Lung Recruitment Before Surfactant Administration in Extremely Preterm Neonates: 2-Year Follow-Up of a Randomized Clinical Trial.

Importance: A multicenter randomized clinical trial (RCT) showed a lung recruitment maneuver using high-frequency oscillatory ventilation just before surfactant administration (ie, intubate-recruit-surfactant-extubate [IN-REC-SUR-E]) improved the efficacy of treatment compared with the standard intubate-surfactant-extubate (IN-SUR-E) technique without increasing the risk of adverse neonatal outcomes. Objective: To examine follow-up outcomes at corrected postnatal age (cPNA) 2 years of preterm infants previously enrolled in an RCT and treated with IN-REC-SUR-E or IN-SUR-E in 35 tertiary neonatal intensive care units. Design, Setting, and Participants: This was a follow-up study of infants recruited into the primary RCT from 2015 to 2018 at 35 tertiary neonatal intensive care units (NICUs) in Italy. Follow-up examinations included neurodevelopmental, growth, and respiratory outcomes of these children at cPNA 2 years. Participants included spontaneously breathing extremely preterm neonates (24 0/7 to 27 6/7 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 hours of life. Data were analyzed from April 2023 to January 2024. Intervention: Infants were randomly assigned (1:1) to IN-REC-SUR-E or IN-SUR-E and then followed up. Main Outcomes and Measures: The primary outcome was the occurrence of death after discharge or major disability at cPNA 2 years. Secondary outcomes were neurodevelopmental outcomes (major disability, cerebral palsy, cognitive impairment, visual deficit, or auditory deficit), anthropometric measurements (weight, length, and head circumference), and recurrent respiratory infections and hospitalizations because of respiratory causes at 2y cPNA. Results: A total of 137 extremely preterm infants (median [IQR] gestational age, 26.5 [25.3-27.5] weeks and 75 [54.7%] female), initially enrolled in the original RCT, were followed up at cPNA 2 years, including 64 infants in the IN-SUR-E group and 73 infants in the IN-REC-SUR-E group. There were no significant differences in the occurrence of death after discharge or major disability at cPNA 2 years (IN-SUR-E: 13 children [20.3%] vs IN-REC-SUR-E: 10 children [13.7%]; P = .36). There were no significant differences in incidence of disability, cerebral palsy, or cognitive impairment in the IN-REC-SUR-E group compared with the IN-SUR-E group. There were no significant differences in anthropometric measurements (weight, length, and head circumference) between groups. There were no significant differences in the incidence of recurrent respiratory infections or in hospitalizations because of respiratory causes between groups. Conclusions and Relevance: In this RCT of lung recruitment before surfactant vs standard care there were no significant differences between the 2 groups in death, neurodevelopmental outcomes, anthropometric measurements, or recurrent respiratory infections at the 2-year follow-up. These findings can aid clinicians in decision-making for the best strategy to administer surfactant, considering long-term outcomes.

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

INTRODUCTION: Noninvasive High-Frequency Oscillatory Ventilation (NHFOV) is increasingly being adopted to reduce the need for invasive ventilation after extubation. OBJECTIVES: To evaluate the benefits and harms of NHFOV as post-extubation respiratory support in newborns compared to other non-invasive respiratory support modes. MATERIAL & METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Association between initial ventilation mode and hospital outcomes for severe congenital diaphragmatic hernia.

OBJECTIVE: To determine the association between initial delivery room (DR) ventilator (conventional mechanical ventilation [CMV] versus high frequency oscillatory ventilation [HFOV] and hospital outcomes for infants with severe congenital diaphragmatic hernia (CDH). STUDY DESIGN: Quasi-experimental design before/after introducing a clinical protocol promoting HFOV. The primary outcome was first blood gas parameters. Secondary outcomes included serial blood gas assessments, ECMO, survival, duration of ventilation, and length of hospitalization. RESULTS: First pH and CO2 were more favorable in the HFOV group (n = 75) than CMV group (n = 85), median (interquartile range (IQR)) pH 7.18 (7.03, 7.24) vs. 7.05 (6.93, 7.17), adjusted p-value < 0.001; median CO2 62.0 (46.0, 82.0) vs 85.9 (59.0, 103.0), adjusted p-value < 0.001. ECMO, survival, duration of ventilation, and length of hospitalization did not differ between groups in adjusted analysis. CONCLUSION: Among infants with severe CDH, initial DR HFOV was associated with improved early gas exchange with no adverse differences in hospital outcomes.

Protocol for the Prone and Oscillation Pediatric Clinical Trial ( PROSpect ).

OBJECTIVES: Respiratory management for pediatric acute respiratory distress syndrome (PARDS) remains largely supportive without data to support one approach over another, including supine versus prone positioning (PP) and conventional mechanical ventilation (CMV) versus high-frequency oscillatory ventilation (HFOV). DESIGN: We present the research methodology of a global, multicenter, two-by-two factorial, response-adaptive, randomized controlled trial of supine versus PP and CMV versus HFOV in high moderate-severe PARDS, the Prone and Oscillation Pediatric Clinical Trial ( PROSpect , www.ClinicalTrials.gov , NCT03896763). SETTING: Approximately 60 PICUs with on-site extracorporeal membrane oxygenation support in North and South America, Europe, Asia, and Oceania with experience using PP and HFOV in the care of patients with PARDS. PATIENTS: Eligible pediatric patients (2 wk old or older and younger than 21 yr) are randomized within 48 h of meeting eligibility criteria occurring within 96 h of endotracheal intubation. INTERVENTIONS: One of four arms, including supine/CMV, prone/CMV, supine/HFOV, or prone/HFOV. We hypothesize that children with high moderate-severe PARDS treated with PP or HFOV will demonstrate greater than or equal to 2 additional ventilator-free days (VFD). MEASUREMENTS AND MAIN RESULTS: The primary outcome is VFD through day 28; nonsurvivors receive zero VFD. Secondary and exploratory outcomes include nonpulmonary organ failure-free days, interaction effects of PP with HFOV on VFD, 90-day in-hospital mortality, and among survivors, duration of mechanical ventilation, PICU and hospital length of stay, and post-PICU functional status and health-related quality of life. Up to 600 patients will be randomized, stratified by age group and direct/indirect lung injury. Adaptive randomization will first occur 28 days after 300 patients are randomized and every 100 patients thereafter. At these randomization updates, new allocation probabilities will be computed based on intention-to-treat trial results, increasing allocation to well-performing arms and decreasing allocation to poorly performing arms. Data will be analyzed per intention-to-treat for the primary analyses and per-protocol for primary, secondary, and exploratory analyses. CONCLUSIONS: PROSpect will provide clinicians with data to inform the practice of PP and HFOV in PARDS.

The effect of NHFOV on hemodynamics in mild and moderately preterm neonates: a randomized clinical trial.

The aim of this study is to study cardio-respiratory effects of nasal high-frequency oscillatory ventilation (NHFOV) vs. NCPAP as an initial mode of ventilation in moderate-late-preterm infants. A randomized controlled trial was conducted in NICU of Alexandria University Maternity Hospital (AUMH). One-hundred late-moderate-preterm infants were randomly assigned to either NHFOV-group (n = 50) or NCPAP-group (n = 50). For both groups, functional echocardiography was performed in the first 24 h to detect hemodynamic changes and respiratory outcome was monitored throughout the hospital stay. The main outcomes were hemodynamic measurements and myocardial function using functional echocardiography of those infants along with the respiratory outcome and complications. Kaplan-Meier survival plot was used representing time course of NCPAP and NHFOV failure. Left ventricular output values were not significantly different in both groups with median 202 ml/kg /min and IQR (176-275) in NCPAP-group and 226 ml/kg/min with IQR (181-286) in NHFOV group. Nevertheless, ejection fraction and fractional shortening were significantly higher in NHFOV-group with P 0.001. The time to weaning, the time to reach 30%-FIO2, the need for invasive ventilation, oxygen support duration, and maximal-FIO2 were significantly more in NCAPAP group.     Conclusion: NHFOV is an effective and promising tool of non-invasive-ventilation which can be used as a primary modality of respiratory support in preterm infants with variable forms of respiratory distress syndrome without causing detrimental effect on hemodynamics or significant respiratory complications.     Trial registration: NCT05706428 (registered on January 21, 2023). What is Known: • NHFOV might be beneficial as a secondary mode of ventilation and might have an impact on hemodynamics. What is New: • NHFOV can be used as an initial mode of ventilation with CDP beyond the reported pressure limits of CPAP without causing neither CO2 retention nor adverse hemodynamic consequences.

Non-invasive high-frequency ventilation in newborn infants with respiratory distress.

BACKGROUND: Respiratory distress occurs in up to 7% of newborns, with respiratory support (RS) provided invasively via an endotracheal (ET) tube or non-invasively via a nasal interface. Invasive ventilation increases the risk of lung injury and chronic lung disease (CLD). Using non-invasive strategies, with or without minimally invasive surfactant, may reduce the need for mechanical ventilation and the risk of lung damage in newborn infants with respiratory distress. OBJECTIVES: To evaluate the benefits and harms of nasal high-frequency ventilation (nHFV) compared to invasive ventilation via an ET tube or other non-invasive ventilation methods on morbidity and mortality in preterm and term infants with or at risk of respiratory distress. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and three trial registries in April 2023. SELECTION CRITERIA: Randomised controlled trials (RCTs), cluster- or quasi-RCTs of nHFV in newborn infants with respiratory distress compared to invasive or non-invasive ventilation. DATA COLLECTION AND ANALYSIS: Two authors independently selected the trials for inclusion, extracted data, assessed the risk of bias, and undertook GRADE assessment. MAIN RESULTS: We identified 33 studies, mostly in low- to middle-income settings, that investigated this therapy in 5068 preterm and 46 term infants. nHFV compared to invasive respiratory therapy for initial RS We are very uncertain whether nHFV reduces mortality before hospital discharge (RR 0.67, 95% CI 0.20 to 2.18; 1 study, 80 infants) or the incidence of CLD (RR 0.38, 95% CI 0.09 to 1.59; 2 studies, 180 infants), both very low-certainty. ET intubation, death or CLD, severe intraventricular haemorrhage (IVH) and neurodevelopmental disability (ND) were not reported. nHFV vs nasal continuous positive airway pressure (nCPAP) used for initial RS We are very uncertain whether nHFV reduces mortality before hospital discharge (RR 1.00, 95% CI 0.41 to 2.41; 4 studies, 531 infants; very low-certainty). nHFV may reduce ET intubation (RR 0.52, 95% CI 0.33 to 0.82; 5 studies, 571 infants), but there may be little or no difference in CLD (RR 1.35, 95% CI 0.80 to 2.27; 4 studies, 481 infants); death or CLD (RR 2.50, 95% CI 0.52 to 12.01; 1 study, 68 participants); or severe IVH (RR 1.17, 95% CI 0.36 to 3.78; 4 studies, 531 infants), all low-certainty evidence. ND was not reported. nHFV vs nasal intermittent positive-pressure ventilation (nIPPV) used for initial RS nHFV may result in little to no difference in mortality before hospital discharge (RR 1.86, 95% CI 0.90 to 3.83; 2 studies, 84 infants; low-certainty). nHFV may have little or no effect in reducing ET intubation (RR 1.33, 95% CI 0.76 to 2.34; 5 studies, 228 infants; low-certainty). There may be a reduction in CLD (RR 0.63, 95% CI 0.42 to 0.95; 5 studies, 307 infants; low-certainty). A single study (36 infants) reported no events for severe IVH. Death or CLD and ND were not reported. nHFV vs high-flow nasal cannula (HFNC) used for initial RS We are very uncertain whether nHFV reduces ET intubation (RR 2.94, 95% CI 0.65 to 13.27; 1 study, 37 infants) or reduces CLD (RR 1.18, 95% CI 0.46 to 2.98; 1 study, 37 participants), both very low-certainty. There were no mortality events before hospital discharge or severe IVH. Other deaths, CLD and ND, were not reported. nHFV vs nCPAP used for RS following planned extubation nHFV probably results in little or no difference in mortality before hospital discharge (RR 0.92, 95% CI 0.52 to 1.64; 6 studies, 1472 infants; moderate-certainty). nHFV may result in a reduction in ET reintubation (RR 0.42, 95% CI 0.35 to 0.51; 11 studies, 1897 infants) and CLD (RR 0.78, 95% CI 0.67 to 0.91; 10 studies, 1829 infants), both low-certainty. nHFV probably has little or no effect on death or CLD (RR 0.90, 95% CI 0.77 to 1.06; 2 studies, 966 infants) and severe IVH (RR 0.80, 95% CI 0.57 to 1.13; 3 studies, 1117 infants), both moderate-certainty. We are very uncertain whether nHFV reduces ND (RR 0.92, 95% CI 0.37 to 2.29; 1 study, 74 infants; very low-certainty). nHFV versus nIPPV used for RS following planned extubation nHFV may have little or no effect on mortality before hospital discharge (RR 1.83, 95% CI 0.70 to 4.79; 2 studies, 984 infants; low-certainty). There is probably a reduction in ET reintubation (RR 0.69, 95% CI 0.54 to 0.89; 6 studies, 1364 infants), but little or no effect on CLD (RR 0.88, 95% CI 0.75 to 1.04; 4 studies, 1236 infants); death or CLD (RR 0.92, 95% CI 0.79 to 1.08; 3 studies, 1070 infants); or severe IVH (RR 0.78, 95% CI 0.55 to 1.10; 4 studies, 1162 infants), all moderate-certainty. One study reported there might be no difference in ND (RR 0.88, 95% CI 0.35 to 2.16; 1 study, 72 infants; low-certainty). nHFV versus nIPPV following initial non-invasive RS failure nHFV may have little or no effect on mortality before hospital discharge (RR 1.44, 95% CI 0.10 to 21.33); or ET intubation (RR 1.23, 95% CI 0.51 to 2.98); or CLD (RR 1.01, 95% CI 0.70 to 1.47); or severe IVH (RR 0.47, 95% CI 0.02 to 10.87); 1 study, 39 participants, all low- or very low-certainty. Other deaths or CLD and ND were not reported. AUTHORS' CONCLUSIONS: For initial RS, we are very uncertain if using nHFV compared to invasive respiratory therapy affects clinical outcomes. However, nHFV may reduce intubation when compared to nCPAP. For planned extubation, nHFV may reduce the risk of reintubation compared to nCPAP and nIPPV. nHFV may reduce the risk of CLD when compared to nCPAP. Following initial non-invasive respiratory support failure, nHFV when compared to nIPPV may result in little to no difference in intubation. Large trials, particularly in high-income settings, are needed to determine the role of nHFV in initial RS and following the failure of other non-invasive respiratory support. Also, the optimal settings of nHVF require further investigation.

Relationship between oscillatory volume and oscillatory pressure in neonatal high-frequency oscillatory ventilators: an in vitro study.

OBJECTIVE: We analysed the relationship between oscillatory volume (VOSC) and pressure amplitude (ΔP) in six neonatal high-frequency oscillatory (HFO) ventilators and related it to (1) the accuracy of VOSC and ΔP measurements and (2) the maximal delivered ΔP. DESIGN: In vitro study. SETTING: Neonatal intensive care unit. INTERVENTIONS: Ventilators tested were VN800 (Dräger), Servo-n (Maquet Getinge), SensorMedics 3100A (Vyaire Medical), Fabian HFOi (Vyaire Medical), SLE6000 (SLE UK) and Humming Vue (Metran). We changed various settings and mechanical characteristics of the test lung to mimic preterm and term conditions. MAIN OUTCOME MEASURES: For each condition, we measured VOSC and ΔP. We assessed the accuracy of the VOSC and ΔP measurements versus a reference measurement system using linear regression and Bland-Altman analysis. We evaluated the maximum delivered ΔP at different oscillatory frequencies. RESULTS: We observed large variability between machines in the ΔP displayed at any target VOSC. Most ventilators over-read ΔP with errors up to 30 cmH2O or 60%. The error in the measurement of VOSC was up to ±2 mL or ±30%. We observed high variability in the accuracy of ΔP and VOSC measurements; the SLE6000 committed the lowest errors in ΔP measurements and the Fabian HFOi in VOSC. The maximum delivered ΔP varied depending on the ventilator, being maximal for the Humming Vue, followed by the SLE6000 and SensorMedics 3100A. CONCLUSIONS: The variability in the relationship between VOSC and ΔP among HFO ventilators is largely explained by the variable accuracy in ΔP and VOSC measurement. Different ventilators also exhibit important differences in the maximal generated ΔP.

Benefits of intratracheal and extrathoracic high-frequency percussive ventilation in a model of capnoperitoneum.

Abdominal inflation with CO2 is used to facilitate laparoscopic surgeries, however, providing adequate mechanical ventilation in this scenario is of major importance during anesthesia management. We characterized high-frequency percussive ventilation (HFPV) in protecting from the gas exchange and respiratory mechanical impairments during capnoperitoneum. In addition, we aimed to assess the difference between conventional pressure-controlled mechanical ventilation (CMV) and HFPV modalities generating the high-frequency signal intratracheally (HFPVi) or extrathoracally (HFPVe). Anesthetized rabbits (n = 16) were mechanically ventilated by random sequences of CMV, HFPVi, and HFPVe. The ventilator superimposed the conventional waveform with two high-frequency signals (5 Hz and 10 Hz) during intratracheal HFPV (HFPVi) and HFPV with extrathoracic application of oscillatory signals through a sealed chest cuirass (HFPVe). Lung oxygenation index ([Formula: see text]/[Formula: see text]), arterial partial pressure of carbon dioxide ([Formula: see text]), intrapulmonary shunt (Qs/Qt), and respiratory mechanics were assessed before abdominal inflation, during capnoperitoneum, and after abdominal deflation. Compared with CMV, HFPVi with additional 5-Hz oscillations during capnoperitoneum resulted in higher [Formula: see text]/[Formula: see text], lower [Formula: see text], and decreased Qs/Qt. These improvements were smaller but remained significant during HFPVi with 10 Hz and HFPVe with either 5 or 10 Hz. The ventilation modes did not protect against capnoperitoneum-induced deteriorations in respiratory tissue mechanics. These findings suggest that high-frequency oscillations combined with conventional pressure-controlled ventilation improved lung oxygenation and CO2 removal in a model of capnoperitoneum. Compared with extrathoracic pressure oscillations, intratracheal generation of oscillatory pressure bursts appeared more effective. These findings may contribute to the optimization of mechanical ventilation during laparoscopic surgery.NEW & NOTEWORTHY The present study examines an alternative and innovative mechanical ventilation modality in improving oxygen delivery, CO2 clearance, and respiratory mechanical abnormalities in a clinically relevant experimental model of capnoperitoneum. Our data reveal that high-frequency oscillations combined with conventional ventilation improve gas exchange, with intratracheal oscillations being more effective than extrathoracic oscillations in this clinically relevant translational model.

Oscillometry for personalizing continuous distending pressure maneuvers: an observational study in extremely preterm infants.

RATIONALE: Lung recruitment and continuous distending pressure (CDP) titration are critical for assuring the efficacy of high-frequency ventilation (HFOV) in preterm infants. The limitation of oxygenation (peripheral oxygen saturation, SpO2) in optimizing CDP calls for evaluating other non-invasive bedside measurements. Respiratory reactance (Xrs) at 10 Hz measured by oscillometry reflects lung volume recruitment and tissue strain. In particular, lung volume recruitment and decreased tissue strain result in increased Xrs values. OBJECTIVES: In extremely preterm infants treated with HFOV as first intention, we aimed to measure the relationship between CDP and Xrs during SpO2-driven CDP optimization. METHODS: In this prospective observational study, extremely preterm infants born before 28 weeks of gestation undergoing SpO2-guided lung recruitment maneuvers were included in the study. SpO2 and Xrs were recorded at each CDP step. The optimal CDP identified by oxygenation (CDPOpt_SpO2) was compared to the CDP providing maximal Xrs on the deflation limb of the recruitment maneuver (CDPXrs). RESULTS: We studied 40 infants (gestational age at birth = 22+ 6-27+ 5 wk; postnatal age = 1-23 days). Measurements were well tolerated and provided reliable results in 96% of cases. On average, Xrs decreased during the inflation limb and increased during the deflation limb. Xrs changes were heterogeneous among the infants for the amount of decrease with increasing CDP, the decrease at the lowest CDP of the deflation limb, and the hysteresis of the Xrs vs. CDP curve. In all but five infants, the hysteresis of the Xrs vs. CDP curve suggested effective lung recruitment. CDPOpt_SpO2 and CDPXrs were highly correlated (ρ = 0.71, p < 0.001) and not statistically different (median difference [range] = -1 [-3; 9] cmH2O). However, CDPXrs were equal to CDPOpt_SpO2 in only 6 infants, greater than CDPOpt_SpO2 in 10, and lower in 24 infants. CONCLUSIONS: The Xrs changes described provide complementary information to oxygenation. Further investigation is warranted to refine recruitment maneuvers and CPD settings in preterm infants.

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

OBJECTIVE: To compare the efficacy and safety of non-invasive high-frequency oscillatory ventilation (NHFOV) and nasal continuous positive airway pressure (NCPAP) in preterm infants. DESIGN: 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. MAIN OUTCOMES MEASURES: 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. RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION NUMBER: CRD42023403968.

Impact on cerebral hemodynamics of the use of volume guarantee combined with high frequency oscillatory ventilation in a neonatal animal respiratory distress model.

High-frequency oscillatory ventilation (HFOV) is an alternative to conventional mechanical ventilation (CMV). Recently, the use of volume guarantee (VG) combined with HFOV has been suggested as a safe strategy capable of reducing the damage induced by ventilation in immature lungs. However, the possible impact of this new ventilation technique on cerebral hemodynamics is unknown. To evaluate the cerebral hemodynamics effect of HFOV combined with VG in an experimental animal model of neonatal respiratory distress syndrome (RDS) due to surfactant deficiency compared with HFOV and CMV+VG (control group). Eighteen newborn piglets were randomized, before and after the induction of RDS by bronchoalveolar lavage, into 3 mechanical ventilation groups: CMV, HFOV and HFOV with VG. Changes in cerebral oxygen transport and consumption and cerebral blood flow were analyzed by non-invasive regional cerebral oxygen saturation (CrSO2), jugular venous saturation (SjO2), the calculated cerebral oxygen extraction fraction (COEF), the calculated cerebral fractional tissue oxygen extraction (cFTOE) and direct measurement of carotid artery flow. To analyze the temporal evolution of these variables, a mixed-effects linear regression model was constructed. After randomization, the following statistically significant results were found in every group: a drop in carotid artery flow: at a rate of -1.7 mL/kg/min (95% CI: -2.5 to -0.81; p < 0.001), CrSO2: at a rate of -6.2% (95% CI: -7.9 to -4.4; p < 0.001) and SjO2: at a rate of -20% (95% CI: -26 to -15; p < 0.001), accompanied by an increase in COEF: at a rate of 20% (95% CI: 15 to 26; p < 0.001) and cFTOE: at a rate of 0.07 (95% CI: 0.05 to 0.08; p < 0.001) in all groups. No statistically significant differences were found between the HFOV groups. CONCLUSION: No differences were observed at cerebral hemodynamic between respiratory assistance in HFOV with and without VG, being the latter ventilatory strategy equally safe. WHAT IS KNOWN: • Preterm have a situation of fragility of cerebral perfusion wich means that any mechanical ventilation strategy can have a significant influence. High-frequency oscillatory ventilation (HFOV) is an alternative to conventional mechanical ventilation (CMV). Recently, the use of volume guarantee (VG) combined with HFOV has been suggested as a safe strategy capable of reducing the damage induced by ventilation in immature lungs. Several studies have compared CMV and HFOV and their effects at hemodynamic level. It is known that the use of high mean airway pressure in HFOV can cause an increase in pulmonary vascular resistance with a decrease in thoracic venous return. WHAT IS NEW: • The possible impact of VAFO + VG on cerebral hemodynamics is unknown. Due the lack of studies and the existing controversy, we have carried out this research project in an experimental animal model with the aim of evaluating the cerebral hemodynamic repercussion of the use of VG in HFOV compared to the classic strategy without VG.

[Therapeutic efficacy of volume-guaranteed high frequency oscillation ventilation on respiratory failure in preterm infants with a gestational age of 28-34 weeks: a prospective randomized controlled study]. / 容量保证的高频振荡通气模式对胎龄28~34å‘¨æ—©äº§å„¿å‘¼å¸è¡°ç«­ç–—æ•ˆçš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the therapeutic efficacy of volume-guaranteed high frequency oscillation ventilation (HFOV-VG) versus conventional mechanical ventilation (CMV) in the treatment of preterm infants with respiratory failure. METHODS: A prospective study was conducted on 112 preterm infants with respiratory failure (a gestational age of 28-34 weeks) who were admitted to the Department of Neonatology, Jiangyin Hospital Affiliated to Medical School of Southeast University, from October 2018 to December 2022. The infants were randomly divided into an HFOV-VG group (44 infants) and a CMV group (68 infants) using the coin tossing method based on the mode of mechanical ventilation. The therapeutic efficacy was compared between the two groups. RESULTS: After 24 hours of treatment, both the HFOV-VG and CMV groups showed significant improvements in arterial blood pH, partial pressure of oxygen, partial pressure of carbon dioxide, and partial pressure of oxygen/fractional concentration of inspired oxygen ratio (P<0.05), and the HFOV-VG group had better improvements than the CMV group (P<0.05). There were no significant differences between the two groups in the incidence rate of complications, 28-day mortality rate, and length of hospital stay (P>0.05), but the HFOV-VG group had a significantly shorter duration of invasive mechanical ventilation than the CMV group (P<0.05). The follow-up at the corrected age of 6 months showed that there were no significant differences between the two groups in the scores of developmental quotient, gross motor function, fine motor function, adaptive ability, language, and social behavior in the Pediatric Neuropsychological Development Scale (P>0.05). CONCLUSIONS: Compared with CMV mode, HFOV-VG mode improves partial pressure of oxygen and promotes carbon dioxide elimination, thereby enhancing oxygenation and shortening the duration of mechanical ventilation in preterm infants with respiratory failure, while it has no significant impact on short-term neurobehavioral development in these infants.

The outcome of high-frequency oscillatory ventilation in pediatric patients with acute respiratory distress syndrome in an intensive care unit.

BACKGROUND: In adults with acute respiratory distress syndrome (ARDS), high-frequency oscillatory ventilation (HFOV) has been associated with higher mortality rates. Therefore, its use in children with ARDS is still controversial. OBJECTIVES: Evaluate the overall mortality of HFOV in children with ARDS and explore mortality-related risk factors; compare the outcome of using HFOV post-endotracheal intubation early (≤24 hours) versus late (≤24 hours). DESIGN: Retrospective (medical record review) SETTING: Pediatric intensive care unit in a tertiary care center in Saudi Arabia. PATIENTS AND METHODS: Data were collected from medical records of all pediatric patients with ARDS aged one week to 14 years, who were admitted to the pediatric intensive care unit (PICU) from January 2016-June 2019 and who required HFOV. MAIN OUTCOME MEASURES: PICU mortality. SAMPLE SIZE AND CHARACTERISTICS: 135 ARDS patients including 74 females (54.8%), and 61 males (45.2%), with a median age (interquar-tile range) of 35 (72) months. RESULTS: The overall mortality rate was 60.0% (81/135), and most died in the first 28 days in the PICU (91.3%, 74/8). Of non-survivors, 75.3% (61/81) were immunocompromised, and 24.7% (20/81) were immuno-competent patients, 52 (64.2%) received inotropic support, 40 (49.4%) had a bone-marrow transplant (BMT) before HFOV initiation. Although the prone position was used in 20.7% (28/135) to improve the survival rate post-HFOV ventilation, only 28.6% (8/28) survived. In addition, altered code status or chemotherapy reported a significant association with mortality (P<.05). Interestingly, early HFOV initiation (≤24 hours) did not seem to have a high impact on survival compared to late initiation (>24 hours); (57.4% vs. 42.6%, P=.721). CONCLUSION: Immunocompromised and oncology patients, including post-BMT, reported poorer outcomes, and neither the prone position nor early use of HFOV improved outcomes. However, it is recommended to replicate the study in a larger cohort to generalize the results. LIMITATIONS: Retrospective single-center study.

Benefits of secretion clearance with high frequency percussive ventilation in tracheostomized critically ill patients: a pilot study.

Clearance of secretions remains a challenge in ventilated patients. Despite high-frequency percussive ventilation (HFPV) showing benefits in patients with cystic fibrosis and neuromuscular disorders, very little is known about its effects on other patient categories. Therefore, we designed a physiological pilot study investigating the effects on lung aeration and gas exchange of short HFPV cycles in tracheostomized patients undergoing mechanical ventilation. Electrical impedance tomography (EIT) was recorded at baseline (T0) by a belt wrapped around the patient's chest, followed by the HFPV cycle lasting 10 min. EIT data was collected again after the HFPV cycle (T1) as well as after 1 h (T2) and 3 h (T3) from T0. Variation from baseline of end-expiratory lung impedance (∆EELI), tidal variation (TIV) and global inhomogeneity index (GI) were computed. Arterial blood was also taken for gas analysis. HFPV cycle significantly improved the ∆EELI at T1, T2 and T3 when compared to baseline (p < 0.05 for all comparisons). The ratio between arterial partial pressure and inspired fraction of oxygen (PaO2/FiO2) also increased after the treatment (p < 0.001 for all comparison) whereas TIV (p = 0.132) and GI (p = 0.114) remained unchanged. Short cycles of HFPV superimposed to mechanical ventilation promoted alveolar recruitment, as suggested by improved ∆EELI, and improved oxygenation in tracheostomized patients with high load of secretion.Trial Registration Prospectively registered on www.clinicaltrials.gov (NCT05200507; dated 6th January 2022).

High-frequency ventilation in preterm infants and neonates.

High-frequency ventilation (HFV) has been used as a respiratory support mode for neonates for over 30 years. HFV is characterized by delivering tidal volumes close to or less than the anatomical dead space. Both animal and clinical studies have shown that HFV can effectively restore lung function, and potentially limit ventilator-induced lung injury, which is considered an important risk factor for developing bronchopulmonary dysplasia (BPD). Knowledge of how HFV works, how it influences cardiorespiratory physiology, and how to apply it in daily clinical practice has proven to be essential for its optimal and safe use. We will present important aspects of gas exchange, lung-protective concepts, clinical use, and possible adverse effects of HFV. We also discuss the study results on the use of HFV in respiratory distress syndrome in preterm infants and respiratory failure in term neonates. IMPACT: Knowledge of how HFV works, how it influences cardiorespiratory physiology, and how to apply it in daily clinical practice has proven to be essential for its optimal and safe use. Therefore, we present important aspects of gas exchange, lung-protective concepts, clinical use, and possible adverse effects of HFV. The use of HFV in daily clinical practice in lung recruitment, determination of the optimal continuous distending pressure and frequency, and typical side effects of HFV are discussed. We also present study results on the use of HFV in respiratory distress syndrome in preterm infants and respiratory failure in term neonates.

Therapeutic efficacy of volume-guaranteed high frequency oscillation ventilation on respiratory failure in preterm infants with a gestational age of 28-34 weeks: a prospective randomized controlled study / 中国当代儿科杂志

OBJECTIVES@#To investigate the therapeutic efficacy of volume-guaranteed high frequency oscillation ventilation (HFOV-VG) versus conventional mechanical ventilation (CMV) in the treatment of preterm infants with respiratory failure.@*METHODS@#A prospective study was conducted on 112 preterm infants with respiratory failure (a gestational age of 28-34 weeks) who were admitted to the Department of Neonatology, Jiangyin Hospital Affiliated to Medical School of Southeast University, from October 2018 to December 2022. The infants were randomly divided into an HFOV-VG group (44 infants) and a CMV group (68 infants) using the coin tossing method based on the mode of mechanical ventilation. The therapeutic efficacy was compared between the two groups.@*RESULTS@#After 24 hours of treatment, both the HFOV-VG and CMV groups showed significant improvements in arterial blood pH, partial pressure of oxygen, partial pressure of carbon dioxide, and partial pressure of oxygen/fractional concentration of inspired oxygen ratio (P<0.05), and the HFOV-VG group had better improvements than the CMV group (P<0.05). There were no significant differences between the two groups in the incidence rate of complications, 28-day mortality rate, and length of hospital stay (P>0.05), but the HFOV-VG group had a significantly shorter duration of invasive mechanical ventilation than the CMV group (P<0.05). The follow-up at the corrected age of 6 months showed that there were no significant differences between the two groups in the scores of developmental quotient, gross motor function, fine motor function, adaptive ability, language, and social behavior in the Pediatric Neuropsychological Development Scale (P>0.05).@*CONCLUSIONS@#Compared with CMV mode, HFOV-VG mode improves partial pressure of oxygen and promotes carbon dioxide elimination, thereby enhancing oxygenation and shortening the duration of mechanical ventilation in preterm infants with respiratory failure, while it has no significant impact on short-term neurobehavioral development in these infants.

Lung protection strategy with high-frequency oscillatory ventilation improves respiratory outcomes at two years in preterm respiratory distress syndrome: a before and after, quality improvement study.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) remains one of the major challenges of extreme prematurity. High-frequency oscillatory ventilation (HFOV) with volume guarantee (HFOV-VG) can be used as an early-rescue ventilation to protect developing lungs. However, the studies exploring the impact of this ventilatory strategy on neonatal respiratory morbidity are very limited. This study aimed at documenting the improvement in respiratory outcomes in mechanically ventilated preterm newborns, after the implementation of a new mechanical ventilation respiratory bundle. METHODS: A prospective, quality improvement study was conducted between January 2012 and December 2018 in a third level NICU in Madrid, Spain. Infants born <32 weeks of gestation with severe respiratory distress syndrome (RDS) and requiring invasive mechanical ventilation were included. The intervention consisted of a new ventilation respiratory care bundle, with HFOV as early rescue therapy using low high-frequency tidal volumes (Vthf) and higher frequencies (15-20 Hz). Criteria for HFOV start were impaired oxygenation or ventilation on conventional ventilation, or peak inspiratory pressures >15 cmH2O. Two cohorts of mechanically ventilated patients were compared, cohort 1 (2012-2013, baseline period) and cohort 2 (2016-2018, after implementation of the new bundle). Clinical outcomes at 36 weeks and 2 years of postmenstrual age were compared between the groups. RESULTS: A total of 216 patients were included, the median gestational age was 26 weeks (IQR 25-28) and median birth weight was 895 g (IQR 720-1160). There were no significant differences in survival between the groups, but patients with the protective ventilation strategy (cohort 2) had higher survival without BPD 2-3 (OR 2.93, 95%CI 1.41-6.05). At 2 years of postmenstrual age, patients in cohort 2 also had a higher survival free of baseline respiratory treatment and hospital respiratory admissions than the control group (adjusted OR 2.33, 95%CI 1.10-4.93, p=.03). The results did not suggest significant differences in neurologic development. CONCLUSIONS: In extreme premature related severe respiratory failure, the use of a lung protective HFOV-VG strategy was proven to be a useful quality improvement intervention in our unit, leading to better pulmonary outcomes at 36 weeks and additional improved respiratory prognosis at two years of age.

Use of intraoperative high frequency oscillatory ventilation in neonates with pulmonary hypoplasia.

High-frequency oscillatory ventilation (HFOV) is a ventilatory modality widely used in neonatal intensive care units. Its main indication is restrictive lung pathology with difficult gas exchange using conventional mechanical ventilation (CMV). Patients receiving CMV require high intensity care, and immature lungs can be at risk for barotrauma and volutrauma. The few studies that have explored the use of HFOV in the operating room are mainly limited to HFVO during congenital diaphragmatic hernia repair. Limited experience of this ventilatory method in the operating room may be a disadvantage for the anesthesiologist. However, it is important to remember the benefits of this technique as a lung protection strategy. We report two cases of neonatal pulmonary hypoplasia of different etiology in which good oxygenation and ventilation was achieved with intraoperative HFOV.

Demonstration of mucus simulant clearance in a Bench-Model using acoustic Field-Integrated Intrapulmonary Percussive ventilation.

Intrapulmonary Percussive Ventilation (IPV) is a high-frequency airway clearance technique used to help in mucus transport for mechanically ventilated and unventilated patients. Despite the many years of usage, this technique does not provide clear evidence of its intended efficacy. This is mainly attributable to the lack of in vitro observations that show "mucokinesis" towards the direction of the mouth. In the current manuscript, we demonstrate and subsequently propose a mechanism that details the movement of a mucus simulant in the proximal (towards the mouthpiece) direction. Towards this end, a novel method utilizing a high-frequency acoustic field in addition to the conventional air pulsations brought forth by traditional IPV is proposed. Under these conditions, at certain parameter settings, it is shown that the simulant is broken down into much smaller parts and subsequently pushed in the upstream direction gradually over a period of half-hour.