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

Background: 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.

Methods: 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).

Results: Twenty-four randomized controlled trials that largely did not correct for mean airway pressure (MAP) and used outdated ventilators were included.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.

Conclusions: 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.