Effect of Early High-Flow Nasal Oxygen vs Standard Oxygen Therapy on Length of Hospital Stay in Hospitalized Children With Acute Hypoxemic Respiratory Failure: The PARIS-2 Randomized Clinical Trial.

Importance: Nasal high-flow oxygen therapy in infants with bronchiolitis and hypoxia has been shown to reduce the requirement to escalate care. The efficacy of high-flow oxygen therapy in children aged 1 to 4 years with acute hypoxemic respiratory failure without bronchiolitis is unknown. Objective: To determine the effect of early high-flow oxygen therapy vs standard oxygen therapy in children with acute hypoxemic respiratory failure. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted at 14 metropolitan and tertiary hospitals in Australia and New Zealand, including 1567 children aged 1 to 4 years (randomized between December 18, 2017, and March 18, 2020) requiring hospital admission for acute hypoxemic respiratory failure. The last participant follow-up was completed on March 22, 2020. Interventions: Enrolled children were randomly allocated 1:1 to high-flow oxygen therapy (n = 753) or standard oxygen therapy (n = 764). The type of oxygen therapy could not be masked, but the investigators remained blinded until the outcome data were locked. Main Outcomes and Measures: The primary outcome was length of hospital stay with the hypothesis that high-flow oxygen therapy reduces length of stay. There were 9 secondary outcomes, including length of oxygen therapy and admission to the intensive care unit. Children were analyzed according to their randomization group. Results: Of the 1567 children who were randomized, 1517 (97%) were included in the primary analysis (median age, 1.9 years [IQR, 1.4-3.0 years]; 732 [46.7%] were female) and all children completed the trial. The length of hospital stay was significantly longer in the high-flow oxygen group with a median of 1.77 days (IQR, 1.03-2.80 days) vs 1.50 days (IQR, 0.85-2.44 days) in the standard oxygen group (adjusted hazard ratio, 0.83 [95% CI, 0.75-0.92]; P < .001). Of the 9 prespecified secondary outcomes, 4 showed no significant difference. The median length of oxygen therapy was 1.07 days (IQR, 0.50-2.06 days) in the high-flow oxygen group vs 0.75 days (IQR, 0.35-1.61 days) in the standard oxygen therapy group (adjusted hazard ratio, 0.78 [95% CI, 0.70-0.86]). In the high-flow oxygen group, there were 94 admissions (12.5%) to the intensive care unit compared with 53 admissions (6.9%) in the standard oxygen group (adjusted odds ratio, 1.93 [95% CI, 1.35-2.75]). There was only 1 death and it occurred in the high-flow oxygen group. Conclusions and Relevance: Nasal high-flow oxygen used as the initial primary therapy in children aged 1 to 4 years with acute hypoxemic respiratory failure did not significantly reduce the length of hospital stay compared with standard oxygen therapy. Trial Registration: anzctr.org.au Identifier: ACTRN12618000210279.

Nasal High Flow in Room Air for Hypoxemic Bronchiolitis Infants.

Background: Bronchiolitis is the most common reason for hospital admission in infants, with one third requiring oxygen therapy due to hypoxemia. It is unknown what proportion of hypoxemic infants with bronchiolitis can be managed with nasal high-flow in room air and their resulting outcomes. Objectives and Settings: To assess the effect of nasal high-flow in room air in a subgroup of infants with bronchiolitis allocated to high-flow therapy in a recent multicenter randomized controlled trial. Patients and Interventions: Infants allocated to the high-flow arm of the trial were initially treated with room air high-flow if saturations were ≥85%. Subsequently, if oxygen saturations did not increase to ≥92%, oxygen was added and FiO2 was titrated to increase the oxygen saturations. In this planned sub-study, infants treated during their entire hospital stay with high-flow room air only were compared to infants receiving either standard-oxygen or high-flow with oxygen. Baseline characteristics, hospital length of stay and length of oxygen therapy were compared. Findings: In the per protocol analysis 64 (10%) of 630 infants commenced on high-flow room air remained in room air only during the entire stay in hospital. These infants on high-flow room air were on average older and presented with moderate hypoxemia at presentation to hospital. Their length of respiratory support and length of stay was also significantly shorter. No pre-enrolment factors could be identified in a multivariable analysis. Conclusions: In a small sub-group of hypoxemic infants with bronchiolitis hypoxemia can be reversed with the application of high-flow in room air only. Trial registration: ACTRN12615001305516.

The effect of high flow nasal cannula therapy on the work of breathing in infants with bronchiolitis.

The main physiological impact of high flow nasal cannula (HFNC) therapy is presumed to be a decrease in work of breathing (WOB). To assess this, diaphragmatic electrical activity and esophageal pressure changes were measured off then on HFNC delivered at 2 L/kg/min, in 14 infants with bronchiolitis and 14 cardiac infants. Electrical activity of the diaphragm (Edi) was measured using an Edi catheter with calculations of signal peak (EdiMAX ) and amplitude (EdiAMPL ). Pressure-rate and pressure-time products (PRP, PTP) were calculated from analyses of esophageal pressure. Changes in end-expiratory lung volume were measured using respiratory inductance plethysmography (RIPEEL ). The EdiMAX and EdiAMPL were significantly higher in infants with bronchiolitis than in cardiac infants (P < 0.05). Within the bronchiolitis group, both were significantly reduced between HFNC states from 27.9 µV [20.4, 35.4] to 21.0 µV [14.8, 27.2] and from 25.1 µV [18.0, 32.2] to 19.2 µV [13.3, 25.1], respectively (mean, 95% CI, P < 0.05). A less prominent offload of the diaphragm was observed in cardiac infants (P < 0.05). WOB decreased in both groups with a significant reduction of PRP and PTP (P < 0.05). RIPEEL increased significantly in bronchiolitis only (P < 0.05). HFNC offloads the diaphragm and reduces the WOB in bronchiolitis. A similar effect was demonstrated in cardiac infants, a group without signs of airway-obstruction.

Physiologic effect of high-flow nasal cannula in infants with bronchiolitis.

OBJECTIVE: To assess the effect of delivering high-flow nasal cannula flow on end-expiratory lung volume, continuous distending pressure, and regional ventilation distribution in infants less than 12 months old with bronchiolitis. DESIGN: Prospective observational clinical study. SETTING: Nineteen bed medical and surgical PICU. PATIENTS: Thirteen infants with bronchiolitis on high-flow nasal therapy. INTERVENTIONS: The study infants were measured on a flow rate applied at 2 and 8 L/min through the high-flow nasal cannula system. MEASUREMENTS AND RESULTS: Ventilation distribution was measured with regional electrical impedance amplitudes and end-expiratory lung volume using electrical impedance tomography. Changes in continuous distending pressure were measured from the esophagus via the nasogastric tube. Physiological variables were also recorded. High-flow nasal cannula delivered at 8 L/min resulted in significant increases in global and anterior end-expiratory lung volume (p < 0.01) and improvements in the physiological variables of respiratory rate, SpO2, and FIO2 when compared with flows of 2 L/min. CONCLUSION: In infants with bronchiolitis, high-flow nasal cannula oxygen/air delivered at 8 L/min resulted in increases in end-expiratory lung volume and improved respiratory rate, FIO2, and SpO2.

Ventilation and cardiac related impedance changes in children undergoing corrective open heart surgery.

Electrical impedance tomography (EIT) can determine ventilation and perfusion relationship. Most of the data obtained so far originates from experimental settings and in healthy subjects. The aim of this study was to demonstrate that EIT measures the perioperative changes in pulmonary blood flow after repair of a ventricular septum defect in children with haemodynamic relevant septal defects undergoing open heart surgery. In a 19 bed intensive care unit in a tertiary children's hospital ventilation and cardiac related impedance changes were measured using EIT before and after surgery in 18 spontaneously breathing patients. The EIT signals were either filtered for ventilation (ΔZV) or for cardiac (ΔZQ) related impedance changes. Impedance signals were then normalized (normΔZV, normΔZQ) for calculation of the global and regional impedance related ventilation perfusion relationship (normΔZV/normΔZQ). We observed a trend towards increased normΔZV in all lung regions, a significantly decreased normΔZQ in the global and anterior, but not the posterior lung region. The normΔZV/normΔZQ was significantly increased in the global and anterior lung region. Our study qualitatively validates our previously published modified EIT filtration technique in the clinical setting of young children with significant left-to-right shunt undergoing corrective open heart surgery, where perioperative assessment of the ventilation perfusion relation is of high clinical relevance.

Effect of body position on ventilation distribution in preterm infants on continuous positive airway pressure.

RATIONALE: Although continuous positive airway pressure is used extensively in neonatal intensive care units, and despite the belief that positioning is considered vital to the maintenance of good lung ventilation, no data exist on regional ventilation distribution in infants on continuous positive airway pressure ventilatory support. OBJECTIVES: To investigate the effect of body position on regional ventilation in preterm infants on continuous positive airway pressure ventilatory support using electrical impedance tomography. DESIGN: Randomized crossover study design. SETTING: Neonatal intensive care unit. PATIENTS: Twenty-four preterm infants on continuous positive airway pressure were compared to six spontaneously breathing preterm infants. INTERVENTIONS: Random assignment of the order of the positions supine, prone, and quarter prone. MEASUREMENTS AND RESULTS: Changes in global and regional lung volume were measured with electrical impedance tomography. Although there were no differences between positions, regional tidal volume was increased in the posterior compared with the anterior lung (p < .01) and in the right compared with the left lung (p < .03) in both the spontaneously breathing infants and in the infants on continuous positive airway pressure. The posterior lung filled earlier than the anterior lung in the spontaneously breathing infants (p < .02), whereas in the infants on continuous positive airway pressure the right lung filled before the left lung (p < .01). There was more ventilation inhomogeneity in the infants on continuous positive airway pressure than in the healthy infants (p < .01). CONCLUSIONS: This study presents the first results on regional ventilation distribution in preterm infants on continuous positive airway pressure using electrical impedance tomography. Gravity had little impact on regional ventilation distribution in preterm infants on continuous positive airway pressure or in spontaneously breathing infants in the supine or prone position, indicating that ventilation distribution in preterm infants is not gravity-dependent but follows an anatomical pattern. AUSTRALIA NEW ZEALAND CLINICAL TRIALS REGISTRY:: ACTRN12606000210572.

The effect of induction of anesthesia and intubation on end-expiratory lung level and regional ventilation distribution in cardiac children.

BACKGROUND: During the induction of anesthesia, changes in functional residual capacity and ventilation distribution (VD) occur. Although these physiological changes are well investigated in adults, little data are available in infants and children. AIM: To describe continuous changes in lung physiology during the induction of anesthesia in infants and children using electrical impedance tomography (EIT). METHODS: Lung mechanics and volume changes in 38 infants and children undergoing elective cardiac surgery were assessed using EIT before, during, and after the induction of anesthesia. End-expiratory level (EEL as an equivalent to FRC) and VD were measured with EIT and referenced to a period of spontaneous breathing prior to induction. RESULTS: EEL changed significantly during induction with the lowest during the intubation phase and normalized with the application of positive end-expiratory pressures (PEEP) after induction. Ventilation prior to induction was preferentially distributed toward the dependent lung, whereas after induction, the nondependent lung was better ventilated. PEEP during mechanical ventilation did not improve ventilation inhomogeneity. CONCLUSION: Lung volume and mechanics deteriorate significantly during the induction of anesthesia and remain altered during mechanical ventilation.