Physiological Changes With High-Flow Nasal Cannula

Physiological Changes With High-Flow Nasal Cannula Compared to Nasal CPAP in Extremely Low Birth Weight Infants

To measure changes in physiologic parameters in extremely low birthweight (ELBW) infants on high-flow nasal cannula compared to nasal continuous positive airway pressure (nCPAP).

Study Overview

• Status: Completed
• Conditions: Respiratory Distress Syndrome in Premature Infant
• Intervention / Treatment: Procedure: Nasal CPAP; Procedure: High flow nasal cannula

Detailed Description

After informed consent is obtained, eligible infants who are stable on nCPAP therapy of 5-7 cm H20 achieved with a ventilator, an underwater "bubble" system, or a variable-flow device will be enrolled.

All subjects will have physiologic data and electrical impedance tomography collected at:

1. Baseline nCPAP for 15 minutes
2. Upon transition to high flow nasal cannula at 8 LPM for 6 hours. Data collection is obtained after infant is calm for 15 minutes at the beginning and end of this 6 hour period
3. Then upon return to baseline NCPAP for a final 15 minutes of data collection.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Sharp Mary Birch Hospital for Women & Newborns

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 6 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 23 to 28+6 weeks gestational age at birth
• Corrected gestational age less than or equal to 30 weeks
• Over 72 hours of life
• Stable on Nasal CPAP of 5-7cm H20
• Hemodynamically stable
• Tolerating routine handling
• Nares size appropriate for Fisher & Paykel Optiflow Jr 2 HFNC size XS or small
• Successfully extubated for 12 hours after administration of surfactant
• Caffeine Citrate at a maintenance dose of 5 to 10 mg /kg
• Transcutaneous monitoring in place
• Stable blood gas (pH>/= 7.25 and PaCO2 <60 mmHg torr)

Exclusion Criteria:

• Prior pneumothorax or evidence of pulmonary interstitial emphysema.
• Prior or current pulmonary hemorrhage
• Congenital airway malformations
• Major cardiopulmonary malformations
• Congenital Diaphragmatic hernia or untreated bowel obstruction
• Poor respiratory drive unresponsive to CPAP therapy
• Requirement of a nCPAP of >8 cmH20 or FiO2 > 0.3 to maintain oxygen saturations between 90-95 percent.
• Receiving positive pressure breaths or SIPAP on prongs
• Conflicting clinical trial
• Clinically unstable per physician discretion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nasal CPAP - Period 1; Eligible infants stable on high flow nasal cannula (nCPAP) therapy of 5-7 cm H20 achieved with a ventilator, an underwater "bubble" system, or a variable-flow device will be enrolled. A data acquisition cart will be placed at the subject's bedside to collect hemodynamic and respiratory parameters measured including: Heart rate (HR), blood pressure (BP), respiratory rate (RR), fraction of inspired oxygen (FiO2), transcutaneous carbon dioxide (TcCO2), and peripheral oxygen saturation (SpO2) via bedside monitoring devices. A neonatal chest belt, sized to the infant's chest circumference (nipple level) using warmed ultrasound gel applied to the belt beforehand, will collect regional lung volume measurements using electrical impedance tomography (EIT). Subject video recording will capture apnea events and the interventions used to resolve them such as positive pressure ventilation, repositioning, or stimulation. Data will be collected for 15 minutes on nCPAP.	Procedure: Nasal CPAP; Nasal continuous positive airway pressure of 5-7 cm/H20 delivered using Ventilator or bubble cpap device through short nasal prongs or a nasal face mask.
Active Comparator: High Flow Nasal Cannula (HFNC) - Period 2 & 3; Respiratory support will be crossed over to a HFNC Optiflow Jr 2 (Fisher & Paykel Healthcare, Auckland, New Zealand) at a flow rate of 8 LPM. The size of the nasal cannula will be determined according to the manufacturer's instructions in order to maintain a leak at the nares. Identical data collection will occur for two 15 minute periods on HFNC, at the beginning and end of the six hour Study period.	Procedure: High flow nasal cannula; 8 liters per minute of blended oxygen through Fisher Paykel Optiflow Jr 2 nasal prongs.
Active Comparator: Nasal CPAP - Period 4; After 6 hours of HFNC of 8 LPM, or sooner if the infant meets failure criteria, the infant will then be crossed back to the nCPAP device and at the settings previously utilized in Study Period 1. The infant will remain on the nCPAP device with identical data collection for 15 minutes. The total duration of the study and data collection will be 8 hours. The infant's body position will be similar for each lung volume measurement during the study periods.	Procedure: Nasal CPAP; Nasal continuous positive airway pressure of 5-7 cm/H20 delivered using Ventilator or bubble cpap device through short nasal prongs or a nasal face mask.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Unventilated Lung as Assessed by Electrical Impedance Tomography	Atelectasis will be calculated using the percentage of the lung fields that are not engaged in tidal volume.(VT) In Period 1 (nCPAP Baseline), infants on nCPAP at 5-7 cmH₂O in the supine position underwent up to 15 minutes of quiet-breathing EIT recording. In Period 2 (30 min on HFNC), infants were transitioned to HFNC at 8 L/min, and if tolerated, up to 15 minutes of EIT were collected at ~30 minutes. In Period 3 (6 hr on HFNC or earlier if failure), infants who tolerated HFNC underwent EIT at 6 hours; those meeting failure criteria returned immediately to nCPAP and were analyzed as Period 3 without a 6-hour EIT. In Period 4 (60 min after return to nCPAP), infants resumed nCPAP and up to 15 minutes of EIT were obtained about 60 minutes later. In period 4 one participant had missing primary outcome data and were analyzed as Period 4 without a 60 min return to nCPAP EIT measurement.	Primary outcome was measured during each study period: baseline on nCPAP, 30 minutes after starting HFNC, at 6 hours on HFNC or earlier if failure, and 60 minutes after returning to nCPAP.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Center of Ventilation (CoV) - Ventral Dorsal	Spatial center of tidal volume distribution in the thorax during ventilation	This secondary outcome was measured during each study period: baseline on nCPAP, 30 minutes after starting HFNC, at 6 hours on HFNC or earlier if failure, and 60 minutes after returning to nCPAP.
End-expiratory Lung Impedance	End-expiratory lung impedance was measured using electrical impedance tomography (EIT) to assess changes in end-expiratory lung volume. EELI reflects the sum of impedance values across all ventilated lung pixels at the end of expiration and provides an estimate of lung aeration. Values were derived from artifact-free tidal breaths captured during quiet breathing using the neonatal EIT belt and LuMon EIT system.	This secondary outcome was measured during each study period: baseline on nCPAP, 30 minutes after starting HFNC, at 6 hours on HFNC or earlier if failure, and 60 minutes after returning to nCPAP.
Relative Tidal Stetch	Measurement of how much stretch the lung tissue undergoes during inspiration relative to baseline impedance	This secondary outcome was measured during each study period: baseline on nCPAP, 30 minutes after starting HFNC, at 6 hours on HFNC or earlier if failure, and 60 minutes after returning to nCPAP.
Oxygenation Ratio	Values <+3 → poor oxygenation relative to ventilation (inefficient V/Q matching) Values 4-6 → moderate efficiency Values >6 → good oxygenation efficiency relative to ventilation	Study Period 1 through 4

Collaborators and Investigators

• Sponsor: Sharp HealthCare
• Investigators: Principal Investigator: Anup Katheria, MD, Sharp Healthcare

Publications and helpful links

General Publications

• Katheria A, Ines F, Hough J, Rich W, Morales A, Sanjay S, Poeltler D, Finer N. Changes in lung aeration with high-flow nasal cannula compared to nasal CPAP in preterm infants. J Perinatol. 2025 Jun;45(6):817-822. doi: 10.1038/s41372-025-02267-4. Epub 2025 Mar 23.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2019
• Primary Completion (Actual): December 20, 2021
• Study Completion (Actual): February 14, 2022

Study Registration Dates

• First Submitted: October 5, 2018
• First Submitted That Met QC Criteria: October 5, 2018
• First Posted (Actual): October 9, 2018

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: high flow nasal cannula; nasal cpap
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Infant, Premature, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
• Other Study ID Numbers: HFNC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No