The Diaphragmatic Initiated Ventilatory Assist (DIVA) trial: study protocol for a randomized controlled trial comparing rates of extubation failure in extremely premature infants undergoing extubation to non-invasive neurally adjusted ventilatory assist versus non-synchronized nasal intermittent positive pressure ventilation.

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 240/7-276/7 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 24-276/7 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 FiO2 at least 20% from pre-extubation for > 2 h, (2) pH ≤ 7.20 or pCO2 ≥ 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.

High-flow nasal cannula (HFNC) vs continuous positive airway pressure (CPAP) vs nasal intermittent positive pressure ventilation as primary respiratory support in infants of ≥ 32 weeks gestational age (GA): study protocol for a three-arm multi-center randomized controlled trial.

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 .

Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation.

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; I2 = 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.

Early nasal intermittent positive pressure ventilation (NIPPV) versus early nasal continuous positive airway pressure (NCPAP) for preterm infants.

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; I2 of 0%; low-certainty evidence), the incidence of pneumothorax (RR 0.92, 95% CI 0.60 to 1.41; 16 RCTs; 1674 infants; I2 of 0%; low-certainty evidence), and rates of severe IVH (RR 0.98, 95% CI 0.53 to 1.79; 8 RCTs; 977 infants; I2 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.

A comparison of the effect of bi-level positive airway pressure and synchronized intermittent mandatory ventilation in preterm infants with respiratory distress syndrome.

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.

Sustained Inflation Versus Intermittent Positive Pressure Ventilation for Preterm Infants at Birth: Respiratory Function and Vital Sign Measurements.

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.

Repeated intermittent hypoxic stimuli to operative lung reduce hypoxemia during subsequent one-lung ventilation for thoracoscopic surgery: A randomized controlled trial.

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.

Continuous positive airway pressure (CPAP) for respiratory distress in preterm infants.

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; I2 = 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; I2 = 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; I2 = 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; I2 = 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; I2 = 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.

[Safety evaluation on different ventilation strategies set for neonatal respiratory distress syndrome: a network Meta-analysis].

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.

Effect of sustained inflations and intermittent positive pressure ventilation on bronchopulmonary dysplasia or death among neonatal: A protocol for systematic review.

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.

Chronic lung disease in preterm infants receiving various modes of noninvasive ventilation at ≤30 weeks' postmenstrual age.

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.

Prolonged non-invasive ventilation in extremely low birth weight preterm infants is associated with bronchopulmonary dysplasia.

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.

Patient-ventilator asynchrony in preterm infants on nasal intermittent positive pressure ventilation.

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.

Impact of delivered tidal volume on the occurrence of intraventricular haemorrhage in preterm infants during positive pressure ventilation in the delivery room.

BACKGROUND AND OBJECTIVES: Delivery of inadvertent high tidal volume (VT) during positive pressure ventilation (PPV) in the delivery room is common. High VT delivery during PPV has been associated with haemodynamic brain injury in animal models. We examined if VT 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. VT values were compared with recently described reference ranges for VT in spontaneously breathing preterm infants at birth. Infants were divided into two groups: VT<6 mL/kg or VT>6 mL/kg (normal and high VT, 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 VT and 41 (25%) normal VT. The mean (SD) gestational age and birth weight in high and normal VT group was similar, 26 (2) and 26 (1) weeks, 858 (251) g and 915 (250) g, respectively. IVH in the high VT group was diagnosed in 63 (51%) infants compared with 5 (13%) infants in the normal VT group (P=0.008).Severe IVH (grade III or IV) developed in 33/124 (27%) infants in the high VT group and 2/41 (6%) in the normal VT group (P=0.01). CONCLUSIONS: High VT delivery during mask PPV at birth was associated with brain injury. Strategies to limit VT delivery during mask PPV should be used to prevent high VT delivery.

Sustained inflations and avoiding mechanical ventilation to prevent death or bronchopulmonary dysplasia: a meta-analysis.

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.

Tidal volume monitoring during emergency neonatal transport.

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.

A Randomized Controlled Trial of a Barrier Dressing to Reduce Nasal Injury in Preterm Infants Receiving Binasal Noninvasive Respiratory Support.

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.

[Comparison of clinical efficacy of two noninvasive respiratory support therapies for respiratory distress syndrome in very low birth weight preterm infants].

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.

Non-invasive neurally adjusted ventilatory assist versus nasal intermittent positive-pressure ventilation in preterm infants born before 30 weeks' gestation.

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.