Klingenberg Claus, Wheeler Kevin I, McCallion Naomi, Morley Colin J, Davis Peter G
Department of Pediatrics, University Hospital of North Norway, Tromsø, Norway, N-9038.
Cochrane Database Syst Rev. 2017 Oct 17;10(10):CD003666. doi: 10.1002/14651858.CD003666.pub4.
Damage caused by lung overdistension (volutrauma) has been implicated in the development of bronchopulmonary dysplasia (BPD). Modern neonatal ventilation modes can target a set tidal volume as an alternative to traditional pressure-limited ventilation (PLV) using a fixed inflation pressure. Volume-targeted ventilation (VTV) aims to produce a more stable tidal volume in order to reduce lung damage and stabilise the partial pressure of carbon dioxide (pCO).
To determine whether VTV compared with PLV leads to reduced rates of death and death or BPD in newborn infants and to determine whether use of VTV affected outcomes including air leak, cranial ultrasound findings and neurodevelopment.
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 12), MEDLINE via PubMed (1966 to 13 January 2017), Embase (1980 to 13 January 2017) and CINAHL (1982 to 13 January 2017). We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We contacted the principal investigators of studies to obtain supplementary information.
Randomised and quasi-randomised trials comparing VTV versus PLV in infants of less than 44 weeks' postmenstrual age and reporting clinically relevant outcomes.
We assessed risk of bias for each trial using Cochrane methodology. We evaluated quality of evidence for each outcome using GRADE criteria. We tabulated mortality, rates of BPD, short-term clinical outcomes and long-term developmental outcomes.
for categorical outcomes, we calculated typical estimates for risk ratios (RR), risk differences (RD) and number needed to treat for an additional beneficial outcome (NNTB). For continuous variables, we calculated typical estimates for mean differences (MD). We used 95% confidence intervals (CI) and assumed a fixed-effect model for meta-analysis.
Twenty randomised trials met our inclusion criteria; 16 parallel trials (977 infants) and four cross-over trials (88 infants). No studies were blinded and the quality of evidence for outcomes assessed varied from moderate to low.We found no difference in the primary outcome, death before hospital discharge, between VTV modes versus PLV modes (typical RR 0.75, 95% CI 0.53 to 1.07; low quality evidence). However, there was moderate quality evidence that the use of VTV modes resulted in a reduction in the primary outcome, death or BPD at 36 weeks' gestation (typical RR 0.73, 95% CI 0.59 to 0.89; typical NNTB 8, 95% CI 5 to 20) and the following secondary outcomes: rates of pneumothorax (typical RR 0.52, 95% CI 0.31 to 0.87; typical NNTB 20, 95% CI 11 to 100), mean days of mechanical ventilation (MD -1.35 days, 95% CI -1.83 to -0.86), rates of hypocarbia (typical RR 0.49, 95% CI 0.33 to 0.72; typical NNTB 3, 95% CI 2 to 5), rates of grade 3 or 4 intraventricular haemorrhage (typical RR 0.53, 95% CI 0.37 to 0.77; typical NNTB 11, 95% CI 7 to 25) and the combined outcome of periventricular leukomalacia with or without grade 3 or 4 intraventricular haemorrhage (typical RR 0.47, 95% CI 0.27 to 0.80; typical NNTB 11, 95% CI 7 to 33). VTV modes were not associated with any increased adverse outcomes.
AUTHORS' CONCLUSIONS: Infants ventilated using VTV modes had reduced rates of death or BPD, pneumothoraces, hypocarbia, severe cranial ultrasound pathologies and duration of ventilation compared with infants ventilated using PLV modes. Further studies are needed to identify whether VTV modes improve neurodevelopmental outcomes and to compare and refine VTV strategies.
肺过度扩张(容积伤)所造成的损害被认为与支气管肺发育不良(BPD)的发生有关。现代新生儿通气模式可以设定潮气量作为目标,以替代使用固定充气压力的传统压力限制通气(PLV)。容量目标通气(VTV)旨在产生更稳定的潮气量,以减少肺损伤并稳定二氧化碳分压(pCO)。
确定与PLV相比,VTV是否能降低新生儿的死亡率以及死亡或患BPD的发生率,并确定使用VTV是否会影响包括气漏、头颅超声检查结果和神经发育等结局。
我们采用Cochrane新生儿组的标准检索策略,检索Cochrane对照试验中心注册库(CENTRAL 2016年第12期)、通过PubMed检索MEDLINE(1966年至2017年1月13日)、Embase(1980年至2017年1月13日)和CINAHL(1982年至2017年1月13日)。我们还检索了临床试验数据库、会议论文集以及检索到的文章的参考文献列表,以查找随机对照试验和半随机试验。我们联系了研究的主要研究者以获取补充信息。
比较VTV与PLV在孕龄小于44周婴儿中的随机和半随机试验,并报告临床相关结局。
我们使用Cochrane方法评估每个试验的偏倚风险。我们使用GRADE标准评估每个结局的证据质量。我们将死亡率、BPD发生率、短期临床结局和长期发育结局制成表格。
对于分类结局,我们计算风险比(RR)、风险差(RD)和为获得额外有益结局所需治疗的人数(NNTB) 的典型估计值。对于连续变量,我们计算平均差(MD)的典型估计值。我们使用95%置信区间(CI),并在Meta分析中采用固定效应模型。
20项随机试验符合我们的纳入标准;16项平行试验(977名婴儿)和4项交叉试验(88名婴儿)。没有研究采用盲法,所评估结局的证据质量从中等到低不等。我们发现,在主要结局即出院前死亡方面,VTV模式与PLV模式之间没有差异(典型RR 0.75,95%CI 0.53至1.07;低质量证据)。然而,有中等质量证据表明,使用VTV模式可使主要结局即孕36周时死亡或患BPD的发生率降低(典型RR 0.73,95%CI 0.59至0.89;典型NNTB 8,95%CI 5至20),以及以下次要结局:气胸发生率(典型RR 0.52,95%CI 0.31至0.87;典型NNTB 20,95%CI 11至100)、机械通气平均天数(MD -1.35天,95%CI -1.83至-0.86)、低碳酸血症发生率(典型RR 0.49,95%CI 0.33至0.72;典型NNTB 3,95%CI 2至5)、3级或4级脑室内出血发生率(典型RR 0.53,95%CI 0.37至0.77;典型NNTB 11,95%CI 7至25)以及脑室周围白质软化合并或不合并3级或4级脑室内出血的联合结局(典型RR 0.47,95%CI 0.27至0.80;典型NNTB 11,95%CI 7至33)。VTV模式与任何不良结局增加均无关。
与使用PLV模式通气的婴儿相比,使用VTV模式通气的婴儿死亡或患BPD的发生率、气胸发生率、低碳酸血症发生率、严重头颅超声病变发生率及通气持续时间均降低。需要进一步研究以确定VTV模式是否能改善神经发育结局,并比较和优化VTV策略。