Noninvasive High-frequency Oscillatory Ventilation Research Articles

Non-invasive high-frequency oscillatory ventilation (NHFOV) versus nasal continuous positive airway pressure (NCPAP) for preterm infants: a systematic review and meta-analysis.

To compare the efficacy and safety of non-invasive high-frequency oscillatory ventilation (NHFOV) and nasal continuous positive airway pressure (NCPAP) in preterm infants. The study conducted a comprehensive analysis across three databases, namely EMBASE, MEDLINE and Cochrane Central, to identify randomised controlled trials comparing NHFOV and NCPAP. Statistical analysis was performed using Review Manager V.5.3 software. The primary outcomes of the study were the intubation or reintubation rate in the NHFOV and NCPAP groups. Additionally, secondary outcomes included the partial pressure of carbon dioxide levels and major complications associated with non-invasive respiratory support ventilation. Ten randomised controlled studies, involving 2031 preterm infants, were included in this meta-analysis. When compared with NCPAP, NHFOV demonstrated a significant reduction in the intubation or reintubation rate (p<0.01, relative risk=0.45, 95% CI 0.37 to 0.55), and there was no statistical difference in related complications. In preterm infants, NHFOV appears to be an effective intervention for decreasing the intubation or reintubation rate compared with NCPAP, with no increase in associated complications. CRD42023403968.

Noninvasive high frequency oscillatory ventilation versus noninvasive positive pressure ventilation in preterm neonates after extubation: A randomized controlled trial.

Weaning from mechanical ventilation is a challenging phase of neonatal respiratory support [1]. Choosing efficient and safe noninvasive modality to prevent re-intubation and choosing the optimal time for weaning are key points for weaning success. The aim of the study is to compare the efficiency and safety of noninvasive high frequency oscillatory ventilation (NHFOV) versus noninvasive positive pressure ventilation (NIPPV) as respiratory support after extubation in preterms with respiratory distress syndrome (RDS). Also, the study compared the lung ultrasound findings between these 2 modalities and assessed the use of lung ultrasound score (LUS) as predictor for extubation outcome. This study is a randomized controlled trial conducted on 60 preterm neonates with RDS. Patients were allocated into one of 2 groups: NIPPV or NHFOV as post-extubation noninvasive respiratory support. The 2 groups were compared regarding the incidence of extubation failure within 72 hours from extubation, oxygen needs, duration of application of the noninvasive modality, duration of admission, safety and mortality rate. LUS was assessed pre-extubation and 2 hours post-extubation. The study did not show a difference in re-ventilation rate in NHFOV group (23.3%) compared to NIPPV group (30.0%), p = 0.56t. Oxygen needs were significantly lower in NHFOV group compared to NIPPV groups (0.38±0.11 vs 0.32±0.06, p = 0.007). The duration of the used noninvasive modality, CO2 concentration, LUS, and mortality rate showed statistically insignificant difference between 2 groups. There was a significant correlation between LUS and extubation outcome. NHFOV is a feasible noninvasive modality for respiratory support post-extubation in premature infants. LUS is a good predictor of extubation outcome in neonates.

Effectiveness of Nasal Continuous Positive Airway Pressure vs Nasal Intermittent Positive Pressure Ventilation vs Noninvasive High-Frequency Oscillatory Ventilation as Support After Extubation of Neonates Born Extremely Preterm or With More Severe Respiratory Failure

The NASONE (Nasal Oscillation Post-Extubation) trial showed that noninvasive high-frequency oscillatory ventilation (NHFOV) slightly reduces the duration of invasive mechanical ventilation (IMV) in preterm infants, whereas NHFOV and noninvasive intermittent positive pressure ventilation (NIPPV) result in fewer reintubations than nasal continuous positive airway pressure (NCPAP). It is unknown whether NHFOV is similarly effective in extremely preterm neonates or in those with more severe respiratory failure (based on the duration of previous ventilation and CO2 levels). To clarify whether NHFOV is better than NIPPV and NCPAP in reducing the duration of IMV in extremely preterm neonates or those with severe respiratory failure. This study is a predefined secondary analyses of a multicenter randomized clinical trial that was performed at tertiary academic neonatal intensive care units (NICUs) in China. Participants included neonates enrolled in the NASONE trial between December 2017 and May 2021 and belonging to 3 predefined subgroups: (1) born at less than or equal to 28 weeks' (plus 6 days) gestation, (2) invasively ventilated for more than 1 week from birth, and (3) with CO2 greater than 50 mm Hg before or in the 24 hours after extubation. Data analysis was performed in August 2022. NCPAP, NIPPV, or NHFOV since the first extubation and until NICU discharge, with airway pressure higher in NHFOV than in NIPPV and than in NCPAP. The co-primary outcomes were total duration of IMV during the NICU stay, need for reintubation, and ventilator-free days calculated as per the original trial protocol. Outcomes were analyzed on an intention-to-treat basis as for the whole trial, and subgroup analyses followed the original statistical plan. Among 1137 preterm infants, 455 (279 boys [61.3%]) were born at 28 weeks' gestation or less, 375 (218 boys [58.1%]) underwent IMV for more than 1 week from birth, and 307 (183 boys [59.6%]) had CO2 greater than 50 mm Hg before or in the 24 hours after extubation. Both NIPPV and NHFOV were associated with significantly fewer reintubations (risk difference range, -28% [95% CI, -39% to -17%] to -15% [95% CI, -25% to -4%]; number needed to treat, 3-7 infants) and early reintubations (risk difference range, -24% [95% CI, -35% to -14%] to -20% [95% CI, -30% to -10%]) than NCPAP, and these reintubations were less frequently due to refractory hypoxemia. IMV was shorter in the NIPPV and NHFOV groups (mean difference range, -5.0 days [95% CI, -6.8 to -3.1 days] to -2.3 days [95% CI, -4.1 to -0.4 days]) than in the NCPAP group. Co-primary outcomes were not different between NIPPV and NHFOV; there was no significant interaction effect. Infants in the NHFOV group showed significantly less moderate-to-severe bronchopulmonary dysplasia than infants in the NCPAP group (range, -12% to -10%; number needed to treat, 8-9 infants) and better postextubation gas exchange in all subgroups. The 3 interventions were provided at different mean airway pressure and were equally safe. The subgroup analyses of extremely preterm or more ill infants confirm the results obtained in the whole population: NIPPV and NHFOV appeared equally effective in reducing duration of IMV compared with NCPAP. ClinicalTrials.gov Identifier: NCT03181958.

Efficacy of noninvasive high-frequency oscillatory ventilation versus nasal intermittent positive pressure ventilation as post-extubation respiratory support in preterm infants: a Meta analysis

To systematically evaluate the efficacy and safety of noninvasive high-frequency oscillatory ventilation (NHFOV) versus nasal intermittent positive pressure ventilation (NIPPV) as post-extubation respiratory support in preterm infants. China National Knowledge Infrastructure, Wanfang Data, Chinese Journal Full-text Database, China Biology Medicine disc, PubMed, Web of Science, and the Cochrane Library were searched for articles on NHFOV and NIPPV as post-extubation respiratory support in preterm infants published up to August 31, 2022. RevMan 5.4 software and Stata 17.0 software were used for a Meta analysis to compare related indices between the NHFOV and NIPPV groups, including reintubation rate within 72 hours after extubation, partial pressure of carbon dioxide (PCO2) at 6-24 hours after switch to noninvasive assisted ventilation, and the incidence rates of bronchopulmonary dysplasia (BPD), air leak, nasal damage, periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). A total of 9 randomized controlled trials were included. The Meta analysis showed that compared with the NIPPV group, the NHFOV group had significantly lower reintubation rate within 72 hours after extubation (RR=0.67, 95%CI: 0.52-0.88, P=0.003) and PCO2 at 6-24 hours after switch to noninvasive assisted ventilation (MD=-4.12, 95%CI: -6.12 to -2.13, P<0.001). There was no significant difference between the two groups in the incidence rates of complications such as BPD, air leak, nasal damage, PVL, IVH, and ROP (P>0.05). Compared with NIPPV, NHFOV can effectively remove CO2 and reduce the risk of reintubation, without increasing the incidence of complications such as BPD, air leak, nasal damage, PVL, and IVH, and therefore, it can be used as a sequential respiratory support mode for preterm infants after extubation.

Non-invasive high-frequency oscillatory ventilation versus nasal continuous positive airway pressure in extremely preterm infants with respiratory distress syndrome: study protocol for a multicentre randomised controlled, superiority trial

IntroductionTracheal intubation and invasive mechanical ventilation (IMV) significantly decreased mortality of respiratory distress syndrome (RDS) in extremely preterm infants (28 weeks’ gestational age) whereas bronchopulmonary dysplasia increased. Thus, consensus guidelines...

Use of NHFOV vs. NIPPV for the respiratory support of preterm newborns after extubation: A meta-analysis.

This meta-analysis evaluated and compared the efficacy and safety of noninvasive high-frequency oscillatory ventilation (NHFOV) and nasal intermittent positive-pressure ventilation (NIPPV) for preterm newborns after extubation. We searched the PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, Wanfang and VIP databases from inception to August 28, 2022. Randomized controlled trials (RCTs) that evaluated and compared the efficacy and safety of NHFOV and NIPPV in newborns were included in the review and meta-analysis, which followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Eight studies involving 1,603 patients were included. Compared with NIPPV, NHFOV could reduce the reintubation rates (RR = 0.68, 95% CI 0.53, 0.86, P = 0.002). Subgroup analysis showed that the significant difference was found in reintubation rates within 72 h (RR = 0.48, 95% CI 0.32, 0.73, P = 0.0005). NHFOV also could decrease the duration of non-invasive ventilation (standard mean difference (SMD) = -1.52, 95% CI -2.58, -0.45, P = 0.005). However, all included studies had a high risk of bias, and the overall quality of the evidence of the outcomes was low or very low. In our study, compared with NIPPV, NHFOV seems to reduce the reintubation rates without increasing adverse outcomes. Nevertheless, definite recommendations cannot be made based on the quality of the published evidence.

Non-invasive high frequency oscillatory ventilation inhibiting respiratory motion in healthy volunteers

Precision radiotherapy needs to manage organ movements to prevent critical organ injury. The purpose of this study is to examine the feasibility of motion control of the lung by suppressing respiratory motion. The non-invasive high frequency oscillatory ventilation (NIHFOV) is a technique commonly used in the protection of lung for patients with acute lung disease. By using a very high respiratory frequency and a low tidal volume, NIHFOV allows gas exchange, maintains a constant mean airway pressure and minimizes the respiratory movements. We tested healthy volunteers NIHFOV to explore the optimal operational parameter setting and the best possible motion suppression achievable. This study was conducted with the approval of Institutional Review Boards of the Wuwei Cancer hospital (approval number: 2021-39) and carried out in accordance with Declaration of Helsinki. The study comprises two parts. Twenty three healthy volunteers participated in the first part of the study. They had 7 sessions of training with the NIHFOV. The duration of uninterrupted, continuous breathing under the NIHFOV and the optimal operational machine settings were defined. Eight healthy volunteers took part in the second part of the study and underwent 4-dimensional CT (4DCT) scanning with and without NIHFOV. Their respiratory waveform under free breathing (FB) and NIHFOV were recorded. The maximum range of motion of the diaphragm from the two scannings was compared, and the variation of bilateral lung volume was obtained to evaluate the impact of NIHFOV technique on lung volume. The following data were collected: comfort score, transcutaneous partial pressure of oxygen (PtcO2), transcutaneous partial pressure of carbon dioxide (PtcCO2), and pulse rate. Data with and without NIHFOV were compared to evaluate its safety, physiological impacts and effect of lung movement suppression. All the volunteers completed the training sessions eventlessly, demonstrating a good tolerability of the procedure. The median NIHFOV-on time was 32 min (22–45 min), and the maximum range of motion in the cephalic-caudal direction was significantly reduced on NIHFOV compared with FB (1.8 ± 0.8 cm vs 0.3 ± 0.1 cm, t = − 3.650, P = 0.003); the median range of motion was only 0.3 ± 0.1 cm on NIHFOV with a good reproducibility. The variation coefficient under NIHFOV of the right lung volume was 2.4% and the left lung volume was 9.2%. The PtcO2 and PtcCO2 were constantly monitored during NIHFOV. The medium PtcCO2 under NIHFOV increased lightly by 4.1 mmHg (interquartile range [IQR], 4–6 mmHg) compared with FB (t = 17.676, P < 0.001). No hypercapnia was found, PtcO2 increased significantly in all volunteers during NIHFOV (t = 25.453, P < 0.001). There was no significant difference in pulse rate between the two data sets (t = 1.257, P = 0.233). NIHFOV is easy to master in healthy volunteers to minimize respiratory movement with good tolerability and reproducibility. It is a feasible approach for lung motion control and could potentially be applied in accurate radiotherapy including carbon-ion radiotherapy through suppression of respiratory movement.

Noninvasive high-frequency oscillatory ventilation versusnasal intermittent positive pressure ventilation for preterm infants as an extubation support: A systematic review and meta-analysis.

We aimed to explore whether noninvasive high-frequency oscillatory ventilation(NHFOV) could reduce the incidence of reintubation compared with nasal intermittent positive pressure ventilation(NIPPV) in the postextubation phase of preterm infants. Randomized controlled trials of NHFOV versusNIPPV were searched in PubMed, EMBASE, Cochrane Central, and MEDLINE. Meta-analysis was performed using Review Manager 5.3. Four randomized controlled trials including 1138 preterm infants were included in this study. Compared with NIPPV, NHFOV reduced the incidence of reintubation in the post-extubation phase of preterm infants (p = 0.01, RR = 0.72, 95% confidence interval (CI): 0.56∼0.94), and no heterogeneity was found in the four studies (p = 0.55, I2 = 0%). In the sensitivity analysis, the result showed that there was no significant difference in the incidence of reintubation between NHFOV and NIPPV after excluding one study (p = 0. 05, RR = 0.76 95%CI: 0.58∼1.00), and no heterogeneity was found in the other three studies (p = 0.95, I2 = 0%). There was no statistical difference between NHFOV and NIPPV in BPD, air leak, IVH (≥Grade III) and mortality. Among mechanically ventilated preterm infants, compared with NIPPV, NHFOV was potentially beneficial to reduce the incidence of reintubation after extubation and did not increase the risk of complications.

Evaluation of three non-invasive ventilation modes after extubation in the treatment of preterm infants with severe respiratory distress syndrome.

To evaluate the efficacy and safety of three different modes of non-invasive post-extubation ventilation support in preterm infants with severe respiratory distress syndrome (RDS). Infants diagnosed with severe RDS after extubation were randomized to receive nasal continuous positive airway pressure ventilation (NCPAP), nasal intermittent positive pressure ventilation (NIPPV), and non-invasive high-frequency oscillatory ventilation (NHFO). The clinical outcomes and complications of infants in different groups were recorded. In infants less than 32 weeks, NCPAP had a significant increase in extubation failure when compared with NIPPV and NHFO, and the gastrointestinal feeding time, the numbers of apnea, and hospitalization costs in the NCPAP group were significantly higher. The incidence of complications was also higher in the NCPAP group. There was no difference in clinical outcomes and complications in infants greater than 32 weeks. For infants with severe RDS less than 32 weeks after extubation, NIPPV and NHFO are more cost-effective in comparison to NCPAP.

Noninvasive High-Frequency Oscillatory Ventilation vs Nasal Continuous Positive Airway Pressure vs Nasal Intermittent Positive Pressure Ventilation as Postextubation Support for Preterm Neonates in China

Several respiratory support techniques are available to minimize the use of invasive mechanical ventilation (IMV) in preterm neonates. It is unknown whether noninvasive high-frequency oscillatory ventilation (NHFOV) is more efficacious than nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive pressure ventilation (NIPPV) in preterm neonates after their first extubation. To test the hypothesis that NHFOV is more efficacious than NCPAP or NIPPV in reducing IMV after extubation and until neonatal intensive care unit discharge among preterm neonates. This multicenter, pathophysiology-based, assessor-blinded, 3-group, randomized clinical trial was conducted in 69 tertiary referral neonatal intensive care units in China, recruiting participants from December 1, 2017, to May 31, 2021. Preterm neonates who were between the gestational age of 25 weeks plus 0 days and 32 weeks plus 6 days and were ready to be extubated were randomized to receive NCPAP, NIPPV or NHFOV. Data were analyzed on an intention-to-treat basis. The NCPAP, NIPPV, or NHFOV treatment was initiated after the first extubation and lasted until discharge. Primary outcomes were total duration of IMV, need for reintubation, and ventilator-free days. These outcomes were chosen to describe the effect of noninvasive ventilation strategy on the general need for IMV. A total of 1440 neonates (mean [SD] age at birth, 29.4 [1.8] weeks; 860 boys [59.7%]) were included in the trial. Duration of IMV was longer in NIPPV (mean difference, 1.2; 95% CI, 0.01-2.3 days; P = .04) and NCPAP (mean difference, 1.5 days; 95% CI, 0.3-2.7 days; P = .01) compared with NHFOV. Neonates who were treated with NCPAP needed reintubations more often than those who were treated with NIPPV (risk difference: 8.1%; 95% CI, 2.9%-13.3%; P = .003) and NHFOV (risk difference, 12.5%; 95% CI, 7.5%-17.4%; P < .001). There were fewer ventilator-free days in neonates treated with NCPAP than in those treated with NIPPV (median [25th-75th percentile] difference, -3 [-6 to -1] days; P = .01). There were no differences between secondary efficacy or safety outcomes, except for the use of postnatal corticosteroids (lower in NHFOV than in NCPAP group; risk difference, 7.3%; 95% CI, 2.6%-12%; P = .002), weekly weight gain (higher in NHFOV than in NCPAP group; mean difference, -0.9 g/d; 95% CI, -1.8 to 0 g/d; P = .04), and duration of study intervention (shorter in NHFOV than in NIPPV group; median [25th-75th percentile] difference, -1 [-3 to 0] days; P = .01). Results of this trial indicated that NHFOV, if used after extubation and until discharge, slightly reduced the duration of IMV in preterm neonates, and both NHFOV and NIPPV resulted in a lower risk of reintubation than NCPAP. All 3 respiratory support techniques were equally safe for this patient population. ClinicalTrials.gov Identifier: NCT03181958.

Non-invasive High-Frequency Oscillatory Ventilation as Initial Respiratory Support for Preterm Infants With Respiratory Distress Syndrome.

Objectives: The aim of this study was to investigate the safety and feasibility of nHFOV as initial respiratory support in preterm infants with RDS.Methods: This study retrospectively analyzed the clinical data of 244 premature infants with RDS who were treated in our hospital from January 2016 to January 2019 and divided into the nHFOV group (n = 115) and the BiPAP group (n = 129) based on the initial respiratory support method.Results: Respiratory outcomes showed that the rate of NIV failure during the first 72 hours of life in the nHFOV group was significantly lower than that in the BiPAP group. The time of NIV in the nHFOV group was significantly shorter than that in the BiPAP group. The time of supplemental oxygen in the nHFOV group was significantly shorter than that in the BiPAP group. The incidence of air leakage syndrome in the nHFOV group was significantly lower than that in the BiPAP group, and the length of hospital stay of the nHFOV group was also significantly shorter than that in the BiPAP group. Although the rate of infants diagnosed with BPD was similar between the two groups, the rate of severe BPD in the nHFOV group was significantly lower than that in the BiPAP group.Conclusion: This study showed that nHFOV as initial respiratory support for preterm infants with RDS was feasible and safe compared to BiPAP. Furthermore, nHFOV can reduce the need for IMV and reduce the incidence of severe BPD and air leak syndrome.

Non-invasive high-frequency oscillatory ventilation in preterm infants after extubation: a randomized, controlled trial.

ObjectiveTo investigate the effectiveness and safety of non-invasive high-frequency oscillatory ventilation (NHFOV) in post-extubation preterm infants.MethodsThis was a randomized, controlled trial. A total of 149 preterm infants aged between 25 to 34 weeks’ gestational age with a birth weight of <1500 g who required invasive mechanical ventilation on admission were included. After extubation, they were randomized to the NHFOV group (n = 47), nasal intermittent positive pressure ventilation (NIPPV) group (n = 51), or nasal continuous positive airway pressure (NCPAP) group (n = 51). We compared the effectiveness and safety among these three groups.ResultsA total of 139 preterm infants finally completed the study. The reintubation rate was significantly lower in the NHFOV group than in the other groups. The duration of non-invasive ventilation and the length of hospital stay in the NHFOV and NIPPV groups were significantly shorter than those in the NCPAP group. The incidence of bronchopulmonary dysplasia in the NHFOV and NIPPV groups was significantly lower than that in the NCPAP group. The NHFOV group had significantly less nasal injury than the NCPAP group.ConclusionAs post-extubation respiratory support in preterm infants, NHFOV has a lower reintubation rate compared with NCPAP and NIPPV, without increasing the rate of complications.

Three non-invasive ventilation strategies for preterm infants with respiratory distress syndrome: a propensity score analysis.

IntroductionThe present study was designed and conducted to compare the efficacy between nasal continuous positive airway pressure (NCPAP), nasal intermittent positive-pressure ventilation (NIPPV), and noninvasive high-frequency oscillatory ventilation (NHFOV) as the primary noninvasive ventilation in preterm infants with respiratory distress syndrome (RDS).Material and methodsThis multicenter retrospective cohort study was performed using data from four tertiary neonatal intensive care units (NICUs) in China between 2016 and 2018. 512 preterm infants with RDS who received early non-invasive ventilation (NIV) were analyzed. Propensity score analysis with 1 : 1 matching was performed with the nearest neighbor matching method using calipers of width equal to 0.1 of the standard deviation of the logit of the propensity score. The primary outcome was the need for intubation and invasive mechanical ventilation (IMV) within the first 7 days after birth. Secondary outcomes were days of hospitalization, predischarge mortality, rate of retinopathy of prematurity (ROP) > stage II, rate of bronchopulmonary dysplasia (BPD) at 36 weeks post-menstrual age, rate of air leaks, rate of intraventricular hemorrhage (IVH) ≥ grade 3, and rate of necrotizing enterocolitis (NEC) ≥ stage II.ResultsPropensity score matching identified 126 infants in each cohort (NHFOV vs. NIPPV), 96 infants in each cohort (NHFOV vs. NCPAP), 134 infants in each cohort (NIPPV vs. NCPAP) respectively. The need for IMV was significantly lower in the NHFOV as compared with NCPAP and NIPPV groups respectively (13/126 vs. 27/126, p = 0.016; 9/96 vs. 20/96, p = 0.027), while no difference was observed between NIPPV and NCPAP groups (25/134 vs. 25/134, p = 0.805). However, the number of days of hospitalization in NIPPV was significantly lower than that of the NCPAP group (24.8 ±14.6 days vs. 33.2 ±20.2 days p = 0.002). In subgroup analyses, the need for IMV was significantly lower in the NHFOV group than in the NCPAP and NIPPV group (7 : 79 vs. 15 : 74; 95% CI: 1.00–6.836; p = 0.044 and 11 : 102 vs. 22 : 98; 95% CI: 1.092–5.251; p = 0.026), and there was no difference between NIPPV and NCPAP in the preterm infants at ≤ 32 weeks’ gestational age. There were no significant differences among three groups (p > 0.05 respectively) regarding secondary outcomes.ConclusionsIn this multicenter retrospective cohort study, NHFOV significantly reduced the need for IMV within the first 7 days as compared to NCPAP and NIPPV in the treatment of preterm infants with RDS without increasing the incidence of adverse events. However, NIPPV was not found to be superior to NCPAP for decreasing the need for IMV in the treatment of preterm infants with RDS.

Continuous positive airway pressure (CPAP) vs noninvasive positive pressure ventilation (NIPPV) vs noninvasive high frequency oscillation ventilation (NHFOV) as post-extubation support in preterm neonates: protocol for an assessor-blinded, multicenter, randomized controlled trial

BackgroundVarious noninvasive respiratory support modalities are available in neonatal critical care in order to minimize invasive ventilation. Continuous positive airway pressure (CPAP) is the more commonly used but noninvasive positive pressure ventilation (NIPPV) seems more efficacious in the early post-extubation phase, although it is not clear if NIPPV may influence longterm outcomes. A recently introduced alternative is noninvasive high frequency oscillatory ventilation (NHFOV) which might be especially useful in babies needing high constant distending pressure. Preterm neonates may receive these respiratory supports for several weeks. Nonetheless, no data are available for the longterm use of NIPPV and NHFOV; few data exist on NHFOV and clinical outcomes, although its safety and suitability are reported in a number of preliminary short-term studies.MethodsWe designed an assessor-blinded, multicenter, three-arms, parallel, pragmatic, randomized, controlled trial with a superiority design, investigating the use of CPAP vs NIPPV vs NHFOV during the whole stay in neonatal intensive care units in China. Since safety data will also be analyzed it may be considered a phase II/III trial. Moreover, subgroup analyses will be performed on patients according to prespecified criteria based on physiopathology traits: these subgroup analyses should be considered preliminary. At least 1440 neonates are supposed to be enrolled. The trial has been designed with the collaboration of international colleagues expert in NHFOV, who will also perform an interim analysis at the about 50% of the enrolment.DiscussionThe study is applying the best trial methodology to neonatal ventilation, a field where it is often difficult to do so for practical reasons. Nonetheless, ours is also a physiology-driven trial, since interventions are applied based on physiological perspective, in order to use ventilatory techniques at their best. The pragmatic design will increase generalizability of our results but subgroup analyses according to predefined physiopathological criteria are also previewed trying to have some advantages of an explanatory design. Since not all clinicians are well versed in all respiratory techniques, the training is pivotal. We intend to apply particular care to train the participating units: a specific 3-month period and several means have been dedicated to this end.Trial registrationNCT03181958 (registered on June 9, 2017).

Mechanics of nasal mask-delivered HFOV in neonates: A physiologic study.

To clarify if nasal mask influences noninvasive high-frequency oscillatory ventilation (NHFOV) mechanics to optimize the clinical use of nasal mask-delivered NHFOV. Nasal mask may affect the mechanical efficacy of NHFOV. We designed a physiologic study composed of an in vitro phase aiming to investigate pressure transmission and volume delivery in a bench model of nasal mask-delivered NHFOV. In a second phase, we measured the leaks in vivo in a series of neonates receiving nasal mask-delivered NHFOV or other forms of noninvasive respiratory support with same nasal masks. In vitro pressure transmission is lower with nasal mask (pressure at the lung [Plung]: 2 [0.8]), than with the endotracheal tube (Plung 9.5 [1.5] cmH2 O; P = 0.007). Same applies for volume delivery (Vol: 0.6 [0.2] vs 1.8 [0.5] mL; P = 0.0001). Increasing ventilatory boundaries slowly affects pressure and volume delivery. Ventilating the model with maximal parameters (∆P = 55 cmH2 O; frequency = 8 Hz) we obtained a Vol 1.5 (0.2) mL. The nasal mask provides lower volume delivery and ventilation, compared with nasal prongs studied in previously published studies. Changing frequency allows a better performance than changing ∆P. In vivo leaks are approximately 30% and are similar during NHFOV or other forms of nasal mask-delivered noninvasive ventilation. Nasal mask-delivered NHFOV is feasible, but it may require more aggressive ventilatory parameters to increase volume delivery and ventilation. The use of the nasal mask is associated with some leaks, but this is independent from the type of noninvasive respiratory support applied.

Carbon dioxide diffusion coefficient in noninvasive high-frequency oscillatory ventilation.

The carbon dioxide (CO2 ) diffusion coefficient (DCO 2 ) reflects CO 2 removal during high-frequency oscillatory ventilation (HFOV). We hypothesized that despite leak flow during noninvasive HFOV (nHFOV) DCO 2 continues to indicate ventilation efficacy. A neonatal airway model including CO2 production and an adjustable oropharyngeal leak was connected to a ventilator via bi-nasal prongs. Pressures and gas flows were measured at prongs, trachea, and leak. Oscillatory tidal volumes below (V T trachea ) and above the leak (V T prong ) were calculated from tracheal and leak flows. DCO 2 was calculated using V T trachea (DCO 2 trachea ) and V T prong (DCO 2 prong ) and compared with CO 2 partial pressure (pCO 2 ). Effects of leak flow (0, 5, or 10L/min) on DCO 2 were assessed at fixed pressure amplitudes or predefined oscillatory volumes under steady-state pCO 2 conditions in the modeled lung. DCO2 trachea correlated strongly with pCO 2 , independent of the leak flow level (P < 0.0001). DCO 2 prong correlated with pCO 2 without and with moderate leak (P < 0.0001) but not with maximum leak (P = 0.1432). V T trachea correlated with the quotient of tracheal pressure amplitude and frequency irrespective of the leak (P < 0.0001). Based on the pressure amplitude at prong level (A prong ) V T trachea continued to follow a linear model of which the slopes decreased with increasing leak flow. V T prong correlated with the quotient of A prong and frequency, irrespective of the leak (P < 0.0001). DCO2 obtained at the airway opening at prong level reflects ventilation efficacy during nHFOV even in the presence of moderate oropharyngeal leak.

Non-invasive high-frequency oscillatory ventilation versus nasal continuous positive airway pressure in preterm infants with respiratory distress syndrome: Study protocol for a multi-center prospective randomized controlled trial

BackgroundInvasive mechanical ventilation (IMV) is associated with the development of adverse pulmonary and non-pulmonary outcomes in very premature infants. Various modes of non-invasive respiratory support are increasingly being used to decrease the incidence of bronchopulmonary dysplasia. The aim of this trial is to compare the effect of non-invasive high-frequency oscillatory ventilation (NHFOV) and nasal continuous positive airway pressure (NCPAP) in preterm infants with respiratory distress syndrome (RDS) as a primary non-invasive ventilation support mode.Methods/designIn this multi-center randomized controlled trial, 300 preterm infants born at a gestational age of 266/7 to 336/7 weeks with a diagnosis of RDS will be randomized to NHFOV or NCPAP as a primary mode of non-invasive respiratory support. The study will be conducted in 18 tertiary neonatal intensive care units in China.The primary outcome is the need for IMV during the first 7 days after enrollment in preterm infants randomized to the two groups. The prespecified secondary outcomes include days of hospitalization, days on non-invasive respiratory support, days on IMV, days on supplemental oxygen, mortality, need for a surfactant, severe retinopathy of prematurity requiring laser treatment or surgery, patent ductus arteriosus needing ligation, bronchopulmonary dysplasia, abdominal distention, air leak syndromes, intraventricular hemorrhage (≥ grade 3), spontaneous intestinal perforation, necrotizing enterocolitis (≥II stage), and nasal trauma. Other secondary outcomes include Bayley Scales of Infant Development at 18–24 months of corrected age.DiscussionIn recent decades, several observational studies have compared the effects of NHFOV and NCPAP in neonates as a rescue mode or during weaning from IMV. To our knowledge, this will be the first multi-center prospective, randomized controlled trial to evaluate NHFOV as a primary mode in preterm infants with RDS in China or any other part of the world. Our trial may help to establish guidelines for NHFOV in preterm infants with RDS to minimize the need for IMV, and to decrease the significant pulmonary and non-pulmonary morbidities associated with IMV.Trial registrationClinicalTrials.gov, NCT03099694. Registered on 4 April 2017.

Non-invasive high-frequency oscillatory ventilation in neonates: review of physiology, biology and clinical data

Non-invasive high-frequency oscillatory ventilation (NHFOV) consists of the application of a bias flow generating a continuous distending positive pressure with superimposed oscillations, which have constant frequency and active expiratory phase....

Oscillation transmission and volume delivery during face mask-delivered HFOV in infants: Bench and in vivo study.

Noninvasive high frequency oscillatory ventilation (NHFOV) has not been studied beyond neonatal age and with interfaces other than nasal prongs. We set up a preliminary study to investigate feasibility, oscillation transmission, and volume delivery of face mask-delivered NHFOV in a bench model mimicking a normal 1-year infant without any lung disease and then in vivo in a series of infants with same characteristics. A mannequin with upper airways was connected to an electronic active lung simulator ventilated through NHFOV with varying parameters. Volume delivered by oscillations (oTv), oscillatory pressure ratio, and estimation of ventilation (DCO2) were measured at the lung simulator. Four infants were ventilated with face mask-delivered NHFOV for 2 hr and monitored with respiratory inductance plethismography. Vital parameters, oscillatory pressure ratio, oscillatory (RIPo), and spontaneous cage/abdomen displacement (RIPs) were recorded. There was a dampening of oscillation amplitude both on the bench model and in vivo: oscillatory pressure ratios at the mask were 80% and 17%, respectively. Significant correlations exist between oscillatory pressure ratio (only when this latter was <0.038) and oTv (r = 0.48; P < 0.001) or DCO2 (r = 0.47; P < 0.001). At multivariate analysis, oscillatory pressure ratio was a main determinant of oTv and DCO2. Oscillations were slightly visible on the chest in vivo and RIPo was about 5% of RIPs. NHFOV did not change vital parameters and did not cause discomfort. Face mask-delivered NHFOV is feasible in a model of 1-year infant. No major complications occurred in vivo. Oscillations are superimposed to the spontaneous breathing and are significantly dampened. Pediatr Pulmonol. Pediatr Pulmonol. 2016;51:705-712. © 2016 Wiley Periodicals, Inc.

A noninvasive high frequency oscillation ventilator: Achieved by utilizing a blower and a valve.

After the High Frequency Oscillatory Ventilation (HFOV) has been applied in the invasive ventilator, the new technique of noninvasive High Frequency Oscillatory Ventilation (nHFOV) which does not require opening the patient's airway has attracted much attention from the field. This paper proposes the design of an experimental positive pressure-controlled nHFOV ventilator which utilizes a blower and a special valve and has three ventilation modes: spontaneous controlled ventilation combining HFOV, time-cycled ventilation combining HFOV (T-HFOV), and continuous positive airway pressure ventilation combining HFOV. Experiments on respiratory model are conducted and demonstrated the feasibility of using nHFOV through the control of fan and valve. The experimental ventilator is able to produce an air flow with small tidal volume (VT) and a large minute ventilation volume (MV) using regular breath tubes and nasal mask (e.g., under T-HFOV mode, with a maximum tidal volume of 100 ml, the minute ventilation volume reached 14,400 ml). In the process of transmission, there is only a minor loss of oscillation pressure. (Under experimental condition and with an oscillation frequency of 2-10 Hz, peak pressure loss was around 0%-50% when it reaches the mask.).