Bruschettini Matteo, O'Donnell Colm Pf, Davis Peter G, Morley Colin J, Moja Lorenzo, Zappettini Simona, Calevo Maria Grazia
Department of Paediatrics, Lund University, Skåne University Hospital, Lund, Sweden.
Cochrane Database Syst Rev. 2017 Jul 14;7(7):CD004953. doi: 10.1002/14651858.CD004953.pub3.
At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable effective breathing. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume within the lungs.
To assess the efficacy of an initial sustained (> 1 second duration) lung inflation versus standard inflations (≤ 1 second) in newly born infants receiving resuscitation with intermittent PPV.
We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1), MEDLINE via PubMed (1966 to 17 February 2017), Embase (1980 to 17 February 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 17 February 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles to identify randomised controlled trials and quasi-randomised trials.
Randomised controlled trials (RCTs) and quasi-RCTs comparing initial sustained lung inflation (SLI) versus standard inflations given to infants receiving resuscitation with PPV at birth.
We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and weighted mean difference (WMD) for continuous data. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
Eight trials enrolling 941 infants met our inclusion criteria. Investigators in seven trials (932 infants) administered sustained inflation with no chest compressions. Use of sustained inflation had no impact on the primary outcomes of this review - mortality in the delivery room (typical RR 2.66, 95% confidence interval (CI) 0.11 to 63.40; participants = 479; studies = 5; I² not applicable) and mortality during hospitalisation (typical RR 1.01, 95% CI 0.67 to 1.51; participants = 932; studies = 7; I² = 19%); the quality of the evidence was low for death in the delivery room (limitations in study design and imprecision of estimates) and was moderate for death before discharge (limitations in study design of most included trials). Amongst secondary outcomes, duration of mechanical ventilation was shorter in the SLI group (mean difference (MD) -5.37 days, 95% CI -6.31 to -4.43; participants = 524; studies = 5; I² = 95%; low-quality evidence). Heterogeneity, statistical significance, and magnitude of effects of this outcome are largely influenced by a single study: When this study was removed from the analysis, the effect was largely reduced (MD -1.71 days, 95% CI -3.04 to -0.39, I² = 0%). Results revealed no differences in any of the other secondary outcomes (e.g. rate of endotracheal intubation outside the delivery room by 72 hours of age (typical RR 0.93, 95% CI 0.79 to 1.09; participants = 811; studies = 5; I² = 0%); need for surfactant administration during hospital admission (typical RR 0.97, 95% CI 0.86 to 1.10; participants = 932; studies = 7; I² = 0%); rate of chronic lung disease (typical RR 0.95, 95% CI 0.74 to 1.22; participants = 683; studies = 5; I² = 47%); pneumothorax (typical RR 1.44, 95% CI 0.76 to 2.72; studies = 6, 851 infants; I² = 26%); or rate of patent ductus arteriosus requiring pharmacological treatment (typical RR 1.08, 95% CI 0.90 to 1.30; studies = 6, 745 infants; I² = 36%). The quality of evidence for these secondary outcomes was moderate (limitations in study design of most included trials - GRADE) except for pneumothorax (low quality: limitations in study design and imprecision of estimates - GRADE).
AUTHORS' CONCLUSIONS: Sustained inflation was not better than intermittent ventilation for reducing mortality in the delivery room and during hospitalisation. The number of events across trials was limited, so differences cannot be excluded. When considering secondary outcomes, such as need for intubation, need for or duration of respiratory support, or bronchopulmonary dysplasia, we found no evidence of relevant benefit for sustained inflation over intermittent ventilation. The duration of mechanical ventilation was shortened in the SLI group. This result should be interpreted cautiously, as it can be influenced by study characteristics other than the intervention. Future RCTs should aim to enrol infants who are at higher risk of morbidity and mortality, should stratify participants by gestational age, and should provide more detailed monitoring of the procedure, including measurements of lung volume and presence of apnoea before or during the SLI.
婴儿出生时肺部充满液体。为使新生儿成功过渡，必须用空气取代这些液体以实现有效呼吸。一些婴儿在出生时被判定呼吸不足，需通过正压通气（PPV）进行复苏。在PPV开始时给予长时间（持续）充气可能有助于清除肺内液体并在肺内建立气体容量。
评估在接受间歇性PPV复苏的新生儿中，初始持续（>1秒）肺充气与标准充气（≤1秒）的疗效。
我们采用Cochrane新生儿综述组的标准检索策略，检索Cochrane对照试验中心注册库（CENTRAL；2017年第1期）、通过PubMed检索MEDLINE（1966年至2017年2月17日）、Embase（1980年至2017年2月17日）以及护理及相关健康文献累积索引（CINAHL）（1982年至2017年2月17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，以识别随机对照试验和半随机试验。
比较初始持续肺充气（SLI）与出生时接受PPV复苏的婴儿的标准充气的随机对照试验（RCT）和半随机试验。
我们使用Cochrane有效实践与护理组织小组（EPOC）标准（评估随机化、盲法、失访以及结局数据的处理）评估纳入试验的方法学质量。我们使用固定效应模型评估治疗效果，分类数据采用风险比（RR），连续数据采用均值、标准差（SD）和加权均值差（WMD）。我们使用推荐分级评估、制定和评价（GRADE）方法评估证据质量。
八项纳入941名婴儿的试验符合我们的纳入标准。七项试验（932名婴儿）的研究者在不进行胸外按压的情况下给予持续充气。使用持续充气对本综述的主要结局——产房死亡率（典型RR 2.66，95%置信区间（CI）0.11至63.40；参与者 = 479；研究 = 5；I²不适用）和住院期间死亡率（典型RR 1.01，95% CI 0.67至1.51；参与者 = 932；研究 = 7；I² = 19%）没有影响；产房死亡的证据质量低（研究设计存在局限性且估计不准确），出院前死亡的证据质量为中等（大多数纳入试验的研究设计存在局限性）。在次要结局中，SLI组机械通气时间较短（均值差（MD） -5.37天，95% CI -6.31至 -4.43；参与者 = 524；研究 = 5；I² = 95%；低质量证据）。这一结局的异质性、统计学显著性和效应大小在很大程度上受一项研究的影响：当将该研究从分析中剔除时，效应大幅降低（MD -1.71天，95% CI -3.04至 -0.39，I² = ）。结果显示，其他任何次要结局均无差异（例如，72小时龄时产房外气管插管率（典型RR 0.93，95% CI 0.79至;参与者 = 811；研究 = 5；I² = 0%）；住院期间使用表面活性剂的需求（典型RR 0.97，95% CI 0.86至1.10；参与者 = 932；研究 = 7；I² = 0%）；慢性肺病发生率（典型RR 0.95，95% CI 0.74至1.22；参与者 = 683；研究 = 5；I² = 47%）；气胸（典型RR 1.44，95% CI 0.76至2.72；研究 = 6，851名婴儿；I² = 26%）；或需要药物治疗的动脉导管未闭发生率（典型RR 1.08，95% CI 0.90至1.30；研究 = 6，745名婴儿；I² = 36%）。除气胸外，这些次要结局的证据质量为中等（大多数纳入试验的研究设计存在局限性——GRADE）（低质量：研究设计存在局限性且估计不准确——GRADE）。
持续充气在降低产房死亡率和住院期间死亡率方面并不优于间歇性通气。各试验中的事件数量有限，因此不能排除差异。在考虑次要结局，如插管需求、呼吸支持需求或持续时间、支气管肺发育不良时，我们没有发现持续充气相对于间歇性通气有相关益处的证据。SLI组机械通气时间缩短。这一结果应谨慎解释，因为它可能受干预以外的研究特征影响。未来的随机对照试验应旨在纳入发病和死亡风险较高的婴儿，应按胎龄对参与者进行分层，并应提供对该操作更详细的监测，包括测量肺容量以及SLI之前或期间的呼吸暂停情况。
