Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial
Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial
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DOI：
10.1001/jama.2019.11825
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发表时间：
2019-10-01
影响因子：
120.7
通讯作者：
Halquist, Matthew
中科院分区：
文献类型：
--
作者：
Fowler, Alpha A., III;Truwit, Jonathon D.;Halquist, Matthew
重要性实验数据表明，静脉注射维生素C可以减轻与脓毒症和急性呼吸窘迫综合征（ARDS）相关的炎症和血管损伤。目的确定静脉注射维生素C对脓毒症和ARDS患者器官衰竭评分和炎症和血管损伤生物标志物的影响。一项在美国7个重症监护病房进行的安慰剂对照、多中心试验，招募了脓毒症和ARDS持续时间少于24小时的患者（N = 167）。该研究于2014年9月至2017年11月进行，最终随访时间为2018年1月。干预患者被随机分配接受静脉输注维生素C（50 mg/kg，溶于5%葡萄糖水溶液，n = 84）或安慰剂主要结果和测量主要结果是器官衰竭的变化，如通过改良的序贯器官衰竭评估评分所评估的（范围，0-20，评分越高表明功能障碍越严重），以及炎症的血浆生物标志物（C反应蛋白水平）和血管损伤在0、48、96和168小时测量血栓调节蛋白水平。（平均[SD]年龄，54.8岁[16.7]; 90例男性[54%]），103例（62%）完成研究至第60天。维生素C组和安慰剂组在主要终点（从基线到96小时的平均改良序贯器官衰竭评估评分变化）方面没有显著差异（维生素C组从9.8到6.8 [3分]，安慰剂组从10.3到6.8 [3.5分];差异，-0.10; 95% CI，-1.23至1.03; P = 0.86）或C反应蛋白水平（54.1 vs 46.1 μ g/mL;差异，7.94 μ g/mL; 95% CI，-8.2至24.11; P = 0.33）和血栓调节蛋白水平（14.5 vs 13.8 ng/mL;差异，0.69 ng/mL; 95% CI，-2.8至4.2; P = .70）。结论和相关性在这项对脓毒症和ARDS患者的初步研究中，与安慰剂相比，96小时的维生素C输注并没有显著改善器官功能障碍评分或改变炎症和血管损伤的标志物。需要进一步的研究来评估维生素C对脓毒症和ARDS其他结局的潜在作用。
IMPORTANCE Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS).OBJECTIVE To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS.DESIGN, SETTING, AND PARTICIPANTS The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018.INTERVENTIONS Patients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours.MAIN OUTCOMES AND MEASURES The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours.RESULTS Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, -0.10; 95% CI, -1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 mu g/mL; difference, 7.94 mu g/mL; 95% CI, -8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70) at 168 hours.CONCLUSIONS AND RELEVANCE In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS.