Mode Of Non-invasive Respiratory Support Research Articles

Noninvasive high-frequency oscillation ventilation as post- extubation respiratory support in neonates: Systematic review and meta-analysis.

Noninvasive High-Frequency Oscillatory Ventilation (NHFOV) is increasingly being adopted to reduce the need for invasive ventilation after extubation. To evaluate the benefits and harms of NHFOV as post-extubation respiratory support in newborns compared to other non-invasive respiratory support modes. We included randomized controlled trials comparing NHFOV with other non-invasive modes post-extubation in newborns. Data sources were MEDLINE (via Pubmed), Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, WHO international clinical trials registry platform and Clinical Trial Registry, forward and backward citation search. Methodological quality of studies was assessed by Cochrane's Risk of Bias tool 1.0. This systematic review included 21 studies and 3294 participants, the majority of whom were preterm. NHFOV compared to nasal continuous positive airway pressure (NCPAP) reduced reintubation within seven days (RR 0.34, 95% CI 0.22 to 0.53) after extubation. It also reduced extubation failure (RR 0.39, 95% CI 0.30 to 0.51) and reintubation within 72 hrs (RR 0.40, 95% CI 0.31 to 0.53), bronchopulmonary dysplasia (RR 0.59, 95% CI 0.37 to 0.94) and pulmonary air leak (RR 0.46, 95% CI 0.27 to 0.79) compared to NCPAP. The rate of reintubation within seven days (RR 0.62, 95% CI 0.18 to 2.14) was similar whereas extubation failure (RR 0.65, 95% CI 0.50 to 0.83) and reintubation (RR 0.68, 95% CI 0.52 to 0.89) within 72 hrs were lower in NHFOV group compared to nasal intermittent positive pressure ventilation. There was no effect on other outcomes. Overall quality of the evidence was low to very low in both comparisons. NHFOV may reduce the rate of reintubation and extubation failure post-extubation without increasing complications. Majority of the trials were exclusively done in preterm neonates. Further research with high methodological quality is warranted.

Nasal High-Frequency Oscillatory Ventilation Use in Romanian Neonatal Intensive Care Units-The Results of a Recent Survey.

Nasal high-frequency oscillatory ventilation (nHFOV) has emerged as an effective initial and rescue noninvasive respiratory support mode for preterm infants with respiratory distress syndrome (RDS); however, little is known about nHFOV use in Romanian neonatal intensive care units (NICUs). We aimed to identify the usage extent and clinical application of nHFOV in Romania. A structured web-based questionnaire was designed to find the rate of nHFOV use and knowledge of this new method of noninvasive respiratory support in Romanian level III NICUs. Using multiple-choice, open-ended, and yes/no questions, we collected information on the NICU's size, noninvasive respiratory support modes used, nHFOV use, indications, settings, nasal interfaces, secondary effects, and equipment used. Descriptive statistics and comparisons were performed using IBM SPSS Statistics 26.0. A total of 21/23 (91.3%) leaders from level III NICUs (median [IQR] number of beds of 10 [10-17.5]) responded to the survey. The most frequently used noninvasive ventilation modes were CPAP mode on mechanical ventilators (76.2%), followed by NIPPV (76.2%); heated, humidified high-flow nasal cannula (HHHFNC) (61.9%); and nHFOV (11/21 units; 52.4%). A total of 5/11 units reported frequent nHFOV use (in two or more newborns/month) in both term and preterm infants. The main indications reported for nHFOV use were CPAP failure (90.9%), hypercapnia (81.8%), and bronchopulmonary dysplasia (72.7%). Face/nasal masks and short binasal prongs are the most commonly used nasal interfaces (90.9% and 72.7%, respectively). Air leaks at the interface level (90.9%), thick secretions (81.8%), and airway obstruction (63.6%) were the most frequently mentioned adverse effects of nHFOV. Only three of the NICUs had a written protocol for nHFOV use. Most units not yet using nHFOV cited lack of equipment, experience, training, or insufficient information and evidence for the clinical use and outcome of nHFOV use in neonates as the main reasons for not implementing this noninvasive respiratory mode. Our survey showed that nHFOV is already used in more than half of the Romanian level III NICUs to support term and preterm infants with respiratory distress despite a lack of consensus regarding indications and settings during nHFOV.

Exploring Heterogeneity in Cost-Effectiveness Using Machine Learning Methods: A Case Study Using the FIRST-ABC Trial.

The aim of this study was to explore heterogeneity in the cost-effectiveness of high-flow nasal cannula (HFNC) therapy compared with continuous positive airway pressure (CPAP) in children following extubation. Using data from the FIRST-line support for Assistance in Breathing in Children (FIRST-ABC) trial, we explore heterogeneity at the individual and subgroup levels using a causal forest approach, alongside a seemingly unrelated regression (SUR) approach for comparison. FIRST-ABC is a noninferiority randomized controlled trial (ISRCTN60048867) including children in UK paediatric intensive care units, which compared HFNC with CPAP as the first-line mode of noninvasive respiratory support. In the step-down FIRST-ABC, 600 children clinically assessed to require noninvasive respiratory support were randomly assigned to HFNC and CPAP groups with 1:1 treatment allocation ratio. In this analysis, 118 patients were excluded because they did not consent to accessing their medical records, did not consent to follow-up questionnaire or did not receive respiratory support. The primary outcome of this study is the incremental net monetary benefit (INB) of HFNC compared with CPAP using a willingness-to-pay threshold of £20,000 per QALY gain. INB is calculated based on total costs and quality adjusted life years (QALYs) at 6 months. The findings suggest modest heterogeneity in cost-effectiveness of HFNC compared with CPAP at the subgroup level, while greater heterogeneity is detected at the individual level. The estimated overall INB of HFNC is smaller than the INB for patients with better baseline status suggesting that HFNC can be more cost-effective among less severely ill patients.

Continuous Positive Airway Pressure versus Nasal Intermittent Positive Pressure Ventilation in Preterm Neonates: What if Mean Airway Pressures Were Equivalent?

Respiratory support for preterm neonates in modern neonatal intensive care units is predominantly with the use of noninvasive interfaces. Continuous positive airway pressure (CPAP) and nasal intermittent positive pressure ventilation (NIPPV) are the prototypical and most commonly utilized forms of noninvasive respiratory support, and each has unique gas flow characteristics. In meta-analyses of clinical trials till date, NIPPV has been shown to likely reduce respiratory failure and need for intubation compared to CPAP. However, a significant limitation of the included studies has been the higher mean airway pressures used during NIPPV. Thus, it is unclear to what extent any benefits seen with NIPPV are due to the cyclic pressure application versus the higher mean airway pressures. In this review, we elaborate on these limitations and summarize the available evidence comparing NIPPV and CPAP at equivalent mean airway pressures. Finally, we call for further studies comparing noninvasive respiratory support modes at equal mean airway pressures. KEY POINTS: · Most current literature on CPAP vs. NIPPV in preterm neonates is confounded by use of higher mean airway pressures during NIPPV.. · In this review, we summarize existing evidence on CPAP vs. NIPPV at equivalent mean airway pressures.. · We call for future research on noninvasive support modes to account for mean airway pressures..

Possibility of using non-invasive modes of respiratory support at the stages of interhospital transportation of newborns

Introduction. Respiratory support remains the most common procedure performed by neonatal transport team specialists. Non-invasive ventilation is a very common method of respiratory support for newborns, reducing the incidence of chronic lung disease. However, the safety and efficacy of this type of support during transportation remain controversial. The aim of the work is to determine the current state of the problem of non-invasive respiratory support in newborns in the initial medical organization, at the stage of pre-transport preparation and during transportation. Materials and methods. Literature sources were searched and selected in PubMed and eLibrary. The following queries were used for the search: nasal continuous positive airway pressure, non invasive ventilation, neonate, newborn, patient transportation, transport, transfer. Types of studies considered: retrospective observational studies, prospective studies (randomized, quasi-randomized, non-randomized), systematic reviews, meta-analyses, clinical protocols. Depth of search − 20 years. The total number of publications included in the review was 61, including 29 studies directly related to the use of noninvasive ventilation in interhospital neonatal transport. Results and discussion. Non-invasive respiratory support is one of the priority and actively used methods of therapy of respiratory disorders of various genesis in neonatology. Nasal CPAP is used both independently and in conjunction with various methods of surfactant administration, reducing the risk of a combined outcome “death or chronic lung disease”. It is recommended both as a method of starting respiratory support and as an intermediate option to increase the probability of successful extubation. There is limited experience with non-invasive respiratory support during interhospital transport of neonates. The available studies suggest that when patients are selected rationally and reasonable criteria are applied to administer nCPAP en route, this method of respiratory support is safe, effective, maintains the benefits of spontaneous breathing, and reduces the duration of intensive care. The small number and poor design quality of studies in this direction do not allow at this stage to form evidence-based recommendations. Conclusion. Medical evacuation of newborns from 1−2 level institutions to level 3 organization with nCPAP is safe and has a number of potential benefits. Existing recommendations are empirical, and there are exceptionally few studies evaluating the validity of such recommendations.

Invasive and non-invasive ventilatory strategies for early and evolving bronchopulmonary dysplasia

In the age of surfactant and antenatal steroids, neonatal care has improved outcomes of preterm infants dramatically. Since the early 2000’s neonatologists have strived to decrease bronchopulmonary dysplasia (BPD) by decreasing ventilator-associated lung injury and utilizing many novel modes of non-invasive respiratory support. After the initial success with nasal continuous positive airway pressure, it was established that discontinuing invasive ventilation early in favor of non-invasive respiratory support is the most effective way to reduce the incidence of BPD.In this review, we discuss the management of the preterm lung from the time of delivery, through the phases of respiratory distress syndrome (early BPD) and then evolving BPD. The goal remains to optimize respiratory support of the preterm lung while minimizing ventilator-associated lung injury and oxygen toxicity. A multidisciplinary approach involving the medical team and family is quintessential in reaching this goal and involves adequate respiratory support, optimizing nutrition and fluid balance as well as preventing infections.

State of the art on neonatal noninvasive respiratory support: How physiological and technological principles explain the clinical outcomes.

Noninvasive respiratory support has gained significant popularity in neonatal units because of its potential to reduce lung injury associated with invasive mechanical ventilation. To minimize lung injury, clinicians aim to apply fornoninvasive respiratory support as early as possible. However, the physiological background and the technology behind such support modes are not always clear, and many open questions remain regarding the indications of use and clinical outcomes. This narrative review discusses the currently available evidence for various noninvasive respiratory support modes applied in Neonatal Medicine in terms of physiological effects and indications. Reviewed modes include nasal continuous positive airway pressure, nasal high-flow therapy, noninvasive high-frequency oscillatory ventilation, nasal intermittent positive pressure ventilation (NIPPV), synchronized NIPPV and noninvasive neurally adjusted ventilatory assist. To enhance clinicians' awareness of each support mode's strengths and limitations, we summarize technical features related to the functioning mechanisms of devices and the physical properties of the interfaces commonly used for providing noninvasive respiratory support to neonates. We finally address areas of current controversy and suggest possible areas of research for implementing noninvasive respiratory support in neonatal intensive care units.

Association of Extubation Failure Rates With High-Flow Nasal Cannula, Continuous Positive Airway Pressure, and Bilevel Positive Airway Pressure vs Conventional Oxygen Therapy in Infants and Young Children

Extubation failure (EF) has been associated with worse outcomes in critically ill children. The relative efficacy of different modes of noninvasive respiratory support (NRS) to prevent EF is unknown. To study the reported relative efficacy of different modes of NRS (high-flow nasal cannula [HFNC], continuous positive airway pressure [CPAP], and bilevel positive airway pressure [BiPAP]) compared to conventional oxygen therapy (COT). MEDLINE, Embase, and CINAHL Complete through May 2022. Randomized clinical trials that enrolled critically ill children receiving invasive mechanical ventilation for more than 24 hours and compared the efficacy of different modes of postextubation NRS. Random-effects models were fit using a bayesian network meta-analysis framework. Between-group comparisons were estimated using odds ratios (ORs) or mean differences with 95% credible intervals (CrIs). Treatment rankings were assessed by rank probabilities and the surface under the cumulative rank curve (SUCRA). The primary outcome was EF (reintubation within 48 to 72 hours). Secondary outcomes were treatment failure (TF, reintubation plus NRS escalation or crossover to another NRS mode), pediatric intensive care unit (PICU) mortality, PICU and hospital length of stay, abdominal distension, and nasal injury. A total of 11 615 citations were screened, and 9 randomized clinical trials with a total of 1421 participants were included. Both CPAP and HFNC were found to be more effective than COT in reducing EF and TF (CPAP: OR for EF, 0.43; 95% CrI, 0.17-1.0 and OR for TF 0.27, 95% CrI 0.11-0.57 and HFNC: OR for EF, 0.64; 95% CrI, 0.24-1.0 and OR for TF, 0.34; 95% CrI, 0.16- 0.65). CPAP had the highest likelihood of being the best intervention for both EF (SUCRA, 0.83) and TF (SUCRA, 0.91). Although not statistically significant, BiPAP was likely to be better than COT for preventing both EF and TF. Compared to COT, CPAP and BiPAP were reported as showing a modest increase (approximately 3%) in nasal injury and abdominal distension. The studies included in this systematic review and network meta-analysis found that compared with COT, EF and TF rates were lower with modest increases in abdominal distension and nasal injury. Of the modes evaluated, CPAP was associated with the lowest rates of EF and TF.

Detection of differences of cardiorespiratory metrics between non-invasive respiratory support modes using machine learning methods

Many preterm infants require invasive mechanical ventilation in the first days of life. Once ventilation is removed, non-invasive respiratory support assists the transition to spontaneous breathing. Three common support modes are Nasal Continuous Positive Airway Pressure (CPAP), Non-Invasive Neurally Adjusted Ventilatory Assist (NIV-NAVA), and Nasal Intermittent Positive Pressure Ventilation (NIPPV). Cardiorespiratory behavior under these supports is not well understood. We hypothesized that if behavior changed with the support, then machine learning should be able to distinguish them, and the most discriminatory features would indicate how the behaviors differ. To test this, we recorded cardiorespiratory signals from infants during CPAP, NIV-NAVA, and NIPPV immediately following extubation. Forty-five metrics related to the amplitude and frequency of these signals were computed at each time and six summary statistics computed for each metric. The feature set was reduced by principal component analysis and used to train a Random Forest classifier. We found that (1) Classification of the three modes performed poorly (accuracy = 58.6%); (2) Classification of CPAP from NIV-NAVA or NIPPV performed well (accuracy = 81.5%). Thus, cardiorespiratory behavior during CPAP is significantly different from NIV-NAVA or NIPPV. The features with the greatest discriminatory power were related to the amplitude of respiratory movements and the correlation between the ribcage and abdomen movements. These results serve to direct further investigation with clinical relevance. Thus, infants with shallow breathing may benefit from the support with largest amplitude respiratory movements, while infants with asynchronous chest and abdominal movements may benefit from the modality with the most correlated movements.

Noninvasive Respiratory Support following Extubation in Preterm Infants.

The use of noninvasive respiratory support is widespread in newborn infants with respiratory distress. As the use of noninvasive respiratory support has increased, so too have the number of modes available. Among these modes, low-flow nasal cannula and nasal continuous positive airway pressure (NCPAP) have been used for a long time and have known efficacy and safety in newborn infants needing respiratory support. High-flow nasal cannula (HFNC) has been newly introduced, and its efficacy and safety are currently being investigated. Bilevel nasal continuous positive airway pressure and nasal intermittent positive-pressure ventilation are often used when NCPAP or HFNC therapy fails. More recently, noninvasive neurally adjusted ventilatory assist and noninvasive high-frequency oscillatory ventilation have been introduced, and their efficacy and safety are currently under evaluation. Comparison of the efficacy and safety among various modes of noninvasive respiratory support after extubation in preterm infants is helping to clarify the position of each mode. The clarification of the strength and characteristics of each device within the same mode will become important as a future direction of noninvasive respiratory support after extubation in such subjects. However, no research has yet reported on long-term outcomes in preterm infants receiving noninvasive respiratory support after extubation. Therefore, further research is needed to evaluate the long-term outcomes.

Respiratory support strategies in the management of severe, longstanding bronchopulmonary dysplasia.

Despite efforts to minimize ventilator-induced lung injury, some preterm infants require positive pressure support after 36 weeks' post-menstrual age. Infants with severe BPD typically experience progressive mismatch of ventilation and perfusion, which manifests as respiratory distress, hypoxemia in room air, hypercarbia, and growth failure. Lung compliance varies, but lung resistance generally increases with prolonged exposure to positive pressure ventilation and other sources of inflammation. Serial lung radiographs reveal a heterogeneous pattern, with areas of both hyperinflation and atelectasis; in extreme cases, macrocystic changes may be noted. Efforts to wean the respiratory support are often unsuccessful, and trials of high frequency ventilation, exogenous corticosteroids, and diuretics are common. The incidence of pulmonary hypertension increases with the severity of BPD, as does the mortality rate. Therefore, periodic screening and efforts to mitigate the risk of PH is fundamental to the management of longstanding BPD. Failure of conventional, lung-protective strategies (e.g., high rate/low tidal-volume and/or high frequency ventilation) warrants consideration of ventilatory strategies individualized to the disease physiology. Non-invasive modes of respiratory support may be successful in infants with mild to moderate BPD phenotypes. However, infants with moderate to severe BPD phenotypes often require invasive respiratory support, and pressure-limited or volume-targeted conventional ventilation may be better suited to the physiology than high-frequency ventilation. The consistent provision of adequate support is fundamental to the management of longstanding BPD and is best achieved with a stepwise increase in ventilator support until comfortable spontaneous respirations are achieved. Adequately supported infants typically experience improvements in both oxygenation and ventilation, which, if sustained, may arrest and generally reverses the course of a potentially lethal lung disease. Care should be individualized to address the most likely pulmonary mechanics, including variable lung compliance, elevated airway resistance, and variable airway obstruction.

Sleep-Wake Cycle in Newborns with 28 - 32 Weeks of Gestation: A Comparative Study of Nasal Continuous Positive Airway Pressure and Nasal Intermittent Positive Pressure Ventilation

Background: Sleep is a central component of brain development. Preterm neonates follow an exclusive sleep-wake rhythm in a way that they can sleep up to 22 hours per day, 70% of which is spent during active sleep. Sleep can create a period of time for the production of active neurotransmitters, which can enhance brain development flexibility. Objectives: It is a matter of controversy whether the widespread use of nonsynchronized nasal intermittent positive pressure ventilation (NIPPV) in neonatal intensive care units and the concerns over the use of nonrespiratory support can affect the quantity and quality of the sleep-wake cycle (SWC). Therefore, the current study aimed to compare two types of intervention, nasal continuous positive airway pressure (nCPAP) and NIPPV, during the SWC. Methods: The present randomized controlled trial crossover study was conducted on neonates with 28 - 32 weeks of gestation receiving nCPAP who had been administered surfactant after being diagnosed with respiratory distress syndrome in Shahid Beheshti hospital in Isfahan, Iran, within March 2018 to August 2020. The SWC was monitored using cerebral function monitoring for all study participants. Results: The present study showed no significant difference between the number of SWCs during nCPAP and NIPPV. The duration of SWCs when participants received nCPAP was significantly higher than when they received NIPPV intervention. Rapid eye movement (REM) sleep duration was significantly longer during nCPAP respiratory support. Furthermore, NonREM sleep duration was significantly longer in nCPAP respiratory support. Conclusions: Noninvasive respiratory support modes can affect the SWC, with nCPAP being the favored in the present study. Nonetheless, further studies are required to be performed in this regard.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Effect of High-Flow Nasal Cannula Therapy vs Continuous Positive Airway Pressure Therapy on Liberation From Respiratory Support in Acutely Ill Children Admitted to Pediatric Critical Care Units

The optimal first-line mode of noninvasive respiratory support for acutely ill children is not known. To evaluate the noninferiority of high-flow nasal cannula therapy (HFNC) as the first-line mode of noninvasive respiratory support for acute illness, compared with continuous positive airway pressure (CPAP), for time to liberation from all forms of respiratory support. Pragmatic, multicenter, randomized noninferiority clinical trial conducted in 24 pediatric critical care units in the United Kingdom among 600 acutely ill children aged 0 to 15 years who were clinically assessed to require noninvasive respiratory support, recruited between August 2019 and November 2021, with last follow-up completed in March 2022. Patients were randomized 1:1 to commence either HFNC at a flow rate based on patient weight (n = 301) or CPAP of 7 to 8 cm H2O (n = 299). The primary outcome was time from randomization to liberation from respiratory support, defined as the start of a 48-hour period during which a participant was free from all forms of respiratory support (invasive or noninvasive), assessed against a noninferiority margin of an adjusted hazard ratio of 0.75. Seven secondary outcomes were assessed, including mortality at critical care unit discharge, intubation within 48 hours, and use of sedation. Of the 600 randomized children, consent was not obtained for 5 (HFNC: 1; CPAP: 4) and respiratory support was not started in 22 (HFNC: 5; CPAP: 17); 573 children (HFNC: 295; CPAP: 278) were included in the primary analysis (median age, 9 months; 226 girls [39%]). The median time to liberation in the HFNC group was 52.9 hours (95% CI, 46.0-60.9 hours) vs 47.9 hours (95% CI, 40.5-55.7 hours) in the CPAP group (absolute difference, 5.0 hours [95% CI -10.1 to 17.4 hours]; adjusted hazard ratio 1.03 [1-sided 97.5% CI, 0.86-∞]). This met the criterion for noninferiority. Of the 7 prespecified secondary outcomes, 3 were significantly lower in the HFNC group: use of sedation (27.7% vs 37%; adjusted odds ratio, 0.59 [95% CI, 0.39-0.88]); mean duration of critical care stay (5 days vs 7.4 days; adjusted mean difference, -3 days [95% CI, -5.1 to -1 days]); and mean duration of acute hospital stay (13.8 days vs 19.5 days; adjusted mean difference, -7.6 days [95% CI, -13.2 to -1.9 days]). The most common adverse event was nasal trauma (HFNC: 6/295 [2.0%]; CPAP: 18/278 [6.5%]). Among acutely ill children clinically assessed to require noninvasive respiratory support in a pediatric critical care unit, HFNC compared with CPAP met the criterion for noninferiority for time to liberation from respiratory support. ISRCTN.org Identifier: ISRCTN60048867.

Effect of High-Flow Nasal Cannula Therapy vs Continuous Positive Airway Pressure Following Extubation on Liberation From Respiratory Support in Critically Ill Children

The optimal first-line mode of noninvasive respiratory support following extubation of critically ill children is not known. To evaluate the noninferiority of high-flow nasal cannula (HFNC) therapy as the first-line mode of noninvasive respiratory support following extubation, compared with continuous positive airway pressure (CPAP), on time to liberation from respiratory support. This was a pragmatic, multicenter, randomized, noninferiority trial conducted at 22 pediatric intensive care units in the United Kingdom. Six hundred children aged 0 to 15 years clinically assessed to require noninvasive respiratory support within 72 hours of extubation were recruited between August 8, 2019, and May 18, 2020, with last follow-up completed on November 22, 2020. Patients were randomized 1:1 to start either HFNC at a flow rate based on patient weight (n = 299) or CPAP of 7 to 8 cm H2O (n = 301). The primary outcome was time from randomization to liberation from respiratory support, defined as the start of a 48-hour period during which the child was free from all forms of respiratory support (invasive or noninvasive), assessed against a noninferiority margin of an adjusted hazard ratio (HR) of 0.75. There were 6 secondary outcomes, including mortality at day 180 and reintubation within 48 hours. Of the 600 children who were randomized, 553 children (HFNC, 281; CPAP, 272) were included in the primary analysis (median age, 3 months; 241 girls [44%]). HFNC failed to meet noninferiority, with a median time to liberation of 50.5 hours (95% CI, 43.0-67.9) vs 42.9 hours (95% CI, 30.5-48.2) for CPAP (adjusted HR, 0.83; 1-sided 97.5% CI, 0.70-∞). Similar results were seen across prespecified subgroups. Of the 6 prespecified secondary outcomes, 5 showed no significant difference, including the rate of reintubation within 48 hours (13.3% for HFNC vs 11.5 % for CPAP). Mortality at day 180 was significantly higher for HFNC (5.6% vs 2.4% for CPAP; adjusted odds ratio, 3.07 [95% CI, 1.1-8.8]). The most common adverse events were abdominal distension (HFNC: 8/281 [2.8%] vs CPAP: 7/272 [2.6%]) and nasal/facial trauma (HFNC: 14/281 [5.0%] vs CPAP: 15/272 [5.5%]). Among critically ill children requiring noninvasive respiratory support following extubation, HFNC compared with CPAP following extubation failed to meet the criterion for noninferiority for time to liberation from respiratory support. isrctn.org Identifier: ISRCTN60048867.

Oxygen Toxicity to the Immature Lung-Part II: The Unmet Clinical Need for Causal Therapy.

Oxygen toxicity continues to be one of the inevitable injuries to the immature lung. Reactive oxygen species (ROS) production is the initial step leading to lung injury and, subsequently, the development of bronchopulmonary dysplasia (BPD). Today, BPD remains the most important disease burden following preterm delivery and results in life-long restrictions in lung function and further important health sequelae. Despite the tremendous progress in the pathomechanistic understanding derived from preclinical models, the clinical needs for preventive or curative therapies remain unmet. This review summarizes the clinical progress on guiding oxygen delivery to the preterm infant and elaborates future directions of research that need to take into account both hyperoxia and hypoxia as ROS sources and BPD drivers. Many strategies have been tested within clinical trials based on the mechanistic understanding of ROS actions, but most have failed to prove efficacy. The majority of these studies were tested in an era before the latest modes of non-invasive respiratory support and surfactant application were introduced or were not appropriately powered. A comprehensive re-evaluation of enzymatic, antioxidant, and anti-inflammatory therapies to prevent ROS injury is therefore indispensable. Strategies will only succeed if they are applied in a timely and vigorous manner and with the appropriate outcome measures.

Nasal high-frequency jet ventilation (NHFJV) as a novel means of respiratory support in extremely low birth weight infants.

ObjectiveDescribe our experience of successfully using nasal high-frequency jet ventilation (NHFJV) in extremely low birth weight infants with respiratory failure.Study designA retrospective review was conducted on 16 infants with birth weights <1000 g who received NHFJV from 2015 to 2019. Successful use was defined as avoiding intubation for at least 72 hours and demonstrating tolerance after being placed on NHFJV.ResultsMedian gestational age was 24.5 weeks (IQR 24, 25), and weight at the start of NHFJV 1090 g (IQR 905, 1250). NHFJV was used successfully in 13/16 (81%) infants with a median duration of 7 days (IQR 3, 12). Days on invasive (30 vs. 186) and noninvasive (46 vs. 81) ventilation were shorter when compared to those who failed the use of NHFJV.ConclusionThis is the first reported case series for the successful use of NHFJV. Our study highlights the feasibility of a potential new mode of noninvasive respiratory support.

Efficacy of noninvasive respiratory support modes for primary respiratory support in preterm neonates with respiratory distress syndrome: Systematic review and network meta-analysis.

To compare the efficacy of different noninvasive respiratory support (NRS) modes for primary respiratory support of preterm infants with respiratory distress syndrome (RDS). Systematic review and network meta-analysis using the Bayesian random-effects approach. MEDLINE, EMBASE, and CENTRAL were searched. High flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), bilevel CPAP (BiPAP), noninvasive positive pressure ventilation (NIPPV). Requirement of invasive mechanical ventilation (MV), any treatment failure. A total of 35 studies including 4078 neonates were included. NIPPV was more effective in decreasing the requirement of MV than CPAP (risk ratios [95% credible interval]: 0.60 [0.44, 0.77]) and HFNC [0.66 (0.43, 0.97)]. Surface under the cumulative ranking curve (SUCRA) for NIPPV, BiPAP, HFNC, and CPAP were 0.95, 0.59, 0.32, and 0.13. For the outcome of treatment failure, both NIPPV and BiPAP were more efficacious compared to CPAP and HFNC (0.56 [0.44, 0.71] {NIPPV vs CPAP}, 0.69 [0.51, 0.93] {BiPAP vs CPAP}, 0.42 [0.30, 0.63] {NIPPV vs HFNC}, 0.53 [0.35, 0.81] {BiPAP vs HFNC}). The SUCRA for NIPPV, BiPAP, CPAP, and HFNC were 0.96, 0.70, 0.32, and 0.01. NIPPV was associated with a reduced risk of air leak compared to BiPAP and CPAP (0.36 [0.16, 0.73]; 0.54 [0.30, 0.87], respectively). NIPPV resulted in lesser incidence of bronchopulmonary dysplasia or mortality when compared to CPAP (0.74 [0.52, 0.98]). Nasal injury was lesser with HFNC compared to CPAP (0.15 [0.01, 0.60]). Most effective primary mode of NRS in preterm neonates with RDS was NIPPV.

Efficacy of noninvasive respiratory support modes as postextubation respiratory support in preterm neonates: A systematic review and network meta-analysis.

Multiple noninvasive respiratory support (NRS) modalities are used for postextubation support in preterm neonates. Seven NRS modalities were compared-constant flow continuous positive airway pressure (CPAP) (CF-CPAP) (bubble CPAP; ventilator CPAP), variable flow CPAP (VF-CPAP), high flow nasal cannula (HFNC), synchronized noninvasive positive pressure ventilation (S-NIPPV), nonsynchronized NIPPV (NS-NIPPV), bilevel CPAP (BiPAP), noninvasive high-frequency oscillation ventilation (nHFOV). Systematic review and network meta-analysis (NMA) using the Bayesian random-effects approach. MEDLINE, EMBASE, CENTRAL, WHO-ICTRP were searched. Requirement of invasive mechanical ventilation within 7 days of extubation. A total of 33 studies with 4080 preterm neonates were included. S-NIPPV, NS-NIPPV, nHFOV, and VF-CPAP were more efficacious in preventing reintubation than CF-CPAP (risk ratio [RR] [95% credible intervals {CrI}]: 0.22 [0.12, 0.35]; 0.44 [0.27, 0.67]; 0.42 [0.18, 0.81]; 0.73 [0.52, 0.99]). Surface under the cumulative ranking curve (SUCRA) value ranked S-NIPPV to be the best postextubation intervention (SUCRA: 0.98). S-NIPPV was more effective than NS-NIPPV, BiPAP, VF-CPAP, and HFNC (RR [95% CrI]: 0.52 [0.24, 0.97]; 0.32 [0.14, 0.64]; 0.30 [0.16, 0.50]; 0.24 [0.12, 0.41]). NS-NIPPV resulted in lesser reintubation compared to VF-CPAP and HFNC (RR [95% CrI]: 0.61 [0.36, 0.97]; 0.49 [0.27, 0.80]). BiPAP, VF-CPAP, and HFNC had comparable efficacies. The overall quality of evidence was very low to moderate. Results of this NMA indicate that S-NIPPV might be the most effective and CF-CPAP the least effective NRS modality for preventing extubation failure.

Use of heated humidified high flow nasal cannula for obstructive sleep apnea in infants

ObjectiveHeated humidified high flow nasal cannula (HHHFNC) has gained popularity in the treatment of children with respiratory distress and bronchiolitis in the past decade. Its efficacy as a mode of non-invasive respiratory support has been demonstrated in both adults and children. However, reports on its use in the treatment of obstructive sleep apnea (OSA) in infants are limited. We aimed to evaluate the efficacy of HHHFNC therapy as treatment in infants with OSA. MethodsA retrospective analysis of OSA infants who had undergone polysomnographic titration between 2015 and 2017 was undertaken. Data about the age, gender, AHI, co-morbid conditions and flow used for each patient were retrieved. ResultsTen infants were included in this study (median age 34 weeks; IQR 27–38 weeks). The median optimal HHHFNC flow rate was 8.0 L/min (IQR 6.7–8.0 L/min). HHHFNC significantly reduced median obstructive apnea–hypopnea index (OAHI) from 9.1 (IQR 5.1–19.3) to 0.9 (IQR 0–1.6; P = 0.005) events/h; median obstructive apnea index (OAI) from 5.8 (IQR 1.1–13.4) to 0 (IQR 0–0.9; P = 0.021) events/h; median obstructive hypopnea index (OHI) from 4.1 (IQR 0.9–6.8) to 0.1 (0–0.9; P = 0.017) events/h; and median oxygen saturation (SpO2) nadir increased from 88% (IQR 83–94%) to 94% (IQR 93–96%; P = 0.040). ConclusionHHHFNC significantly reduced respiratory events and improved oxygenation in infants with OSA.