PDF(Pubmed)
Abstract：
UNASSIGNED: MecROX is a mechanistic sub-study of the UK-ROX trial which was designed to evaluate the clinical and cost-effectiveness of a conservative approach to oxygen therapy for invasively ventilated adults in intensive care. This is based on the scientific rationale that excess oxygen is harmful. Epithelial cell damage with alveolar surfactant deficiency is characteristic of hyperoxic acute lung injury. Additionally, hyperoxaemia (excess blood oxygen levels) may exacerbate whole-body oxidative stress leading to cell death, autophagy, mitochondrial dysfunction, bioenergetic failure and multi-organ failure resulting in poor clinical outcomes. However, there is a lack of in-vivo human models evaluating the mechanisms that underpin oxygen-induced organ damage in mechanically ventilated patients.
UNASSIGNED: The aim of the MecROX mechanistic sub-study is to assess lung surfactant composition and global systemic redox status to provide a mechanistic and complementary scientific rationale to the UK-ROX trial findings. The objectives are to quantify in-vivo surfactant composition, synthesis, and metabolism with markers of oxidative stress and systemic redox disequilibrium (as evidenced by alterations in the \'reactive species interactome\') to differentiate between groups of conservative and usual oxygen targets.
UNASSIGNED: After randomisation into the UK-ROX trial, 100 adult participants (50 in the conservative and 50 in usual care group) will be recruited at two trial sites. Blood and endotracheal samples will be taken at 0, 48 and 72 hours following an infusion of 3 mg/kg methyl-D 9-choline chloride. This is a non-radioactive, stable isotope of choline (vitamin), which has been extensively used to study surfactant phospholipid kinetics in humans. This study will mechanistically evaluate the in-vivo surfactant synthesis and breakdown (by hydrolysis and oxidation), oxidative stress and redox disequilibrium from sequential plasma and bronchial samples using an array of analytical platforms. We will compare conservative and usual oxygenation groups according to the amount of oxygen administered. Trial registration: ISRCTNISRCTN61929838, 27/03/2023 https://doi.org/10.1186/ISRCTN61929838.
UNASSIGNED: The aim of the MecROX mechanistic sub-study is to assess lung surfactant composition and global systemic redox status to provide a mechanistic and complementary scientific rationale to the UK-ROX trial findings. The objectives are to quantify in-vivo surfactant composition, synthesis, and metabolism with markers of oxidative stress and systemic redox disequilibrium (as evidenced by alterations in the \'reactive species interactome\') to differentiate between groups of conservative and usual oxygen targets.
UNASSIGNED: After randomisation into the UK-ROX trial, 100 adult participants (50 in the conservative and 50 in usual care group) will be recruited at two trial sites. Blood and endotracheal samples will be taken at 0, 48 and 72 hours following an infusion of 3 mg/kg methyl-D 9-choline chloride. This is a non-radioactive, stable isotope of choline (vitamin), which has been extensively used to study surfactant phospholipid kinetics in humans. This study will mechanistically evaluate the in-vivo surfactant synthesis and breakdown (by hydrolysis and oxidation), oxidative stress and redox disequilibrium from sequential plasma and bronchial samples using an array of analytical platforms. We will compare conservative and usual oxygenation groups according to the amount of oxygen administered. Trial registration: ISRCTNISRCTN61929838, 27/03/2023 https://doi.org/10.1186/ISRCTN61929838.
摘要：
■MecROX是UK-ROX试验的一项机械性子研究，旨在评估重症监护中侵入性通气成人的保守氧疗方法的临床和成本效益。这是基于过量氧气有害的科学原理。肺泡表面活性剂缺乏引起的上皮细胞损伤是高氧急性肺损伤的特征。此外,高氧血症（过量的血氧水平）可能会加剧全身氧化应激，导致细胞死亡，自噬,线粒体功能障碍，生物能量衰竭和多器官衰竭导致不良的临床结果。然而,缺乏体内人体模型评估机械通气患者氧诱导器官损伤的机制.
■MecROX机制子研究的目的是评估肺表面活性物质组成和全身氧化还原状态，为UK-ROX试验结果提供机制和互补的科学依据。目标是量化体内表面活性剂组成，合成，以及具有氧化应激和全身氧化还原不平衡标记物的代谢（如“反应性物种相互作用组”的变化所证明的），以区分保守和通常的氧目标组。
■在随机进入UK-ROX试验后，将在两个试验地点招募100名成年参与者（保守组50名，常规护理组50名）。在输注3mg/kg甲基-D9-胆碱氯化物后0、48和72小时采集血液和气管内样品。这是非放射性的,胆碱（维生素）的稳定同位素，已被广泛用于研究人体表面活性剂磷脂动力学。这项研究将机械评估体内表面活性剂的合成和分解（通过水解和氧化），使用一系列分析平台从连续的血浆和支气管样品中获得氧化应激和氧化还原不平衡。我们将根据给药的氧气量比较保守和常规氧合组。试用注册：ISRCTNISRCTN61929838,27/03/2023https://doi.org/10.1186/ISRCTN61929838。
■MecROX机制子研究的目的是评估肺表面活性物质组成和全身氧化还原状态，为UK-ROX试验结果提供机制和互补的科学依据。目标是量化体内表面活性剂组成，合成，以及具有氧化应激和全身氧化还原不平衡标记物的代谢（如“反应性物种相互作用组”的变化所证明的），以区分保守和通常的氧目标组。
■在随机进入UK-ROX试验后，将在两个试验地点招募100名成年参与者（保守组50名，常规护理组50名）。在输注3mg/kg甲基-D9-胆碱氯化物后0、48和72小时采集血液和气管内样品。这是非放射性的,胆碱（维生素）的稳定同位素，已被广泛用于研究人体表面活性剂磷脂动力学。这项研究将机械评估体内表面活性剂的合成和分解（通过水解和氧化），使用一系列分析平台从连续的血浆和支气管样品中获得氧化应激和氧化还原不平衡。我们将根据给药的氧气量比较保守和常规氧合组。试用注册：ISRCTNISRCTN61929838,27/03/2023https://doi.org/10.1186/ISRCTN61929838。
