吸入性一氧化氮在A型主动脉夹层术后低氧 血症中的应用与展望
Application and Future Perspectives of Inhaled Nitric Oxide in Hypoxemia Following Surgery for Type A Aortic Dissection
DOI: 10.12677/acm.2026.1641502, PDF,    科研立项经费支持
作者: 孙铁皞, 蔡 馨, 刘丁豪, 张 鑫：济宁医学院临床医学院，山东 济宁；刘新梅*：济宁医学院附属医院心脏重症医学科，山东 济宁
关键词: 吸入性一氧化氮；A型主动脉夹层；心脏外科手术；低氧血症；Inhaled Nitric Oxide； Type A Aortic Dissection； Cardiothoracic Surgery； Hypoxemia
摘要: A型主动脉夹层(AAD)术后低氧血症是导致患者预后不良的关键并发症之一，与患者术前基础状态、手术操作及术后炎症反应密切相关。吸入性一氧化氮(iNO)作为一种选择性肺血管扩张剂，通过激活鸟苷酸环化酶(sGC)-环磷酸鸟苷(cGMP)通路降低肺血管阻力，同时改善通气/血流(V/Q)匹配，为AAD术后低氧血症的治疗提供了新策略。本文系统综述了iNO在AAD术后低氧血症中的基础理论、临床实践、技术进展、争议挑战及未来展望，重点分析了iNO的药理机制、疗效评估、联合治疗策略及个性化治疗潜力。现有研究表明，低剂量Ino (5~20 ppm)可显著提高患者氧合指数(PaO₂/FiO₂)，缩短机械通气时间，但长期使用可能增加肾损伤风险，且疗效存在个体差异。未来需通过多中心随机对照试验明确iNO的最佳剂量与疗程，并结合分子生物学技术探索个性化治疗方案，以推动iNO在AAD术后低氧血症中的规范化应用。
Abstract: Postoperative hypoxemia after type A aortic dissection (AAD) surgery is a major complication associated with poor outcomes and is influenced by preoperative status, intraoperative factors, and postoperative inflammation. Inhaled nitric oxide (iNO), a selective pulmonary vasodilator, reduces pulmonary vascular resistance via the soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway and may improve ventilation/perfusion (V/Q) matching, offering a potential therapeutic option. This review summarizes the rationale, clinical use, technical advances, ongoing controversies, and future directions of iNO for AAD-related postoperative hypoxemia, focusing on mechanisms, efficacy evaluation, combination strategies, and individualized treatment. Available studies suggest that low-dose iNO (5~20 ppm) can improve PaO₂/FiO₂ and shorten mechanical ventilation duration, but prolonged use may increase renal injury risk and responses vary across patients. Multicenter randomized trials are needed to determine optimal dosing and duration, and molecular approaches may support personalized protocols to standardize iNO application in this setting.
文章引用：孙铁皞, 蔡馨, 刘丁豪, 张鑫, 刘新梅. 吸入性一氧化氮在A型主动脉夹层术后低氧 血症中的应用与展望[J]. 临床医学进展, 2026, 16(4): 2516-2524. https://doi.org/10.12677/acm.2026.1641502

参考文献

[1] Wu, J., Kao, L., Wu, B., Dai, Z., Wang, Y., Chai, C., et al. (2015) Buffered L‐Ascorbic Acid, Alone or Bound to KMUP‐1 or Sildenafil, Reduces Vascular Endothelium Growth Factor and Restores Endothelium Nitric Oxide Synthase in Hypoxic Pulmonary Artery. The Kaohsiung Journal of Medical Sciences, 31, 241-254. [Google Scholar] [CrossRef] [PubMed]
[2] Hao, G., Tu, G., Yu, S., Luo, J., Liu, K., Wang, H., et al. (2021) Inhaled Nitric Oxide Reduces the Intrapulmonary Shunt to Ameliorate Severe Hypoxemia after Acute Type A Aortic Dissection Surgery. Nitric Oxide, 109, 26-32. [Google Scholar] [CrossRef] [PubMed]
[3] Liu, H., Liang, X., Wang, D., Zhang, H., Liu, L., Chen, H., et al. (2015) Combination Therapy with Nitric Oxide and Molecular Hydrogen in a Murine Model of Acute Lung Injury. Shock, 43, 504-511. [Google Scholar] [CrossRef] [PubMed]
[4] Bhatt, D.P., Puig, K.L., Gorr, M.W., Wold, L.E. and Combs, C.K. (2015) A Pilot Study to Assess Effects of Long-Term Inhalation of Airborne Particulate Matter on Early Alzheimer-Like Changes in the Mouse Brain. PLOS ONE, 10, e0127102. [Google Scholar] [CrossRef] [PubMed]
[5] Filipczak, P.T., Senft, A.P., Seagrave, J., Weber, W., Kuehl, P.J., Fredenburgh, L.E., et al. (2015) NOS-2 Inhibition in Phosgene-Induced Acute Lung Injury. Toxicological Sciences, 146, 89-100. [Google Scholar] [CrossRef] [PubMed]
[6] Sheng, W., Yang, H., Chi, Y., Niu, Z., Lin, M. and Long, S. (2015) Independent Risk Factors for Hypoxemia after Surgery for Acute Aortic Dissection. Saudi Medical Journal, 36, 940-946. [Google Scholar] [CrossRef] [PubMed]
[7] Afolabi, M., Li, J., Wang, J., Abass, M., Lin, A., Debora, A., et al. (2025) Postoperative Acute Refractory Hypoxemia after Acute Type A Aortic Dissection Surgery: Supporting the Two-Hit Mechanism of Transfusion-Related Acute Lung Injury. a Retrospective Cohort Study. Vascular Health and Risk Management, 21, 797-811. [Google Scholar] [CrossRef] 
[8] Gao, H., Sun, X., Liu, Y., Liang, S., Zhang, B., Wang, L., et al. (2021) Analysis of Hub Genes and the Mechanism of Immune Infiltration in Stanford Type A Aortic Dissection. Frontiers in Cardiovascular Medicine, 8, Article 680065. [Google Scholar] [CrossRef] [PubMed]
[9] Zhang, L., Zhang, L., Zhao, Z., Liu, Y., Wang, J., Niu, M., et al. (2022) Metabolic Syndrome and Its Components Are Associated with Hypoxemia after Surgery for Acute Type A Aortic Dissection: An Observational Study. Journal of Cardiothoracic Surgery, 17, Article No. 151. [Google Scholar] [CrossRef] [PubMed]
[10] Song, X., Nie, S., Xiao, J., Shen, X., Hong, L., Chen, S., et al. (2022) Risk Factors and Long-Term Prognosis for Postoperative Hypoxemia in Patients with Acute Type A Aortic Dissection: A Retrospective Observational Study. Medicine, 101, e32337. [Google Scholar] [CrossRef] [PubMed]
[11] Zhang, H., Liu, Y., Meng, X., Yang, D., Shi, S., Liu, J., et al. (2020) Effects of Inhaled Nitric Oxide for Postoperative Hypoxemia in Acute Type A Aortic Dissection: A Retrospective Observational Study. Journal of Cardiothoracic Surgery, 15, Article No. 25. [Google Scholar] [CrossRef] [PubMed]
[12] Matsugi, E., Takashima, S., Doteguchi, S., Kobayashi, T. and Okayasu, M. (2024) Real-World Safety and Effectiveness of Inhaled Nitric Oxide Therapy for Pulmonary Hypertension during the Perioperative Period of Cardiac Surgery: A Post-Marketing Study of 2817 Patients in Japan. General Thoracic and Cardiovascular Surgery, 72, 311-323. [Google Scholar] [CrossRef] [PubMed]
[13] Ma, G., Hao, G., Lai, H., Yang, X., Liu, L., Wang, C., et al. (2019) Initial Clinical Impact of Inhaled Nitric Oxide Therapy for Refractory Hypoxemia Following Type A Acute Aortic Dissection Surgery. Journal of Thoracic Disease, 11, 495-504. [Google Scholar] [CrossRef] [PubMed]
[14] Respiratory Care Group of Chinese Thoracic Society; Respiratory Therapist Working Group of Respiratory Career Development Committee and Chinese Association of Chest Physician (2024) [Expert Consensus on Clinical Application of Inhaled Nitric Oxide Therapy (2024 Edition)]. National Medical Journal of China, 104, 2386-2400.
[15] Ruan, S., Huang, T., Wu, H., Wu, H., Yu, C. and Lai, M. (2015) Inhaled Nitric Oxide Therapy and Risk of Renal Dysfunction: A Systematic Review and Meta-Analysis of Randomized Trials. Critical Care, 19, Article No. 137. [Google Scholar] [CrossRef] [PubMed]
[16] Kumon, K. and Yahagi, N. (1998) Nitric Oxide Inhalation Increases Oxygen Delivery after Cardiovascular Surgery in Adult Patients Whether or Not They Have Pulmonary Hypertension. Journal of Anesthesia, 12, 180-184. [Google Scholar] [CrossRef] [PubMed]
[17] Nagasaka, Y., Fernandez, B.O., Garcia-Saura, M.F., Petersen, B., Ichinose, F., Bloch, K.D., et al. (2008) Brief Periods of Nitric Oxide Inhalation Protect against Myocardial Ischemia–reperfusion Injury. Anesthesiology, 109, 675-682. [Google Scholar] [CrossRef] [PubMed]
[18] Nakane, T., Esaki, J., Ueda, R., Honda, M. and Okabayashi, H. (2021) Inhaled Nitric Oxide Improves Pulmonary Hypertension and Organ Functions after Adult Heart Valve Surgeries. General Thoracic and Cardiovascular Surgery, 69, 1519-1526. [Google Scholar] [CrossRef] [PubMed]
[19] Lin, Y., Chen, Q., Zhang, H., Chen, L., Peng, Y., Huang, X., et al. (2020) Risk Factors for Postoperative Delirium in Patients with Triple-Branched Stent Graft Implantation. Journal of Cardiothoracic Surgery, 15, Article No. 171. [Google Scholar] [CrossRef] [PubMed]
[20] Tominaga, Y., Iwai, S., Yamauchi, S., Kyogoku, M., Kugo, Y., Hasegawa, M., et al. (2019) Post-Extubation Inhaled Nitric Oxide Therapy via High-Flow Nasal Cannula after Fontan Procedure. Pediatric Cardiology, 40, 1064-1071. [Google Scholar] [CrossRef] [PubMed]
[21] Hadaya, J. and Benharash, P. (2020) Prone Positioning for Acute Respiratory Distress Syndrome (ARDS). JAMA, 324, 1361. [Google Scholar] [CrossRef] [PubMed]
[22] Yuan, X., Zhao, Z., Chao, Y., Chen, D., Chen, H., Zhang, R., et al. (2023) Effects of Early versus Delayed Application of Prone Position on Ventilation-Perfusion Mismatch in Patients with Acute Respiratory Distress Syndrome: A Prospective Observational Study. Critical Care, 27, Article No. 462. [Google Scholar] [CrossRef] [PubMed]
[23] Kenny, J.S. (2023) A Framework for Heart-Lung Interaction and Its Application to Prone Position in the Acute Respiratory Distress Syndrome. Frontiers in Physiology, 14, Article 1230654. [Google Scholar] [CrossRef] [PubMed]
[24] Gebistorf, F., Karam, O., Wetterslev, J. and Afshari, A. (2016) Inhaled Nitric Oxide for Acute Respiratory Distress Syndrome (ARDS) in Children and Adults. Cochrane Database of Systematic Reviews, No. 6, CD002787. [Google Scholar] [CrossRef] [PubMed]
[25] Stephens, R.S., Shah, A.S. and Whitman, G.J.R. (2013) Lung Injury and Acute Respiratory Distress Syndrome after Cardiac Surgery. The Annals of Thoracic Surgery, 95, 1122-1129. [Google Scholar] [CrossRef] [PubMed]
[26] Jin, M., Cheng, Y., Yang, Y., Pan, X., Lu, J. and Cheng, W. (2017) Protection of Xenon against Postoperative Oxygen Impairment in Adults Undergoing Stanford Type-A Acute Aortic Dissection Surgery: Study Protocol for a Prospective, Randomized Controlled Clinical Trial. Medicine, 96, e7857. [Google Scholar] [CrossRef] [PubMed]
[27] Stawicki, S.P., Goyal, M. and Sarani, B. (2009) Analytic Reviews: High-Frequency Oscillatory Ventilation (HFOV) and Airway Pressure Release Ventilation (APRV): A Practical Guide. Journal of Intensive Care Medicine, 24, 215-229. [Google Scholar] [CrossRef] [PubMed]
[28] Dreyfuss, D., Ricard, J. and Gaudry, S. (2015) Did Studies on HFOV Fail to Improve ARDS Survival Because They Did Not Decrease VILI? On the Potential Validity of a Physiological Concept Enounced Several Decades Ago. Intensive Care Medicine, 41, 2076-2086. [Google Scholar] [CrossRef] [PubMed]
[29] Matamis, D., Pampori, S., Papathanasiou, A., Papakonstantinou, P., Tsagourias, M., Galiatsou, E., et al. (2012) Inhaled NO and Sildenafil Combination in Cardiac Surgery Patients with Out-of-Proportion Pulmonary Hypertension: Acute Effects on Postoperative Gas Exchange and Hemodynamics. Circulation: Heart Failure, 5, 47-53. [Google Scholar] [CrossRef] [PubMed]
[30] Zheng, P., Jiang, D., Liu, C., Wei, X. and Li, S. (2022) Nitric Oxide Inhalation Therapy Attenuates Postoperative Hypoxemia in Obese Patients with Acute Type A Aortic Dissection. Computational and Mathematical Methods in Medicine, 2022, Article ID: 9612548. [Google Scholar] [CrossRef] [PubMed]
[31] Distefano, G. and Sciacca, P. (2015) Molecular Physiopathogenetic Mechanisms and Development of New Potential Therapeutic Strategies in Persistent Pulmonary Hypertension of the Newborn. Italian Journal of Pediatrics, 41, Article No. 6. [Google Scholar] [CrossRef] [PubMed]
[32] Puligandla, P.S., Grabowski, J., Austin, M., Hedrick, H., Renaud, E., Arnold, M., et al. (2015) Management of Congenital Diaphragmatic Hernia: A Systematic Review from the APSA Outcomes and Evidence Based Practice Committee. Journal of Pediatric Surgery, 50, 1958-1970. [Google Scholar] [CrossRef] [PubMed]

为你推荐