICIPANTS: Twenty-one patients with septic shock enrolled in a randomised trial of high dose vitamin C therapy in septic shock.
INTERVENTION: Patients received 1.5 g intravenous vitamin C every 6 hours. Plasma samples were obtained before and at 1, 4 and 6 hours after drug administration, and vitamin C concentrations were measured by high performance liquid chromatography.
MAIN OUTCOME MEASURES: Clearance, volume of distribution, and half-life were calculated using noncompartmental analysis. Data are presented as median (interquartile range [IQR]).
RESULTS: Of the 11 participants who had plasma collected before any intravenous vitamin C administration, two (18%) were deficient (concentrations < 11 μmol/L) and three (27%) had hypovitaminosis C (concentrations between 11 and 23 μmol/L), with a median concentration 28 μmol/L (IQR, 11-44 μmol/L). Volume of distribution was 23.3 L (IQR, 21.9-27.8 L), clearance 5.2 L/h (IQR, 3.3-5.4 L/h), and half-life 4.3 h (IQR, 2.6-7.5 h). For the participants who had received at least one dose of intravenous vitamin C before sampling, T0 concentration was 258 μmol/L (IQR, 162- 301 μmol/L). Pharmacokinetic parameters for subsequent doses were a median volume of distribution 39.9 L (IQR, 31.4-44.4 L), clearance 3.6 L/h (IQR, 2.6-6.5 L/h), and half-life 6.9 h (IQR, 5.7-8.5 h).
CONCLUSION: Intravenous vitamin C (1.5 g every 6 hours) corrects vitamin C deficiency and hypovitaminosis C and provides an appropriate dosing schedule to achieve and maintain normal or elevated vitamin C levels in septic shock.
DESIGN: Prospective pharmacokinetic study.
SETTING: Two intensive care units.
PARTICIPANTS: Twenty-one patients with septic shock enrolled in a randomised trial of high dose vitamin C therapy in septic shock.
INTERVENTION: Patients received 1.5 g intravenous vitamin C every 6 hours. Plasma samples were obtained before and at 1, 4 and 6 hours after drug administration, and vitamin C concentrations were measured by high performance liquid chromatography.
MAIN OUTCOME MEASURES: Clearance, volume of distribution, and half-life were calculated using noncompartmental analysis. Data are presented as median (interquartile range [IQR]).
RESULTS: Of the 11 participants who had plasma collected before any intravenous vitamin C administration, two (18%) were deficient (concentrations < 11 μmol/L) and three (27%) had hypovitaminosis C (concentrations between 11 and 23 μmol/L), with a median concentration 28 μmol/L (IQR, 11-44 μmol/L). Volume of distribution was 23.3 L (IQR, 21.9-27.8 L), clearance 5.2 L/h (IQR, 3.3-5.4 L/h), and half-life 4.3 h (IQR, 2.6-7.5 h). For the participants who had received at least one dose of intravenous vitamin C before sampling, T0 concentration was 258 μmol/L (IQR, 162- 301 μmol/L). Pharmacokinetic parameters for subsequent doses were a median volume of distribution 39.9 L (IQR, 31.4-44.4 L), clearance 3.6 L/h (IQR, 2.6-6.5 L/h), and half-life 6.9 h (IQR, 5.7-8.5 h).
CONCLUSION: Intravenous vitamin C (1.5 g every 6 hours) corrects vitamin C deficiency and hypovitaminosis C and provides an appropriate dosing schedule to achieve and maintain normal or elevated vitamin C levels in septic shock.