吸入一氧化氮治疗重及危重型新型冠状病毒感染的疗效与安全性的Meta分析

doi:10.19983/j.issn.2096-8493.20220145

摘要/Abstract

摘要：

目的: 通过Meta分析评价吸入一氧化氮(inhaled nitric oxide,iNO)治疗重及危重型新型冠状病毒感染(简称“新冠病毒感染”)的临床疗效与安全性。方法: 检索中文数据库(中国知网、万方数据库、维普数据库)和英文数据库(PubMed、Embase、Web of Science、Cochrane)从2020年1月至2021年11月发表的有关iNO治疗新冠病毒感染的临床随机对照研究和观察性研究,结局指标包括氧合指数(PaO₂/FiO₂)、病亡率、需气管插管率、住院时间、病毒载量和并发症发生情况。使用Cochrane手册和纽卡斯尔·渥太华量表(Newcastle Ottawa scale,NOS)对纳入研究进行质量评价,使用RevMan 5.3软件对符合质量标准的文献进行Meta分析。结果: 最终纳入15篇研究,共538例患者,平均年龄58.5±3.0岁,男性363例,占67.5%,其中RCT研究1篇,观察性研究14篇,NOS量表评分均为5分以上。Meta分析结果显示:与iNO治疗前相比,iNO治疗后氧合指数明显改善(SMD=-0.52,95%CI:-0.73~-0.31);非iNO治疗组和iNO治疗组患者短期病亡率差异无统计学意义(OR=0.76,95%CI:0.17~3.44),将iNO治疗阳性反应组和阴性反应组比较,病亡率差异无统计学意义(OR=0.66,95%CI:0.24~1.80)。结论: 在重及危重型新冠病毒感染患者中,iNO治疗安全性较好,可改善短期氧合,但对短期病亡率无影响。

关键词: 一氧化氮, 冠状病毒感染, 严重急性呼吸综合征, Meta分析

Abstract:

Objective: To evaluate the clinical efficacy and safety of inhaled nitric oxide (iNO) in the treatment of severe and critical novel coronavirus infection by Meta-analysis. Methods: Chinese database (CNKI,Wanfang,Wiper) and English database (PubMed, Embase Web of Science, Cochrane) were searched to retrieve the randomized controlled trials (RCTs) and observational studies about the iNO in the treatment of novel coronavirus infection published from January 2020 to November 2021. The outcomes included oxygenation index (PaO₂/FiO₂), mortality, needs for endotracheal intubation, length of hospital stay, viral load and incidence of complications. The Cochrane manual and Newcastle Ottawa scale (NOS) were used to evaluate the quality of the included studies, and RevMan 5.3 software was used to perform meta-analysis of the literature that met the quality criteria. Results: Fifteen studies were included, including 538 patients, with an average age of 58.5±3.0 years and 67.5% (363/538) male, including 1 RCT study with quality evaluation of “B” and 14 observational studies with NOS score above 5. Meta-analysis showed that oxygenation index was significantly improved after iNO treatment compared with before iNO treatment (SMD=-0.52, 95%CI: -0.73--0.31). There was no significant difference in short-term mortality between the non-iNO treatment group and the iNO treatment group (OR=0.76, 95%CI: 0.17-3.44), and there was no significant difference in mortality between the positive and negative iNO treatment groups (OR=0.66, 95%CI: 0.24-1.80). Conclusion: In patients with novel coronavirus infection, iNO treatment was safe and could improve oxygenation in a short time, but had no effect on short-term mortality.

Key words: Nitric oxide, Coronavirus infections, Severe acute respiratory syndrome, Meta-analysis

中图分类号:

周永芳, 付江泉, 董文涛, 房东海, 胡晓纯. 吸入一氧化氮治疗重及危重型新型冠状病毒感染的疗效与安全性的Meta分析[J]. 结核与肺部疾病杂志, 2023, 4(1): 33-40. doi: 10.19983/j.issn.2096-8493.20220145

Zhou Yongfang, Fu Jiangquan, Dong Wentao, Fang Donghai, Hu Xiaochun. Meta-analysis of efficacy and safety of inhaled nitric oxide in the treatment of severe and critical novel coronavirus pneumonia[J]. Journal of Tuberculosis and Lung Disease, 2023, 4(1): 33-40. doi: 10.19983/j.issn.2096-8493.20220145

图/表 6

图1

表1

纳入Meta分析研究的基本特征

研究者及发表时间	国家		平均年龄 (岁)	性别 (男/女)	入选标准		iNO治疗方式、剂量及时间
Robba等2021年3月^[22]	意大利		62±8.8	5/4	ARDS;机械通气;氧合指数<100;超声或CT显示肺动脉高压		经呼吸回路吸入;≥20mg/L;>1h每次;连续3d
Cardinale等2020年8月^[23]	英国		59±10.3	17/16	ARDS;机械通气		具体量和时间未提
Lotz等2021年5月^[24]	德国		-	-	重度ARDS;机械通气		经呼吸回路吸入;20mg/L;>30min
DeGrado等2020年10月^[25]	美国		61±12.0	24/14	中、重度ARDS;机械通气		经呼吸机回路吸入;20~80mg/L;>1h
Abou-Arab等2020年11月^[26]	法国		-	-	机械通气;氧合指数<150		经呼吸机回路吸入;10mg/L;15~30min
Ferrari等2020年12月^[27]	意大利		55±9.0	-	机械通气;氧合指数<100		经呼吸机回路吸入;20mg/L;30min
Tavazzi等2020年8月^[28]	意大利		66±7.4	15/1	机械通气;氧合指数<100;4例患者心脏超声诊断为肺心病		经呼吸机回路吸入;20~30mg/L;30min
Garfield等2021年2月^[29]	英国		57.6±8.1	28/7	ARDS;机械通气;氧合指数<100		经呼吸机回路吸入;20~40mg/L;平均治疗时间146.4h
Bagate等2020年11月^[30]	法国		60±14.8	7/3	ARDS;机械通气;氧合指数<150		经呼吸机回路吸入;10mg/L;30min
Ziehr等2021年1月^[31]	美国		60±14.8	-	ARDS;机械通气;氧合指数<150		经呼吸机回路吸入;20~80mg/L;16h
研究者及发表时间	国家	平均年龄 (岁)		性别 (男/女)		入选标准		iNO治疗方式、剂量及时间
Laghlam等2021年7月^[32]	法国	71.8±8.7		9/3		ARDS;机械通气;氧合指数<200;排除肺动脉高压		经呼吸机回路吸入;10mg/L;30min;持续时间平均50.2h
Feng等2021年11月^[21]	中国	66.4±2.6		5/0		机械通气;肺动脉收缩压>50mmHg		经呼吸机回路吸入;10~20mg/L;具体时间不确定
Moni等2021年4月^[12]	印度	59.1±10.5		18/7		自主呼吸;血氧饱和度<94%;呼吸频率>24次/min		面罩吸入;30min内由10mg/L逐渐升至80mg/L;每次30min,q12h,持续3d
Chandel等2021年9月^[20]	美国	57±13.0		180/92		急性呼吸衰竭需行高流量氧疗		经高流量管路吸入;20~40mg/L;平均治疗时间88h
Longobardo等2020年1月^[33]	英国	59±10.3		13/7		ARDS;机械通气		具体量和时间未提

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图5

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