Feasibility of synchronized high flow nasal cannula.

BACKGROUND: A high-flow nasal cannula (cHFNC) delivers flow continuously (during inspiration and expiration). Using the diaphragm electrical activity (Edi), synchronizing HFNC could be an alternative (cycling high/low flow on inspiration/expiration, respectively). The objective of this study was to demonstrate the feasibility of synchronized HFNC (sHFNC) and compare it to cHFNC. METHODS: Different levels of cHFNC and sHFNC (4, 6, 8, and 10 liters per minute [LPM], with 2 LPM on expiration for sHFNC) were compared in eight rabbits (mean weight 3.16 kg), before and after acute lung injury (pre-ALI and post-ALI). Edi, tracheal pressure (Ptr), esophageal pressure (Pes), flow, and arterial CO2 were measured. In addition to the animal study, one 3.52 kg infant received sHFNC and cHFNC using a Servo-U ventilator. RESULTS: In the animal study, there were more pronounced decreases in Edi, reduced Pes swings and reduced PaCO2 at comparable flows during sHFNC compared to cHFNC both pre and post-ALI (p < .05). Baseline (pre-inspiratory) Ptr was 2-7 cmH2O greater during cHFNC (p < .05) indicating more dynamic hyperinflation. In one infant, the ventilator performed as expected, delivering Edi-synchronized high/low flow. CONCLUSION: Synchronizing high flow unloaded breathing, decreased Edi, and reduced PaCO2 in an animal model and is feasible in infants.

The Diaphragmatic Initiated Ventilatory Assist (DIVA) trial: study protocol for a randomized controlled trial comparing rates of extubation failure in extremely premature infants undergoing extubation to non-invasive neurally adjusted ventilatory assist versus non-synchronized nasal intermittent positive pressure ventilation.

BACKGROUND: Invasive mechanical ventilation contributes to bronchopulmonary dysplasia (BPD), the most common complication of prematurity and the leading respiratory cause of childhood morbidity. Non-invasive ventilation (NIV) may limit invasive ventilation exposure and can be either synchronized or non-synchronized (NS). Pooled data suggest synchronized forms may be superior. Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) delivers NIV synchronized to the neural signal for breathing, which is detected with a specialized catheter. The DIVA (Diaphragmatic Initiated Ventilatory Assist) trial aims to determine in infants born 240/7-276/7 weeks' gestation undergoing extubation whether NIV-NAVA compared to non-synchronized nasal intermittent positive pressure ventilation (NS-NIPPV) reduces the incidence of extubation failure within 5 days of extubation. METHODS: This is a prospective, unblinded, pragmatic, multicenter phase III randomized clinical trial. Inclusion criteria are preterm infants 24-276/7 weeks gestational age who were intubated within the first 7 days of life for at least 12 h and are undergoing extubation in the first 28 postnatal days. All sites will enter an initial run-in phase, where all infants are allocated to NIV-NAVA, and an independent technical committee assesses site performance. Subsequently, all enrolled infants are randomized to NIV-NAVA or NS-NIPPV at extubation. The primary outcome is extubation failure within 5 days of extubation, defined as any of the following: (1) rise in FiO2 at least 20% from pre-extubation for > 2 h, (2) pH ≤ 7.20 or pCO2 ≥ 70 mmHg; (3) > 1 apnea requiring positive pressure ventilation (PPV) or ≥ 6 apneas requiring stimulation within 6 h; (4) emergent intubation for cardiovascular instability or surgery. Our sample size of 478 provides 90% power to detect a 15% absolute reduction in the primary outcome. Enrolled infants will be followed for safety and secondary outcomes through 36 weeks' postmenstrual age, discharge, death, or transfer. DISCUSSION: The DIVA trial is the first large multicenter trial designed to assess the impact of NIV-NAVA on relevant clinical outcomes for preterm infants. The DIVA trial design incorporates input from clinical NAVA experts and includes innovative features, such as a run-in phase, to ensure consistent technical performance across sites. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , trial identifier NCT05446272 , registered July 6, 2022.

The effect of bethanechol on tracheobronchomalacia in preterm infants with bronchopulmonary dysplasia: a retrospective cohort study.

OBJECTIVE: Bethanechol has demonstrated improvement in trachealis tone in animal models, but no trials have studied efficacy in infants. This study aimed to examine if bethanechol improves a standardized pulmonary severity score (PSS) in infants with severe bronchopulmonary dysplasia with a diagnosis of tracheobronchomalacia (TBM). STUDY DESIGN: This retrospective cohort study evaluated cases treated with bethanechol matched with controls who did not receive bethanechol. TBM was diagnosed by dynamic computography. Daily PSS was recorded for each infant from 40 to 55 weeks post-menstrual age. RESULTS: Cases' mean PSS change was 21% lower than the controls' mean PSS change pre- and post-bethanechol (95% CI -40%, -2%) by paired t-test (p = 0.03). Matched differences (controls' PSS - cases' PSS) demonstrated greater mean PSS difference post-bethanechol compared to pre-bethanechol 0.17, (95% CI 0.05, 0.29) by paired t-test (p = 0.009). CONCLUSION: Infants with TBM treated with bethanechol compared to those not treated had a lower PSS reflecting improved respiratory status.

Tidal volume delivery during nasal intermittent positive pressure ventilation: infant cannula vs. nasal continuous positive airway pressure prongs.

OBJECTIVE: To measure tidal volume delivery during nasal intermittent positive pressure ventilation with two nasal interfaces: infant cannula and nasal prongs. STUDY DESIGN: A single-center crossover study of neonates with mild respiratory distress. Fifteen preterm neonates were randomized to initial interface of infant cannula or nasal prongs and monitored on a sequence of pressure settings first on the initial interface, then repeated on the alternate interface. We compared relative tidal volumes between the two interfaces with two-way repeated measures ANOVA during three breath types: synchronized (I), patient effort without ventilator breaths (II), and ventilator breaths without patient effort (III). Clinical trial #NCT04326270. RESULTS: Type III breaths delivered no significant tidal volume. No significant difference was measured in relative tidal volume delivery between the interfaces when breath types were matched. CONCLUSIONS: Nasal intermittent positive pressure ventilation delivers neither clinically nor statistically significant tidal volume with either infant cannula or nasal prongs.

Dynamic computed tomography for evaluation of tracheobronchomalacia in premature infants with bronchopulmonary dysplasia.

INTRODUCTION: Dynamic computed tomography (dCT) gives real-time physiological information and objective descriptions of airway narrowing in tracheobronchomalacia (TBM). There is a paucity of literature in the evaluation of TBM by dCT in premature infants with bronchopulmonary dysplasia (BPD). The aim of this study is to describe the findings of dCT and resultant changes in management in premature infants with TBM. METHODS: A retrospective study of 70 infants was performed. Infants included were <32 weeks gestation without major anomalies. TBM was defined as ≥50% expiratory reduction in cross-sectional area with severity defined as mild (50%-75%), moderate (≥75%-90%), or severe (≥90%). RESULTS: Dynamic CT diagnosed malacia in 53% of infants. Tracheomalacia was identified in 49% of infants with severity as 76% mild, 18% moderate, and 6% severe. Bronchomalacia was identified in 43% of infants with varying severity (53% mild, 40% moderate, 7% severe). Resultant management changes included PEEP titration (44%), initiation of bethanechol (23%), planned tracheostomy (20%), extubation trial (13%), and inhaled ipratropium bromide (7%). CONCLUSION: Dynamic CT is a useful noninvasive diagnostic tool for airway evaluation of premature infants. Presence and severity of TBM can provide actionable information to guide more precise clinical decision making.

Implementing a Weaning Protocol for Noninvasive Respiratory Support in Neonates Decreases Overuse and Length of Stay.

BACKGROUND: As part of efforts to decrease length of hospital stay, a protocol for weaning noninvasive respiratory support was implemented using quality improvement methodology. The objective of this study was to determine whether protocol implementation decreased the time to wean to no respiratory support by 24 h (30% reduction) over 3 months in preterm infants 30-34 weeks gestational age. METHODS: A quality improvement project was conducted with the following outcome measures: primary outcome measured was hours to wean; secondary outcomes included duration of respiratory support, length of stay, and postmenstrual age at feeding milestones; and balance measures were duration of oxygen exposure and growth velocity. RESULTS: Data from 89 subjects were included. Following implementation, decreases were seen in time to wean (40% reduction, P < .001), length of stay (25% reduction, P = .02), and growth velocity (21% reduction, P = .02). CONCLUSIONS: Implementing a weaning protocol decreases duration of support and length of stay in infants 30-34 weeks gestational age. Weaning respiratory support more quickly may decrease growth velocity.

Work of Breathing in Premature Neonates: Noninvasive Neurally-Adjusted Ventilatory Assist versus Noninvasive Ventilation.

BACKGROUND: We tested whether work of breathing in premature newborns estimated by phase angle (θ) by using respiratory inductance plethysmography is decreased during neurally-adjusted ventilatory assist (NAVA) noninvasive ventilation (NIV) versus NIV alone. METHODS: NAVA NIV and NIV were applied in random order while using respiratory inductance plethysmography to measure the phase angle. RESULTS: Patient-ventilator asynchrony was decreased during NAVA NIV; however, the phase angle was not different between the modes. A large number of repeated assists with switches to backup were found when using NAVA NIV. Results of the analysis indicated these were due to the apnea alarm limit set during NAVA NIV. CONCLUSIONS: The improvement in patient-ventilator synchrony supports the hypothesis that work of breathing may be decreased with NAVA NIV; however, we were unable to demonstrate this with our study design. Short apnea time settings with NAVA NIV led to a large number of switches to backup and repeated assists during the same neural effort. (ClinicalTrials.gov registration NCT02788110.).

Tidal volume transmission during non-synchronized nasal intermittent positive pressure ventilation via RAM® cannula.

BACKGROUND: Nasal intermittent positive pressure ventilation (NIPPV) is a widely used mode of support in neonates, during which ventilator inflations may or may not coincide with spontaneous breathing. OBJECTIVE: We tested the hypothesis that inflations delivered with NIPPV via RAM® cannula and not accompanied by patient effort produce minimal tidal volume as measured by respiratory inductance plethysmography. DESIGN/METHODS: Fourteen subjects were monitored while receiving NIPPV. We compared tidal volumes during ventilator-supported breaths, unsupported breaths, and ventilator inflations not accompanied by patient effort (defined using electrical activity of the diaphragm). RESULTS: Mean tidal volumes in arbitrary units were 0.30 ± 0.22 in NIPPV inflations associated with patient effort and 0.27 ± 0.15 in spontaneous breaths without ventilator assistance (p = 0.82). Tidal volumes during ventilator-only inflations were 0.06 ± 0.04 (p < 0.005 vs. both ventilator-assisted and unassisted efforts). CONCLUSIONS: NIPPV via RAM cannula produces minimal, clinically insignificant tidal volumes during non-spontaneous inflations.

Effect of Transcutaneous Electrode Temperature on Accuracy and Precision of Carbon Dioxide and Oxygen Measurements in the Preterm Infants.

BACKGROUND: High electrode temperature during transcutaneous monitoring is associated with skin burns in extremely premature infants. We evaluated the accuracy and precision of CO2 and O2 measurements using lower transcutaneous electrode temperatures below 42°C. METHODS: We enrolled 20 neonates. Two transcutaneous monitors were placed simultaneously on each neonate, with one electrode maintained at 42°C and the other randomized to temperatures of 38, 39, 40, 41, and 42°C. Arterial blood was collected twice at each temperature. RESULTS: At the time of arterial blood sampling, values for transcutaneously measured partial pressure of CO2 (PtcCO2 ) were not significantly different among test temperatures. There was no evidence of skin burning at any temperature. For PtcCO2 , Bland-Altman analyses of all test temperatures versus 42°C showed good precision and low bias. Transcutaneously measured partial pressure of O2 (PtcO2 ) values trended arterial values but had large negative bias. CONCLUSION: Transcutaneous electrode temperatures as low as 38°C allow an assessment of PtcCO2 as accurate as that with electrodes at 42°C.