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HFNCandEOB: HFNC Flow Titration and Effort of Breathing in the PICU

Sponsor
Children's Hospital Los Angeles (Other)
Overall Status
Completed
CT.gov ID
NCT02793674
Collaborator
(none)
21
Enrollment
1
Location
2
Arms
22
Duration (Months)
1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

High-flow nasal cannula (HFNC) is a method of non-invasive respiratory support used to decrease the effort of breathing (EOB) in patients with a wide variety of respiratory diseases in the pediatric intensive care unit. While its use has shown association with decreased rates of mechanical ventilation, there is a paucity of data examining its direct effect upon objective measurements of EOB. This study will aim to evaluate objective measurements of EOB in response to different levels of HFNC support, characterize the natural course of respiratory diseases treated with HFNC, evaluate changes in EOB secondary to the administration of supplemental medical therapies used in conjunction with HFNC, and compare different physiologic metrics for quantifying EOB in patients on HFNC.

Condition or Disease Intervention/Treatment Phase
  • Device: Fisher & Paykel high flow nasal cannula
  • Device: Vapotherm high flow nasal cannula
 N/A

Study Design

Study Type:
Interventional
Actual Enrollment :
21 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
High-Flow Nasal Cannula Flow Titration and Effort of Breathing in the Pediatric Intensive Care Unit
Study Start Date :
Sep 1, 2014
Actual Primary Completion Date :
Jul 1, 2016
Actual Study Completion Date :
Jul 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Other: Fisher & Paykel high flow nasal cannula

All participants in the study were on one or two high flow nasal cannula (HFNC) delivery systems. All were measured on the Fisher & Paykel HFNC delivery system. The flow rate of the HFNC was adjusted to determine if there exists a change in their effort of breathing.

Device: Fisher & Paykel high flow nasal cannula
Measurements of effort of breathing will be obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time will be allowed at each flow rate for stabilization of EOB and flow levels will be trialed in a random order, each being trialed for approximately 5 minutes.
Other: Vapotherm high flow nasal cannula

All participants in the study were on one or two high flow nasal cannula (HFNC) delivery systems. A subgroup was measured on the Vapotherm HFNC delivery system. The flow rate of the HFNC was adjusted to determine if there exists a change in their effort of breathing.

Device: Vapotherm high flow nasal cannula
Measurements of effort of breathing will be obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time will be allowed at each flow rate for stabilization of EOB and flow levels will be trialed in a random order, each being trialed for approximately 5 minutes.

Outcome Measures

Primary Outcome Measures

  1. Percent Change in Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) [median percent change in PRP over 5 minute measurement period]

    PRP is a validated objective metric of effort of breathing which is derived from the product of the peak-to-trough change in esophageal pressure (in cmH20) and the respiratory rate (breaths per minute). The percent change in PRP is derived from the quotient of the absolute PRP at increased HFNC flow rates (1.0, 1.5, and 2.0 L/kg/min) divided by the absolute PRP at a baseline HFNC flow rate (0.5 L/kg/min). Percent change in PRP was used because a) there was a large degree of heterogeneity in baseline absolute PRP values in our study population based upon patient size, disease severity, and time point of illness, and b) we allowed for repeated measures on the same patient which would bias absolute PRP values in favor of those who were measured more frequently. It was not pre-specified to compare the two different HFNC delivery systems.

Secondary Outcome Measures

  1. Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) [median PRP over a 5 minute period]

    PRP is a validated objective metric of effort of breathing which is derived from the product of the peak-to-trough change in esophageal pressure (in cmH20) and the respiratory rate (breaths per minute). These values were obtained from 5 minute flow titration periods. For this outcome, the PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). It was not pre-specified to compare the two different HFNC delivery systems.

  2. Phase Angle as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) [median phase angle over a 5 minute period]

    Phase angle is a measure of asynchrony between thoracic and abdominal breathing compartments that has correlated with increased effort of breathing. It is derived by measuring the relative expansion of these two breathing compartments and describing the synchrony between them as an angle (theta). For this outcome, the phase angle was obtained for all titrations on both types of HFNC delivery system (FP and VT). It was not pre-specified to compare the two different HFNC delivery systems.

  3. Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Different HFNC Delivery Systems [median PRP over a 5 minute period]

    For this outcome, a subgroup of patients (N=12) were examined who had PRP measurements obtained on two different HFNC delivery systems (Fisher & Paykel (FP) and Vapotherm (VT)) in back-to-back flow titration periods. With one exception, patients were first studied on the FP and then transitioned to the VT HFNC delivery system.

  4. Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Weight-Stratified Subgroups on Both Types of HFNC Delivery System (FP and VT) [medain percent change in PRP over a 5 minute period]

    To assess the relationship between patient size and dose-response of HFNC flow rate, we compared subgroups stratified by weight (patients <8 kg and >8 kg). For this outcome, the median percent change in PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). It was not pre-specified to compare the two different HFNC delivery systems.

  5. Maximum Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Weight-Stratified Subgroups on Both Types of HFNC Delivery System (FP and VT) [median of the maximum percent change in PRP over a 5 minute period]

    Exploratory analysis of patients by further stratified weight groupings (<5 kg, 5-8 kg, and >8 kg) was performed to determine the greatest observed benefit of HFNC flow titration in patients of different sizes. For this outcome, the maximum percent change in PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). It was not pre-specified to compare the two different HFNC delivery systems.

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A to 3 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • All participants less than or equal to three years old admitted to the PICU placed on high flow nasal cannula will be considered eligible for the study.
Exclusion Criteria:
  • Participants will be excluded if they have a corrected gestational age less than 37 weeks or contraindications to nasoesophageal catheter placement (nasopharyngeal or esophageal abnormalities) or RIP bands (abdominal wall defects such as omphalocele). Patients greater than three years of age will be excluded.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Children's Hospital Los Angeles Los Angeles California United States 90027

Sponsors and Collaborators

  • Children's Hospital Los Angeles

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:
Children's Hospital Los Angeles
ClinicalTrials.gov Identifier:
NCT02793674
Other Study ID Numbers:
  • CHLA-14-00239
First Posted:
Jun 8, 2016
Last Update Posted:
Mar 4, 2021
Last Verified:
Jul 1, 2018
Keywords provided by Children's Hospital Los Angeles
effort of breathing
high flow nasal cannula
respiratory distress
Additional relevant MeSH terms:
Respiratory Aspiration

Study Results

Participant Flow

Recruitment Details This study screened patients admitted to the PICU during the study period (September 2014 to June 2016) who were <3 years of age and started on high flow nasal cannula by the clinical team.
Pre-assignment Detail Of the 54 patients who met eligibility criteria on screening, 39% (N=21) underwent high flow nasal cannula flow titrations and had effort of breathing measurements taken.
Arm/Group Title Fisher & Paykel (FP) HFNC Vapotherm (VT) HFNC
Arm/Group Description A subgroup of participants were placed exclusively on Fisher & Paykel (FP) high flow nasal cannula (HFNC) (N=9). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes. A subgroup of patients (N=12) had flow titrations performed on both Fisher & Paykel (FP) and Vapotherm (VT) high flow nasal cannula (HFNC) delivery systems. The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. These patients had flow titrations on both HFNC delivery systems performed to compare EOB on these two different HFNC delivery systems. With one exception, titrations were performed on FP first, then crossed over to VT. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes.
Period Title: Overall Study
STARTED 9 12
COMPLETED 9 12
NOT COMPLETED 0 0

Baseline Characteristics

Arm/Group Title Fisher & Paykel (FP) HFNC Vapotherm (VT) HFNC Total
Arm/Group Description A subgroup was studied on Fisher & Paykel (FP) high flow nasal cannula (HFNC) exclusively (N=9). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes. A subgroup was studied on Vapotherm (VT) high flow nasal cannula (HFNC) (N=12). These patients then crossed over to the other arm and had back-to-back titrations on both types of HFNC (FP and VT). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes. Total of all reporting groups
Overall Participants 9 12 21
Age (months) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [months]
15
4
6
Sex: Female, Male (Count of Participants)
Female
4
44.4%
5
41.7%
9
42.9%
Male
5
55.6%
7
58.3%
12
57.1%
Race/Ethnicity, Customized (Count of Participants)
African-American
0
0%
2
16.7%
2
9.5%
Hispanic
6
66.7%
9
75%
15
71.4%
Not specified
3
33.3%
1
8.3%
4
19%
Weight (kilograms) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kilograms]
9
6.5
6.5
Respiratory Illness (participants) [Number]
Bronchiolitis
6
66.7%
7
58.3%
13
61.9%
Pneumonia
2
22.2%
0
0%
2
9.5%
Other
1
11.1%
5
41.7%
6
28.6%

Outcome Measures

1. Primary Outcome
Title Percent Change in Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT)
Description PRP is a validated objective metric of effort of breathing which is derived from the product of the peak-to-trough change in esophageal pressure (in cmH20) and the respiratory rate (breaths per minute). The percent change in PRP is derived from the quotient of the absolute PRP at increased HFNC flow rates (1.0, 1.5, and 2.0 L/kg/min) divided by the absolute PRP at a baseline HFNC flow rate (0.5 L/kg/min). Percent change in PRP was used because a) there was a large degree of heterogeneity in baseline absolute PRP values in our study population based upon patient size, disease severity, and time point of illness, and b) we allowed for repeated measures on the same patient which would bias absolute PRP values in favor of those who were measured more frequently. It was not pre-specified to compare the two different HFNC delivery systems.
Time Frame median percent change in PRP over 5 minute measurement period

Outcome Measure Data

Analysis Population Description
For this outcome measure, the arms/groups were combined to include all patients enrolled in the study. This included the patients studied on FP only (n=9) and those studied on VT and FP both (n=12) for a total n=21.
Arm/Group Title Percent Change in Pressure-Rate Product
Arm/Group Description All participants in the study were placed on high flow nasal cannula (HFNC). For this outcome, the median percent change in PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes.
Measure Participants 21
Percent Change in PRP at 1.0 L/kg/min
-10
Percent Change in PRP at 1.5 L/kg/min
-20
Percent Change in PRP at 2.0 L/kg/min
-23
2. Secondary Outcome
Title Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT)
Description PRP is a validated objective metric of effort of breathing which is derived from the product of the peak-to-trough change in esophageal pressure (in cmH20) and the respiratory rate (breaths per minute). These values were obtained from 5 minute flow titration periods. For this outcome, the PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). It was not pre-specified to compare the two different HFNC delivery systems.
Time Frame median PRP over a 5 minute period

Outcome Measure Data

Analysis Population Description
For this outcome measure, the arms/groups were combined to include all patients enrolled in the study. This included the patients studied on FP only (n=9) and those studied on VT and FP both (n=12) for a total n=21.
Arm/Group Title Pressure-Rate Product
Arm/Group Description All participants in the study were placed on high flow nasal cannula (HFNC). or this outcome, the PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT).The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. Measurements of effort of breathing was obtained at flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/min. Adequate time was allowed at each flow rate for stabilization of EOB and flow levels were trialed in a random order, each for approximately 5 minutes.
Measure Participants 21
PRP at 0.5 L/kg/min
824
PRP at 1.0 L/kg/min
699
PRP at 1.5 L/kg/min
596
PRP at 2.0 L/kg/min
594
3. Secondary Outcome
Title Phase Angle as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT)
Description Phase angle is a measure of asynchrony between thoracic and abdominal breathing compartments that has correlated with increased effort of breathing. It is derived by measuring the relative expansion of these two breathing compartments and describing the synchrony between them as an angle (theta). For this outcome, the phase angle was obtained for all titrations on both types of HFNC delivery system (FP and VT). It was not pre-specified to compare the two different HFNC delivery systems.
Time Frame median phase angle over a 5 minute period

Outcome Measure Data

Analysis Population Description
For this outcome measure, the arms/groups were combined to include all patients enrolled in the study. This included the patients studied on FP only (n=9) and those studied on VT and FP both (n=12) for a total n=21.
Arm/Group Title Phase Angle
Arm/Group Description The phase angle was measured at all flow titrations for all patients on both types of HFNC delivery systems (FP and VT). This is a measure of thoracoabdominal asynchrony and a proxy for effort of breathing.
Measure Participants 21
0.5 L/kg/min
61
1.0 L/kg/min
61
1.5 L/kg/min
68
2.0 L/kg/min
59
4. Secondary Outcome
Title Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Different HFNC Delivery Systems
Description For this outcome, a subgroup of patients (N=12) were examined who had PRP measurements obtained on two different HFNC delivery systems (Fisher & Paykel (FP) and Vapotherm (VT)) in back-to-back flow titration periods. With one exception, patients were first studied on the FP and then transitioned to the VT HFNC delivery system.
Time Frame median PRP over a 5 minute period

Outcome Measure Data

Analysis Population Description
Percent change in PRP from baseline (of 0.5 L/kg/min) was measured at different flow rates (1.0, 1.5, and 2.0 L/kg/min) for patients who had flow titrations done on the two different HFNC delivery systems (Fisher & Paykel (FP) and Vapotherm (VT)).
Arm/Group Title Fisher & Paykel HFNC Delivery System Vapotherm HFNC Delivery System
Arm/Group Description This arm shows the outcome (the median of the percent change in PRP from baseline as a function of flow rate) for these patients when they were studied on the FP HFNC delivery system. This arm shows the outcome (the median of the percent change in PRP from baseline as a function of flow rate) for these patients when they were studied on the VT HFNC delivery system.
Measure Participants 12 12
1.0 L/kg/min
-15
-9
1.5 L/kg/min
-19
-22
2.0 L/kg/min
-23
-11
5. Secondary Outcome
Title Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Weight-Stratified Subgroups on Both Types of HFNC Delivery System (FP and VT)
Description To assess the relationship between patient size and dose-response of HFNC flow rate, we compared subgroups stratified by weight (patients <8 kg and >8 kg). For this outcome, the median percent change in PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). It was not pre-specified to compare the two different HFNC delivery systems.
Time Frame medain percent change in PRP over a 5 minute period

Outcome Measure Data

Analysis Population Description
For this outcome measure, the arms/groups were combined to include all patients enrolled in the study. This included the patients studied on FP only (n=9) and those studied on VT and FP both (n=12) for a total n=21.
Arm/Group Title Less Than or Equal to 8 kg Greater Than 8 kg
Arm/Group Description The percent change in Pressure-rate Product (PRP) from baseline as a function of increasing HFNC flow rate was analyzed comparing weight-stratified subgroups. This analysis looked at the first titration performed on the HFNC delivery system for patients less than or equal to 8 kg (12 patients, 20 episodes) and greater than 8 kg (9 patients, 12 episodes). This outcome was derived from flow titraitons on both types of HFNC delivery system (FP and VT). The percent change in Pressure-rate Product (PRP) from baseline as a function of increasing HFNC flow rate was analyzed comparing weight-stratified subgroups. This analysis looked at the first titration performed on the HFNC delivery system for patients less than or equal to 8 kg (12 patients, 20 episodes) and greater than 8 kg (9 patients, 12 episodes). This outcome was derived from flow titraitons on both types of HFNC delivery system (FP and VT).
Measure Participants 12 9
1.0 L/kg/min
-14
-5
1.5 L/kg/min
-27
-2
2.0 L/kg/min
-25
-15
6. Secondary Outcome
Title Maximum Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Weight-Stratified Subgroups on Both Types of HFNC Delivery System (FP and VT)
Description Exploratory analysis of patients by further stratified weight groupings (<5 kg, 5-8 kg, and >8 kg) was performed to determine the greatest observed benefit of HFNC flow titration in patients of different sizes. For this outcome, the maximum percent change in PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT). It was not pre-specified to compare the two different HFNC delivery systems.
Time Frame median of the maximum percent change in PRP over a 5 minute period

Outcome Measure Data

Analysis Population Description
For this outcome measure, the arms/groups were combined to include all patients enrolled in the study. This included the patients studied on FP only (n=9) and those studied on VT and FP both (n=12) for a total n=21.
Arm/Group Title Maximum Percent Change in PRP From Baseline Stratified by Wt
Arm/Group Description This analysis looked at the largest decrease in PRP for all flow titrations for weight stratified subgroups. For this outcome, the maximum percent change in PRP was obtained for all titrations on both types of HFNC delivery system (FP and VT).
Measure Participants 21
<5 kg
-46
5-8 kg
-30
>8 kg
-17

Adverse Events

Time Frame 22 months
Adverse Event Reporting Description
Arm/Group Title Fisher & Paykel (FP) High Flow Nasal Cannula Vapotherm (VT) High Flow Nasal Cannula
Arm/Group Description A subgroup was studied on Fisher & Paykel (FP) high flow nasal cannula (HFNC) exclusively (N=9). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions. A subgroup was studied on Vapotherm (VT) high flow nasal cannula (HFNC) (N=12). These patients then crossed over to the other arm and had back-to-back titrations on both types of HFNC (FP and VT). The flow rate of the HFNC was adjusted to determine if there existed a change in their effort of breathing (EOB) at different conditions.
All Cause Mortality
Fisher & Paykel (FP) High Flow Nasal Cannula Vapotherm (VT) High Flow Nasal Cannula
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/21 (0%) 0/12 (0%)
Serious Adverse Events
Fisher & Paykel (FP) High Flow Nasal Cannula Vapotherm (VT) High Flow Nasal Cannula
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/21 (0%) 0/12 (0%)
Other (Not Including Serious) Adverse Events
Fisher & Paykel (FP) High Flow Nasal Cannula Vapotherm (VT) High Flow Nasal Cannula
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/21 (0%) 0/12 (0%)
Product Issues
any adverse event 0/21 (0%) 0 0/12 (0%) 0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Thomas Weiler, MD
Organization Presbyterian Hospital
Phone 505-724-7044
Email tweiler@gmail.com
Responsible Party:
Children's Hospital Los Angeles
ClinicalTrials.gov Identifier:
NCT02793674
Other Study ID Numbers:
  • CHLA-14-00239
First Posted:
Jun 8, 2016
Last Update Posted:
Mar 4, 2021
Last Verified:
Jul 1, 2018