High Flow Nasal Cannula
Conditions
Keywords
effort of breathing, high flow nasal cannula, respiratory distress
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.
Interventions
DEVICEFisher & 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.
DEVICEVapotherm 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.
Sponsors
Children's Hospital Los Angeles
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 3 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Fisher & Paykel (FP) HFNC 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. | 9 |
| Vapotherm (VT) HFNC 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. | 12 |
| Total | 21 |
Baseline characteristics
| Characteristic | Fisher & Paykel (FP) HFNC | Vapotherm (VT) HFNC | Total |
|---|---|---|---|
| Age, Continuous | 15 months | 4 months | 6 months |
| Race/Ethnicity, Customized Ethnicity / Race African-American | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Ethnicity / Race Hispanic | 6 Participants | 9 Participants | 15 Participants |
| Race/Ethnicity, Customized Ethnicity / Race Not specified | 3 Participants | 1 Participants | 4 Participants |
| Respiratory Illness Bronchiolitis | 6 participants | 7 participants | 13 participants |
| Respiratory Illness Other | 1 participants | 5 participants | 6 participants |
| Respiratory Illness Pneumonia | 2 participants | 0 participants | 2 participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 12 Participants |
| Weight | 9 kilograms | 6.5 kilograms | 6.5 kilograms |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 12 |
| other Total, other adverse events | 0 / 21 | 0 / 12 |
| serious Total, serious adverse events | 0 / 21 | 0 / 12 |
Outcome results
Primary
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)
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Percent Change in Pressure-Rate Product | 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) | Percent Change in PRP at 1.0 L/kg/min | -10 percent change in PRP |
| Percent Change in Pressure-Rate Product | 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) | Percent Change in PRP at 1.5 L/kg/min | -20 percent change in PRP |
| Percent Change in Pressure-Rate Product | 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) | Percent Change in PRP at 2.0 L/kg/min | -23 percent change in PRP |
Secondary
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)
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Percent Change in Pressure-Rate Product | 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) | <5 kg | -46 percent |
| Percent Change in Pressure-Rate Product | 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) | 5-8 kg | -30 percent |
| Percent Change in Pressure-Rate Product | 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) | >8 kg | -17 percent |
Secondary
Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Different HFNC Delivery Systems
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Percent Change in Pressure-Rate Product | Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Different HFNC Delivery Systems | 1.0 L/kg/min | -15 percent change in PRP |
| Percent Change in Pressure-Rate Product | Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Different HFNC Delivery Systems | 1.5 L/kg/min | -19 percent change in PRP |
| Percent Change in Pressure-Rate Product | Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Different HFNC Delivery Systems | 2.0 L/kg/min | -23 percent change in PRP |
| Vapotherm HFNC Delivery System | Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Different HFNC Delivery Systems | 1.0 L/kg/min | -9 percent change in PRP |
| Vapotherm HFNC Delivery System | Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Different HFNC Delivery Systems | 1.5 L/kg/min | -22 percent change in PRP |
| Vapotherm HFNC Delivery System | Percent Change in Pressure-rate Product (PRP) From Baseline as a Function of Increasing HFNC Flow Rate, Comparing Different HFNC Delivery Systems | 2.0 L/kg/min | -11 percent change in PRP |
Secondary
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)
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Percent Change in Pressure-Rate Product | 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) | 1.0 L/kg/min | -14 percent change in PRP from baseline |
| Percent Change in Pressure-Rate Product | 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) | 1.5 L/kg/min | -27 percent change in PRP from baseline |
| Percent Change in Pressure-Rate Product | 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) | 2.0 L/kg/min | -25 percent change in PRP from baseline |
| Vapotherm HFNC Delivery System | 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) | 1.0 L/kg/min | -5 percent change in PRP from baseline |
| Vapotherm HFNC Delivery System | 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) | 1.5 L/kg/min | -2 percent change in PRP from baseline |
| Vapotherm HFNC Delivery System | 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) | 2.0 L/kg/min | -15 percent change in PRP from baseline |
Secondary
Phase Angle as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT)
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Percent Change in Pressure-Rate Product | Phase Angle as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) | 0.5 L/kg/min | 61 degrees |
| Percent Change in Pressure-Rate Product | Phase Angle as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) | 1.0 L/kg/min | 61 degrees |
| Percent Change in Pressure-Rate Product | Phase Angle as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) | 1.5 L/kg/min | 68 degrees |
| Percent Change in Pressure-Rate Product | Phase Angle as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) | 2.0 L/kg/min | 59 degrees |
Secondary
Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT)
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Percent Change in Pressure-Rate Product | Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) | PRP at 0.5 L/kg/min | 824 cmH20 * breaths/minute |
| Percent Change in Pressure-Rate Product | Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) | PRP at 1.0 L/kg/min | 699 cmH20 * breaths/minute |
| Percent Change in Pressure-Rate Product | Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) | PRP at 1.5 L/kg/min | 596 cmH20 * breaths/minute |
| Percent Change in Pressure-Rate Product | Pressure-rate Product (PRP) as a Function of Increasing HFNC Flow Rate on Both Types of HFNC Delivery System (FP and VT) | PRP at 2.0 L/kg/min | 594 cmH20 * breaths/minute |