Supplementary Material for: Bi-Level Noninvasive Ventilation in Neonatal Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis

<b><i>Background:</i></b> Bi-level noninvasive ventilation (NIV) has been used in respiratory distress syndrome (RDS) as primary treatment, post-extubation, and to treat apnea. This review summarizes studies on bi-level NIV in premature infants with RDS. Nonsynchronized nasal intermittent positive pressure ventilation (nsNIPPV) and synchronized NIPPV (SNIPPV) use pressure settings ≥ those used during mechanical ventilation (MV), and biphasic continuous positive airway pressure (BiPAP) use two nasal continuous positive airway pressure (NCPAP) levels ≤4 cm H₂O apart. <b><i>Methods:</i></b> A systematic review (Medline OVID and Pubmed) and meta-analysis of randomized controlled trials. Primary outcomes were bronchopulmonary dysplasia (BPD) and mortality. Secondary outcomes included NIV failure (intubation) and extubation failure (re-intubation). Data were pooled using a fixed-effects model to calculate the relative risk (RR) with 95% confidence interval (CI) between NIV modes (RevMan v 5.3, Copenhagen, Denmark). <b><i>Results:</i></b> Twenty-four randomized controlled trials that largely did not correct for mean airway pressure (MAP) and used outdated ventilators were included. Compared with NCPAP, both nsNIPPV and SNIPPV resulted in less re-intubation (RR 0.88 with 95% CI (0.80, 0.97) and RR 0.20 (0.10, 0.38), respectively) and BPD (RR 0.69 (0.49, 0.97) and RR 0.51 (0.29, 0.88), respectively). nsNIPPV also resulted in less intubation (RR 0.57 (0.45, 0.73) versus NCPAP, with no difference in mortality. One study showed less intubation in BiPAP versus NCPAP. <b><i>Conclusions:</i></b> Bi-level NIV versus NCPAP may reduce MV and BPD in premature infants with RDS. Studies comparing equivalent MAP utilizing currently available machines are needed.<b><i>背景：</i></b> 双水平无创通气（Bi-level noninvasive ventilation, NIV）曾作为呼吸窘迫综合征（respiratory distress syndrome, RDS）的一线治疗方案，应用于拔管后护理及呼吸暂停的治疗。本综述总结了针对呼吸窘迫综合征早产儿应用双水平无创通气的相关研究。非同步鼻间歇正压通气（nonsynchronized nasal intermittent positive pressure ventilation, nsNIPPV）与同步鼻间歇正压通气（synchronized NIPPV, SNIPPV）的压力设置高于机械通气（mechanical ventilation, MV）期间的参数，而双相持续气道正压通气（biphasic continuous positive airway pressure, BiPAP）采用的两个鼻持续气道正压（nasal continuous positive airway pressure, NCPAP）水平差值不超过4cm H₂O。 <b><i>方法：</i></b> 本研究为针对随机对照试验的系统评价（检索数据库为Medline OVID及PubMed）与荟萃分析。主要结局指标为支气管肺发育不良（bronchopulmonary dysplasia, BPD）与病死率；次要结局指标包括无创通气失败（需实施气管插管）及拔管失败（需再次气管插管）。采用固定效应模型合并数据，通过RevMan v5.3（丹麦哥本哈根）计算各无创通气模式间的相对危险度（relative risk, RR）及95%置信区间（confidence interval, CI）。 <b><i>结果：</i></b> 最终纳入24项随机对照试验，此类研究大多未校正平均气道压（mean airway pressure, MAP）且使用了过时的呼吸机。与NCPAP相比，nsNIPPV与SNIPPV均可降低再插管率（RR分别为0.88，95%CI(0.80, 0.97)与0.20，95%CI(0.10, 0.38)）及支气管肺发育不良发生率（RR分别为0.69，95%CI(0.49, 0.97)与0.51，95%CI(0.29, 0.88)）。nsNIPPV还可降低需插管率（RR=0.57，95%CI(0.45, 0.73)，对比NCPAP），但二者病死率无显著差异。另有一项研究显示，BiPAP对比NCPAP可减少需气管插管的情况。 <b><i>结论：</i></b> 相较于NCPAP，双水平无创通气或可降低呼吸窘迫综合征早产儿的机械通气需求与支气管肺发育不良发生率。未来仍需开展采用当前可用呼吸机、且校正平均气道压的等效性对比研究。