ARTICLE IN PRESS

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ARTICLES
The Relationship between High Flow Nasal Cannula Flow Rate
and Effort of Breathing in Children
Thomas Weiler, MD1, Asavari Kamerkar, DO1,2, Justin Hotz, RRT1, Patrick A. Ross, MD1,2,
Christopher J. L. Newth, MD, FRCPC1,2, and Robinder G. Khemani, MD, MsCI1,2

Objective To use an objective metric of effort of breathing to determine optimal high flow nasal cannula (HFNC)
flow rates in children <3 years of age.
Study design Single-center prospective trial in a 24-bed pediatric intensive care unit of children <3 years of age
on HFNC. We measured the percent change in pressure∙rate product (PRP) (an objective measure of effort of breath-
ing) as a function of weight-indexed flow rates of 0.5, 1.0, 1.5, and 2.0 L/kg/minute. For a subgroup of patients, 2
different HFNC delivery systems (Fisher & Paykel [Auckland, New Zealand] and Vapotherm [Exeter, New Hamp-
shire]) were compared.
Results Twenty-one patients (49 titration episodes) were studied. The most common diagnoses were bronchi-
olitis and pneumonia. Overall, there was a significant difference in the percent change in PRP from baseline (of
0.5 L/kg/minute) with increasing flow rates for the entire cohort (P < .001) with largest change at 2.0 L/kg/min (−21%).
Subgroup analyses showed no significant difference in percent change in PRP from baseline when comparing the
2 different HFNC delivery systems (P = .12). Patients ≤8 kg experienced a larger percent change in PRP as HFNC
flow rates were increased (P = .001) than patients >8 kg.
Conclusions The optimal HFNC flow rate to reduce effort of breathing in infants and young children is approxi-
mately 1.5-2.0 L/kg/minute with more benefit seen in children ≤8 kg. (J Pediatr 2017;■■:■■-■■).

See editorial, p •••

H
igh flow nasal cannula (HFNC) oxygen delivery is a commonly used method of noninvasive respiratory support for
critically ill children.1 Recent randomized controlled trial data highlight that HFNC may be superior to “regular” nasal
cannula in preventing treatment failure or the need for intensive care for children with moderate bronchiolitis.2 Several
retrospective studies have agreed with this finding on intensive care utilization and shown that HFNC is associated with lower
rates of intubation and mechanical ventilation.3-5
Emerging literature also demonstrates that HFNC can improve respiratory mechanics. In preterm infants, HFNC has been
shown to reduce thoracoabdominal asynchrony,6 improve gas exchange,7 and lower effort of breathing.6 In term infants, Pham
et al8 showed that there was a significant decrease in effort of breathing (as measured by pressure∙rate product [PRP]) in infants
with bronchiolitis supported with 2 L/kg/minute of HFNC compared with those with no respiratory support, but they did not
evaluate any intermediate levels of support. Previous studies have also described a dose-dependent relationship between in-
creasing levels of HFNC and decreasing objective metrics of effort of breathing in neonatal9 and pediatric10 literature, but these
prior studies have measured effort of breathing at absolute flow rates, not evaluating potentially significant differences in optimal
flow rates for patients of varied ages (eg, between a 1-month-old and 3-year-old child).
Building on this previous work, we hypothesized that there is a relationship between HFNC flow rate and patient effort of
breathing and that this relationship may be affected by the type of HFNC delivery system used and patient weight.

Methods
We performed a single-center prospective trial in the 24-bed multidisciplinary From the 1Department of Anesthesiology Critical Care
Medicine, Children’s Hospital Los Angeles; and
medical-surgical pediatric intensive care unit at Children’s Hospital Los Angeles 2Department of Pediatrics, University of Southern

California, Keck School of Medicine, Los Angeles, CA

(CHLA) from September 2014 to June 2016. This study was approved by the CHLA
Vapotherm, Inc. provided a limited number of high flow
nasal cannula delivery systems for use in this study but
this company did not have any role in (1) study design, (2)
collection, analysis, and interpretation of data, (3) the
writing of the report, or (4) the decision to submit the
paper for publication. The authors declare no conflicts of
CHLA Children’s Hospital Los Angeles PA Phase angle interest.
FP Fisher & Paykel PRP Pressure∙rate product
HFNC High flow nasal cannula RIP Respiratory inductance plethysmography 0022-3476/$ - see front matter. © 2017 Elsevier Inc. All rights
IBW Ideal body weight VT Vapotherm reserved.
http://dx.doi.org10.1016/j.jpeds.2017.06.006

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institutional review board, and informed consent was ob- Secondary outcomes included absolute PRP value and PA.
tained. All patients ≤3 years of age admitted to the CHLA pe- Baseline demographic characteristics of each patient were noted
diatric intensive care unit and placed on HFNC by the clinical including patient diagnosis, age, race, sex, and weight.
team were eligible. We excluded patients if they had a cor- Analysis was performed in Statistica v 12 (Statsoft, Tulsa,
rected gestational age less than 37 weeks or contraindications Oklahoma), and continuous data were presented as median
to either esophageal pressure probe placement (eg, nasopha- with IQR given that they were not always normally distrib-
ryngeal or esophageal anomalies) or respiratory inductance uted. Differences in the primary outcome of percent change
plethysmography (RIP) bands (eg, abdominal wall defects such in PRP from baseline were evaluated using Wilcoxon signed-
as omphalocele). rank test. Secondary outcomes were analyzed using Fried-
Measurements were performed using a pair of RIP bands man or Kruskal-Wallis ANOVA for non-normal distribution
(Nox Medical, Reykjavik, Iceland) and an esophageal pressure with multiple comparisons analysis based on a Bonferroni ad-
probe (CareFusion, Avea, SmartCath, Houten, The Nether- justment. Based on previous data from our group,10 a differ-
lands). The RIP bands and esophageal pressure probe were con- ence in PRP of approximately 100 cmH2O*breaths/minute was
nected to the BiCore II instrument (CareFusion), which provided considered clinically significant. Using this effect size, with an
interface between these sensors and a laptop computer. We re- alpha of 0.05 and desired power of 0.8, our goal sample size
corded and analyzed data on a laptop computer using Polybench was calculated at 20 patients.
software (Applied Biosignals GmbH, Weener, Germany) and
performed postprocessing of the measurements using Vivosense
software package (Vivonetics, San Diego, California).
Results
Measurements were obtained at flow rates of 0.5, 1.0, 1.5,
A total of 54 patients meeting inclusion criteria were ap-
and 2.0 L/kg/minute up to a maximum flow rate of 30 L/
proached, and 21 patients were consented and studied for a
minute on 2 different HFNC delivery systems: Fisher & Paykel
total of 49 titration episodes. Demographic and clinical char-
(FP [Auckland, New Zealand]) and Vapotherm (VT [Exeter,
acteristics were recorded (Table) and patients screened and
New Hampshire]). The respiratory pattern was allowed to sta-
studied are described in a CONSORT diagram (Figure 2; avail-
bilize at each flow rate for an average of 2 minutes before mea-
able at www.jpeds.com). The most common reason consent
surement began. Flow levels were trialed in a random order,
was refused was related to placement of the esophageal catheter.
each for a 5-minute period. Measurements were collected during
Analyzing all titration episodes on all types of HFNC de-
quiet tidal breathing and periods of artifact, such as crying or
livery systems, the median absolute PRP decreased as weight-
coughing, were removed from analysis using the postprocess-
indexed flow rates increased (P < .001) (Figure 3; available at
ing software (Vivosense). With one exception, patients were
www.jpeds.com). The median PA did not exhibit a change
first studied on the FP HFNC delivery system and then (when
with increasing flow rates (P = .91) (Figure 4; available at
available) transitioned to the VT HFNC delivery system. Pa-
www.jpeds.com). When analyzing the primary outcome of
tients were left on the VT HFNC delivery system for the re-
percent change in PRP from baseline, there was a dose-
mainder of their measurements until weaned off HFNC. Each
dependent relationship between increasing flow rates and
subject had up to 2 daily measurements at each of the stated
greater percent change in PRP from baseline with the largest
flow rates as long as they remained on HFNC (up to a
reduction seen at 2.0 L/kg/minute (P < .001) (Figure 5). Flow
maximum of 5 days).
rates between 1.5 and 2.0 L/kg/minute resulted in similar
Using esophageal manometry, we calculated the PRP: the
percent change in PRP from baseline (−20% and −21%, re-
product of the peak-to-trough change in esophageal pres-
spectively). Multiple comparisons analysis showed that flow
sure (cmH2O) and the respiratory rate (breaths per minute)
(Figure 1; available at www.jpeds.com). This has been previ-
ously validated as a metric of patient effort of breathing11-14
where larger absolute values signify greater effort of breath- Table. Patient demographics (n = 21): median (IQR or
ing. From RIP, we calculated the phase angle (PA). PA is a percent)
measure of thoracoabdominal asynchrony and is a nonspe- Median age (mo) 6 (2, 12)
cific surrogate metric for effort of breathing.15 Median weight (kg) 6.5 (5, 9)
Median weight compared with IBW (kg) −0.5 (−1.7, 0.6)
For each 5-minute titration episode, we calculated the median Ethnicity/race: n (%)
PRP and PA, which were used for analysis. After each set of African American 2 (10)
measurements, we informed the clinical team of the flow rate Hispanic 15 (71)
Not specified 4 (19)
that resulted in the lowest effort of breathing. Respiratory illness: n (%)
Bronchiolitis 13 (62)
Statistical Analyses Pneumonia 3 (14)
Other 5 (24)
The primary outcome was percent change in PRP from base- Patients intubated: n (%) 2 (10)
line, to account for within subject variability and repeated mea- Median HFNC duration (d) 2 (1-4)
surements per patient. Because we hypothesized that the effects Median PICU LOS (d) 4 (2-6)
Median hospital LOS (d) 7.5 (5.8-14.3)
of HFNC flow rates may be dependent on patient size, we
further stratified our cohort into subgroups of ≤8 kg and >8 kg. LOS, length of stay; PICU, pediatric intensive care unit.

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Figure 5. Percent change in PRP from baseline as a function of flow rate. The largest reduction in PRP happened at flow rates
of 1.5 and 2.0 L/kg/minute (−20% and −21%, respectively). Multiple comparisons analysis showed significant percent change
in PRP when comparing against 0.5 (*) and 1.0 (†) L/kg/min.

rates of 1.0, 1.5, and 2.0 L/kg/minute resulted in lower PRP analysis of patients by further stratified weight groupings (<5 kg,
than at 0.5 L/kg/minute (all P < .03) and that flow rates of 5-8 kg, and >8 kg) showed that the largest maximum de-
2.0 L/kg/minute resulted in lower PRP than at 1.0 L/kg/ crease in PRP (for all titrations) from optimal HFNC flow rate
minute (P = .005) (Figure 5). For all titration episodes, the occurred in the lightest weight group (<5 kg) and that there
lowest PRP occurred at 2.0 L/kg/minute for 51% of all pa- was a significant difference in percent change in PRP from base-
tients, at 1.5 L/kg/minute for 35%, at 1.0 L/kg/minute for 12%, line when comparing the three groups (P = .028) (Figure 8;
and at 0.5 L/kg/minute for 2%. available at www.jpeds.com).
Twelve patients had back-to-back titrations on FP and VT.
When comparing the 2 HFNC delivery systems, there was no Discussion
difference in the percent change in PRP from baseline as flow
rates were increased (P = .18). Of note, the maximum de- Using esophageal manometry to capture a direct metric of effort
crease in percent change in PRP from baseline occurred at 1.5 L/ of breathing (PRP), we have demonstrated that increasing
kg/minute on VT and at 2.0 L/kg/minute on FP (Figure 6). weight-indexed flow rates of HFNC (up to 2.0 L/kg/minute)
To assess the relationship between patient size and dose- decrease effort of breathing in a dose-dependent fashion with
response of HFNC flow rate, we compared subgroups strati- the largest effect seen in lighter children.
fied by weight (patients ≤8 kg and >8 kg). For this analysis, we In the setting of respiratory illness, patients increase effort
looked only at the first titration performed on the HFNC de- of breathing to maintain ventilation and oxygenation and com-
livery systems. For patients ≤8 kg (12 patients, 20 episodes), pensate for changes in airway resistance and pulmonary com-
there was a significant dose-dependent relationship between pliance. Fundamentally, sustained periods of high effort of
increasing flow rate and greater percent change in PRP from breathing lead to respiratory muscle fatigue. As such, thera-
baseline (P = .001) with a maximum reduction at flow rates peutic interventions such as HFNC aim to reduce effort of
of 1.5 L/kg/minute. Multiple comparisons analysis was similar breathing with the hope of preventing progression to respi-
to the entire group, showing that flow rates of 1.0, 1.5, and 2.0 L/ ratory failure. Historically, assessment of effort of breathing
kg/minute resulted in lower PRP than at 0.5 L/kg/minute (all has been based upon subjective clinical scoring systems that
P values <.024) and flow rates of 2.0 resulted in lower PRP than are subject to variations in inter-rater reliability and as a whole
at 1.0 L/kg/minute (P = .017) (Figure 7). Patients >8 kg (9 pa- have not been validated for clinically meaningful use.16 More
tients, 12 episodes) had a trend toward reduction in PRP as objective measures of effort of breathing, such as PRP, can char-
flow rate increased but the treatment effect was smaller and acterize the activity of respiratory muscles and are useful tools
not statistically significant (P = .38) (Figure 7). Exploratory to evaluate the efficacy of therapies.15 First used in pediatric
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Figure 6. Percent change in PRP from baseline as a function of flow rate comparing HFNC delivery systems. Both systems
resulted in a similar median reduction in PRP but the VT delivery system showed maximum reduction (−23%) at 1.5 L/kg/
minute (IQR: −1 to −30%) while the FP delivery system showed maximum reduction (−24%) at 2.0 L/kg/minute (IQR: −17 to
−34%).

patients by Klein et al,17 PRP serves as an estimate of the energy from our institution showed that patients on flow rates of 8 L/
cost of the work of breathing because oxygen consumption by minute had significantly lower effort of breathing than those
muscle is proportional to the integral of muscle tension with on 5 and 2 L/minute.10 However, we believe that a flow rate
respect to time. PRP is relatively easy to calculate and is robust of 8 L/minute for a 4 kg infant will likely have a different effect
against artifact, which is why we choose to use it over other than 8 L/minute for a 10 kg child. For our analysis, we strati-
objective measures of effort of breathing such as pressure∙time fied our cohort into subgroups of ≤8 kg and >8 kg. This cut-
product.18 off is the 50th percentile weight for age for 6-month-old male
For our study, the percent change in PRP from baseline (of children on Centers for Disease Control and Prevention growth
0.5 L/kg/minute) was used rather than absolute PRP because charts19 and was chosen as a breakpoint between early infancy
there was a large degree of heterogeneity in the absolute PRP and late infancy/early toddlerhood. This stratified analysis high-
values in our study population based on patient size, disease lights the importance of titrating HFNC flow as a function of
severity, and time point of disease process, and we allowed for weight. We believe that our findings should prompt clini-
repeated measurements on the same patient (which would bias cians to consider increasing HFNC flow rates above levels they
absolute PRP values in favor of those who were measured more may normally use. Indeed, the results of a recent random-
frequently). ized controlled trial data highlight the superiority of HFNC
Interestingly, the other objective measure of effort of breath- compared with “regular” nasal cannula in preventing treat-
ing we initially set out to analyze (PA as a measure of ment failure or the need for intensive care for children with
thoracoabdominal asynchrony) did not show a dose-dependent moderate bronchiolitis despite only utilizing flow rates of
relationship with increasing HFNC flow rates (Figure 4). Physi- 1 L/kg/minute.2 We hypothesize that these results might be even
ologically, one can infer from this finding that although re- more dramatic with higher flow rates.
spiratory disease in children requires larger negative Similarly, the flow rates used by the clinical team at our center
intrathoracic pressure and/or respiratory rate to maintain ad- were generally lower than what would be considered “optimal”
equate ventilation (reflected in the PRP), it does not cause in- based on our observations, and this did not differ by study day,
creased thoracoabdominal asynchrony in a measurable way, even after sharing the information with the clinical team (analy-
even though this sign is traditionally used as a subjective as- sis not shown). However, as respiratory disease improved, PRP
sessment of increased effort of breathing. generally decreased on subsequent days after day 1. As such,
Practitioners often select HFNC flow rates without overt con- the clinical team may have chosen not to increase flow rates
sideration of a patient’s weight or age. In fact, previous work on subsequent study days because their patient was improving
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Figure 7. Percent change in PRP from baseline as a function of flow rate stratified by patient weight. Patients weighing ≤8 kg
showed greater maximum reduction in PRP (−26%, P = .001) compared with those weighing >8 kg (−15%, P = .38). Multiple
comparisons analysis in the patients weighing ≤8 kg showed significant percent change in PRP when comparing against 0.5
(*) and 1.0 (†) L/kg/minute.

and our institutional practice is gradual weaning of HFNC did not appear to have clinically significant effects on effort
rather than abrupt transition or discontinuation. of breathing in our study.
We did not increase flow rates beyond 2 L/kg/minute because One of our most important findings was that HFNC has
we hypothesized that increasing beyond this point would result the largest effect on reducing effort of breathing in the small-
in increased incidence of adverse effects of HFNC therapy (eg, est children. This implies that the benefit of HFNC is at least
air leak syndrome20 or patient agitation) without additional partially due to physiologic factors that change with patient
benefit. Looking closely at our data, there was minimal im- age or size. The proposed mechanisms of action of HFNC
provement in PRP when increasing flow from 1.5 to 2.0 L/kg/ include washout of dead space, reduction of inspiratory re-
minute, inferring a plateau effect. Therefore, if a patient sistance, improving pulmonary mechanics, improving secre-
continues to have high effort of breathing on HFNC flow rates tion mobilization, and generation of increased pharyngeal
of 2 L/kg/minute, practitioners should consider alternative pressure.23 Milési et al24 found that HFNC >2 L/kg/minute gen-
methods of respiratory support (such as invasive mechanical erated clinically significant increases in pharyngeal pressure,
ventilation) as further increases in HFNC flow rate are un- improved breathing patterns, and unloading of respiratory
likely to be beneficial. Recent data support this, showing that muscles in patients with bronchiolitis. Other groups argue that
nasal continuous positive airway pressure may be a better dead space washout is the primary mechanism given a plateau
method to reduce intubation rates compared with HFNC (at phenomenon observed beyond, which increasing flow rates did
rates of 2 L/kg/minute) for children with bronchiolitis,21 re- not correspond with continued increase in partial pressure of
inforcing the importance of quickly escalating support beyond oxygen.7
HFNC if a patient’s effort of breathing does not improve at We also observed this plateau in physiological improve-
optimal flow rates of 1.5 to 2.0 L/kg/minute. ment (effort of breathing as measured by PRP) between 1.5
Although others have shown that neonatal patients on the and 2.0 L/kg/minute of HFNC flow. We believe this plateau
Vapotherm HFNC delivery system have improved respira- phenomenon supports dead space washout as a crucial mecha-
tory rate, respiratory effort scores, and lower rates of nism leading to HFNC benefit and is the most likely expla-
reintubation than standard nasal cannula,22 we did not find a nation for our findings of HFNC’s greater effect in smaller
significant difference in effort of breathing between the 2 dif- patients. This is because of previous work by Numa et al25 that
ferent HFNC delivery systems evaluated. Even though each showed that anatomic dead space is higher in infancy
HFNC delivery system has unique design aspects (eg, nasal (>3 mL/kg) than in children >6 years old (0.8 mL/kg). Because
cannula interface, humidification, and flow properties), these of this, younger infants may have continued dead space washout
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at higher weight-indexed flow rates while older children reach 4. Schibler A, Pham TMT, Dunster KR, Foster K, Barlow A, Gibbons K, et al.
a plateau of this benefit at an earlier point. However, our data Reduced intubation rates for infants after introduction of high-flow nasal
prong oxygen delivery. Intensive Care Med 2011;37:847-52.
cannot confirm or deny other physiological mechanisms in the 5. Wing R, James C, Maranda LS, Armsby CC. Use of high-flow nasal cannula
effect of HFNC on reducing effort of breathing, such as some support in the emergency department reduces the need for intubation
amount of continuous positive airway pressure being delivered. in pediatric acute respiratory insufficiency. Pediatr Emerg Care
There are a few limitations of our study worth consider- 2012;28:1117-23.
ation. First, this is a single-center trial with a relatively small 6. Shetty S, Hickey A, Rafferty GF, Peacock JL, Greenough A. Work of breath-
ing during CPAP and heated humidified high-flow nasal cannula. Arch
sample size (although adequately powered). Dis Child Fetal Neonatal Ed 2016;101:F404-7.
For our analysis, we used measured body weight to calcu- 7. Frizzola M, Miller TL, Rodriguez ME, Zhu Y, Rojas J, Hesek A, et al. High-
late weight-indexed flow rates and not ideal body weight (IBW). flow nasal cannula: impact on oxygenation and ventilation in an acute
Upon retrospective analysis, our patient population had a lung injury model. Pediatr Pulmonol 2011;46:67-74.
median weight slightly less than the IBW (Table) for this aged 8. Pham TMT, O’Malley L, Mayfield S, Martin S, Schibler A. The effect of
high flow nasal cannula therapy on the work of breathing in infants with
cohort.17 It may be that IBW would be more suitable to use bronchiolitis. Pediatr Pulmonol 2015;50:713-20.
in obese patients, which were not prevalent in our patient popu- 9. Saslow JG, Aghai ZH, Nakhla TA, Hart JJ, Lawrysh R, Stahl GE, et al. Work
lation but could be of minor importance here. of breathing using high-flow nasal cannula in preterm infants. J Perinatol
Furthermore, obtaining effort of breathing measurements 2006;26:476-80.
during quiet tidal breathing can be challenging in some infants 10. Rubin S, Ghuman A, Deakers T, Khemani R, Ross P, Newth CJ. Effort
of breathing in children receiving high-flow nasal cannula. Pediatr Crit
and young children. Despite our best efforts to assure calm Care Med 2014;15:1-6.
periods of breathing for accurate measurements while filter- 11. Ross PA, Hammer J, Khemani R, Klein M, Newth CJL. Pressure-rate
ing artifact, the dynamic nature of effort of breathing can vary product and phase angle as measures of acute inspiratory upper
during observation periods. Moreover, we did not random- airway obstruction in rhesus monkeys. Pediatr Pulmonol 2010;45:639-
ize the order of FP and VT for patients that had a head-to- 44.
12. Diblasi RM, Zignego JC, Tang DM, Hildebrandt J, Smith CV, Hansen TN,
head comparison. However, the physiologic effects of HFNC et al. Noninvasive respiratory support of juvenile rabbits by high-
have rapid onset and resolution, making it unlikely that the amplitude bubble continuous positive airway pressure. Pediatr Res
previous HFNC delivery system has a long-lasting impact on 2010;67:624-9.
effort of breathing. 13. Argent AC, Hatherill M, Newth CJL, Klein M. The effect of epinephrine
Finally, it is possible that the presence of the esophageal pres- by nebulization on measures of airway obstruction in patients with acute
severe croup. Intensive Care Med 2007;34:138-47.
sure probe may have an impact upon the airway physiology. 14. Argent AC, Newth CJL, Klein M. The mechanics of breathing in chil-
It could increase inspiratory and expiratory resistance, cause dren with acute severe croup. Intensive Care Med 2007;34:324-32.
discomfort, decrease the total cross-sectional area of the nares, 15. Hammer J, Eber E. Paediatric pulmonary function testing. Basel, NY:
or increase nasopharyngeal pressure by limiting the space for Karger; 2005.
gas efflux. This could have attenuated the efficacy of HFNC 16. Bekhof J, Reimink R, Brand PLP. Systematic review: insufficient valida-
tion of clinical scores for the assessment of acute dyspnoea in wheezing
therapy and may affect the magnitude of the flow vs effort of children. Paediatr Respir Rev 2013;15:98-112.
breathing dose-dependence relationship. 17. Klein M, Reynolds LG. Relief of sleep-related oropharyngeal airway ob-
There is a dose-dependent relationship between increas- struction by continuous insufflation of the pharynx. Lancet 1986;1:935-
ing HFNC flow rates and lower effort of breathing in chil- 9.
dren with the optimal HFNC flow rate between 1.5 and 2.0 L/ 18. Collett PW, Perry C, Engel LA. Pressure-time product, flow, and oxygen
cost of resistive breathing in humans. J Appl Physiol 1985;58:1263-72.
kg/min. This dose-dependent relationship is greatest for lower 19. Birth to 36 months: Boys, Length-for-age and Weight-for-age percen-
weight patients and does not appear to be dependent upon the tiles [Internet]. http://www.cdc.gov/growthcharts/data/set1clinical/
type of HFNC delivery system. ■ cj41l017.pdf. Accessed April 28, 2016.
20. Hegde S, Prodhan P. Serious air leak syndrome complicating high-flow
Submitted for publication Feb 21, 2017; last revision received Apr 17, 2017; nasal cannula therapy: a report of 3 cases. Pediatrics 2013;131:e939-
accepted Jun 2, 2017 44.
21. Milési C, Essouri S, Pouyau R, Liet J-M, Afanetti M, Portefaix A, et al.
Reprint requests: Thomas Weiler, MD, Pediatric Intensive Care, Presbyterian
Hospital, 1100 Central Ave SE, 6th Floor, Albuquerque, NM 87106. E-mail:
High flow nasal cannula (HFNC) versus nasal continuous positive airway
[email protected] pressure (nCPAP) for the initial respiratory management of acute viral
bronchiolitis in young infants: a multicenter randomized controlled trial
(TRAMONTANE study). Intensive Care Med 2017;43:209-16.
22. Woodhead DD, Lambert DK, Clark JM, Christensen RD. Comparing two
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of the literature. Intensive Care Med 2013;39:247-57. 23. Dysart K, Miller TL, Wolfson MR, Shaffer TH. Research in high flow
2. Kepreotes E, Whitehead B, Attia J, Oldmeadow C, Collison A, Searles A, therapy: mechanisms of action. Respir Med 2009;103:1400-5.
et al. High-flow warm humidified oxygen versus standard low-flow nasal 24. Milési C, Baleine J, Matecki S, Durand S, Combes C, Novais ARB, et al.
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3. McKiernan C, Chua LC, Visintainer PF, Allen H. High flow nasal can- 25. Numa AH, Newth CJ. Anatomic dead space in infants and children. J Appl
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Figure 1. Diagram of the derivation of PRP from esophageal manometry. DPES, peak-to-trough change in esophageal pres-
sure; RR, respiratory rate.

Figure 2. CONSORT diagram showing patient enrollment and data collection process. BiPAP, bilevel positive airway pres-
sure; IMV, invasive mechanical ventilation.

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Figure 3. PRP as a function of flow rate. Absolute PRP showed significant reduction with increasing flow rates (P < .001) with
the largest reduction at flow rates of 1.5 and 2.0 L/kg/minute. Multiple comparisons analysis showed significant change in PRP
when comparing against 0.5 (*) and 1.0 (†) L/kg/minute.

Figure 4. PA as a function of flow rate. PA showed no significant change with increasing flow rates (P = .91).

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■■ 2017 ORIGINAL ARTICLES

Figure 8. Maximum percent change in PRP from baseline stratified by patient weight. There was a significant difference between
the 3 weight groups when looking only at the maximum percent change in PRP for each titration (P = .028).

The Relationship between High Flow Nasal Cannula Flow Rate and Effort of Breathing in Children 6.e3

FLA 5.4.0 DTD ■ YMPD9260_proof ■ June 29, 2017