一氧化氮在新型冠状病毒感染中的应用

doi:10.16138/j.1673-6087.2024.01.15

摘要/Abstract

摘要：

新型冠状病毒感染（coronavirus disease 2019, COVID-19）的发生造成了世界范围的医疗危机和卫生资源紧张。一氧化氮（nitric oxide， NO）在2003年严重急性呼吸综合征（severe acute respiratory syndrome， SARS）期间被证明可以改善氧合，降低肺动脉压力，减少无创通气的需求。SARS冠状病毒（SARS coronavirus， SARS-CoV）与SARS-CoV-2遗传结构和病理特征具有重叠性，并且NO具有抗病毒、舒张血管、抗凝、抗炎作用。本文拟对NO在COVID-19中的应用展开综述，以期为后续COVID-19患者的治疗提供思路。

关键词: 一氧化氮, 新型冠状病毒感染, 急性呼吸综合征冠状病毒-2, 血管舒张, 抗病毒

Abstract:

The outbreak of coronavirus disease 2019 (COVID-19) has caused a worldwide medical crisis and strained health resources. Nitric oxide (NO) is shown to improve oxygenation, reduce pulmonary artery pressure, and reduce the need for noninvasive ventilation during severe acute respiratory syndrome (SARS) in 2003. SARS coronavirus (SARS-CoV) and SARS-CoV-2 have overlapping genetic structure and pathological characteristics, and NO has antiviral, vasodilator, anticoagulant and anti-inflammatory effects. This article reviewed the application of NO in COVID-19 patients, to provide the treatment strategy for new COVID-19 patients.

Key words: Nitric oxide, Coronavirus disease 2019, Severe acute respiratory syndrome coronavirus 2, Vasodilation, Antivirus

中图分类号:

R511

王亚婷, 贺春伟, 付紫玉, 王慧, 马德东. 一氧化氮在新型冠状病毒感染中的应用[J]. 内科理论与实践, 2024, 19(01): 82-87.

WANG Yating, HE Chunwei, FU Ziyu, WANG Hui, MA Dedong. Application of nitric oxide in corona virus disease 2019[J]. Journal of Internal Medicine Concepts & Practice, 2024, 19(01): 82-87.

图/表 1

表1

NO在COVID-19患者中的应用

患者	iNO剂量	治疗时间	研究结果	参考文献
自主呼吸轻中型COVID-19 （n=39）	30 ppm	2.1 d	53.9%患者不再需要有创机械通气， SpO₂/ FiO₂较基线提高54.9%；46.1%患者需要机械通气，SpO₂/ FiO₂较基线降低8.6%	[42]
自主呼吸轻中型COVID-19 （n=29）	160 ppm	30 min/次，2次/d，14 d或直到出院或 SARS-CoV-2核酸阴性或连续3 d没有呼吸道症状	呼吸频率降低2次/min，SpO₂/ FiO₂提高49%。治疗期间NO₂最高浓度为1.47 ppm；MetHb最高为4.7%，停用NO 5 min后 MetHb 下降；未发生不良事件和死亡。出院患者在随访28 d内均未出现需要再次住院或COVID-19相关长期后遗症	[43]
轻型COVID-19 （n=80）	2喷/鼻孔，120~140 μL/喷	5~6次/d,9 d	与安慰剂组相比，NO鼻喷雾剂组患者SARS-CoV-2载量24 h内降低95%， 72 h 内降低99%以上	[44]
危重型COVID-19 （n=10）	20 ppm	30 min	PaO₂从（62 ± 9） mmHg升至（64 ± 14） mmHg；PaO₂/FiO₂从（81 ± 19）mmHg升至（84 ± 22 ）mmHg	[47]
危重型COVID-19 （n=34）	10 ppm	30 min	65%患者为应答者	[48]
COVID-19合并ARDS （n=7）	20 ppm	15-30 min	PaO₂从78.2 mmHg升至105 mmHg。肺血管阻力降低9.9%，肺分流未观察到明显变化（39.0% 到40.0%）	[49]
危重型COVID-19合并ARDS （n=9）	20 ppm	1 h	PaO₂/FiO₂从65 mmHg增加到72 mmHg和 SpO₂从53%增加到57%	[50]
COVID-19合并ARDS （n=33）	10~20 ppm	24 h	COVID-19合并ARDS组PaO₂/FiO₂增加3%，其中40%患者 PaO₂/FiO₂增加>10%；非COVID-19的ARDS组PaO₂/FiO₂增加47%，其中 77%患者 PaO₂/FiO₂增加>10%	[51]
危重型COVID-19 （n=193）	80 ppm	前48 h为80 ppm，随后减少至40 ppm，维持在该浓度直至严重低氧血症消退（PaO₂/FiO₂>300 mmHg）	与常规护理组相比，NO组48 hPaO₂/FiO₂改善（分别为-1.4 mmHg和 28.3 mmHg），低氧血症消退时间延长（8.4 d和8.7 d），28 d内低氧血症消退的患者比例增加（17.2%和27.7%），28 d和90 d死亡率无差异，无严重不良事件发生	[52]
危重型COVID-19 （n=16）	20~30 ppm	15~30 min	PaO₂/FiO₂无改善（91.7到91.5 mmHg）。合并右心室功能障碍组PaO₂/FiO₂增加24.1%，无右心室功能障碍组PaO₂/FiO₂增加3.3%	[54]
COVID-19合并ARDS （n=35）	20 ppm	6.1 d	吸入NO后PaO₂/FiO₂增加（13.6到17.4 kPa）和氧合指数降低(20.6到14.4)和死腔率减少(0.28到0.24)。在停止NO治疗后PaO₂/FiO₂与死腔率没有明显改变。65.7%患者为应答者。应答者脑钠肽和高敏肌钙蛋白高于非应答者	[55]
危重型COVID-19合并肺动脉高压（n=5）	10~20 ppm	5~10 d	iNO的患者PaO₂/FiO₂均升高，心功能保持正常，肺动脉压力降低。未iNO治疗的患者发生右心衰竭，肺动脉压力和 PaO₂/FiO₂突然降低，随后死亡	[56]
COVID-19合并 ARDS和重度肺动脉高压（n=1）	15 ppm	7 d	iNO 24 h后，PaO₂/FiO₂从100 mmHg升高至216 mmHg。吸入7d后，PaO₂/FiO₂比值从100 mmHg持续升高至321 mmHg。停止使用NO后，氧合和血流动力学的改善得以保留，允许呼吸脱机。重复经胸超声心动图示，肺动脉高压、三尖瓣反流、右心室收缩力和扩张程度均改善	[57]
COVID-19合并肺动脉高压（n=1）	20 ppm	12~14 h/d, 11 d	患者症状和6 min步行试验改善，肺血管阻力降低，高铁血红蛋白水平保持在参考范围内	[58]
重型或危重COVID-19孕妇（n=6）	160~200 ppm	30 min/次，2次/d，共 39次	患者心肺功能改善，全身氧合增加，呼吸急促减少，并且在入院后的28 d内，5例鼻咽拭子SARS-CoV-2检测结果为2次阴性，3例患者在住院期间共分娩了4名新生儿，且新生儿状况良好，核酸检测为阴性，所有患者对NO耐受性良好	[61]
重型COVID-19孕妇（n=71）	200 ppm	30 min/次，2次/d，共 144次	与常规护理组相比，NO+常规护理组28 d内的吸氧需求减少，住院时间缩短	[62]

表1

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