Donati Abele, Damiani Elisa, Zuccari Samuele, Domizi Roberta, Scorcella Claudia, Girardis Massimo, Giulietti Alessia, Vignini Arianna, Adrario Erica, Romano Rocco, Mazzanti Laura, Pelaia Paolo, Singer Mervyn
Anesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, via Tronto 10, 6126, Torrette di Ancona, Italy.
Department of Anesthesiology and Intensive Care, Modena University Hospital, L.go del Pozzo 71, 41100, Modena, Italy.
BMC Anesthesiol. 2017 Mar 23;17(1):49. doi: 10.1186/s12871-017-0342-2.
The normobaric oxygen paradox states that a short exposure to normobaric hyperoxia followed by rapid return to normoxia creates a condition of 'relative hypoxia' which stimulates erythropoietin (EPO) production. Alterations in glutathione and reactive oxygen species (ROS) may be involved in this process. We tested the effects of short-term hyperoxia on EPO levels and the microcirculation in critically ill patients.
In this prospective, observational study, 20 hemodynamically stable, mechanically ventilated patients with inspired oxygen concentration (FiO) ≤0.5 and PaO/FiO ≥ 200 mmHg underwent a 2-hour exposure to hyperoxia (FiO 1.0). A further 20 patients acted as controls. Serum EPO was measured at baseline, 24 h and 48 h. Serum glutathione (antioxidant) and ROS levels were assessed at baseline (t0), after 2 h of hyperoxia (t1) and 2 h after returning to their baseline FiO (t2). The microvascular response to hyperoxia was assessed using sublingual sidestream dark field videomicroscopy and thenar near-infrared spectroscopy with a vascular occlusion test.
EPO increased within 48 h in patients exposed to hyperoxia from 16.1 [7.4-20.2] to 22.9 [14.1-37.2] IU/L (p = 0.022). Serum ROS transiently increased at t1, and glutathione increased at t2. Early reductions in microvascular density and perfusion were seen during hyperoxia (perfused small vessel density: 85% [95% confidence interval 79-90] of baseline). The response after 2 h of hyperoxia exposure was heterogeneous. Microvascular perfusion/density normalized upon returning to baseline FiO.
A two-hour exposure to hyperoxia in critically ill patients was associated with a slight increase in EPO levels within 48 h. Adequately controlled studies are needed to confirm the effect of short-term hyperoxia on erythropoiesis.
ClinicalTrials.gov ( www.clinicaltrials.gov ), NCT02481843 , registered 15th June 2015, retrospectively registered.
常压氧悖论指出，短时间暴露于常压高氧环境后迅速恢复至常压，会产生一种“相对缺氧”状态，从而刺激促红细胞生成素（EPO）的产生。谷胱甘肽和活性氧（ROS）的变化可能参与了这一过程。我们测试了短期高氧对危重症患者EPO水平和微循环的影响。
在这项前瞻性观察研究中，20名血流动力学稳定、接受机械通气且吸入氧浓度（FiO）≤0.5、动脉血氧分压/吸入氧浓度（PaO/FiO）≥200 mmHg的患者接受了2小时的高氧暴露（FiO 1.0）。另外20名患者作为对照。在基线、24小时和48小时测量血清EPO。在基线（t0）、高氧暴露2小时后（t1）以及恢复至基线FiO 2小时后（t2）评估血清谷胱甘肽（抗氧化剂）和ROS水平。使用舌下侧流暗视野视频显微镜和带有血管闭塞试验的鱼际近红外光谱法评估高氧对微循环的反应。
暴露于高氧的患者在48小时内EPO从16.1 [7.4 - 20.2] 升至22.9 [14.1 - 37.2] IU/L（p = 0.022）。血清ROS在t1时短暂升高，谷胱甘肽在t2时升高。高氧期间可见微血管密度和灌注早期降低（灌注小血管密度：为基线的85% [95%置信区间79 - 90]）。高氧暴露2小时后的反应存在异质性。恢复至基线FiO后微血管灌注/密度恢复正常。
危重症患者暴露于高氧2小时与48小时内EPO水平略有升高有关。需要进行充分对照研究以证实短期高氧对红细胞生成的影响。
ClinicalTrials.gov（www.clinicaltrials.gov），NCT0248
