允许性高碳酸血症通气法用于新生儿机械通气的安全性及有效性meta分析

Efficacy and safety of permissive hypercapnia ventilation in mechanically ventilated newborns： a meta-analysis

目的 评价允许性高碳酸血症通气法应用于新生儿机械通气的有效性及安全性.方法 检索PubMed、Embase、Cochrane图书馆、中国期刊全文数据库、万方数据库和中国生物医学文献数据库从建库至201 3年3月31日的文献.纳入文献同时满足以下条件：随机对照研究;研究对象为使用机械通气的新生儿;研究依据动脉血二氧化碳分压（partial pressure of carbon dioxide,PCO2）水平分为允许性高碳酸血症（permissive hypercapnia,PHC）组和血碳酸正常（normocapnia,NC）组.主要结局指标包括呼吸机相关性肺损伤（ventilator associated lung injury,VALI）、支气管肺发育不良（bronchopulmonary dysplasia,BPD）、脑室内出血、脑室周围白质软化、动脉导管未闭、坏死性小肠结肠炎、神经发育损伤的发生率和住院期间病死率;次要结局指标包括机械通气时间和住院时间.采用Cochrane评价手册5.1.0推荐的标准对纳入文献进行质量评价.Meta分析采用Revman 5.1软件,根据文献的异质性采用固定效应模型或随机效应模型分析. 结果 （1）一般情况：检索到325篇文献,筛选出8篇文献进入meta分析,共纳入605例新生儿,其中PHC组305例,NC组300例.7篇文献均控制PCO2＜65 mmHg（1 mmHg=0.133 kPa）且pH≥7.2,1篇文献PHC组PCO2未设定具体上限,仅控制PCO2＞52 mmHg且pH＞7.2.（2）文献质量评价结果：4篇文献描述了随机分配方法,3篇文献描述了分配方案隐藏,8篇文献均对研究对象采用盲法,2篇文献对研究结果测量者采用盲法,8篇文献均有完整数据结果且均无选择性报告结果,3篇文献描述了其他偏倚.（3） Meta分析结果：8篇文献报道了VALI发生率,文献间具有异质性（I2=56％,P=0.03）,采用随机效应模型分析,2组VALI发生率差异有统计学意义（RR=0.52,95％CI：0.29～0.93,P=0.03）.进一步根据胎龄分为2个亚组,3篇平均胎龄25周的文献为同质性研究（I2=0％,P=0.46）,2组VALI发生率差异无统计学意义（RR=1.05,95％CI：0.72～1.54,P=0.78）;5篇胎龄＞27周的文献为同质性研究（I2=0％,P=0.68）,2组VALI发生率差异有统计学意义（RR=0.27,95％CI：0.14～0.50,P＜0.01）.住院期间的病死率及机械通气时间均为同质性研究（I2值均为0％,P值均＞0.10）,2组比较差异均有统计学意义（住院期间病死率：RR=0.40,95％CI：0.22～0.74,P＜0.01;机械通气时间：均数差=-0.75,95％CI：-1.04～-0.46,P＜0.01）.支气管肺发育不良、脑室内出血、脑室周围白质软化、动脉导管未闭、坏死性小肠结肠炎以及神经发育损伤的发生率比较,差异均无统计学意义（P值均＞0.05）. 结论 目前的证据显示,允许性高碳酸血症通气法应用于新生儿机械通气,可以减少患儿VALI的发生率、住院期间的病死率以及机械通气时间,但对BPD无明显预防作用.控制PCO2＜65 mmHg且pH≥7.2,不会增加脑室内出血、脑室周围白质软化、动脉导管未闭、坏死性小肠结肠炎以及神经发育损伤的风险.

Objective To evaluate the efficacy and safety of permissive hypercapnia ventilation in mechanically ventilated newborns.Methods PubMed,Embase,the Cochrane Library,China National Knowledge Infrastructure （CKNI）,Wanfang Data and Chinese BioMedical Literature Database （CBM） were searched up until March 31,2013.Randomized controlled trials （RCTs） comparing permissive hypercapnia （PHC） group with normocapnia （NC） group in mechanically ventilated newborns were included.The primary outcomes included the incidence of ventilator associated lung injury （VALI）,bronchopulmonary dysplasia （BPD）,intraventricular hemorrhage （IVH）,periventricular leukomalacia （PVL）,patent ductus arteriosus （PDA）,neonatal necrotizing enterocolitis （NEC）,neurodevelopmental injury and the mortality rate.Secondary outcomes included the duration of ventilatory support and the length of hospital stay.The Cochrane Handbook 5.1.0 was used to evaluate the methodological quality and RevMan 5.1 software from Cochrane Collaboration was used for meta-analysis.The fixed effects model or the random effects model was adopted according to the result of heterogeneity.Results （1） A total of 325 articles were searched,and eight RCTs involving 605 newborns （302 newborns in PHC group while 300 newborns in NC group） which met the inclusion criteria were selected.In seven studies,the partial pressure of carbon dioxide （PCO2） was controlled at 〈 65 mmHg （1 mmHg=0.133 kPa） and pH at ≥ 7.2 in PHC group.In one study,PCO2 was 〉 52 mmHg and pH〉7.2,without descripition of the upper limit of PCO2.（2） Four articles described the method of random allocation in detail; three described allocation concealment; all eight studies used blinding method for research subjects; two used blinding method for outcome assessment; all eight studies reported complete data; and three articles described the source of other bias.（3） All eight studies reported the incidence of VALI （I2=56%,P=0.03）.The random effects model was used for the meta-analysis,and there was significant difference between PHC group and NC group （RR=0.52,95%CI：0.29-0.93,P=0.03）.According to the gestational age,the eight studies were divided into two subgroups.One subgroup,including three studies with an average gestational age of 25 weeks （I2=0%,P=0.46）,showed no significant difference in the incidence of VALI between PHC and NC group （RR=1.05,95%CI：0.72-1.54,P=0.78）.The other subgroup,including five studies with gestational age of 〉27 weeks （I2=0%,P=0.68）,showed significant difference in the incidence of VALI between the two groups （RR=0.27,95%CI：0.14-0.50,P〈0.01）.The in-hospital mortality and duration of ventilation showed significant difference between the two groups （in-hospital mortality：RR=0.40,95%CI：0.22-0.74,P〈0.01; duration of ventilation：difference in means=-0.75,95%CI：-1.04--0.46,P〈0.01）.There was no significant difference in the incidence of BPD,IVH,PVL,PDA,NEC and neurodevelopmental impairment between the two groups （all P〉0.05）.Conclusions PHC ventilation in mechanically ventilated newborns can decrease the incidence of VALI,the in-hospital mortality and the duration of ventilation,while its protective efficacy against BPD is not remarkable.It does not increase the risk of IVH,PVL,PDA,NEC and neurodevelopmental injury,when the PCO2 is 〈 65 mmHg and pH ≥ 7.2.