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Objective: Nasal Intermittent Positive Pressure Ventilation (NIPPV) is an effective therapy for infants in respiratory distress. We here report the safety of a novel, low-cost, non-electric bubble NIPPV device in comparison with bubble NCPAP., Study Design: At Paramitha Children's Hospital (Hyderabad, India), preterm (n = 60) neonates with moderate respiratory distress were pragmatically allocated to bubble NCPAP (5-8 cm H 2 O) or bubble NIPPV (P high 8-12 cm H 2 O/P low 5-8 cm H 2 O) based on staff and equipment availability. Primary outcomes to assess safety included clinically relevant pneumothorax, nasal septal necrosis, or abdominal distention., Results: One patient in each arm developed minor nasal septal injury (grade 3 on NCPAP, grade 2 on NIPPV); no patients in either arm developed a clinically significant pneumothorax or abdominal distention., Conclusion: The similar rates of nasal septal injury, pneumothorax and abdominal distention suggest that bubble NIPPV has a similar safety profile as bubble NCPAP for preterm infants in respiratory distress., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Invasive mechanical ventilation contributes to bronchopulmonary dysplasia (BPD), the most common complication of prematurity and the leading respiratory cause of childhood morbidity. Non-invasive ventilation (NIV) may limit invasive ventilation exposure and can be either synchronized or non-synchronized (NS). Pooled data suggest synchronized forms may be superior. Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) delivers NIV synchronized to the neural signal for breathing, which is detected with a specialized catheter. The DIVA (Diaphragmatic Initiated Ventilatory Assist) trial aims to determine in infants born 24 0/7 -27 6/7  weeks' gestation undergoing extubation whether NIV-NAVA compared to non-synchronized nasal intermittent positive pressure ventilation (NS-NIPPV) reduces the incidence of extubation failure within 5 days of extubation., Methods: This is a prospective, unblinded, pragmatic, multicenter phase III randomized clinical trial. Inclusion criteria are preterm infants 24-27 6/7  weeks gestational age who were intubated within the first 7 days of life for at least 12 h and are undergoing extubation in the first 28 postnatal days. All sites will enter an initial run-in phase, where all infants are allocated to NIV-NAVA, and an independent technical committee assesses site performance. Subsequently, all enrolled infants are randomized to NIV-NAVA or NS-NIPPV at extubation. The primary outcome is extubation failure within 5 days of extubation, defined as any of the following: (1) rise in FiO 2 at least 20% from pre-extubation for > 2 h, (2) pH ≤ 7.20 or pCO 2  ≥ 70 mmHg; (3) > 1 apnea requiring positive pressure ventilation (PPV) or ≥ 6 apneas requiring stimulation within 6 h; (4) emergent intubation for cardiovascular instability or surgery. Our sample size of 478 provides 90% power to detect a 15% absolute reduction in the primary outcome. Enrolled infants will be followed for safety and secondary outcomes through 36 weeks' postmenstrual age, discharge, death, or transfer., Discussion: The DIVA trial is the first large multicenter trial designed to assess the impact of NIV-NAVA on relevant clinical outcomes for preterm infants. The DIVA trial design incorporates input from clinical NAVA experts and includes innovative features, such as a run-in phase, to ensure consistent technical performance across sites., Trial Registration: www., Clinicaltrials: gov , trial identifier NCT05446272 , registered July 6, 2022., (© 2024. The Author(s).)

Background: Health problems in neonates with gestational age (GA) ≥ 32 weeks remain a major medical concern. Respiratory distress (RD) is one of the common reasons for admission of neonates with GA ≥ 32 weeks. Noninvasive ventilation (NIV) represents a crucial approach to treat RD, and currently, the most used NIV modes in neonatal intensive care unit include high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and nasal intermittent positive pressure ventilation. Although extensive evidence supports the use of NIPPV in neonates with a GA < 32 weeks, limited data exist regarding its effectiveness in neonates with GA ≥ 32 weeks. Therefore, the aim of this study is to compare the clinical efficacy of HFNC, CPAP, and NIPPV as primary NIV in neonates with GA ≥ 32 weeks who experience RD., Methods: This trial is designed as an assessor-blinded, three-arm, multi-center, parallel, randomized controlled trial, conducted in neonates ≥ 32 weeks' GA requiring primary NIV in the first 24 h of life. The neonates will be randomly assigned to one of three groups: HFNC, CPAP or NIPPV group. The effectiveness, safety and comfort of NIV will be evaluated. The primary outcome is the occurrence of treatment failure within 72 h after enrollment. Secondary outcomes include death before discharge, surfactant treatment within 72 h after randomization, duration of both noninvasive and invasive mechanical ventilation, duration of oxygen therapy, bronchopulmonary dysplasia, time to achieve full enteral nutrition, necrotizing enterocolitis, duration of admission, cost of admission, air leak syndrome, nasal trauma, and comfort score., Discussion: Currently, there is a paucity of data regarding the utilization of NIPPV in neonates with GA ≥ 32 weeks. This study will provide clinical evidence for the development of respiratory treatment strategies in neonates at GA ≥ 32 weeks with RD, with the aim of minimizing the incidence of tracheal intubation and reducing the complications associated with NIV., Trial Registration: Chinese Clinical Trial Registry: ChiCTR2300069192. Registered on March 9, 2023, https://www.chictr.org.cn/showproj.html?proj=171491 ., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Nasal continuous positive airway pressure (NCPAP) is a useful method for providing respiratory support after extubation. Nasal intermittent positive pressure ventilation (NIPPV) can augment NCPAP by delivering ventilator breaths via nasal prongs., Objectives: Primary objective To determine the effects of management with NIPPV versus NCPAP on the need for additional ventilatory support in preterm infants whose endotracheal tube was removed after a period of intermittent positive pressure ventilation. Secondary objectives To compare rates of abdominal distension, gastrointestinal perforation, necrotising enterocolitis, chronic lung disease, pulmonary air leak, mortality, duration of hospitalisation, rates of apnoea and neurodevelopmental status at 18 to 24 months for NIPPV and NCPAP. To compare the effect of NIPPV versus NCPAP delivered via ventilators versus bilevel devices, and assess the effects of the synchronisation of ventilation, and the strength of interventions in different economic settings., Search Methods: We used standard, extensive Cochrane search methods. The latest search date was January 2023., Selection Criteria: We included randomised and quasi-randomised trials of ventilated preterm infants (less than 37 weeks' gestational age (GA)) ready for extubation to non-invasive respiratory support. Interventions were NIPPV and NCPAP., Data Collection and Analysis: We used standard Cochrane methods. Our primary outcome was 1. respiratory failure. Our secondary outcomes were 2. endotracheal reintubation, 3. abdominal distension, 4. gastrointestinal perforation, 5. necrotising enterocolitis (NEC), 6. chronic lung disease, 7. pulmonary air leak, 8. mortality, 9. hospitalisation, 10. apnoea and bradycardia, and 11. neurodevelopmental status. We used GRADE to assess the certainty of evidence., Main Results: We included 19 trials (2738 infants). Compared to NCPAP, NIPPV likely reduces the risk of respiratory failure postextubation (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.67 to 0.84; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 8 to 17; 19 trials, 2738 infants; moderate-certainty evidence) and endotracheal reintubation (RR 0.78, 95% CI 0.70 to 0.87; NNTB 12, 95% CI 9 to 25; 17 trials, 2608 infants, moderate-certainty evidence), and may reduce pulmonary air leaks (RR 0.57, 95% CI 0.37 to 0.87; NNTB 50, 95% CI 33 to infinite; 13 trials, 2404 infants; low-certainty evidence). NIPPV likely results in little to no difference in gastrointestinal perforation (RR 0.89, 95% CI 0.58 to 1.38; 8 trials, 1478 infants, low-certainty evidence), NEC (RR 0.86, 95% CI 0.65 to 1.15; 10 trials, 2069 infants; moderate-certainty evidence), chronic lung disease defined as oxygen requirement at 36 weeks (RR 0.93, 95% CI 0.84 to 1.05; 9 trials, 2001 infants; moderate-certainty evidence) and mortality prior to discharge (RR 0.81, 95% CI 0.61 to 1.07; 11 trials, 2258 infants; low-certainty evidence). When considering subgroup analysis, ventilator-generated NIPPV likely reduces respiratory failure postextubation (RR 0.49, 95% CI 0.40 to 0.62; 1057 infants; I 2 = 47%; moderate-certainty evidence), while bilevel devices (RR 0.95, 95% CI 0.77 to 1.17; 716 infants) or a mix of both ventilator-generated and bilevel devices likely results in little to no difference (RR 0.87, 95% CI 0.73 to 1.02; 965 infants)., Authors' Conclusions: NIPPV likely reduces the incidence of extubation failure and the need for reintubation within 48 hours to one-week postextubation more effectively than NCPAP in very preterm infants (GA 28 weeks and above). There is a paucity of data for infants less than 28 weeks' gestation. Pulmonary air leaks were also potentially reduced in the NIPPV group. However, it has no effect on other clinically relevant outcomes such as gastrointestinal perforation, NEC, chronic lung disease or mortality. Ventilator-generated NIPPV appears superior to bilevel devices in reducing the incidence of respiratory failure postextubation failure and need for reintubation. Synchronisation used to deliver NIPPV may be important; however, data are insufficient to support strong conclusions. Future trials should enrol a sufficient number of infants, particularly those less than 28 weeks' GA, to detect differences in death or chronic lung disease and should compare different categories of devices, establish the impact of synchronisation of NIPPV on safety and efficacy of the technique as well as the best combination of settings for NIPPV (rate, peak pressure and positive end-expiratory). Trials should strive to match the mean airway pressure between the intervention groups to allow a better comparison. Neurally adjusted ventilatory assist needs further assessment with properly powered randomised trials., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Nasal continuous positive airway pressure (NCPAP) is a strategy to maintain positive airway pressure throughout the respiratory cycle through the application of a bias flow of respiratory gas to an apparatus attached to the nose. Early treatment with NCPAP is associated with decreased risk of mechanical ventilation exposure and might reduce chronic lung disease. Nasal intermittent positive pressure ventilation (NIPPV) is a form of noninvasive ventilation delivered through the same nasal interface during which patients are exposed to short inflations, along with background end-expiratory pressure., Objectives: To examine the risks and benefits of early (within the first six hours after birth) NIPPV versus early NCPAP for preterm infants at risk of or with respiratory distress syndrome (RDS). Primary endpoints are respiratory failure and the need for intubated ventilatory support during the first week of life. Secondary endpoints include the incidence of mortality, chronic lung disease (CLD) (oxygen therapy at 36 weeks' postmenstrual age), pneumothorax, duration of respiratory support, duration of oxygen therapy, and intraventricular hemorrhage (IVH)., Search Methods: Searches were conducted in January 2023 in CENTRAL, MEDLINE, Embase, Web of Science, and Dissertation Abstracts. The reference lists of related systematic reviews and of studies selected for inclusion were also searched., Selection Criteria: We considered all randomized and quasi-randomized controlled trials. Eligible studies compared NIPPV versus NCPAP treatment, starting within six hours after birth in preterm infants (< 37 weeks' gestational age (GA))., Data Collection and Analysis: We collected and analyzed data using the recommendations of the Cochrane Neonatal Review Group., Main Results: We included 17 trials, enrolling 1958 infants in this review. NIPPV likely reduces the rate of respiratory failure (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.54 to 0.78; risk difference (RD) -0.08, 95% CI -0.12 to -0.05; 17 RCTs, 1958 infants; moderate-certainty evidence) and needing endotracheal tube ventilation (RR 0.67, 95% CI 0.56 to 0.81; RD -0.07, 95% CI -0.11 to -0.04; 16 RCTs; 1848 infants; moderate-certainty evidence) amongst infants treated with early NIPPV compared with early NCPAP. The meta-analysis demonstrated that NIPPV may reduce the risk of developing CLD compared to CPAP (RR 0.70, 95% CI 0.52 to 0.92; 12 RCTs, 1284 infants; low-certainty evidence) slightly. NIPPV may result in little to no difference in mortality (RR 0.82, 95% CI 0.62 to 1.10; 17 RCTs; 1958 infants; I 2 of 0%; low-certainty evidence), the incidence of pneumothorax (RR 0.92, 95% CI 0.60 to 1.41; 16 RCTs; 1674 infants; I 2 of 0%; low-certainty evidence), and rates of severe IVH (RR 0.98, 95% CI 0.53 to 1.79; 8 RCTs; 977 infants; I 2 of 0%; low-certainty evidence)., Authors' Conclusions: When applied within six hours after birth, NIPPV likely reduces the risk of respiratory failure and the need for intubation and endotracheal tube ventilation in very preterm infants (GA 28 weeks and above) with respiratory distress syndrome or at risk for RDS. It may also decrease the rate of CLD slightly. However, most trials enrolled infants with a gestational age of approximately 28 to 32 weeks with an overall mean gestational age of around 30 weeks. As such, the results of this review may not apply to extremely preterm infants that are most at risk of needing mechanical ventilation or developing CLD. Additional studies are needed to confirm these results and to assess the safety of NIPPV compared with NCPAP alone in a larger patient population., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: Bi-level positive airway pressure (BiPAP) and synchronized intermittent mandatory ventilation (SIMV) can be used to achieve peak inspiratory pressure and positive end-expiratory pressure to avoid alveolar collapse and improve oxygenation in preterm infants during the treatment of respiratory distress syndrome (RDS), and there is an urgent demand for evaluating the effects and prognoses of these two ventilation modes., Study Design: We conducted a retrospective study on preterm infants (≤32 weeks and <2500 g) from March 2015 to March 2020 with BiPAP ( n  = 63) and SIMV ( n  = 63). The primary outcomes were successful treatment and weaning within 72 h, the demand for a second pulmonary surfactant supply and the need for a second respiratory support. The secondary outcome was the incidence of complications., Results: There were no significant differences ( p  > .05) in the primary outcomes or the incidence of complications (pneumonia, apnea, respiratory failure, air leak syndrome, persistence of patent ductus arteriosus, neonatal sepsis, necrotizing enterocolitis, retinopathy of prematurity, and intraventricular hemorrhage). There were significant differences ( p  < .05) in the incidence of pulmonary hemorrhage, bronchopulmonary dysplasia and IVH (≥grade II)., Conclusions: Although both BiPAP and SIMV achieved good early treatment outcomes of RDS in preterm infants, BiPAP support is recommended for reducing the incidence of pulmonary hemorrhage, bronchopulmonary dysplasia and IVH (≥grade II) if infants are tolerant. Attempts should be made to prevent these complications from happening with the use of SIMV support if infants are intolerant.

Objective: To characterize respiratory function monitor (RFM) measurements of sustained inflations and intermittent positive pressure ventilation (IPPV) delivered noninvasively to infants in the Sustained Aeration of Infant Lungs (SAIL) trial and to compare vital sign measurements between treatment arms., Study Design: We analyzed RFM data from SAIL participants at 5 trial sites. We assessed tidal volumes, rates of airway obstruction, and mask leak among infants allocated to sustained inflations and IPPV, and we compared pulse rate and oxygen saturation measurements between treatment groups., Results: Among 70 SAIL participants (36 sustained inflations, 34 IPPV) with RFM measurements, 40 (57%) were spontaneously breathing prior to the randomized intervention. The median expiratory tidal volume of sustained inflations administered was 5.3 mL/kg (IQR 1.1-9.2). Significant mask leak occurred in 15% and airway obstruction occurred during 17% of sustained inflations. Among 34 control infants, the median expiratory tidal volume of IPPV inflations was 4.3 mL/kg (IQR 1.3-6.6). Mask leak was present in 3%, and airway obstruction was present in 17% of IPPV inflations. There were no significant differences in pulse rate or oxygen saturation measurements between groups at any point during resuscitation., Conclusion: Expiratory tidal volumes of sustained inflations and IPPV inflations administered in the SAIL trial were highly variable in both treatment arms. Vital sign values were similar between groups throughout resuscitation. Sustained inflation as operationalized in the SAIL trial was not superior to IPPV to promote lung aeration after birth in this study subgroup., Trial Registration: Clinicaltrials.gov: NCT02139800., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: An intervention to potentiate hypoxic pulmonary vasoconstriction may reduce intrapulmonary shunt and hypoxemia during one-lung ventilation. Previous animal studies reported that repeated intermittent hypoxic stimuli potentiated hypoxic pulmonary vasoconstriction, but no clinical study has examined the effects of this intervention on hypoxemia during one-lung ventilation. We thus performed a single-center, parallel-group, double-blind, randomized controlled trial to investigate whether repeated intermittent hypoxic stimuli to the operative lung reduce hypoxemia during the subsequent one-lung ventilation for thoracoscopic surgery., Methods: Patients undergoing one-lung ventilation were randomized into two groups (n = 68 each). Before one-lung ventilation, in the intermittent hypoxia group, the nondependent lung was not ventilated for 2 min and then ventilated for 2 min while the dependent lung was continuously ventilated. This was repeated five times. In the continuous normoxia group, both lungs were ventilated for 20 min. We measured SpO2, PaO2, FiO2, PaCO2, SaO2, and central venous oxygen saturation during one-lung ventilation. The primary outcome was the number of patients with hypoxemia defined as a SpO2 <95% during one-lung ventilation, which was analyzed with a chi-squared test., Results: Hypoxemia was less frequent in the intermittent hypoxia group than in the continuous normoxia group during OLV [6/68 (8.8%) vs 17/68 (25.0%), risk ratio (95% CI) 0.35 (0.15-0.84), p = 0.012]. The PaO2 (p = 0.008 for 30 min and 0.007 for 60 min) and PaO2/FiO2 (p = 0.008 for both) were higher 30 and 60 min after starting one-lung ventilation, and the alveolar-arterial pressure gradient (p = 0.010) and shunt index (p = 0.008) were lower 30 min after starting one-lung ventilation in the intermittent hypoxia group than in the continuous normoxia group. Postoperative adverse events did not differ significantly between groups., Conclusions: Repeated intermittent hypoxic stimuli to the operative lung seemed to potentiate hypoxic pulmonary vasoconstriction, and thus reduced hypoxemia during the subsequent one-lung ventilation., Competing Interests: The authors have declared that no competing interests exist.

Background: Respiratory distress, particularly respiratory distress syndrome (RDS), is the single most important cause of morbidity and mortality in preterm infants. In infants with progressive respiratory insufficiency, intermittent positive pressure ventilation (IPPV) with surfactant has been the usual treatment, but it is invasive, potentially resulting in airway and lung injury. Continuous positive airway pressure (CPAP) has been used for the prevention and treatment of respiratory distress, as well as for the prevention of apnoea, and in weaning from IPPV. Its use in the treatment of RDS might reduce the need for IPPV and its sequelae., Objectives: To determine the effect of continuous distending pressure in the form of CPAP on the need for IPPV and associated morbidity in spontaneously breathing preterm infants with respiratory distress., Search Methods: We used the standard strategy of Cochrane Neonatal to search CENTRAL (2020, Issue 6); Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions; and CINAHL on 30 June 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials., Selection Criteria: All randomised or quasi-randomised trials of preterm infants with respiratory distress were eligible. Interventions were CPAP by mask, nasal prong, nasopharyngeal tube or endotracheal tube, compared with spontaneous breathing with supplemental oxygen as necessary., Data Collection and Analysis: We used standard methods of Cochrane and its Neonatal Review Group, including independent assessment of risk of bias and extraction of data by two review authors. We used the GRADE approach to assess the certainty of evidence. Subgroup analyses were planned on the basis of birth weight (greater than or less than 1000 g or 1500 g), gestational age (groups divided at about 28 weeks and 32 weeks), timing of application (early versus late in the course of respiratory distress), pressure applied (high versus low) and trial setting (tertiary compared with non-tertiary hospitals; high income compared with low income) MAIN RESULTS: We included five studies involving 322 infants; two studies used face mask CPAP, two studies used nasal CPAP and one study used endotracheal CPAP and continuing negative pressure for a small number of less ill babies. For this update, we included one new trial. CPAP was associated with lower risk of treatment failure (death or use of assisted ventilation) (typical risk ratio (RR) 0.64, 95% confidence interval (CI) 0.50 to 0.82; typical risk difference (RD) -0.19, 95% CI -0.28 to -0.09; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 4 to 11; I 2 = 50%; 5 studies, 322 infants; very low-certainty evidence), lower use of ventilatory assistance (typical RR 0.72, 95% CI 0.54 to 0.96; typical RD -0.13, 95% CI -0.25 to -0.02; NNTB 8, 95% CI 4 to 50; I 2 = 55%; very low-certainty evidence) and lower overall mortality (typical RR 0.53, 95% CI 0.34 to 0.83; typical RD -0.11, 95% CI -0.18 to -0.04; NNTB 9, 95% CI 2 to 13; I 2 = 0%; 5 studies, 322 infants; moderate-certainty evidence). CPAP was associated with increased risk of pneumothorax (typical RR 2.48, 95% CI 1.16 to 5.30; typical RD 0.09, 95% CI 0.02 to 0.16; number needed to treat for an additional harmful outcome (NNTH) 11, 95% CI 7 to 50; I 2 = 0%; 4 studies, 274 infants; low-certainty evidence). There was no evidence of a difference in bronchopulmonary dysplasia, defined as oxygen dependency at 28 days (RR 1.04, 95% CI 0.35 to 3.13; I 2 = 0%; 2 studies, 209 infants; very low-certainty evidence). The trials did not report use of surfactant, intraventricular haemorrhage, retinopathy of prematurity, necrotising enterocolitis and neurodevelopment outcomes in childhood., Authors' Conclusions: In preterm infants with respiratory distress, the application of CPAP is associated with reduced respiratory failure, use of mechanical ventilation and mortality and an increased rate of pneumothorax compared to spontaneous breathing with supplemental oxygen as necessary. Three out of five of these trials were conducted in the 1970s. Therefore, the applicability of these results to current practice is unclear. Further studies in resource-poor settings should be considered and research to determine the most appropriate pressure level needs to be considered., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: To determine the incidence of chronic lung disease (CLD) in mechanically ventilated infants who were born at <29 weeks' gestational age (GA), extubated to continuous positive airway pressure (CPAP) or nasal intermittent positive pressure ventilation (NIPPV), and treated with CPAP/NIPPV alone, changed to heated humidified high flow nasal cannula (HHHFNC), or exposed to a combination of CPAP/NIPPV and HHHFNC at ≤30 weeks' postmenstrual age (PMA). Study design: Retrospective cohort study of infants born at <29 weeks' GA admitted to tertiary Canadian neonatal intensive care units between 2011 and 2015. Infants were grouped according to the type of noninvasive ventilation they received at ≤30 weeks' PMA: CPAP/NIPPV alone, HHHFNC alone, or a combination of both. Results: Of the 2378 eligible infants, 1091 (46%) were on CPAP/NIPPV alone, 173 (7.3%) were on HHHFNC alone, and 1114 (47%) were on a combination of CPAP/NIPPV and HHHFNC at ≤30 weeks' PMA until weaned to room air or low flow nasal cannula. After adjustment for confounders, infants in both the CPAP/NIPPV (odds ratio [95% confidence interval]; 2.37 [1.18, 4.79]) and Combination (3.47 [2.06, 5.86]) groups had higher odds of developing CLD than infants in the HHHFNC group. Conclusions: Our results demonstrate that infants transitioned to HHHFNC ≤30 weeks' PMA after extubation to CPAP/NIPPV were associated with a lower odds of CLD than infants maintained on CPAP/NIPPV or a combination of CPAP/NIPPV and HHHFNC.

Objective: To evaluate the relative safety of different ventilation methods regarding mortality and rates of complication, on neonatal respiratory distress syndrome (NRDS). Methods: Network Meta-analysis was used to collect data on randomized controlled trials of pulmonary ventilation strategies in preterm infants with a mean gestational age of less than 32 weeks. Diagnostic criteria on NRDS were published in the PubMed, Cochrane, Web of Science, EBSCO, and Springer Link databases from January 1986 to June 2018. Revman 5.3 software was used to evaluate the quality of studies, based on the Cochrane quality assessment tool. Data were analyzed by Bayesian and frequency methods, using both Win BUGS 1.4.3 and STATA 13.0 software. Safety of different ventilation strategies for NRDS mortality and complications would include intraventricular hemorrhage (IVH), patent ductus arteriosus (PDA) and retinopathy of prematurity (ROP) and were evaluated. Counted data was displayed by OR and 95 %CI . Results: A total of 31 RCTs were included in this paper, including 5 827 preterm infants and 11 ventilation strategies. There were no statistically significant differences appearing in 11 ventilation strategies on mortality, PDA or ROP. IVH results were reported in 28 studies. Compared with nasal intermittent positive pressure ventilation (NIPPV), both high- frequency oscillation ventilation (HFOV) ( OR =3.33, 95 %CI : 1.08-16.67, P <0.05) and synchronized intermittent mechanical ventilation (SIMV) ( OR =8.22, 95 %CI : 1.25-29.44, P <0.05) schemes seemed to have increased the risk of IVH in preterm infants with NRDS. NIPPV appeared the optimal ventilation strategy in the rankings of cumulative probability. Results on clustering showed that NIPPV was probably the best ventilation strategy for children with NRDS after considering the orders of IVH, PDA and ROP on mortality, respectively. However, HFOV, IMV, and SIMV did not seem to be the ideal ventilated strategies. Conclusions: Most of the clinical decision makers might prefer using NIPPV in the treatment of children with NRDS through mechanical ventilation systems to reduce both the incidence and death caused by IVH, PDA and ROP. It was not recommended to use HFOV, SIMV and IMV in treating NRDS with gestational less than 32 weeks. We suggested that larger numbers of multi-center RCTs ba carried out to make the above conclusions more convincing.

Background: Sustained Inflations (SI) and Intermittent Positive Pressure Ventilation (IPPV) are two interventions to prevent Bronchopulmonary dysplasia (BPD). The aim of this study is to assess the effect of these two interventions., Methods: The databases of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) will be comprehensively searched from inception to September 2019. All RCTs and quasi-RCTs which compare the efficacy of SI vs IPPV among preterm infants are eligible. We will assess the methodological quality using the Cochrane Handbook version 5.1.0. A meta-analysis will be performed using RevMan 5.3 software and the results will be presented using risk ratios (RRs) and 95% confidence intervals (CIs)., Conclusions: This study will provide strong evidence for assessing the effect of SI and IPPV on BPD or death among preterm infants., Prospero Registration Number: CRD42019135816.

Objective: To describe the incidence of patient-ventilator asynchrony and different types of asynchrony in preterm infants treated with non-synchronised nasal intermittent positive pressure ventilation (nIPPV)., Design: An observational study was conducted including preterm infants born with a gestational age (GA) less than 32 weeks treated with non-synchronised nIPPV. During 1 hour, spontaneous breathing was measured with transcutaneous electromyography of the diaphragm simultaneous with ventilator inflations. An asynchrony index (AI), a percentage of asynchronous breaths, was calculated and the incidence of different types of inspiratory and expiratory asynchrony were reported., Results: Twenty-one preterm infants with a mean GA of 26.0±1.2 weeks were included in the study. The mean inspiratory AI was 68.3%±4.7% and the mean expiratory AI was 67.1%±7.3%. Out of 5044 comparisons of spontaneous inspirations and mechanical inflations, 45.3% of the mechanical inflations occurred late, 23.3% of the mechanical inflations were early and 31.4% of the mechanical inflation were synchronous. 40.3% of 5127 expiratory comparisons showed an early termination of ventilator inflations, 26.7% of the mechanical inflations terminated late and 33.0% mechanical inflations terminated in synchrony with a spontaneous expiration. In addition, 1380 spontaneous breaths were unsupported and 611 extra mechanical inflations were delivered., Conclusion: Non-synchronised nIPPV results in high patient-ventilator asynchrony in preterm infants during both the inspiratory and expiratory phase of the breathing cycle. New synchronisation techniques are urgently needed and should address both inspiratory and expiratory asynchrony., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Delivery of inadvertent high tidal volume (V T ) during positive pressure ventilation (PPV) in the delivery room is common. High V T delivery during PPV has been associated with haemodynamic brain injury in animal models. We examined if V T delivery during PPV at birth is associated with brain injury in preterm infants <29 weeks' gestation., Methods: A flow-sensor was placed between the mask and the ventilation device. V T values were compared with recently described reference ranges for V T in spontaneously breathing preterm infants at birth. Infants were divided into two groups: V T <6  mL/kg or V T >6 mL/kg (normal and high V T , respectively). Brain injury (eg, intraventricular haemorrhage (IVH)) was assessed using routine ultrasound imaging within the first days after birth., Results: A total of 165 preterm infants were included, 124 (75%) had high V T and 41 (25%) normal V T . The mean (SD) gestational age and birth weight in high and normal V T group was similar, 26 (2) and 26 (1) weeks, 858 (251) g and 915 (250) g, respectively. IVH in the high V T group was diagnosed in 63 (51%) infants compared with 5 (13%) infants in the normal V T group (P=0.008).Severe IVH (grade III or IV) developed in 33/124 (27%) infants in the high V T group and 2/41 (6%) in the normal V T group (P=0.01)., Conclusions: High V T delivery during mask PPV at birth was associated with brain injury. Strategies to limit V T delivery during mask PPV should be used to prevent high V T delivery., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim: To evaluate the association between the use of nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) with the development of bronchopulmonary dysplasia (BPD)., Methods: This is a single center retrospective cohort analysis of infants born at ≤1000 grams and ≤28 weeks gestation with respiratory distress treated with nCPAP or NIPPV. Groups were compared using Student's t test or chi-square, and associations estimated by logistic regression., Results: Compared to nCPAP, infants who received NIPPV had a higher incidence of moderate to severe (M-S) BPD (84.2 vs 65.5%, p = 0.044) and death or severe BPD (75.0 vs 47.6%, p = 0.003). Each day on NIPPV was associated with an increased risk of M-S BPD (OR 1.08, p < 0.001) and an increased risk of death or severe BPD (OR 1.03, p = 0.006). After adjusting for days on oxygen, ventilator days, and days on all respiratory support, the odds of developing M-S BPD increased by 4.9% for each additional week on NIPPV (CI 2.1-7.7%, p = .0001)., Conclusion: In this cohort, use of NIPPV was associated with an increased risk for developing BPD when compared to infants receiving nCPAP, and each additional day on NIPPV carried significant increased risk for developing BPD.

Objective: The study aim was to identify the frequency with which tidal volumes were achieved in a target range in infants requiring positive pressure ventilation on emergency transport., Study Design: We performed a prospective observational study of infants requiring continued positive pressure ventilation during emergency transport after resuscitation and stabilization. Blindly recorded data were analyzed for percentage of breaths that were below range, in range, and above desired range of 4-6 mL/kg., Result: Fourteen patients were monitored during transport from the delivery room to the neonatal intensive care unit, and 15 patients were monitored during inter-facility transport. During delivery room transport, 21 and 7% of patients were in target range greater than 50 and 90% of the time, respectively. During inter-hospital transport, 60 and 7% of patients were in target range greater than 50 and 90% of the time, respectively., Conclusion: Clinical assessment of appropriate ventilation is difficult and often inaccurate during emergency neonatal transport. Improved monitoring of respiratory function to guide clinical status during transport is necessary. More investigation and implementation are urgently needed.

Sustained inflations and avoidance of endotracheal mechanical ventilation (eMV) are delivery room interventions aimed at preventing bronchopulmonary dysplasia (BPD). Their effectiveness is the subject of the present meta-analysis.The databases MEDLINE, EMBASE and CENTRAL were searched for randomised controlled trials (RCTs) of preterm infants that compared: 1) sustained inflations with intermittent positive-pressure ventilation; and 2) a non-intubated strategy of respiratory support with one that prescribed eMV at an earlier stage. Data extraction and analysis followed the standard methods of the Cochrane Collaboration. The primary outcome was death or BPD, defined as need for oxygen or positive pressure treatment at 36 weeks' postmenstrual age.Avoiding eMV (nine RCTs, 3486 infants) reduced the risk of death or BPD, with a risk ratio of 0.90 (95% CI 0.84-0.97) and a number needed to treat of 35. After sustained inflations (six RCTs, 854 infants), the risk ratio was 0.85 (95% CI 0.65-1.12). A current multicentre RCT of sustained inflations in very preterm infants was halted for increased early mortality in the sustained inflations arm.While strategies aimed at avoiding eMV had a small but significant impact on preventing BPD, sustained inflations had no effect and may even increase mortality in very preterm infants., Competing Interests: Conflict of interest: H.S. Fischer has nothing to disclose. Conflict of interest: G.M. Schmölzer has nothing to disclose. Conflict of interest: P-Y. Cheung has nothing to disclose. Conflict of interest: C. Bührer reports personal fees from Chiesi Pharmaceuticals (manufacturer of surfacant), outside the submitted work., (Copyright ©ERS 2018.)

Background: Non-invasive neurally adjusted ventilatory assist (NIV-NAVA), a mode of non-invasive ventilation (NIV) controlled by diaphragmatic electrical activity, may be superior to other NIV as a respiratory support after extubation in preterm infants, but no report has compared NIV-NAVA with other NIV methods. We evaluated the effectiveness and adverse effects of NIV-NAVA after extubation in preterm infants <30 weeks of gestation., Methods: This retrospective study involved patients who were born before 30 weeks of gestation. We mainly used NIV-NAVA or nasal intermittent positive-pressure ventilation (NIPPV) for preterm infants as the NIV after extubation and compared these two groups. The primary outcome was treatment failure. The secondary outcomes were extubation failure and adverse events. Treatment failure was defined as a change of NIV (NIPPV was switched to NIV-NAVA, or NIV-NAVA was switched to NIPPV) or reintubation ≤7 days after extubation., Results: Fifteen patients were in the NIV-NAVA group, and 19 were in the NIPPV group. The gestational age of the NIV-NAVA group was younger than that of the NIPPV group (25.7 ± 2.4 weeks vs 27.3 ± 1.8 weeks). Treatment failure occurred in six cases (40%) in the NIV-NAVA group and in nine cases (47.4%) in the NIPPV group, and no significant difference was demonstrated. No significant difference in adverse events was noted., Conclusions: NIV-NAVA has advantages compared with NIPPV as the NIV for premature infants after extubation. NIV-NAVA can also be used safely without a significant difference in the rate of complications compared with NIPPV., (© 2018 Japan Pediatric Society.)

Objective: To determine whether the use of a hydrocolloid nasal barrier dressing during binasal continuous positive airway pressure (CPAP) therapy, compared with no barrier dressing, reduces the rate of nasal injury in very preterm and/or very low birth weight infants., Study Design: A single-center randomized controlled trial conducted in the neonatal intensive care unit at The Royal Women's Hospital, Melbourne. Eligible infants were born <30 weeks of gestation and/or with birth weight <1250 g, and had received ≥4 hours, but <48 hours, of CPAP. Infants were randomly allocated to receive either a hydrocolloid nasal barrier dressing during CPAP (barrier group), or no barrier dressing (no barrier group). The primary outcome was the incidence of any nasal injury during CPAP support, until the infant was both >30 weeks of postmenstrual age and >1250 g, unless CPAP therapy was stopped earlier. Nasal injury was regularly assessed by bedside nurses using a standardized form., Results: A total of 108 preterm infants were enrolled: 53 infants in the barrier group and 55 infants in the no barrier group. Infants in the barrier group had a significantly lower rate of nasal injury compared with the no barrier group: 18 of 53 (34%) vs 31 of 55 (56%), respectively (P = .02), number needed to treat; 5 infants. No significant differences were detected in any secondary respiratory outcomes, or in the rate of common neonatal morbidities., Conclusions: Prophylactic use of a nasal barrier dressing within 48 hours of commencing treatment with binasal CPAP in very preterm or very low birth weight infants reduces nasal injury., Trial Registration: Australian and New Zealand Clinical Trials Register ACTRN12616000438459., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Effective positive pressure ventilation (PPV) of non-breathing newborns is crucial in facilitating cardio-respiratory adaptation at birth. Identifying predictors of death in newborns receiving PPV is important in order to facilitate preventative strategies., Objective: The objective of this study was to determine the perinatal predictors of death including the quality of PPV administered among admitted newborns., Methods: An observational study of admitted newborns who received PPV after birth was conducted. Research assistants observed all deliveries and recorded perinatal events on data collection forms. Measured heart rate (HR) and ventilation parameters were then compared between newborns who died and survivors., Results: Newborns (n = 232) were studied between October 2014 and November 2016. Newborns who died (n = 53) compared to survivors (n = 179) had more fetal heart rate (FHRT) abnormalities (12/53 vs 19/179; p = 0.03); lower initial HR (<100 beats/minute) at start of PPV (44/48 vs 77/139; p<0.001); and a longer time for HR to increase >100 beats/minute from birth (180 vs 149 seconds; p = 0.07). Newborns who died compared to survivors took longer time (14 vs 4 seconds; p = 0.008) and more inflations (7 vs 3; p = 0.006) to achieve an expired volume (Vt) of 6 ml/kg, respectively. Median delivered Vt during the first 60 seconds of PPV was less in newborns who died compared to survivors (5 vs 6 ml/kg; p = 0.12). Newborns who died proceeded to severe encephalopathy (15/31 vs 1/59; p<0.001) compared to survivors., Conclusion: Depressed newborns who proceeded to death compared to survivors, exhibited delayed HR response to PPV which may partly reflect FHRT abnormalities related to interruption of placental blood flow, and/or a timely delay in establishing adequate Vt. Depressed newborns progressed to moderate/severe encephalopathy. Improving FHRT monitoring to identify fetuses at risk for expedited delivery, coupled with optimizing delivery room PPV might decrease mortality in this setting., Competing Interests: Jeffrey M. Perlman has received a research travel award from the Laerdal Foundation for Acute Medicine for work in Tanzania. Haydom Lutheran Hospital has received research grants from the Laerdal Foundation for Acute Medicine. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To compare the clinical efficacy of nasal intermittent positive pressure ventilation (NIPPV) and heated humidified high flow nasal cannula (HHHFNC) in the treatment of respiratory distress syndrome (RDS) among very low birth weight (VLBW) preterm infants., Methods: A total of 89 very low birth weight premature infants with respiratory distress syndrome (RDS) who were randomly administered with NIPPV (n=46) and HHHFNC (n=43) as an initial respiratory support. The incidence of initial treatment failure, the usage of pulmonary surfactant (PS), the parameters of respiratory support treatment and the incidence of complications were compared between the two groups., Results: There were no significant differences between the NIPPV and HHHFNC groups in the following items: the rate of intubation within 72 hours, rate of PS use, duration of invasive or non-invasive mechanical ventilation, duration of oxygen therapy, and incidence rates of severe apnea and pneumonia (P>0.05). There were also no significant differences in the incidence rates of bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus, intracranial hemorrhage, and air leak between the two group (P>0.05). The incidence rate of nose injury in the NIPPV group was higher than that in the HHHFNC group (P<0.05)., Conclusions: As an initial respiratory support for very low birth weight preterm infants with RDS, HHHFNC has a similar clinical effect as NIPPV, suggesting that HHHFNC is a safe and effective clinical option as a non-invasive ventilation treatment.

Nasal intermittent positive pressure ventilation (NIPPV) can augment nasal continuous positive airway pressure (nCPAP) by delivering intermittent positive pressure ventilation in a noninvasive way and can provide a new option for neonatal noninvasive respiratory support. NIPPV has an advantage over nCPAP in primary and post-extubation respiratory support. Moreover, it can reduce severe apnea of prematurity. Synchronized NIPPV has promising application prospects. This review article summarizes the advances in the application of NIPPV in neonatal respiratory support to promote the understanding and standardization of this technique.

Purpose: To describe the incidence, indications and clinical outcomes following high pressures on noninvasive respiratory support (NRS) in preterm neonates., Study Design: Retrospective cohort study of all neonates with BW <1.500 g admitted from July 2012 to June 2014 and placed on high noninvasive respiratory support (NRS), defined as mean airway pressure ≥10 cm H 2 O for at least 12 continuous hours using nasal continuous positive airway pressure (NCPAP) and/or nasal high-frequency ventilation (NIHFV). Clinical and physiological outcomes following high NRS were ascertained. Median (IQR) and percentages were used to describe continuous and categorical data, respectively., Results: There were 131 instances of high NRS use in 70 of 315 eligible infants. Most common indication was post-extubation, observed in 37% (49/131) of high NRS instances. Intubation was avoided in 71% (93/131) of instances in the first 7 days following high NRS initiation. There were no physiological perturbations in heart rate, blood pressure or oxygen requirement. Furthermore, there were no instances of lung hyperinflation, pneumothoraces or spontaneous intestinal perforation following high NRS., Conclusion: The use of high NRS pressure was followed by avoidance of intubation in the majority of cases without adverse effects. Further research on high NRS use including its indications, clinical outcomes and safety profile is warranted.

Background: Previous randomised trials and meta-analyses have shown that nasal continuous positive airway pressure (NCPAP) is a useful method for providing respiratory support after extubation. However, this treatment sometimes 'fails' in infants, and they may require endotracheal re-intubation with its attendant risks and expense. Nasal intermittent positive pressure ventilation (NIPPV) can augment NCPAP by delivering ventilator breaths via nasal prongs. Older children and adults with chronic respiratory failure benefit from NIPPV, and the technique has been applied to neonates. However, serious side effects including gastric perforation have been reported with older methods of providing NIPPV., Objectives: Primary objective To compare effects of management with NIPPV versus NCPAP on the need for additional ventilatory support in preterm infants whose endotracheal tube was removed after a period of intermittent positive pressure ventilation. Secondary objectives To compare rates of gastric distension, gastrointestinal perforation, necrotising enterocolitis and chronic lung disease; duration of hospitalisation; and rates of apnoea, air leak and mortality for NIPPV and NCPAP., Search Methods: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 9), MEDLINE via PubMed (1966 to 28 September 2015), Embase (1980 to 28 September 2015) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 28 September 2015). We also searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials., Selection Criteria: We included randomised and quasi-randomised trials comparing use of NIPPV versus NCPAP in extubated preterm infants. NIPPV included non-invasive support delivered by a mechanical ventilator or a bilevel device in a synchronised or non-synchronised way. Participants included ventilated preterm infants who were ready to be extubated to non-invasive respiratory support. Interventions compared were NIPPV, delivered by short nasal prongs or nasopharyngeal tube, and NCPAP, delivered by the same methods.Types of outcomes measures included failure of therapy (respiratory failure, rates of endotracheal re-intubation); gastrointestinal complications (i.e. abdominal distension requiring cessation of feeds, gastrointestinal perforation or necrotising enterocolitis); pulmonary air leak; chronic lung disease (oxygen requirement at 36 weeks' postmenstrual age) and mortality., Data Collection and Analysis: Three review authors independently extracted data regarding clinical outcomes including extubation failure; endotracheal re-intubation; rates of apnoea, gastrointestinal perforation, feeding intolerance, necrotising enterocolitis, chronic lung disease and air leak; and duration of hospital stay. We analysed trials using risk ratio (RR), risk difference (RD) and the number needed to treat for an additional beneficial outcome (NNTB) or an additional harmful outcome (NNTH) for dichotomous outcomes, and mean difference (MD) for continuous outcomes. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence., Main Results: Through the search, we identified 10 trials enrolling a total of 1431 infants and comparing extubation of infants to NIPPV or NCPAP. Three trials had methodological limitations and possible selection bias.Five trials used the synchronised form of NIPPV, four used the non-synchronised form and one used both methods. Eight studies used NIPPV delivered by a ventilator, one used a bilevel device and one used both methods. When all studies were included, meta-analysis demonstrated a statistically and clinically significant reduction in the risk of meeting extubation failure criteria (typical RR 0.70, 95% CI 0.60 to 0.80; typical RD -0.13, 95% CI -0.17 to -0.08; NNTB 8, 95% CI 6 to 13; 10 trials, 1431 infants) and needing re-intubation (typical RR 0.76, 95% CI 0.65 to 0.88; typical RD -0.10, 95% CI -0.15 to -0.05; NNTB 10, 95% CI 7 to 20; 10 trials, 1431 infants). We graded evidence for these outcomes as moderate, as all trial interventions were unblinded. Although methods of synchronisation varied (Graseby capsule or pneumotachograph/flow-trigger), the five trials that synchronised NIPPV showed a statistically significant benefit for infants extubated to NIPPV in terms of prevention of extubation failure up to one week after extubation.Unsynchronised NIPPV also reduced extubation failure. NIPPV provided via a ventilator is more beneficial than that provided by bilevel devices in reducing extubation failure during the first week. When comparing interventions, investigators found no significant reduction in rates of chronic lung disease (typical RR 0.94, 95% CI 0.80 to 1.10; typical RD -0.02, 95% CI -0.08 to 0.03) or death, and no difference in the incidence of necrotising enterocolitis. Air leaks were reduced in infants randomised to NIPPV (typical RR 0.48, 95% CI 0.28 to 0.82; typical RD -0.03, 95% CI -0.05 to -0.01; NNTB 33, 95% CI 20 to 100). We graded evidence quality as moderate (unblinded studies) or low (imprecision) for secondary outcomes., Authors' Conclusions: Implications for practice NIPPV reduces the incidence of extubation failure and the need for re-intubation within 48 hours to one week more effectively than NCPAP; however, it has no effect on chronic lung disease nor on mortality. Synchronisation may be important in delivering effective NIPPV. The device used to deliver NIPPV may be important; however, data are insufficient to support strong conclusions. NIPPV does not appear to be associated with increased gastrointestinal side effects. Implications for research Large trials should establish the impact of synchronisation of NIPPV on safety and efficacy of the technique and should compare the efficacy of bilevel devices versus a ventilator for providing NIPPV.

Background: Nasal continuous positive airway pressure (NCPAP) is a strategy for maintaining positive airway pressure throughout the respiratory cycle through the application of bias flow of respiratory gas to an apparatus attached to the nose. Treatment with NCPAP is associated with decreased risk of mechanical ventilation and might be effective in reducing chronic lung disease. Nasal intermittent positive pressure ventilation (NIPPV) is a form of noninvasive ventilation during which patients are exposed intermittently to higher levels of airway pressure, along with NCPAP through the same nasal device., Objectives: To examine the risks and benefits of early NIPPV versus early NCPAP alone for preterm infants at risk of or in respiratory distress within the first hours after birth.Primary endpoints are respiratory failure and the need for intubated ventilatory support during the first week of life. Secondary endpoints include chronic lung disease (CLD) (oxygen therapy at 36 weeks' postmenstrual age), air leaks, duration of respiratory support, duration of oxygen therapy, intraventricular hemorrhage, and incidence of mortality., Search Methods: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 9), MEDLINE via PubMed (1966 to September 28, 2015), Embase (1980 to September 28, 2015), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to September 28, 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. A member of the Cochrane Neonatal Review Group handsearched abstracts from the European Society of Pediatric Research (ESPR). We contacted the authors of ongoing clinical trials to ask for information., Selection Criteria: We considered all randomized and quasi-randomized controlled trials. Studies selected compared NIPPV versus NCPAP treatment, starting at birth or shortly thereafter in preterm infants (< 37 weeks' gestational age)., Data Collection and Analysis: We performed data collection and analysis using the recommendations of the Cochrane Neonatal Review Group., Main Results: Ten trials, enrolling a total of 1061 infants, met criteria for inclusion in this review. Meta-analyses of these studies showed significantly reduced risk of meeting respiratory failure criteria (typical risk ratio (RR) 0.65, 95% confidence interval (CI) 0.51 to 0.82; typical risk difference (RD) -0.09, 95% CI -0.13 to -0.04) and needing intubation (typical RR 0.78, 95% CI 0.64 to 0.94; typical RD -0.07, 95% CI -0.12 to -0.02) among infants treated with early NIPPV compared with early NCPAP. The meta-analysis did not demonstrate a reduction in the risk of CLD among infants randomized to NIPPV (typical RR 0.78, 95% CI 0.58 to 1.06). Investigators observed no evidence of harm. Review authors graded the quality of the evidence as moderate (unblinded studies)., Authors' Conclusions: Early NIPPV does appear to be superior to NCPAP alone for decreasing respiratory failure and the need for intubation and endotracheal tube ventilation among preterm infants with respiratory distress syndrome. Additional studies are needed to confirm these results and to assess the safety of NIPPV compared with NCPAP alone in a larger patient population.

Objective: To compare the effectiveness of nasal continuous positive airway pressure (NCPAP) and nasal intermittent positive-pressure ventilation (NIPPV) as the initial respiratory support within the minimally invasive surfactant therapy (MIST) approach in preterm infants with respiratory distress syndrome., Design: Prospective, randomised controlled study., Setting: Tertiary neonatal intensive care unit., Patients and Interventions: This study enrolled 200 preterm infants with a gestational age of 26-32 weeks who showed signs of respiratory distress but did not require intubation in the delivery room. Surfactant therapy was performed using the MIST approach in the patients who met the criteria for surfactant administration., Main Outcome Measures: The primary outcomes were a need for intubation within the first 72 h of life and a surfactant requirement., Results: The infants in the study displayed similar characteristics at birth. Fewer infants in the NIPPV group required surfactant therapy (38% vs 60%; p=0.002) or invasive ventilation during the first 72 h of life (13% vs 29%; p=0.005), and NIPPV reduced the rate of moderate-to-severe bronchopulmonary dysplasia (BPD) (7% vs 16%; p=0.046). Multivariate logistic regression analysis showed that NIPPV support (OR: 0.36, 95% CI 0.17 to 0.76; p=0.008) and higher gestational age (OR: 0.76, 95% CI 0.59 to 0.98; p=0.041) reduced the need for invasive ventilation within the first 72 h of life. Surfactant requirement was also decreased with NIPPV support (OR: 0.39, 95% CI 0.22 to 0.71; p=0.002). However, there was no impact on BPD, based on the multivariate analysis., Conclusions: In infants born at 26-32 weeks' gestation, NIPPV reduced the need for invasive ventilation and the surfactant requirement within the MIST approach., Trial Registration Number: ClinicalTrials.gov under identifier NCT01741129., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Intermittent mandatory ventilation (IMV) was introduced nearly 50 years ago. Despite the initial fanfare and early adoption by many, the role of IMV continues to be questioned. The use of small tidal volumes complicates the application of IMV, and issues with work of breathing, weaning and lack of clear advantages have many calling for a moratorium on its use. Spontaneous breathing, however, has a number of salutatory effects on gas exchange, the distribution of ventilation, and hemodynamics. These issues will be explored in light of a growing body of evidence., (Copyright © 2016 by Daedalus Enterprises.)

Background: Respiratory muscle weakness contributes to respiratory failure in ICU patients. Unfortunately, assessment of weakness is difficult since the most objective test, transdiaphragmatic pressure in response to phrenic nerve stimulation (PdiTw), is difficult to perform. While most clinicians utilize maximum inspiratory pressure (Pimax) to assess strength, the relationship of this index to PdiTw has not been evaluated in a large ICU population. The purpose of the present study was to assess both PdiTw and Pimax in ICU patients to determine how these indices correlate with each other, what factors influence these indices, and how well these indices predict outcomes., Methods: Studies were performed on adult mechanically ventilated patients in the University of Kentucky MICU (n = 60). We assessed PdiTw by measuring transdiaphragmatic pressure (Pdi) in response to bilateral twitch stimulation of the phrenic nerves using dual magnetic stimulators (Magstim 200). Pimax was determined by measuring airway pressure during a 30-second inspiratory occlusion. We also assessed the twitch and maximum force generation for diaphragms excised from control and septic mice., Results: Both Pimax and PdiTw measurements were profoundly reduced for mechanically ventilated MICU patients when compared to normal reference values, e.g., Pimax averaged 56% of the predicted value for normal subjects. For the ICU population as a whole, PdiTw and Pimax values correlated with each other (r(2) = 0.373, p < 0.001), but there was wide scatter and, as a result, PdiTw could not be reliably calculated from Pimax levels for individual subjects. Infection selectively reduced low-frequency force generation more than high-frequency force generation for both our mouse experiments (comparing muscle twitch to 150 Hz tetanic force) and for MICU patients (comparing PdiTw to Pimax). This effect of infection may contribute to scatter in the PdiTw to Pimax relationship. We also found that both PdiTw and Pimax were significantly correlated with both patient survival and the duration of mechanical ventilation, albeit statistically, PdiTw was the better predictor., Conclusions: While more difficult to measure, the PdiTw is a better predictor of outcomes in mechanically ventilated MICU patients than the Pimax. Nevertheless, for some clinical applications, the Pimax determination is a reasonable alternative.

Objective: To compare the rates of death or bronchopulmonary dysplasia (BPD) in infants who received nasal intermittent positive pressure ventilation (NIPPV) delivered by a conventional mechanical ventilator (CMV) or a bilevel device., Design: A preplanned non-randomised comparison of infants randomised to the NIPPV arm of the NIPPV trial., Setting: Thirty-six tertiary neonatal units in three continents., Patients: Infants <1000 g and <30 weeks gestational age at birth., Interventions: Infants received treatment with CMV NIPPV or bilevel NIPPV, as a primary mode of respiratory support or following first extubation., Results: 241 received mainly bilevel NIPPV and 215 mainly CMV NIPPV. No difference was found in death or BPD at 36 weeks corrected age (adjusted OR 0.88 (95% CI 0.57 to 1.35)). More deaths occurred in infants receiving bilevel NIPPV (9.4%) than in CMV NIPPV (2.3%) (adjusted OR 5.01: 95% CI 1.74 to 14.4). There was a corresponding but not statistically significant decrease in BPD in the bilevel NIPPV group (30% vs 37%) (adjusted OR 0.64 (95% CI 0.41 to 1.02)). No difference was observed in extubation failure or age at last extubation. A post hoc test of interaction between device type and synchronisation was not statistically significant., Conclusions: We did not observe a statistically significant difference in the composite outcome of death or BPD between infants who received mostly bilevel NIPPV compared with mostly CMV NIPPV. Differences in component outcomes of morbidity and BPD may be due to the competing nature of these outcomes or differences in baseline characteristics of infants., Trial Registration Number: NCT00433212., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Purpose: To determine if a foam septum protector prevents nasal injury in preterm infants receiving nasal heated humidified oxygen., Design: A retrospective before and after comparative design was used., Sample: Medical records of 101 preterm infants receiving either nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive pressure ventilation (NIPPV) were reviewed; 50 were in the control group and 51 were in the intervention group that had the NeoSeal septum protector applied. The groups were not different in terms of gender, birth weight, gestational age, days intubated, or on days on NCPAP/NIPPV. Skin condition of nares was scored daily using the Neonatal Skin Risk Assessment Scale (NSRAS)., Results: Infants who had the NeoSeal applied had significantly less nasal injuries, OR = 4.08; 95% confidence interval (CI), 1.22-9.59; p = .01. The best predictors of nasal injury were gestational age and whether the NeoSeal was applied or not.

Last black box on adaptive servoventilation in central apnoea syndrome generate many connective problems concerning the alternative therapies. The authors are starting from two recent french articles on this same subject and are trying to see what is missing and what we have to do.

Mechanical ventilation is a risk factor for cerebral inflammation and brain injury in preterm neonates. The risk increases proportionally with the intensity of treatment. Recent studies have shown that cerebral inflammation and injury can be initiated in the delivery room. At present, initiation of intermittent positive pressure ventilation (IPPV) in the delivery room is one of the least controlled interventions a preterm infant will likely face. Varying pressures and volumes administered shortly after birth are sufficient to trigger pathways of ventilation-induced lung and brain injury. The pathways involved in ventilation-induced brain injury include a complex inflammatory cascade and haemodynamic instability, both of which have an impact on the brain. However, regardless of the strategy employed to deliver IPPV, any ventilation has the potential to have an impact on the immature brain. This is particularly important given that preterm infants are already at a high risk for brain injury simply due to immaturity. This highlights the importance of improving the initial respiratory support in the delivery room. We review the mechanisms of ventilation-induced brain injury and discuss the need for, and the most likely, current therapeutic agents to protect the preterm brain. These include therapies already employed clinically, such as maternal glucocorticoid therapy and allopurinol, as well as other agents, such as erythropoietin, human amnion epithelial cells and melatonin, already showing promise in preclinical studies. Their mechanisms of action are discussed, highlighting their potential for use immediately after birth., (© 2016 S. Karger AG, Basel.)

Background: Noninvasive ventilation (NIV) in preterm infants is currently applied using intermittent positive pressure (2 positive-pressure levels) or in a conventional manner (one pressure level). However, there are no studies in the literature comparing the chances of failure of these NIV methods. The aim of this study was to evaluate the occurrence of failure of 2 noninvasive ventilatory support systems in preterm neonates over a period of 48 h., Methods: A randomized, prospective, clinical study was conducted on 80 newborns (gestational age < 37 weeks, birthweight < 2,500 g). The infants were randomized into 2 groups: 40 infants were treated with nasal CPAP and 40 infants with nasal intermittent positive-pressure ventilation (NIPPV). The occurrence of apnea, progression of respiratory distress, nose bleeding, and agitation was defined as ventilation failure. The need for intubation and re-intubation after failure was also observed., Results: There were no significant differences in birth characteristics between groups. Ventilatory support failure was observed in 25 (62.5%) newborns treated with nasal CPAP and in 12 (30%) newborns treated with NIPPV, indicating an association between NIV failure and the absence of intermittent positive pressure (odds ratio [OR] 1.22, P < .05). Apnea (32.5%) was the main reason for nasal CPAP failure. After failure, 25% (OR 0.33) of the newborns receiving nasal CPAP and 12.5% (OR 0.14) receiving NIPPV required invasive mechanical ventilation., Conclusions: Ventilatory support failure was significantly more frequent when nasal CPAP was used., (Copyright © 2015 by Daedalus Enterprises.)

Objective: The objective of this study was to evaluate carbon dioxide (CO2) clearance, delivered pressures and tidal volume (VT) during neonatal nasal intermittent positive pressure ventilation (NIPPV) with two commonly used interfaces., Study Design: A neonatal lung model, with either short binasal prongs (SBP) or a small caliber nasal cannula (RAM) interface, was tested over a range of clinically relevant settings. A fixed amount of CO2 was infused and the fraction remaining in the lung 100 s postinfusion was measured. Pressure transmission to the lung and VT was measured at the level of the trachea., Result: CO2 elimination was directly proportional to the inspiratory pressure during NIPPV. At peak pressures of 22 to 34 cm H2O, CO2 clearance was greater (P<0.001) with SBP as compared with RAM. Relative to the set ventilator parameters, a substantial pressure dampening effect was documented at the lung level, which was significantly lower with RAM when compared with SBP (2.8% (0.2) versus 11.9% (1.5), P<0.0001). CO2 elimination was dependent on VT and effective despite only a small fraction of physiological VT (maximum delivered VT%: SBP 15.5 (0.7) versus RAM 6.1 (1.4), P<0.0001)., Conclusion: NIPPV promotes CO2 elimination even at low transmitted airway pressures, but less effective with RAM as compared with SBP. CO2 elimination despite small VT suggests that NIPPV may depend on a non-conventional gas-exchange mechanism.

Background: Respiratory distress syndrome (RDS) is the single most important cause of morbidity and mortality in preterm infants. In infants with progressive respiratory insufficiency, intermittent positive pressure ventilation (IPPV) with surfactant is the standard treatment for the condition, but it is invasive, potentially resulting in airway and lung injury. Continuous distending pressure (CDP) has been used for the prevention and treatment of RDS, as well as for the prevention of apnoea, and in weaning from IPPV. Its use in the treatment of RDS might reduce the need for IPPV and its sequelae., Objectives: To determine the effect of continuous distending pressure (CDP) on the need for IPPV and associated morbidity in spontaneously breathing preterm infants with respiratory distress.Subgroup analyses were planned on the basis of birth weight (> or < 1000 or 1500 g), gestational age (groups divided at about 28 weeks and 32 weeks), methods of application of CDP (i.e. CPAP and CNP), application early versus late in the course of respiratory distress and high versus low pressure CDP and application of CDP in tertiary compared with non-tertiary hospitals, with the need for sensitivity analysis determined by trial quality.At the 2008 update, the objectives were modified to include preterm infants with respiratory failure., Search Methods: We used the standard search strategy of the Neonatal Review Group. This included searches of the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, 2015 Issue 4), MEDLINE (1966 to 30 April 2015) and EMBASE (1980 to 30 April 2015) with no language restriction, as well as controlled-trials.com, clinicaltrials.gov and the International Clinical Trials Registry Platform of the World Health Organization (WHO)., Selection Criteria: All random or quasi-random trials of preterm infants with respiratory distress were eligible. Interventions were continuous distending pressure including continuous positive airway pressure (CPAP) by mask, nasal prong, nasopharyngeal tube or endotracheal tube, or continuous negative pressure (CNP) via a chamber enclosing the thorax and the lower body, compared with spontaneous breathing with oxygen added as necessary., Data Collection and Analysis: We used standard methods of The Cochrane Collaboration and its Neonatal Review Group, including independent assessment of trial quality and extraction of data by each review author., Main Results: We included six studies involving 355 infants - two using face mask CPAP, two CNP, one nasal CPAP and one both CNP (for less ill babies) and endotracheal CPAP (for sicker babies). For this update, we included no new trials.Continuous distending pressure (CDP) is associated with lower risk of treatment failure (death or use of assisted ventilation) (typical risk ratio (RR) 0.65, 95% confidence interval (CI) 0.52 to 0.81; typical risk difference (RD) -0.20, 95% CI -0.29 to -0.10; number needed to treat for an additional beneficial outcome (NNTB) 5, 95% CI 4 to 10; six studies; 355 infants), lower overall mortality (typical RR 0.52, 95% CI 0.32 to 0.87; typical RD -0.15, 95% CI -0.26 to -0.04; NNTB 7, 95% CI 4 to 25; six studies; 355 infants) and lower mortality in infants with birth weight above 1500 g (typical RR 0.24, 95% CI 0.07 to 0.84; typical RD -0.28, 95% CI -0.48 to -0.08; NNTB 4, 95% CI 2.00 to 13.00; two studies; 60 infants). Use of CDP is associated with increased risk of pneumothorax (typical RR 2.64, 95% CI 1.39 to 5.04; typical RD 0.10, 95% CI 0.04 to 0.17; number needed to treat for an additional harmful outcome (NNTH) 17, 95% CI 17.00 to 25.00; six studies; 355 infants). We found no difference in bronchopulmonary dysplasia (BPD), defined as oxygen dependency at 28 days (three studies, 260 infants), as well as no difference in outcome at nine to 14 years (one study, 37 infants)., Authors' Conclusions: In preterm infants with respiratory distress, the application of CDP as CPAP or CNP is associated with reduced respiratory failure and mortality and an increased rate of pneumothorax. Four out of six of these trials were done in the 1970s. Therefore, the applicability of these results to current practice is difficult to assess. Further research is required to determine the best mode of administration.

Context: Sustained inflation (SI) has been advocated as an alternative to intermittent positive pressure ventilation (IPPV) during the resuscitation of neonates at birth, to facilitate the early development of an effective functional residual capacity, reduce atelectotrauma and improve oxygenation after the birth of preterm infants., Objective: The primary aim was to review the available literature on the use of SI compared with IPPV at birth in preterm infants for major neonatal outcomes, including bronchopulmonary dysplasia (BPD) and death., Data Source: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials, until 6 October 2014., Study Selection: Randomised clinical trials comparing the effects of SI with IPPV at birth in preterm infants for neonatal outcomes., Data Extraction and Synthesis: Descriptive and quantitative information was extracted; data were pooled using a random effects model. Heterogeneity was assessed using the Q statistic and I(2)., Results: Pooled analysis showed significant reduction in the need for mechanical ventilation within 72 h after birth (relative risk (RR) 0.87 (0.77 to 0.97), absolute risk reduction (ARR) -0.10 (-0.17 to -0.03), number needed to treat 10) in preterm infants treated with an initial SI compared with IPPV. However, significantly more infants treated with SI received treatment for patent ductus arteriosus (RR 1.27 (1.05 to 1.54), ARR 0.10 (0.03 to 0.16), number needed to harm 10). There were no differences in BPD, death at the latest follow-up and the combined outcome of death or BPD among survivors between the groups., Conclusions: Compared with IPPV, preterm infants initially treated with SI at birth required less mechanical ventilation with no improvement in the rate of BPD and/or death. The use of SI should be restricted to randomised trials until future studies demonstrate the efficacy and safety of this lung aeration manoeuvre., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: Compared with pressure-controlled ventilation (PCV), volume-targeted ventilation is associated with decreased neonatal complications, including the combined outcome of death or bronchopulmonary dysplasia. However, little is known about its effect on neurodevelopmental outcome. We evaluated the hypothesis that as compared with PCV, volume-targeted ventilation reduces the risk of the combined outcome of neurodevelopmental impairment or death in very low birth weight infants., Study Design: We studied a cohort of extremely preterm infants managed with either volume guarantee pressure support ventilation (VGPSV; n=135) or PCV (n=135). Infants were evaluated at 18 months adjusted age with a standardized neurological examination and the Bayley Scales of Infant and Toddler Development-third edition. Logistic regression models were used to evaluate the association of ventilation mode and neurodevelopmental outcome., Result: Rates of pulmonary interstitial emphysema (odds ratio 0.6; 95% confidence limits: 0.4, 0.8), hypotension (odds ratio: 0.7; 95% confidence limits: 0.5, 0.9) and mortality (odds ratio 0.45; 95% confidence limits: 0.22, 0.9) were lower among infants treated with VGPSV. The infants in the VGPSV group had a significantly shorter duration on mechanical ventilation compared with infants in the PCV group (log-rank test P<0.01). Seventy percent (155/221) of survivors were evaluated at 18 months adjusted age. A trend towards benefit for the combined outcome of death or neurodevelopmental impairment was seen in the VGPSV group but did not reach statistical significance (odds ratio: 0.59; 95% confidence limits: 0.32, 1.08)., Conclusion: VGPSV was associated with a decreased risk of short-term complications but not long-term developmental impairment in this modest-sized cohort.

Objective: To evaluate the clinical efficacy of the RAM nasal cannula (NC) with different modes of non-invasive ventilation (NIV) in the neonatal intensive care unit (NICU)., Methods: A single center prospective, observational study of infants placed on RAM NC. A small trial (Study 1) was completed in 16 infants on NIV via the RAM NC over a 48-h period to create Summary Statement recommendations. Next, over a 10-month period (Study 2), data were prospectively collected for the outcome of all infants receiving respiratory support with the RAM NC. Outcomes were compared between different modes of NIV and whether the recommendations were followed., Results: The Study 2 population consisted of 88 infants of whom 67 infants received nasal continuous positive airway pressure ventilation (NCPAP) and 21 received nasal intermittent positive pressure ventilation (NIPPV) via the RAM NC. The NIPPV group tended to be younger, smaller and stayed on the RAM NC longer. The overall success rate in weaning off the RAM NC, if our guidelines were followed, was 63%., Conclusion: RAM NC use with NIV was well tolerated in the neonatal population with the use of our guidelines. We speculate that use of our guidelines will lead to a more systematic use of the RAM NC in the NICU.

Background: Extremely preterm infants require assistance recruiting the lung to establish a functional residual capacity after birth. Sustained inflation (SI) combined with positive end expiratory pressure (PEEP) may be a superior method of aerating the lung compared with intermittent positive pressure ventilation (IPPV) with PEEP in extremely preterm infants. The Sustained Aeration of Infant Lungs (SAIL) trial was designed to study this question., Methods/design: This multisite prospective randomized controlled unblinded trial will recruit 600 infants of 23 to 26 weeks gestational age who require respiratory support at birth. Infants in both arms will be treated with PEEP 5 to 7 cm H2O throughout the resuscitation. The study intervention consists of performing an initial SI (20 cm H20 for 15 seconds) followed by a second SI (25 cm H2O for 15 seconds), and then PEEP with or without IPPV, as needed. The control group will be treated with initial IPPV with PEEP. The primary outcome is the combined endpoint of bronchopulmonary dysplasia or death at 36 weeks post-menstrual age., Trial Registration: www.clinicaltrials.gov , Trial identifier NCT02139800 , Registered 13 May 2014.

Background: Nasal intermittent positive pressure ventilation (NIPPV) is becoming more important as a mode of ventilation in premature neonates predisposed to development of bronchopulmonary dysplasia (BPD). To the best of our knowledge, there have been no detailed studies characterizing neonates who fail NIPPV., Objective: To determine the differences between neonates who are successfully extubated to NIPPV and those who require re-intubation from NIPPV, and the impact of timing of NIPPV failure on BPD rates., Study Design: This was a retrospective cohort study in which we included infants with gestational age (GA) ⩽ 28 weeks and birth weight ⩽ 1000 g. χ²-test, analysis of variance and multivariate logistic regression models were used., Results: Two hundred and forty infants were studied; 180 failed NIPPV and of those, 33 (18%), 39 (22%) and 108 (60%) failed NIPPV within 0 to 6 h, ⩾ 6 to 24 h and ⩾ 24 h, respectively. Female sex and increased weight were protective against NIPPV failure (adjusted odds ratio (95% confidence interval): 0.28 (0.14 to 0.58), 0.04 (0.01 to 0.22)). Increased GA at extubation and female sex were both associated with increased time to failure (P=0.008, <0.001, respectively). Apnea was more likely the cause for failure ⩾ 24 h (P=0.015), whereas increased work of breathing/fraction of inspired oxygen requirements were more significant when NIPPV failure occurred earlier (P=0.001). Neonates who failed NIPPV within 24 h did not have any association with likelihood of developing BPD or severity of BPD, after adjusting for confounding variables., Conclusion: Significant differences in neonatal characteristics may help identify which neonates are more likely to fail NIPPV, and their timing of failure.

Objective: To determine the effect of unsynchronized nasal intermittent positive pressure ventilation compared to continuous positive airway pressure in preterm infants after extubation., Methods: A total of 67 premature infants who were <35 weeks gestation and/or <2000 g birth weight and received mechanical ventilation because of respiratory distress syndrome (RDS) were studied. Infants were randomized to receive either unsynchronized nasal intermittent positive pressure ventilation (NIPPV) with shortened endotracheal tube (Group 1) or nasal continuous positive airway pressure (NCPAP) with binasal prongs (Group 2) after extubation. Extubation failure and neonatal outcomes were recorded in each group., Results: There were no significant differences in clinical characteristics between the two groups. The prevalence of re-intubation and post-extubation atelectasis were higher in CPAP group (p = 0.03 and p = 0.01). No differences were observed in the prevalence of IVH, ROP, PDA, NEC, sepsis, pneumothorax, BPD and BPD/death between the groups while the mortality was higher in NCPAP group (p < 0.01). Neither procedure had any serious side effects such as intestinal perforation., Conclusion: NIPPV (although non-synchronized and delivered by single nasal prong) had a better effect than NCPAP after extubation of preterm infants on mechanical ventilation in respect to reducing the prevalence of post-extubation atelectasis, re-intubation and also death.

Objective: To compare the effects and short-term outcomes of pressure support ventilation with volume guarantee versus synchronized intermittent mandatory ventilation in the weaning phase of very low-birth weight infants with respiratory distress syndrome., Design: Randomized controlled prospective study., Setting: Tertiary care neonatal unit., Patients: A total of 60 premature infants who were less than 33 weeks' gestation and/or less than 1,500 g birth weight and received mechanical ventilation because of respiratory distress syndrome were studied., Interventions: All infants were ventilated from the time of admission with synchronized intermittent positive pressure ventilation mode after surfactant treatment for respiratory distress syndrome and then switched to pressure support ventilation with volume guarantee or synchronized intermittent mandatory ventilation mode in the weaning phase. The ventilatory variables and neonatal outcomes were recorded in each group., Measurements and Main Results: The mean peak inflation pressure was higher in synchronized intermittent mandatory ventilation group (p < 0.001) and the mean airway pressure was higher in pressure support ventilation with volume guarantee group (p = 0.03), whereas mean tidal volume and respiratory rates were similar in both groups. The prevalence of postextubation atelectasis was higher in synchronized intermittent mandatory ventilation group, but the difference was not statistically significant (p = 0.08). No differences were found in the prevalence of reintubation, patent ductus arteriosus, intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and pneumothorax between the groups., Conclusions: Pressure support ventilation with volume guarantee mode may be a safe and feasible mode during the weaning phase of very low-birth weight infants on mechanical ventilation support for respiratory distress syndrome with respect to reducing the frequency of postextubation atelectasis and using less peak inflation pressure.

Introduction: Biphasic positive airway pressure (BIVENT) is a partial support mode that employs pressure-controlled, time-cycled ventilation set at two levels of continuous positive airway pressure with unrestricted spontaneous breathing. BIVENT can modulate inspiratory effort by modifying the frequency of controlled breaths. Nevertheless, the optimal amount of inspiratory effort to improve respiratory function while minimizing ventilator-associated lung injury during partial ventilatory assistance has not been determined. Furthermore, it is unclear whether the effects of partial ventilatory support depend on acute lung injury (ALI) etiology. This study aimed to investigate the impact of spontaneous and time-cycled control breaths during BIVENT on the lung and diaphragm in experimental pulmonary (p) and extrapulmonary (exp) ALI., Methods: This was a prospective, randomized, controlled experimental study of 60 adult male Wistar rats. Mild ALI was induced by Escherichia coli lipopolysaccharide either intratracheally (ALI(p)) or intraperitoneally (ALI(exp)). After 24 hours, animals were anesthetized and further randomized as follows: (1) pressure-controlled ventilation (PCV) with tidal volume (V(t)) = 6 ml/kg, respiratory rate = 100 breaths/min, PEEP = 5 cmH2O, and inspiratory-to-expiratory ratio (I:E) = 1:2; or (2) BIVENT with three spontaneous and time-cycled control breath modes (100, 75, and 50 breaths/min). BIVENT was set with two levels of CPAP (P(high) = 10 cmH2O and P(low) = 5 cmH2O). Inspiratory time was kept constant (T(high) = 0.3 s)., Results: BIVENT was associated with reduced markers of inflammation, apoptosis, fibrogenesis, and epithelial and endothelial cell damage in lung tissue in both ALI models when compared to PCV. The inspiratory effort during spontaneous breaths increased during BIVENT-50 in both ALI models. In ALI(p), alveolar collapse was higher in BIVENT-100 than PCV, but decreased during BIVENT-50, and diaphragmatic injury was lower during BIVENT-50 compared to PCV and BIVENT-100. In ALI(exp), alveolar collapse during BIVENT-100 and BIVENT-75 was comparable to PCV, while decreasing with BIVENT-50, and diaphragmatic injury increased during BIVENT-50., Conclusions: In mild ALI, BIVENT had a lower biological impact on lung tissue compared to PCV. In contrast, the response of atelectasis and diaphragmatic injury to BIVENT differed according to the rate of spontaneous/controlled breaths and ALI etiology.

Infants born prematurely with respiratory distress syndrome are at high risk for complications from mechanical ventilation. Strategies are needed to minimize their days on the ventilator. The purpose of this study was to compare extubation success rates in infants treated with 2 different types of continuous positive airway pressure devices. A retrospective cohort study design was used. Data were retrieved from electronic medical records for patients in a large, metropolitan, level III neonatal intensive care unit. A sample of 194 premature infants with respiratory distress syndrome was selected, 124 of whom were treated with nasal intermittent positive pressure ventilation and 70 with bi-level variable flow nasal continuous positive airway pressure (bi-level nasal continuous positive airway pressure). Infants in both groups had high extubation success rates (79% of nasal intermittent positive pressure ventilation group and 77% of bi-level nasal continuous positive airway pressure group). Although infants in the bi-level nasal continuous positive airway pressure group were extubated sooner, there was no difference in duration of oxygen therapy between the 2 groups. Promoting early extubation and extubation success is a vital strategy to reduce complications of mechanical ventilation that adversely affect premature infants with respiratory distress syndrome.

Objective: To compare the clinical effects of nasal intermittent positive pressure ventilation (NIPPV) and nasal continuous positive airway pressure (NCPAP) in the treatment of neonatal respiratory distress syndrome., Methods: A prospective, randomized, controlled, single-center study was performed on 67 premature infants with NRDS between March 2011 and May 2012 and selected according to the inclusion and exclusion criteria. These premature infants were randomly assigned to receive NIPPV and NCPAP. Oxygenation index (OI), pH, PaCO2, duration of respiratory support, complications, success rate, hospital mortality, and incidence of bronchopulmonary dysplasia (BPD) were compared between the two groups., Results: Sixty-two patients were finally enrolled in the study, including 32 cases in the NIPPV group and 30 cases in the NCPAP group. After one hour of non-invasive ventilation, OI in the NIPPV group was higher than the NCPAP group (P<0.05), but there were no significant differences in pH and PaCO2 between the two groups (P>0.05 for both). A significantly lower proportion of infants needed mechanical ventilation via endotracheal tube (MVET) when they were treated initially with NIPPV than when they were treated initially with NCPAP (P<0.05). The NIPPV group had a significant higher success rate than the NCPAP group (P<0.05), but there was no significant difference in duration of respiratory support between the two groups (P>0.05). In addition, no significant differences in incidence of pneumothorax, hospital mortality and incidence of BPD were seen between the two groups (P>0.05 for all)., Conclusions: Compared with NCPAP, NIPPV can significantly decrease the proportion of premature infants with NRDS in need of MVET. However, there is no evidence that NIPPV can significantly reduce hospital mortality and incidence of BPD in premature infants with NRDS.

Background: To reduce the risk of bronchopulmonary dysplasia in extremely-low-birth-weight infants, clinicians attempt to minimize the use of endotracheal intubation by the early introduction of less invasive forms of positive airway pressure., Methods: We randomly assigned 1009 infants with a birth weight of less than 1000 g and a gestational age of less than 30 weeks to one of two forms of noninvasive respiratory support--nasal intermittent positive-pressure ventilation (IPPV) or nasal continuous positive airway pressure (CPAP)--at the time of the first use of noninvasive respiratory support during the first 28 days of life. The primary outcome was death before 36 weeks of postmenstrual age or survival with bronchopulmonary dysplasia., Results: Of the 497 infants assigned to nasal IPPV for whom adequate data were available, 191 died or survived with bronchopulmonary dysplasia (38.4%), as compared with 180 of 490 infants assigned to nasal CPAP (36.7%) (adjusted odds ratio, 1.09; 95% confidence interval, 0.83 to 1.43; P=0.56). The frequencies of air leaks and necrotizing enterocolitis, the duration of respiratory support, and the time to full feedings did not differ significantly between treatment groups., Conclusions: Among extremely-low-birth-weight infants, the rate of survival to 36 weeks of postmenstrual age without bronchopulmonary dysplasia did not differ significantly after noninvasive respiratory support with nasal IPPV as compared with nasal CPAP. (Funded by the Canadian Institutes of Health Research; NIPPV ClinicalTrials.gov number, NCT00433212; Controlled-Trials.com number, ISRCTN15233270.).