Ortality reduction was not found. We hypothesize that the effect of vitamin C can be improved by very early administration of a high intravenous dose as part of the resuscitation bundle in patients with shock.Conclusion This narrative review summarizes the role of vitamin C in mitigating ROS-induced microcirculatory impairment and associated organ failure in ischemia/reperfusion or MS023 chemical information sepsis. Preclinical studies show that high-dose vitamin COudemans-van Straaten et al. Critical Care 2014, 18:460 http://ccforum.com/content/18/1/Page 10 ofTable 3 Controlled studies on the effect of vitamin C in critically ill patientsStudy Nathens and colleagues [104] Design RCT; trauma and MOF Intervention i.v. vitamin C 1 g three times daily; enteral vitamin E 1,000 IU three times daily With TPN, vitamin C 100 mg and vitamin E 10 IU daily; with EN, vitamin C 340 mg/l, vitamin E 60 IU/l Crimi and colleagues [107] RCT; critically ill (mainly trauma, cardiogenic shock) Vitamin C 500 mg/day and vitamin E (400 IU/day) in EN Saline solution for 10 days Collier and colleagues [103] Prospective vs. retrospective 1-year cohort; trauma i.v. or oral vitamin C 1 g three times daily + oral vitamin E 1,000 IU three times daily + selenium 200 g i.v. Standard therapy Berger and colleagues [105] RCT; complicated cardiac surgery, trauma, SAB Selenium 540 i.v. day 1, 270 g days 2 to 5; zinc 60 mg i.v. day 1, 30 mg days 2 to 5; vitamin B1 305 mg i.v. day 1, 205 mg days 2 to 5; vitamin C 2.7 g i.v. day 1, 1.6 g days 2 to 5; vitamin E 600 mg i.v. day 1, 300 mg days 2 to 5 Vitamin B1 100 mg i.v. days 1 to 3 (both groups); vitamin C 500 mg i.v. days 1 to 5 (both groups) Heyland and colleagues [106] Burn Tanaka and colleagues [84] RCT; severe burn <2 hours RCT, 2 ?2 factorial; critically ill adults with multiple organ failure Selenium 500 g i.v., selenium 300 g or zinc 20 mg or -carotene 10 mg; vitamin E 500 mg or vitamin C 1,500 mg Placebo Ringer lactate + 66 mg/kg/hour vitamin C Number of patients 301 294 Outcome Pulmonary morbidity , new MOF , LOS ventilation , LOS ICU105 111 2,Ventilator-free days , 28-day mortalityLOS ICU , LOS hospital , mortality ; OR 0.32, 95 CI 0.22 to 0.2,022 102 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25768400 New organ failure ND, new infections ND, LOS shorter in trauma, CRP in cardiac surgery and trauma, recovery of health after dischargeNo difference in 28-day mortality or length of stay300 19 Fluid requirements , body weight gain , PF ratio , days on mechanical ventilation Fluid requirements , urinary outputRinger lactate for 24 hours Kahn and colleagues [85] Retrospective; severe burn <10 hours Ringer lacate + 66 mg/kg/hour vitamin C Ringer lactate for 24 hours18 17CI, confidence interval; CRP, C-reactive protein; EN, enteral nutrition; i.v., intravenously; LOS, length of stay; OR, odds ratio; MOF, multiple organ failure; ND, no difference; PF, ratio of partial oxygen pressure in arterial blood to fraction of inspired oxygen; RCT, randomized controlled trial; TPN, total parenteral nutrition; SAB, subarachnoid bleeding. , increase; , decrease; =, constant.can prevent or restore ROS-induced microcirculatory flow impairment, prevent or restore vascular responsiveness to vasoconstrictors, preserve endothelial barrier and augment antibacterial defense. These protective effects against oxidative stress seem to mitigate organ injury and dysfunction, and promote recovery in most but not all clinical studies after cardiac revascularization and in critically ill patients. Of note, many questions remai.