体外膜肺氧合并发血栓发生率的meta分析

doi:10.3969/j.issn.1004-583X.2024.01.001

摘要/Abstract

摘要：

目的系统评价体外膜肺氧合技术(extracorporeal membrane oxygenation,ECMO)治疗患者血栓发生率。方法通过“Extracorporeal Membrane Oxygenation或ECMO” 、“thrombus或 complication等关键词检索文献,检索PubMed、EMBASE、万方和中国知网数据库建库至2022年12月有关ECMO及血栓并发症的相关研究,指定2人按照纳排标准对检索的文章进行筛选,应用Review Manager 5.4软件进行meta分析及亚组分析,依据纽卡斯尔-渥太华量表(Newcastle-Ottawa Scale, NOS)评价文章质量。结果经筛选共纳入16篇文献和1 136例患者,Meta分析结果显示ECMO治疗患者血栓的发生率为52.0%(95% $C I$ :0.30~0.88), $I 2$ =91%( $P$ <0.01),亚组分析结果显示<45岁、45~59岁ECMO治疗患者并发血栓的发生率分别为27.0%(95% $C I$ :0.14~0.50)、53.0%(95% $C I$ :0.29~0.97),ECMO平均持续时间≤10 d、>10 d血栓发生率分别为50.0%(95% $C I$ :0.34~0.74)、39.0%(95% $C I$ :0.11~1.38),体质量指数为24~27.9 kg/m²、≥28 kg/m²的血栓发生率分别为27.0%(95% $C I$ :0.07~1.07)、66.0%(95% $C I$ :0.36~1.23),活化部分凝血活酶时间(APTT)、激活全血凝固时间(ACT)、抗fxa 3种不同的抗凝监测方式血栓发生率分别为57.0%(95% $C I$ :0.47~0.69)、13.0%(95% $C I$ :0.08~0.20)、45.0%(95% $C I$ :0.36~0.57)。结论 ECMO治疗患者血栓发生率为52.0%,年龄大、ECMO持续时间短、高体质量指数、采用APTT监测抗凝者血栓发生率较高。

关键词: 体外膜氧合作用, 血栓, 发生率

Abstract:

Objective To systematically evaluate the incidence of thrombotic complications in patients treated with extracorporeal membrane oxygenation technology (ECMO). Methods Articles reporting ECMO and incident thrombosis published before December 2022 were systematically searched in the PubMed, EMBASE, Wanfang and CNKI database using the following keywords: “Extracorporeal Membrane Oxygenation or ECMO”, “thrombus or complication”. Two investigators were responsible for screening eligible articles based on the inclusion and exclusion criteria. Meta-analysis and subgroup analysis were performed using Review Manager 5.4 software. The quality of the included articles was evaluated according to the Newcastle-Ottawa Scale (NOS) scoring system. Results A total of 16 literatures involving 1136 patients were selected. Meta-analysis showed that the incidence of thrombosis in ECMO patients was 52.0%(95% $C I$ : 0.30-0.88) and $I 2$ was 91% ( $P$ <0.01). Subgroup analysis showed that the incidence of ECMO concurrent thrombosis in patients <45 years old and 45-59 years old was 27.0%(95% $C I$ : 0.14-0.50) and 53.0%(95% $C I$ : 0.29-0.97), respectively. The incidence of patients with a mean duration of ECMO ≤10 days and >10 days was 50.0%(95% $C I$ : 0.34-0.74) and 39.0%(95% $C I$ : 0.11-1.38), respectively. The incidence of thrombosis with a body mass index(BMI) of 24-27.9 kg/m² and ≥28 kg/m² was 27.0%(95% $C I$ : 0.07-1.07) and 66.0% (95% $C I$ : 0.36-1.23), respectively. The incidence of thrombosis detected by the anticoagulation monitoring methods of partial thromboplastin time (APTT), activated clotting time (ACT) and anti-factor-Xa (anti-Xa) was 57.0%(95% $C I$ : 0.47-0.69), 13.0%(95% $C I$ : 0.08-0.20) and 45.0% (95% $C I$ : 0.36-0.57), respectively. Conclusion The incidence of thrombotic complications in patients treated with ECMO is 52.0%. Patients with an older age, shorter duration of ECMO, greater BMI and monitored for APTT have a higher incidence of thrombotic complications.

Key words: extracorporeal membrane oxygenation, thrombosis, incidence rate

中图分类号:

R654.1

彭伊梦, 姚杨, 李思雨, 丁格, 孙亚楠, 王胜昱. 体外膜肺氧合并发血栓发生率的meta分析[J]. 临床荟萃, 2024, 39(1): 5-11.

Peng Yimeng, Yao Yang, Li Siyu, Ding Ge, Sun Yanan, Wang Shengyu. Meta-analysis of the incidence of extracorporeal membrane oxygenation combined with incident thrombosis[J]. Clinical Focus, 2024, 39(1): 5-11.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2024.01.001

https://huicui.hebmu.edu.cn/CN/Y2024/V39/I1/5

图/表 7

图1 纳入文献筛选流程

Fig.1 Screening process for included literature

表1 纳入文献的基本特征

Tab.1 Basic characteristics of included literature

纳入研究	年份	国家/地区	年龄 (岁)	男性 [例(%)]	病例总数	研究类型	V-V	V-A	VA-V	持续时间 (d)	血栓例数
Parzy^[6]	2020	France	48.0±16.0	71(67.6)	105	回顾性研究	105	0	0	10(6,16)	75
Weber^[7]	2018	Germany	59.1±14.4	216(76.9)	281	回顾性研究	281	0	0	99(28,75)	11
Cartwright^[8]	2021	Australia	46.7(41.1, 63.7)	23(59.0)	39	回顾性研究	17	22	0	VA:3(2,5); VV:10(6,13)	26
Chandel^[9]	2021	USA	46(37, 53)	4(16.7)	24	回顾性研究	24	0	0	13(9, 21)	12
Ripoll^[10]	2022	UK	45(39, 56)	24(80.0)	30	回顾性研究	30	0	0	4(1, 5)	13
Moussa^[11]	2021	France	55±14	183(69.1)	265	回顾性研究	265	0	0	7(3,11)	87
Salas De Armas^[12]	2022	USA	30.6±12.6	14(93.3)	15	回顾性研究	15	0	0	11.0(7.5,20.0)	1
Kohs^[13]	2022	USA	51.1±15.9	44(65.7)	67	回顾性研究	23	44	0	7.0±5.0	16
Zhang^[14]	2021	China	47(25,73)	11(73.3)	15	回顾性研究	5	10	0	15.0±18.0	4
Beyls^[15]	2020	France	62(56,66)	10(83.3)	12	回顾性研究	12	0	0	4.0(1.5,7.5)	11
Riera^[16]	2020	Spain	50.5(31.0,64.0)	16(84.2)	19	回顾性研究	19	0	0	8.6(0,17.0)	9
Fong^[17]	2021	Hong Kong	55.0(41.3,62.0)	85(65.4)	130	回顾性研究	79	51	0	5.9(3.6,7.9)	37
Agerstrand^[18]	2016	New York	32.6(26.0,39.0)	0	18	回顾性研究	14	1	3	6.6(6.0,17.8)	5
Trudzinski^[19]	2016	Germany	46.0±14.4	37(58.7)	63	回顾性研究	63	0	0	22.4±17.0	29
Agerstrand^[20]	2015	New York	33(24,53)	24(63.2)	38	回顾性研究	34	2	1	9.0(7.0,11.5)	8
Roussel^[21]	2012	France	52(22, 86)	7(46.7)	15	回顾性研究	0	15	0	4.9(1.0,12.0)	1

表2 纳入文献的质量评价

Tab.2 Quality evaluation of included literature

纳入研究	①	②	③	④	⑤	⑥	⑦	⑧	⑨	⑩	总分
Parzy^[6]	1	1	1	1	1	0	1	0	1	0	7
Weber^[7]	1	1	1	1	1	0	1	1	0	0	7
Cartwright^[8]	1	1	1	1	1	1	1	1	0	0	8
Chandel^[9]	1	1	1	1	1	1	1	1	0	1	9
Ripoll^[10]	1	1	1	1	1	0	1	1	0	1	8
Moussa^[11]	1	1	1	1	1	1	1	1	0	1	9
Salas De Armas^[12]	1	1	1	1	1	0	1	1	1	1	9
Kohs^[13]	1	1	1	1	1	1	1	1	0	0	8
Zhang^[14]	1	1	1	1	1	0	1	1	0	1	8
Beyls^[15]	1	1	1	1	1	0	1	1	1	0	8
Riera^[16]	1	1	1	1	1	0	1	1	1	0	8
Fong^[17]	1	1	1	1	1	0	1	1	0	1	9
Agerstrand^[18]	1	1	1	1	0	1	0	0	0	1	6
Trudzinski^[19]	1	1	1	1	1	1	1	1	0	1	9
Agerstrand^[20]	1	1	1	1	1	1	1	1	0	1	9
Roussel^[21]	1	1	1	1	0	1	0	0	0	1	6

图2 ECMO患者血栓发生率的森林图

Fig. 2 Forest plot of thrombosis incidence in ECMO patients

图3 ECMO患者血栓发生率的漏斗图

Fig. 3 Funnel plot of thrombosis incidence in ECMO patients

表3 Meta分析结果汇总表

Tab.3 Summary table of Meta-analysis results

亚组	纳入研究数	异质性检验结果		效应模型	患病率(95% $C I$ )
亚组	纳入研究数	$P$ 值	$I 2$ 值	效应模型	患病率(95% $C I$ )
总发生率	16^{[6⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓-21]}	<0.01	91%	随机	52.0%(95% $C I$ :0.30~0.88)
年龄(岁)
<45岁	3^[12,18,20]	0.35	5%	随机	27.0%(95% $C I$ :0.14~0.50)
45~59岁	12^{[6⇓⇓⇓⇓-11,13 -14,16 -17,19,21]}	<0.01	93%	随机	53.0%(95% $C I$ :0.29~0.97)
ECMO时间(d)
≤10	8^{[10,11,13,15⇓⇓ -18,21]}	0.008	63%	随机	50.0%(95% $C I$ :0.34~0.74)
>10	7^{[6-7,9,12,14,18 -19]}	<0.01	95%	随机	39.0%(95% $C I$ :0.11~1.38)
BMI( kg/m²)
24~27.9	5^{[6-7,11 -12,20]}	<0.01	97%	随机	27.0%(95% $C I$ :0.07~1.07)
≥28	6^{[8,13 -14,16,18 -19]}	0.0009	76%	随机	66.0%(95% $C I$ :0.36~1.23)
抗凝监测方式
APTT	8^{[6⇓-8,11 -12,15,18,20]}	<0.01	95%	随机	57.0%(95% $C I$ :0.47~0.69)
ACT	3^[7,14,16]	<0.01	94%	随机	13.0%(95% $C I$ :0.08~0.20)
抗fxa	2^[11,13]	0.16	50%	随机	46.0%(95% $C I$ :0.36~0.57)

表3 Meta分析结果汇总表

Tab.3 Summary table of Meta-analysis results

亚组	纳入研究数	异质性检验结果		效应模型	患病率(95% $C I$ )
亚组	纳入研究数	$P$ 值	$I 2$ 值	效应模型	患病率(95% $C I$ )
总发生率	16^{[6⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓-21]}	<0.01	91%	随机	52.0%(95% $C I$ :0.30~0.88)
年龄(岁)
<45岁	3^[12,18,20]	0.35	5%	随机	27.0%(95% $C I$ :0.14~0.50)
45~59岁	12^{[6⇓⇓⇓⇓-11,13 -14,16 -17,19,21]}	<0.01	93%	随机	53.0%(95% $C I$ :0.29~0.97)
ECMO时间(d)
≤10	8^{[10,11,13,15⇓⇓ -18,21]}	0.008	63%	随机	50.0%(95% $C I$ :0.34~0.74)
>10	7^{[6-7,9,12,14,18 -19]}	<0.01	95%	随机	39.0%(95% $C I$ :0.11~1.38)
BMI( kg/m²)
24~27.9	5^{[6-7,11 -12,20]}	<0.01	97%	随机	27.0%(95% $C I$ :0.07~1.07)
≥28	6^{[8,13 -14,16,18 -19]}	0.0009	76%	随机	66.0%(95% $C I$ :0.36~1.23)
抗凝监测方式
APTT	8^{[6⇓-8,11 -12,15,18,20]}	<0.01	95%	随机	57.0%(95% $C I$ :0.47~0.69)
ACT	3^[7,14,16]	<0.01	94%	随机	13.0%(95% $C I$ :0.08~0.20)
抗fxa	2^[11,13]	0.16	50%	随机	46.0%(95% $C I$ :0.36~0.57)

表4 ECMO患者血栓发生率的敏感性分析

Tab.4 Sensitivity analysis of thrombosis incidence in ECMO patients

剔除研究	$O R$	$P$ 值	$I 2$ 值	95% $C I$	Tau²
Parzy^[6] 2020	0.45	<0.01	88%	0.28~0.75	0.74
Weber^[7] 2018	0.64	<0.01	85%	0.41~0.99	0.54
Cartwright^[8] 2021	0.47	<0.01	91%	0.27~0.81	0.95
Chandel^[9] 2021	0.49	<0.01	92%	0.28~0.87	1.01
Ripoll^[10] 2022	0.50	<0.01	92%	0.28~0.89	1.03
Moussa^[11] 2021	0.51	<0.01	92%	0.27~0.98	1.36
Salas De Armas^[12] 2022	0.56	<0.01	92%	0.32~0.96	0.96
Kohs^[13] 2021	0.53	<0.01	92%	0.30~0.95	1.04
Zhang^[14] 2021	0.53	<0.01	92%	0.30~0.92	1.00
Beyls^[15] 2020	0.46	<0.01	91%	0.27~0.79	0.94
Riera^[16] 2020	0.50	<0.01	92%	0.28~0.87	1.01
Fong^[17] 2021	0.52	<0.01	92%	0.29~0.96	1.16
Agerstrand^[18] 2016	0.52	<0.01	92%	0.32~0.92	1.01
Trudzinski ^[19]2016	0.49	<0.01	92%	0.28~0.89	1.08
Agerstrand^[20] 2015	0.54	<0.01	92%	0.31~0.95	1.01
Roussel^[21] 2012	0.56	<0.01	92%	0.32~0.96	0.96

表4 ECMO患者血栓发生率的敏感性分析

Tab.4 Sensitivity analysis of thrombosis incidence in ECMO patients

剔除研究	$O R$	$P$ 值	$I 2$ 值	95% $C I$	Tau²
Parzy^[6] 2020	0.45	<0.01	88%	0.28~0.75	0.74
Weber^[7] 2018	0.64	<0.01	85%	0.41~0.99	0.54
Cartwright^[8] 2021	0.47	<0.01	91%	0.27~0.81	0.95
Chandel^[9] 2021	0.49	<0.01	92%	0.28~0.87	1.01
Ripoll^[10] 2022	0.50	<0.01	92%	0.28~0.89	1.03
Moussa^[11] 2021	0.51	<0.01	92%	0.27~0.98	1.36
Salas De Armas^[12] 2022	0.56	<0.01	92%	0.32~0.96	0.96
Kohs^[13] 2021	0.53	<0.01	92%	0.30~0.95	1.04
Zhang^[14] 2021	0.53	<0.01	92%	0.30~0.92	1.00
Beyls^[15] 2020	0.46	<0.01	91%	0.27~0.79	0.94
Riera^[16] 2020	0.50	<0.01	92%	0.28~0.87	1.01
Fong^[17] 2021	0.52	<0.01	92%	0.29~0.96	1.16
Agerstrand^[18] 2016	0.52	<0.01	92%	0.32~0.92	1.01
Trudzinski ^[19]2016	0.49	<0.01	92%	0.28~0.89	1.08
Agerstrand^[20] 2015	0.54	<0.01	92%	0.31~0.95	1.01
Roussel^[21] 2012	0.56	<0.01	92%	0.32~0.96	0.96

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