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应用原卟啉 IX 三重态寿命技术无创评估危重症患者线粒体氧代谢:一项可行性研究。

Non-invasive Assessment of Mitochondrial Oxygen Metabolism in the Critically Ill Patient Using the Protoporphyrin IX-Triplet State Lifetime Technique-A Feasibility Study.

机构信息

Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.

Septomics Research Center, Jena University Hospital, Jena, Germany.

出版信息

Front Immunol. 2020 May 7;11:757. doi: 10.3389/fimmu.2020.00757. eCollection 2020.

Abstract

The imbalance of oxygen delivery and oxygen consumption resulting in insufficient tissue oxygenation is pathognomonic for all forms of shock. Mitochondrial function plays an important role in the cellular oxygen metabolism and has been shown to impact a variety of diseases in the intensive care setting, specifically sepsis. Clinical assessment of tissue oxygenation and mitochondrial function remains elusive. The protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) allows the direct, non-invasive measurement of mitochondrial oxygen tension (mitoPO) in the human skin. Our recently established measurement protocol for the Cellular Oxygen Metabolism (COMET) Monitor, a novel device employing the PpIX-TSLT, additionally allows the evaluation of oxygen consumption (mitoVO) and delivery (mitoDO). In the intensive care setting, these variables might provide new insight into mitochondrial oxygen metabolism and especially mitoDO might be a surrogate parameter of microcirculatory function. However, the feasibility of the PpIX-TSLT in critically ill patients has not been analyzed systematically. In this interim study analysis, we evaluated PpIX-TSLT measurements of 40 patients during the acute phase of sepsis. We assessed (a) potential adverse side effects of the method, (b) the rate of analyzable measurements, (c) the stability of mitoPO, mitoVO, and mitoDO, and (d) potential covariates. Due to excessive edema in patients with sepsis, we specifically analyzed the association of patients' hydration status, assessed by bioimpedance analysis (BIA), with the aforementioned variables. We observed no side effects and acquired analyzable measurements sessions in 92.5% of patients ( = 37/40). Different measures of stability indicated moderate to good repeatability of the PpIX-TSLT variables within one session of multiple measurements. The determined limits of agreement and minimum detectable differences may be helpful in identifying outlier measurements. In conjunction with signal quality they mark a first step in developing a previously unavailable standardized measurement quality protocol. Notably, higher levels of hydration were associated with lower mitochondrial oxygen tension. We conclude that COMET measurements are viable in patients with sepsis. To validate the clinical and diagnostic relevance of the PpIX-TSLT using the COMET in the intensive care setting, future studies in critically ill patients and healthy controls are needed.

摘要

氧输送与氧消耗失衡导致组织氧合不足是所有类型休克的特征。线粒体功能在细胞氧代谢中起着重要作用,并已被证明会影响重症监护环境中的多种疾病,特别是脓毒症。目前仍难以对组织氧合和线粒体功能进行临床评估。原卟啉 IX 三重态寿命技术 (PpIX-TSLT) 可直接、无创地测量人体皮肤中的线粒体氧张力 (mitoPO)。我们最近建立的细胞氧代谢 (COMET) 监测仪测量协议,采用 PpIX-TSLT 技术,还可评估氧消耗 (mitoVO) 和氧输送 (mitoDO)。在重症监护环境中,这些变量可能为线粒体氧代谢提供新的见解,特别是 mitoDO 可能是微循环功能的替代参数。然而,尚未系统分析 PpIX-TSLT 在危重病患者中的可行性。在这项临时研究分析中,我们评估了 40 例脓毒症急性期患者的 PpIX-TSLT 测量结果。我们评估了 (a) 该方法的潜在不良副作用,(b) 可分析测量的比例,(c) mitoPO、mitoVO 和 mitoDO 的稳定性,以及 (d) 潜在的协变量。由于脓毒症患者存在过度水肿,我们特别分析了患者水合状态(通过生物阻抗分析 [BIA] 评估)与上述变量的关系。我们观察到没有副作用,并且 92.5%的患者(=37/40)可获得可分析的测量结果。稳定性的不同衡量标准表明,在多次测量的一次测量中,PpIX-TSLT 变量具有中等至良好的可重复性。确定的一致性界限和最小可检测差异可有助于识别异常测量值。结合信号质量,它们标志着制定以前无法获得的标准化测量质量协议的第一步。值得注意的是,较高的水合水平与较低的线粒体氧张力相关。我们得出结论,COMET 测量在脓毒症患者中是可行的。为了使用 COMET 通过 PpIX-TSLT 在重症监护环境中验证其临床和诊断相关性,需要对重症患者和健康对照者进行进一步的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/864a/7221153/678fc10b8c7a/fimmu-11-00757-g0001.jpg

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