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

BACKGROUND: Health problems in neonates with gestational age (GA) ≥ 32 weeks remain a major medical concern. Respiratory distress (RD) is one of the common reasons for admission of neonates with GA ≥ 32 weeks. Noninvasive ventilation (NIV) represents a crucial approach to treat RD, and currently, the most used NIV modes in neonatal intensive care unit include high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and nasal intermittent positive pressure ventilation. Although extensive evidence supports the use of NIPPV in neonates with a GA < 32 weeks, limited data exist regarding its effectiveness in neonates with GA ≥ 32 weeks. Therefore, the aim of this study is to compare the clinical efficacy of HFNC, CPAP, and NIPPV as primary NIV in neonates with GA ≥ 32 weeks who experience RD. METHODS: This trial is designed as an assessor-blinded, three-arm, multi-center, parallel, randomized controlled trial, conducted in neonates ≥ 32 weeks' GA requiring primary NIV in the first 24 h of life. The neonates will be randomly assigned to one of three groups: HFNC, CPAP or NIPPV group. The effectiveness, safety and comfort of NIV will be evaluated. The primary outcome is the occurrence of treatment failure within 72 h after enrollment. Secondary outcomes include death before discharge, surfactant treatment within 72 h after randomization, duration of both noninvasive and invasive mechanical ventilation, duration of oxygen therapy, bronchopulmonary dysplasia, time to achieve full enteral nutrition, necrotizing enterocolitis, duration of admission, cost of admission, air leak syndrome, nasal trauma, and comfort score. DISCUSSION: Currently, there is a paucity of data regarding the utilization of NIPPV in neonates with GA ≥ 32 weeks. This study will provide clinical evidence for the development of respiratory treatment strategies in neonates at GA ≥ 32 weeks with RD, with the aim of minimizing the incidence of tracheal intubation and reducing the complications associated with NIV. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2300069192. Registered on March 9, 2023, https://www.chictr.org.cn/showproj.html?proj=171491 .

Volume-targeted ventilation vs pressure-controlled ventilation for very low birthweight infants: a protocol of a randomized controlled trial.

BACKGROUND: Mechanical ventilation (MV) is essential in the management of critically ill neonates, especially preterm infants. However, inappropriate or prolonged use of invasive MV may result in ventilator-associated lung injury. A systemic review comparing pressure control ventilation (PCV) with volume-targeted ventilation mode (VTV) approved that VTV reduces the incidence of death or bronchopulmonary dysplasia (BPD) in neonates; however, this study did not analyze subgroups of very low birthweight (VLBW) infants. Therefore, the aim of this study was to compare the use of VTV and PCV in VLBW infants and to provide clinical evidence for reducing mortality and complications of MV in VLBW infants. METHOD: A single-center randomized controlled trial will be performed. All eligible infants will be randomized and assigned to either VTV or PCV group with 1:1 ratio using sealed envelopes. Death or BPD at 36 weeks' postmenstrual age will be used as the primary outcome. Secondary outcomes include BPD, death, length of invasive MV, noninvasive mechanical ventilation, and oxygen use, length of hospital stay, failure of conventional MV, rate of using high-frequency oscillatory ventilation (HFOV) as rescue therapy, rate of reintubation within 48 h, and hospital expenses. DISCUSSION: Systemic review suggested that VTV decreases the incidence of death or BPD in neonates compared to PLV; however, this study did not specifically analyze subgroups of VLBW infants. We designed this single-center randomized controlled trials (RCT) to add a significant contribution regarding the benefits of VTV for VLBW patients.

Worldwide Clinical Practice of High-Flow Nasal Cannula and Concomitant Aerosol Therapy in the Adult ICU Setting.

BACKGROUND: High-flow nasal cannula (HFNC) oxygen therapy has been broadly used. However, no consensus has been achieved on the practical implementation of HFNC and how to provide aerosol delivery during HFNC therapy in adult patients. METHODS: An online anonymous questionnaire survey endorsed by 4 academic societies from America, Europe, mainland China, and Taiwan was administered from May to December 2019. Clinicians who had worked in adult ICUs for > 1 year and had used HFNC to treat patients within 30 days were included. RESULTS: A total of 2,279 participants clicked on the survey link, 1,358 respondents completed the HFNC section of the questionnaire, whereas 1,014 completed the whole survey. Postextubation hypoxemia and moderate hypoxemia were major indications for HFNC. The initial flow was mainly set at 40-50 L/min. Aerosol delivery via HFNC was used by 24% of the participants (248/1,014), 30% (74/248) of whom reported reducing flow during aerosol delivery. For the patients who required aerosol treatment during HFNC therapy, 40% of the participants (403/1,014) reported placing a nebulizer with a mask or mouthpiece while pursuing HFNC whereas 33% (331/1,014) discontinued HFNC to use conventional aerosol devices. A vibrating mesh nebulizer was the most commonly used nebulizer (40%) and was mainly placed at the inlet of the humidifier. CONCLUSIONS: The clinical utilization of HFNC was variable, as were indications, flow settings, and criteria for adjustment. Many practices associated with concomitant aerosol therapy were not consistent with available evidence for optimal use. More efforts are warranted to close the knowledge gap.

Aerosol Delivery During Continuous High Frequency Oscillation for Simulated Adults During Quiet and Distressed Spontaneous Breathing.

BACKGROUND: Continuous high-frequency oscillation (CHFO) is a therapeutic mode for the mobilization of secretions. The Metaneb CHFO device also incorporates aerosol administration using an integrated jet nebulizer. However, the effectiveness of aerosol delivery and influential factors remain largely unreported. METHODS: A collecting filter was placed between an adult manikin with a representative upper airway and a breath simulator, set to simulate quiet and distressed patterns of spontaneous adult breathing. The Metaneb CHFO device was attached to the manikin via a mask. Two jet nebulizers were tested in 2 different positions: placement in the manifold and placement between manifold and mask. A vibrating mesh nebulizer was placed between the manifold and mask with and without extension tubing. Aerosol administration was compared during CHFO and during nebulization mode alone. Albuterol (2.5 mg in 3 mL) was nebulized for each condition. The drug was eluted from the filter and assayed with ultraviolet spectrophotometry (276 nm). RESULTS: During CHFO, inhaled doses with jet nebulizers were low (∼ 2%), regardless of nebulizer placement. Inhaled dose was improved with the vibrating mesh nebulizer placed between the manifold and mask (12.48 ± 2.24% vs 2.58 ± 0.48%, P = .004). Inhaled doses with the jet nebulizer in the manifold with nebulization mode alone was lower than with the jet nebulizer with an aerosol mask (4.03 ± 1.82% vs 10.39 ± 2.79%, P = .004). Inhaled dose was greater with distressed breathing than quiet breathing. The use of a vibrating mesh nebulizer (P < .001) and distressed breathing (P = .001) were identified as predictors of increased inhaled dose. CONCLUSIONS: Inhaled dose with a jet nebulizer via the Metaneb CHFO device was lower than with a jet nebulizer alone. Placement of a vibrating mesh nebulizer at the airway and distressed breathing increased inhaled dose.

The Ratio of Nasal Cannula Gas Flow to Patient Inspiratory Flow on Trans-nasal Pulmonary Aerosol Delivery for Adults: An in Vitro Study.

Trans-nasal aerosol deposition during distressed breathing is higher than quiet breathing, and decreases as administered gas flow increases. We hypothesize that inhaled dose is related to the ratio of gas flow to patient inspiratory flow (GF:IF). An adult manikin (Laerdal) with a collecting filter placed at trachea was connected to a dual-chamber model lung, which was driven by a ventilator to simulate quiet and distressed breathing with different inspiratory flows. Gas flow was set at 5, 10, 20, 40 and 60 L/min. Albuterol (2.5mg in 1 mL) was nebulized by vibrating mesh nebulizer at the inlet of humidifier at 37 °C for each condition (n = 3). Drug was eluted from the filter and assayed with UV spectrophotometry (276 nm). GF:IF was the primary predictor of inhaled dose (p < 0.001). When the ratio was < 1.0, the inhaled dose was higher than ratio > 1.0 (21.8 ± 3.8% vs. 9.0 ± 3.7%, p < 0.001), and the inhaled dose was similar between quiet and distressed breathing (22.3 ± 5.0% vs. 21.3 ± 2.7%, p = 0.379). During trans-nasal aerosol delivery, GF:IF primarily affected the inhaled dose. Compared to the ratio above 1.0, the ratio below 1.0 produced a higher and more-consistent inhaled dose.

Decrease the flow setting to improve trans-nasal pulmonary aerosol delivery via "high-flow nasal cannula" to infants and toddlers.

OBJECTIVES: Trans-nasal pulmonary aerosol delivery for infants and toddlers has recently gained popularity, however, the reported lung deposition is low. We aimed to investigate the influential factors to improve the delivery. METHODS: Anatomic airway manikins simulating infant (5 kg) and toddler (15 kg) with collecting filter connected the trachea and breath simulator, were set to represent quiet and distressed breathing. Nasal cannula flow was set at 0.125, 0.25, 0.5, 1, and 2 L/kg/min. A mesh nebulizer (Aerogen) was placed at the inlet of humidifier (Fisher & Paykel) and proximal to patient. Albuterol (5 mg in 1 mL) was nebulized for each condition (n = 3). Drug was eluted from the filter and assayed with UV spectrophotometry (276 nm). RESULTS: Inhaled dose was higher with nebulizer placed at the inlet of humidifier than proximal to patient in all settings, except the infant model at low gas flow settings (0.125 and 0.25 L/kg/min). When nebulizer was placed at the inlet of humidifier, inhaled dose was higher when gas flow was below patient's inspiratory flow than when gas flow exceeded patient's inspiratory flow (8.77 ± 3.84 vs 2.16 ± 1.29%, P < 0.001); aerosol deposition increased as gas flow decreased, with greatest deposition at gas flow of 0.25 L/kg/min (11.29 ± 2.15%). A multiple linear regression identified gas flow as the primary predictor of aerosol delivery. CONCLUSIONS: Trans-nasal pulmonary aerosol delivery was significantly improved when gas flow was below patient's inspiratory flow, aerosol deposition increased with decreased nasal cannula flow, with greatest deposition at 0.25 L/kg/min.