Muenster Stefan, Zarragoikoetxea Iratxe, Moscatelli Andrea, Balcells Joan, Gaudard Philippe, Pouard Philippe, Marczin Nandor, Janssens Stefan P
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
Department of Anesthesiology and Intensive Care Medicine, Hospital Universitari I Politècnic Fe, Valencia, Spain.
Front Cardiovasc Med. 2024 Apr 5;11:1374635. doi: 10.3389/fcvm.2024.1374635. eCollection 2024.
Inhaled nitric oxide (NO) has been used in pediatric and adult perioperative cardiac intensive care for over three decades. NO is a cellular signaling molecule that induces smooth muscle relaxation in the mammalian vasculature. Inhaled NO has the unique ability to exert its vasodilatory effects in the pulmonary vasculature without any hypotensive side-effects in the systemic circulation. In patients undergoing cardiac surgery, NO has been reported in numerous studies to exert beneficial effects on acutely lowering pulmonary artery pressure and reversing right ventricular dysfunction and/or failure. Yet, various investigations failed to demonstrate significant differences in long-term clinical outcomes. The authors, serving as an advisory board of international experts in the field of inhaled NO within pediatric and adult cardiac surgery, will discuss how the existing scientific evidence can be further improved. We will summarize the basic mechanisms underlying the clinical applications of inhaled NO and how this translates into the mandate for inhaled NO in cardiac surgery. We will move on to the popular use of inhaled NO and will talk about the evidence base of the use of this selective pulmonary vasodilator. This review will elucidate what kind of clinical and biological barriers and gaps in knowledge need to be solved and how this has impacted in the development of clinical trials. The authors will elaborate on how the optimization of inhaled NO therapy, the development of biomarkers to identify the target population and the definition of response can improve the design of future large clinical trials. We will explain why it is mandatory to gain an international consensus for the state of the art of NO therapy far beyond this expert advisory board by including the different major players in the field, such as the different medical societies and the pharma industry to improve our understanding of the real-life effects of inhaled NO in large scale observational studies. The design for future innovative randomized controlled trials on inhaled NO therapy in cardiac surgery, adequately powered and based on enhanced biological phenotyping, will be crucial to eventually provide scientific evidence of its clinical efficacy beyond its beneficial hemodynamic properties.
吸入一氧化氮（NO）已在儿科和成人围手术期心脏重症监护中使用了三十多年。NO是一种细胞信号分子，可诱导哺乳动物血管系统中的平滑肌松弛。吸入NO具有独特的能力，可在肺血管系统中发挥血管舒张作用，而在体循环中无任何降压副作用。在接受心脏手术的患者中，大量研究报告称NO对急性降低肺动脉压、逆转右心室功能障碍和/或衰竭具有有益作用。然而，各种调查未能证明长期临床结果存在显著差异。作为儿科和成人心脏手术领域吸入NO国际专家咨询委员会的成员，作者将讨论如何进一步完善现有科学证据。我们将总结吸入NO临床应用的基本机制，以及这如何转化为心脏手术中使用吸入NO的要求。我们将继续讨论吸入NO的广泛应用，并探讨这种选择性肺血管扩张剂使用的证据基础。本综述将阐明需要解决哪些临床和生物学障碍以及知识差距，以及这如何影响临床试验的开展。作者将详细阐述如何优化吸入NO治疗、开发生物标志物以识别目标人群以及定义反应，从而改善未来大型临床试验的设计。我们将解释为何必须超越这个专家咨询委员会，通过纳入该领域的不同主要参与者，如不同的医学协会和制药行业，就NO治疗的最新情况达成国际共识，以增进我们对大规模观察性研究中吸入NO实际效果的理解。未来针对心脏手术中吸入NO治疗的创新性随机对照试验的设计，要有足够的样本量并基于增强的生物学表型分析，这对于最终提供其临床疗效的科学证据（超越其有益的血流动力学特性）至关重要。
