Moving on from clinical animal-derived surfactants to peptide-based synthetic pulmonary surfactant.

Research on lung surfactant has exerted a great impact on newborn respiratory care and significantly improved survival and outcome of preterm infants with respiratory distress syndrome (RDS) due to surfactant deficiency because of lung immaturity. Current clinical, animal-derived, surfactants are among the most widely tested compounds in neonatology However, limited availability, high production costs, and ethical concerns about using animal-derived products constitute important limitations in their universal application. Synthetic lung surfactant offers a promising alternative to animal-derived surfactant by providing improved consistency, quality and purity, availability and scalability, ease of production and lower costs, acceptance, and safety for the treatment of neonatal RDS and other lung conditions. Third-generation synthetic surfactants built around surfactant protein B (SP-B) and C (SP-C) peptide mimics stand at the forefront of innovation in neonatal pulmonary medicine, while nasal continuous positive airway pressure (nCPAP) has become the standard non-invasive respiratory support for preterm infants. nCPAP can prevent the risk of chronic lung disease (bronchopulmonary dysplasia) and reduce lung injury by avoiding intubation and mechanical ventilation, is a relatively simple technique and can be initiated safely and effectively in the delivery room. Combining nCPAP with noninvasive, preferably aerosol, delivery of synthetic lung surfactant promises to improve respiratory outcomes for preterm infants, especially in low-and-middle income countries.

Nasal Continuous Positive Airway Pressure Inhibits Gastroesophageal Refluxes in the Preterm Lamb.

BACKGROUND: Gastroesophageal refluxes (GERs) are universal in newborns and may induce deleterious consequences, especially in preemies. We have previously shown that nasal continuous positive airway pressure (nCPAP) inhibits GERs in full-term lambs, complementing similar results in adult humans. The effect of high-flow nasal cannula (HFNC) on GERs, however, remains unknown. This study aimed to assess the effects of nCPAP and HFNC on GERs in our preterm lamb model. METHODS: Eleven preterm lambs born 14 days before full-term (~ 34 weeks of human gestation) were studied. Esophageal pH-impedancemetry and polysomnography recordings were performed simultaneously for six hours under three randomly ordered conditions: nCPAP 6 cmH2O, HFNC 7 L/min and no respiratory support (control). The indexes (/hour) of GERs and air-containing swallows were analyzed during each condition. The states of alertness and cardiorespiratory events were also analyzed during the identified GERs. RESULTS: nCPAP significantly decreased the GER index compared to control and HFNC during both quiet wakefulness and non-rapid eye movement sleep, whereas HFNC did not alter the GER index. In addition, nCPAP significantly increased the air-containing swallow index compared to control and HFNC. No significant differences were observed between the tested conditions for GER-related cardiorespiratory events, which were nevertheless rarely observed. CONCLUSION: Similar to full-term lambs, nCPAP strongly inhibited GERs in the preterm lamb, despite an increase in air-containing swallows. In contrast, HFNC did not impact GERs. Our results are clinically relevant when discussing the use of CPAP in preemies with GERs.

Effect of different ventilation modalities on the early prognosis of patients with sleep apnea after acute ischemic stroke---protocol for a prospective, open-label and randomised controlled trial.

BACKGROUND: Sleep apnea is highly prevalent after acute ischemic stroke (AIS) and has increased stroke-related mortality and morbidity. The conventional sleep apnea treatment is continuous positive airway pressure (CPAP) ventilation. However, it is poorly tolerated by patients and is not used in all stroke patients. This protocol describes the impact of high-flow nasal cannula (HFNC) oxygen therapy compared to nasal continuous positive airway pressure (nCPAP) ventilation or usual care on the early prognosis of patients with sleep apnea after AIS. METHODS: This randomised controlled study will be conducted in the intensive care unit of the Department of Neurology at the Wuhan Union Hospital. According to the study plan, 150 patients with sleep apnea after AIS will be recruited. All patients are randomly allocated in a 1:1:1 ratio to one of three groups: the nasal catheter group (standard oxygen group), the HFNC group, and the nCPAP group. Patients receive different types of ventilation after admission to the group, and their tolerance while using the different ventilation is recorded. Patients will be followed up by telephone three months after discharge, and stroke recovery is recorded. The primary outcomes were 28-day mortality, the incidence of pulmonary infection and endotracheal intubation. DISCUSSION: This study analyses different ventilation modalities for early interventions in patients with sleep apnea after AIS. We will investigate whether nCPAP and HFNC reduce early mortality and endotracheal intubation rates and improve distant neurological recovery in patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT05323266; 25 March 2022).

The effect of non-invasive high-frequency oscillatory ventilation on the duration of non-invasive respiratory support in late preterm and term infants with transient tachypnea of the newborn: a randomized controlled trial.

Nasal continuous positive airway pressure (nCPAP) is one of the most commonly used non-invasive respiratory support modes in neonates with transient tachypnea of the newborn (TTN). Non-invasive high-frequency oscillatory ventilation (nHFOV) is a non-invasive respiratory support mode that has been increasingly used in neonatal respiratory disorders. This prospective randomized controlled study compared the efficacy of nHFOV and nCPAP in reducing the duration of non-invasive respiratory support. Late preterm and term infants > 34 weeks' gestation were included in the study. The infants were randomly assigned to receive either nHFOV or nCPAP. Treatment was started with standard settings in both groups. Infants who met treatment failure criteria were switched to nasal intermittent mandatory ventilation for further positive-pressure support. A total of 60 infants were included in the study. Thirty of these infants were included in the nHFOV group and 30 were included in the nCPAP group. The median duration of non-invasive respiratory support was not significantly different between the two groups (21 h [IQR: 16-68] for nHFOV vs 15 h [IQR: 11-33] for nCPAP; p = 0.09). However, after adjusting for potential confounders, nHFOV was associated with a shorter duration of non-invasive respiratory support than nCPAP (adjusted mean difference: 16.3 h; 95% CI: 0.7 to 31.9; p = 0.04). nHFOV was well tolerated and did not increase the risk of complications.    Conclusion: Our findings suggest that nHFOV is an effective and safe ventilation mode for late preterm and term neonates with TTN.   Trial registry: Clinicaltrials.gov (NCT03006354). Date of registration: December 30, 2016. What is Known: • nHFOV is a ventilation model that has been increasingly used for the management of RDS. • TTN is one of the most common causes of neonatal respiratory distress. What is New: • nHFOV is associated with shorter duration of non-invasive respiratory support and duration of oxygen support. • nHFOV may be a safe and effective alternative to nCPAP for neonates with TTN.

Efficay of high-flow nasal cannula in the paediatric population: A systematic evidence map.

PROBLEM: High-flow nasal cannula (HFNC) has been widely used in paediatric medicine as a non-invasive ventilation mode for respiratory support. However, the differences in its efficacy across different diseases and intervention types remain poorly understood. ELIGIBILITY CRITERIA: An extensive literature search was performed across multiple academic databases to investigate the systematic reviews and meta-analyses of HFNC. SAMPLE: This study included 35 systematic reviews and meta-analyses, which collectively examined 355 randomised controlled trials and assessed 51 outcome indicators. RESULTS: The findings suggest that the existing clinical research evidence predominantly supports the therapeutic efficacy of HFNC. Notably, there is a significant focus on treating acute lower respiratory infection, hypoxaemia, bronchiolitis, and respiratory distress syndrome following extubation. However, concerning the respiratory status, the existing clinical research evidence mainly demonstrates the therapeutic benefits in post-extubation respiratory support and primary respiratory support. CONCLUSIONS: The research on HFNC has witnessed significant expansion, primarily focusing on respiratory disorders, post-extubation respiratory support, conscious sedation, and related fields. The evidence mapping provides a systematic and comprehensive overview of the available evidence on HFNC therapy in paediatric patients. IMPLICATIONS: This study systematically and comprehensively assessed the clinical subjects and populations involved in HFNC therapy. Notably, this study analyzed the trends, current status, and evidence gaps of research, and furnished decision-makers and relevant researchers with a more comprehensive reference basis.

Noninvasive Neurally Adjusted Ventilation in Postextubation Stabilization of Preterm Infants: A Randomized Controlled Study.

OBJECTIVE: To compare the effects of noninvasive neurally adjusted ventilatory assist (NIV-NAVA) to nasal continuous positive airway pressure (NCPAP) in achieving successful extubation in preterm infants. STUDY DESIGN: This prospective, single-center, randomized controlled trial enrolled preterm infants born at <30 weeks of gestation who received invasive ventilation. Participants were assigned at random to either NIV-NAVA or NCPAP after their first extubation from invasive ventilation. The primary outcome of the study was extubation failure within 72 hours of extubation. Electrical activity of the diaphragm (Edi) values were collected before extubation and at 1, 4, 12, and 24 hours after extubation. RESULTS: A total of 78 infants were enrolled, including 35 infants in the NIV-NAVA group and 35 infants in the NCPAP group. Extubation failure within 72 hours of extubation was higher in the NCPAP group than in the NIV-NAVA group (28.6% vs 8.6%; P = .031). The duration of respiratory support and incidence of severe bronchopulmonary dysplasia were similar in the 2 groups. Peak and swing Edi values were comparable before and at 1 hour after extubation, but values at 4, 12, and 24 hours after extubation were lower in the NIV-NAVA group compared with the NCPAP group. CONCLUSIONS: In the present trial, NIV-NAVA was more effective than NCPAP in preventing extubation failure in preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02590757.

Nasal high-frequency oscillatory ventilation versus nasal continuous positive airway pressure as primary respiratory support strategies for respiratory distress syndrome in preterm infants: a systematic review and meta-analysis.

Nasal high-frequency oscillatory ventilation (NHFOV) is a new respiratory support strategy despite lacking of enough evidence in preterm infants with respiratory distress syndrome (RDS). The aim of the present systematic review was to explore whether NHFOV reduced the intubation rate as compared with nasal continuous positive airway pressure (NCPAP) as the primary respiratory support strategies in preterm infants with RDS. Medline, the Cochrane library, the Cochrane Controlled Trials Register, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and Wanfang data Information Site were searched from inception to Jan 1, 2021(Prospero2019 CRD42019129316, date and name of registration: Apr 23,2019, The clinical effectiveness of NHFOV vs NCPAP for preterm babies with respiratory distress syndrome). Pooled data from clinically randomized controlled trials (RCTs) comparing NHFOV with NCPAP as the primary respiratory supporting strategies in preterm infants with RDS were performed using the fixed-effects models whenever no heterogeneity was shown. The primary outcome was intubation rate. Four randomized controlled trials involving 570 participants were included. Comparing with NCPAP, NHFOV resulted in less intubation (relative risk (RR) 0.44; 95% confidence interval (CI) 0.29-0.67, P = 0.0002), and heterogeneity was not found among the trials in the fixed-effects model (P = 0.78, I2 = 0%). Similar result also appeared in sensitivity analysis after excluding one study with significant difference (RR 0.44; 95% CI 0.25-0.78, P = 0.005) (P = 0.58, I2 = 0%).Conclusion: NHFOV decreased the intubation rate as compared with NCPAP as primary respiratory supporting strategies in preterm infants suffering from RDS. Future research should assess whether NHFOV can reduce the incidence of bronchopulmonary dysplasia (BPD) and intubation rate in preterm infants with BPD. Fund by Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0197), and "guan'ai" preterm Study Program of Renze Foundation of Beijing(K022). What is Known: • Nasal high-frequency oscillatory ventilation (NHFOV) has been described to be another advanced version of nasal continuous positive airway pressure (NCPAP). However, its beneficial effects among different studies as the primary modes in the early life of preterm infants with respiratory distress syndrome (RDS) were inconsistent. What is New: • Comparing with NCPAP, NHFOV decreases the risk of intubation as a primary respiratory supporting strategy in early life for preterm infants suffering from RDS.

Noninvasive high-frequency oscillatory ventilation versus bi-level positive pressure ventilation in premature infants with respiratory failure: A retrospective study.

Objectives: Noninvasive high-frequency oscillatory ventilation (nHFOV) is a novel respiratory support mode for premature infants. This retrospective study aimed to compare the effect of nHFOV and bi-level nasal continuous positive airway pressure (BiPAP) in premature infants with neonatal respiratory failure (NRF) as initial noninvasive ventilation (NIV) support mode. Methods: We retrospectively analyzed medical records of preterm infants admitted to the tertiary neonatal intensive care units (NICUs) of Fujian Maternal and Child Health Hospital from January 2019 to December 2020. Preterm infants with the gestational age of 25-34 weeks, diagnosed with NRF, used nHFOV or BiPAP as the initial respiratory support mode were analyzed. The rates of invasive mechanical ventilation (IMV) within the first seven days after birth and adverse outcomes were compared between the two groups. Results: Two hundred fifty-five preterm infants were analyzed (128 in nHFOV group,127 in BiPAP group). There was no significant difference in baseline characteristics between the two groups. Compared with the BiPAP group, the nHFOV group had significantly lower need for IMV within the first seven days after birth (18/128 vs. 33/127, p = 0.01) and PCO2 at 12 and 24 hours post-treatment (46.34±5.24mmHg vs. 51.18±4.83mmHg, P<0.01; 40.72±4.02mmHg vs. 42.50±3.86mmHg, P<0.01). The incidence of BPD, ROP, air leak syndromes, IVH≥ grade 3, PVL, NEC≥II stage, abdominal distension, and nasal trauma were similar between the two groups. Conclusion: nHFOV significantly reduced the need for IMV and improved the elimination of CO2 compared with BiPAP in preterm infants with NRF without increasing the incidence of adverse effects.

Discontinuing Nasal Continuous Positive Airway Pressure in Infants ≤32 Weeks of Gestational Age: A Randomized Control Trial.

OBJECTIVES: To compare immediate cessation of nasal continuous positive airway pressure (NCPAP) vs a stepwise decrease in pressure on the duration of NCPAP therapy in infants born prematurely. STUDY DESIGN: A single center study in infants 230-326 weeks of gestational age. NCPAP was stopped either at 5 cm H2O (control) or 3 cm H2O after a stepwise pressure wean (wean) using defined stability and failure criteria. Primary outcome is total NCPAP days. RESULTS: We enrolled 226 infants; 116 were randomly assigned to control and 110 to the wean group. There was no difference in the total NCPAP days between groups (median [25th, 75th percentiles] 16 [5, 36] vs 14 [7, 33] respectively). There were no differences between groups in secondary outcomes, including duration of hospital stay, critical care days, and oxygen supplementation. A higher proportion of control infants failed the initial attempt to discontinue NCPAP (43% vs 27%, respectively; P < .01) and required ≥2 attempts (20% vs 5%, respectively; P < .01). In addition, infants 23-27 weeks of gestational age in the wean group were 2.4-times more likely to successfully stop NCPAP at the first attempt (P = .02) vs controls. CONCLUSIONS: Discontinuation of NCPAP after a gradual pressure wean to 3 cm H2O did not decrease the duration of NCPAP therapy compared with stopping from 5 cm H2O in infants ≤32 weeks of gestational age. However, weaning decreased failed initial attempts to stop NCPAP, particularly among infants <28 weeks of gestational age. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02064712.

Oscillatory mechanics at birth for identifying infants requiring surfactant: a prospective, observational trial.

BACKGROUND: Current criteria for surfactant administration assume that hypoxia is a direct marker of lung-volume de-recruitment. We first introduced an early, non-invasive assessment of lung mechanics by the Forced Oscillation Technique (FOT) and evaluated its role in predicting the need for surfactant therapy. OBJECTIVES: To evaluate whether lung reactance (Xrs) assessment by FOT within 2 h of birth identifies infants who would need surfactant within 24 h; to eventually determine Xrs performance and a cut-off value for early detection of infants requiring surfactant. METHODS: We conducted a prospective, observational, non-randomized study in our tertiary NICU in Milan. Eligible infants were born between 27+0 and 34+6 weeks' gestation, presenting respiratory distress after birth. EXCLUSION CRITERIA: endotracheal intubation at birth, major malformations participation in other interventional trials, parental consent denied. We assessed Xrs during nasal CPAP at 5 cmH2O at 10 Hz within 2 h of life, recording flow and pressure tracing through a Fabian Ventilator for off-line analysis. Clinicians were blinded to FOT results. RESULTS: We enrolled 61 infants, with a median [IQR] gestational age of 31.9 [30.3; 32.9] weeks and birth weight 1490 [1230; 1816] g; 2 infants were excluded from the analysis for set-up malfunctioning. 14/59 infants received surfactant within 24 h. Xrs predicted surfactant need with a cut-off - 33.4 cmH2O*s/L and AUC-ROC = 0.86 (0.76-0.96), with sensitivity 0.85 and specificity 0.83. An Xrs cut-off value of - 23.3 cmH2O*s/L identified infants needing surfactant or respiratory support > 28 days with AUC-ROC = 0.89 (0.81-0.97), sensitivity 0.86 and specificity 0.77. Interestingly, 12 infants with Xrs < - 23.3 cmH2O*s/L (i.e. de-recruited lungs) did not receive surfactant and subsequently required prolonged respiratory support. CONCLUSION: Xrs assessed within 2 h of life predicts surfactant need and respiratory support duration in preterm infants. The possible role of Xrs in improving the individualization of respiratory management in preterm infants deserves further investigation.

Can high-flow nasal cannula reduce the risk of bronchopulmonary dysplasia compared with CPAP in preterm infants? A systematic review and meta-analysis.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects the premature lung, and to reduce its incidence has been used non-invasive ventilatory support, such as continuous positive airway (CPAP) and high-flow nasal cannula (HFNC). Thus, the objective of this review was to assess whether the use of high flow nasal cannula (HFNC) compared to continuous positive airway pressure (CPAP) decreases the risk of bronchopulmonary dysplasia (BPD) in premature newborns. METHODS: The protocol was registered (Prospero: CRD42019136631) and the search was conducted in the MEDLINE, PEDro, Cochrane Library, CINAHL, Embase, and LILACS databases, and in the clinical trials registries, until July 2020. We included randomized clinical trials comparing HFNC versus CPAP use in premature infants born at less than 37 weeks of gestational age. The main outcome measures were the development of BPD, air leak syndrome, and nasal injury. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool and the GRADE system was used to summarize the evidence recommendations. Meta-analyses were performed using software R. RESULTS: No difference was found between HFNC or CPAP for the risk of BPD (RR: 1.10; 95% CI: 0.90-1.34), air leak syndrome (RR: 1.06; 95% CI: 0.52-2.14), and nasal trauma (RR: 2.00; 95% CI: 0.64-6.25), with a very low level of evidence. CONCLUSION(S): The HFNC showed similar results when compared to CPAP in relation to the risk of BPD, air leak syndrome, and nasal injury. In the literature, no randomized clinical trial has been found with BPD as the primary outcome to support possible outcomes.

Reintubation rates after extubation to different non-invasive ventilation modes in preterm infants.

INTRODUCTION: Respiratory Distress Syndrome (RDS) is a common cause of neonatal morbidity and mortality in premature newborns. In this study, we aim to compare the reintubation rate in preterm babies with RDS who were extubated to Nasal Continuous Positive Airway Pressure (NCPAP) versus those extubated to Nasal Intermittent Positive Pressure Ventilation (NIPPV). METHODS: This is a retrospective study conducted in the Neonatal Intensive Care Unit (NICU) of Women's Wellness and Research Center (WWRC), Doha, Qatar. The medical files (n = 220) of ventilated preterm infants with gestational age ranging between 28 weeks 0 days and 36 weeks + 6 days gestation and extubated to non-invasive respiratory support (whether NCPAP, NIPPV, or Nasal Cannula) during the period from January 2016 to December 2017 were reviewed. RESULTS: From the study group of 220 babies, n = 97 (44%) babies were extubated to CPAP, n = 77 (35%) were extubated to NIPPV, and n = 46 (21%) babies were extubated to Nasal Cannula (NC). Out of the n = 220 babies, 18 (8.2%) were reintubated within 1 week after extubation. 14 of the 18 (77.8%) were reintubated within 48 h of extubation. Eleven babies needed reintubation after being extubated to NCPAP (11.2%) and seven were reintubated after extubation to NIPPV (9.2%), none of those who were extubated to NC required reintubation (P = 0.203). The reintubation rate was not affected by extubation to any form of non-invasive ventilation (P = 0.625). The mode of ventilation before extubation does not affect the reintubation rate (P = 0.877). The presence of PDA and NEC was strongly associated with reintubation which increased by two and four-folds respectively in those morbidities. There is an increased risk of reintubation with babies suffering from NEC and BPD and this was associated with an increased risk of hospital stay with a P-value ranging (from 0.02-0.003). Using multivariate logistic regression, NEC the NEC (OR = 5.52, 95% CI 1.26, 24.11, P = 0.023) and the vaginal delivery (OR = 0.23, 95% CI 0.07, 0.78, P = 0.018) remained significantly associated with reintubation. CONCLUSION: Reintubation rates were less with NIPPV when compared with NCPAP, however, this difference was not statistically significant. This study highlights the need for further research studies with a larger number of neonates in different gestational ages birth weight categories. Ascertaining this information will provide valuable data for the factors that contribute to re-intubation rates and influence the decision-making and management of RDS patients in the future.

Non-invasive duo positive airway pressure ventilation versus nasal continuous positive airway pressure in preterm infants with respiratory distress syndrome: a randomized controlled trial.

BACKGROUND: The most common cause of respiratory failure in premature infants is respiratory distress syndrome. Historically, respiratory distress syndrome has been treated by intratracheal surfactant injection followed by mechanical ventilation. In view of the risk of pulmonary injury associated with mechanical ventilation and subsequent chronic pulmonary lung disease, less invasive treatment modalities have been suggested to reduce pulmonary complications. METHODS: 148 neonates (with gestational age of 28 to 34 weeks) with respiratory distress syndrome admitted to Imam Khomeini Hospital in Ahwaz in 2018 were enrolled in this clinical trial study. 74 neonates were assigned to duo positive airway pressure (NDUOPAP) group and 74 neonates to nasal continuous positive airway pressure (NCPAP) group. The primary outcome in this study was failure of N-DUOPAP and NCPAP treatments within the first 72 h after birth and secondary outcomes included treatment complications. RESULTS: there was not significant difference between DUOPAP (4.1 %) and NCPAP (8.1 %) in treatment failure at the first 72 h of birth (p = 0.494), but non-invasive ventilation time was less in the DUOPAP group (p = 0.004). There were not significant differences in the frequency of patent ductus arteriosus (PDA), pneumothorax, intraventricular hemorrhage (IVH) and bronchopulmonary dysplasia (BPD), apnea and mortality between the two groups. Need for repeated doses of surfactant (p = 0.042) in the NDUOPAP group was significantly lower than that of the NCPAP group. The duration of oxygen therapy in the NDUOPAP group was significantly lower than that of the NCPAP group (p = 0.034). Also, the duration of hospitalization in the NDUOPAP group was shorter than that of the NCPAP group (p = 0.002). CONCLUSIONS: In the present study, DUOPAP compared to NCPAP did not reduce the need for mechanical ventilation during the first 72 h of birth, but the duration of non-invasive ventilation and oxygen demand, the need for multiple doses of surfactant and length of stay in the DUOPAP group were less than those in the CPAP group. TRIAL REGISTRATION: IRCT20180821040847N1 , Approved on 2018-09-10.

Heated Humidified High-Flow Nasal Cannula vs. Nasal Continuous Positive Airway Pressure for Post-extubation Respiratory Support in Preterm Infants: A Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to compare the efficacy and safety of heated humidified high-flow nasal cannula (HHHFNC) and nasal continuous positive airway pressure (nCPAP) for prevention of extubation failure in preterm infants. METHODS: Preterm infants (gestation ≥28 weeks) were randomized to HHHFNC or nCPAP after extubation. Primary outcome was extubation failure within 72 h of extubation. RESULTS: A total of 128 preterm infants were randomized to receive either HHHFNC (n = 63) or nCPAP (n = 65) after extubation. The primary outcome of extubation failure within 72 h after extubation was not different between the two groups (HHHFNC, 22.2% vs. nCPAP, 18.5%, risk difference of 3.7% and 95% CI -10.3 to 17.6, p = 0.604). The incidence of nasal trauma was significantly lower in the HHHFNC group than in the nCPAP group 6.3% vs. 21.5%, p = 0.020. CONCLUSIONS: In our study, HHHFNC was as effective as nCPAP for prevention of extubation failure in preterm infants. Also, HHHFNC was associated with significantly less nasal trauma compared with nCPAP.

Increased age adversely affects the therapeutic effect of CPAP treatment for olfactory functions.

PURPOSE: The aim of this study was to compare olfactory functions pre- and post-CPAP treatment in patients with moderate to severe OSA, and to evaluate the factors that cause changes in olfactory functions. METHODS: Twenty-two patients who had completed regular usage of CPAP treatment for 2 months were included in this prospective study. Olfactory tests using Sniffin' Sticks were performed pre- and post-treatment. RESULTS: The mean age of the subjects was 47.6 ± 9.5 years. We did not find a significant change in olfactory functions after 2 months of CPAP treatment in our study group. When the patients were divided into two groups-those whose olfactory functions showed improvement and those whose functions did not-it was found that the mean age of the patients whose olfactory functions did not improve was significantly higher statistically. A significant adverse correlation was found between age and post-treatment olfactory functions, specifically in odour threshold and odour identification scores. CONCLUSIONS: Increased age adversely affects the therapeutic effect of CPAP treatment for olfactory functions.

Effectiveness of nCPAP for moderate preterm infants compared to BiPAP: A Randomized, Controlled Non-Inferiority Trial.

BACKGROUND: Bilevel positive airway pressure (BiPAP) has recently been used in preterm infants with respiratory distress as an alternative to nasal continuous positive airway pressure (nCPAP) because, theoretically, BiPAP is thought to be more effective than nCPAP. However, the results of some studies comparing nCPAP with BiPAP as the initial respiratory support were controversial. The aim of this study is to compare the clinical effectiveness and safety of nCPAP with BiPAP at gestational ages of 30+0 to 34+6  weeks. METHODS: A total of 93 infants with gestational ages of 30+0 to 34+6  weeks, who presented with respiratory distress within 24 h after birth, were randomized to the nCPAP group or the BiPAP group. The primary outcome was the incidence of treatment failure with these two non-invasive respiratory support devices. Criteria for treatment failure included any of the following: respiratory acidosis (PaCO2 >65 mmHg with pH <7.2), hypoxia (FiO2 >0.4), or apnea (>2-3 episodes of apnea/h). RESULTS: There was no statistically significant difference in treatment failure between the two groups (P = 0.576). The risk difference comparing treatment failure rate between nCPAP and BiPAP groups was -4.7% (95% CI: -21.5-11.9). CONCLUSIONS: Nasal continuous positive airway pressure is not inferior to BiPAP as an initial management of respiratory distress in these premature infants. We therefore conclude that nCPAP can be used as an initial management for preterm infants at gestational age of between 30 and 35 weeks as a substitute for BiPAP.

Effect of Body Position on Cardiorespiratory Stabilization and Comfort in Preterm Infants on Continuous Positive Airway Pressure.

PURPOSE: The purpose of the study is to investigate the effect of four body positions (supine, prone, left lateral, right lateral) on cardiorespiratory stabilization and comfort in preterm infants receiving Nasal Continuous Positive Airway Pressure (NCPAP). DESIGN AND METHODS: In the study conducted as a randomized crossover design, the sample was composed of 20 preterm infants receiving NCPAP therapy. At each change of position, the baby was allowed to stabilize for 15 min, and heart rate and oxygen saturation values were recorded every 10 min for the next 60 min. The comfort levels of the infants in each position were evaluated at 30th and 60th minutes using the Premature Infant Comfort Scale. RESULTS: At the end of the study, it was determined that there was no statistically significant difference between heart rate (p = .83), respiratory rate (p = .90) and oxygen saturation (p = .15) of the infants in terms of their positions. When the mean comfort scores of the preterm infants were compared in terms of position, it was found that there was a difference between the positions (p < .01). According to the scale evaluation, the highest comfort level of the infants was in the prone position, which was followed by right lateral, supine and left lateral positions. PRACTICE IMPLICATIONS: Prone position was the most comfortable for preterm infants. However, comfort levels of preterm infants were also high enough in other positions so that no intervention is needed. In order to ensure comfort and cardiorespiratory stabilization, any of the four body positions can be chosen.

A Comparison of Moderate to Late Preterm Neonates Receiving Nasal Continuous Positive Airway Pressure in Australian Tertiary and Nontertiary Centers.

PURPOSE: Transfer of neonates ≥32 weeks' gestation with acute respiratory distress to tertiary (T) centers can be reduced by treatment with nasal continuous positive airway pressure (nCPAP) in nontertiary (NT) centers. This can lead to considerable financial and emotional benefits. The aim of this project was to compare management of nCPAP in T and NT centers. DESIGN: Five-year retrospective, observational cohort study (2010-2014). SAMPLE: All NT eligible neonates from four sites (n = 484) were compared with a similar randomized cohort of inborn neonates at two T centers (n = 601) in Victoria, Australia. MAIN OUTCOME VARIABLE: Any difference in management or short-term outcome. RESULTS: Moderately preterm and term neonates born in NT centers had lower Apgar scores at five minutes of age and received more conservative management delivered by different equipment. Despite a higher incidence of air leaks in NT centers, the short-term outcomes were otherwise similar between centers. T centers were more likely to administer nCPAP to term babies for <24 hours.

Efficacy of High-Flow Nasal Cannula vs Standard Oxygen Therapy or Nasal Continuous Positive Airway Pressure in Children with Respiratory Distress: A Meta-Analysis.

OBJECTIVES: To evaluate the efficacy of high-flow nasal cannula (HFNC) oxygen therapy in providing respiratory support of children with acute lower respiratory infection (ALRI), hypoxemia, and respiratory distress. STUDY DESIGN: We performed a meta-analysis of randomized controlled trials that compared HFNC and standard flow oxygen therapy or nasal continuous positive airway pressure (nCPAP) and reported treatment failure as an outcome. Data were synthesized using Mann-Whitney U test. RESULTS: Compared with standard oxygen therapy, HFNC significantly reduced treatment failure (risk ratio [RR] 0.49, 95% CI 0.40-0.60, P < .001) in children with mild hypoxemia (arterial pulse oximetry [SpO2] >90% on room air). HFNC had an increased risk of treatment failure compared with nCPAP in infants age 1-6 months with severe hypoxemia (SpO2 <90% on room air or SpO2 >90% on supplemental oxygen) (RR 1.77, 95% CI 1.17-2.67, P = .007). No significant differences were found in intubation rates and mortality between HFNC and standard oxygen therapy or nCPAP. HFNC had a lower risk of nasal trauma compared with nCPAP (RR 0.35, 95% CI 0.16-0.77, P = .009). CONCLUSIONS: Among children <5 years of age with ALRI, respiratory distress, and mild hypoxemia, HFNC reduced the risk of treatment failure when compared with standard oxygen therapy. However, nCPAP was associated with a lower risk of treatment failure than HFNC in infants age 1-6 months with ALRI, moderate-to-severe respiratory distress, and severe hypoxemia. No differences were found in intubation and mortality between HFNC and standard oxygen therapy or nCPAP.

National surveys of UK and Italian neonatal units highlighted significant differences in the use of non-invasive respiratory support.

AIM: This study compared how non-invasive respiratory support (NRS) was provided in neonatal units in Italy and the UK. METHODS: An NRS questionnaire was sent to tertiary neonatal centres, identified by national societies, from November 2015 to May 2016. RESULTS: Responses were received from 49/57 (86%) UK units and 103/115 (90%) Italian units. NRS was started in the delivery room by 61% of UK units and 85% of Italian units. In neonatal intensive care units, 33% of UK units used nasal high-flow therapy (HFT) as primary support, compared to 3% in Italy. Nasal continuous positive airway pressure (CPAP) was used in 57% of UK units and 90% of Italian units. The commonest starting flow rate on nasal HFT for term and preterm infants was 6 L/min in the UK, while Italian units mainly used this flow for term infants. In the UK, 67% of units decreased nasal HFT by 1 L/min per day. In Italy, infants on nasal CPAP were weaned by 1 cm H2 O per day in 39% of units. CONCLUSION: The way that NRS was managed for very preterm infants differed between the UK and Italy, reflecting a lack of evidence on optimal NRS and the use of local protocols.