Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, PO Box 980050, Richmond, VA 23298-0050, USA.
J Transl Med. 2014 Jan 31;12:32. doi: 10.1186/1479-5876-12-32.
Parenterally administered ascorbic acid modulates sepsis-induced inflammation and coagulation in experimental animal models. The objective of this randomized, double-blind, placebo-controlled, phase I trial was to determine the safety of intravenously infused ascorbic acid in patients with severe sepsis.
Twenty-four patients with severe sepsis in the medical intensive care unit were randomized 1:1:1 to receive intravenous infusions every six hours for four days of ascorbic acid: Lo-AscA (50 mg/kg/24 h, n = 8), or Hi-AscA (200 mg/kg/24 h, n = 8), or Placebo (5% dextrose/water, n = 8). The primary end points were ascorbic acid safety and tolerability, assessed as treatment-related adverse-event frequency and severity. Patients were monitored for worsened arterial hypotension, tachycardia, hypernatremia, and nausea or vomiting. In addition Sequential Organ Failure Assessment (SOFA) scores and plasma levels of ascorbic acid, C-reactive protein, procalcitonin, and thrombomodulin were monitored.
Mean plasma ascorbic acid levels at entry for the entire cohort were 17.9 ± 2.4 μM (normal range 50-70 μM). Ascorbic acid infusion rapidly and significantly increased plasma ascorbic acid levels. No adverse safety events were observed in ascorbic acid-infused patients. Patients receiving ascorbic acid exhibited prompt reductions in SOFA scores while placebo patients exhibited no such reduction. Ascorbic acid significantly reduced the proinflammatory biomarkers C-reactive protein and procalcitonin. Unlike placebo patients, thrombomodulin in ascorbic acid infused patients exhibited no significant rise, suggesting attenuation of vascular endothelial injury.
Intravenous ascorbic acid infusion was safe and well tolerated in this study and may positively impact the extent of multiple organ failure and biomarkers of inflammation and endothelial injury.
ClinicalTrials.gov identifier NCT01434121.
静脉内给予抗坏血酸可调节实验动物模型中的脓毒症引起的炎症和凝血。本随机、双盲、安慰剂对照、I 期试验的目的是确定静脉输注抗坏血酸在严重脓毒症患者中的安全性。
24 名重症监护病房的严重脓毒症患者被随机分为 1:1:1 组，分别接受静脉输注，每 6 小时一次，连续 4 天：Lo-AscA（50mg/kg/24h，n=8）、Hi-AscA（200mg/kg/24h，n=8）或安慰剂（5%葡萄糖水，n=8）。主要终点是抗坏血酸的安全性和耐受性，评估为治疗相关不良事件的频率和严重程度。监测患者的动脉低血压、心动过速、高钠血症和恶心或呕吐是否恶化。此外，监测序贯器官衰竭评估（SOFA）评分和抗坏血酸、C 反应蛋白、降钙素原和血栓调节蛋白的血浆水平。
整个队列的患者进入时平均血浆抗坏血酸水平为 17.9±2.4μM（正常范围为 50-70μM）。抗坏血酸输注迅速且显著增加了血浆抗坏血酸水平。在接受抗坏血酸输注的患者中未观察到不良安全事件。接受抗坏血酸的患者的 SOFA 评分迅速降低，而安慰剂患者则没有这种降低。抗坏血酸显著降低了促炎生物标志物 C 反应蛋白和降钙素原。与安慰剂患者不同，接受抗坏血酸输注的患者的血栓调节蛋白没有明显升高，表明血管内皮损伤得到了抑制。
在这项研究中，静脉内给予抗坏血酸输注是安全且耐受良好的，并且可能对多种器官衰竭的程度以及炎症和内皮损伤的生物标志物产生积极影响。
ClinicalTrials.gov 标识符 NCT01434121。
