Opinion

High-Flow Nasal Cannula Therapy for Pediatric Patients

Shawn L. Ralston, MD, The proliferation of observational literature on the topic with higher failure rates in the standard therapy group
MS of high-flow nasal cannula (HFNC) as a therapy for acute (23% [167 of 733]) compared with the HFNC group (12%
Department of viral bronchiolitis is nothing short of remarkable. A brief [87 of 739]); however, the same pattern of events oc-
Pediatrics, Johns
PubMed search reveals a ratio of observational studies curred after treatment failure as in the trial by Kepreo-
Hopkins University
School of Medicine, to randomized trials of at least 10 to 1 in the past 3 years tes et al. Of the 162 patients in the standard cannula arm
Baltimore, Maryland. alone. This proliferation suggests that, right or wrong, who experienced treatment failure, 102 (61%) were con-
we have embraced the widespread use of HFNC clini- sidered rescued by HFNC, almost exactly the same per-
cally. This ratio also hints at a bigger problem, which is centage considered to have been rescued in the study
that we have moved on to answering somewhat periph- by Kepreotes et al (62.5%). Ultimately, only 9% of chil-
eral questions about the therapy prior to answering the dren receiving standard therapy went on to have failed
most important questions about clinical utility. rescue HFNC and experience admission to an ICU, which
A recent meta-analysis concluded that HFNC, when is equivalent to the 12% transfer rate in the early HFNC
compared with standard nasal cannula, reduced the in- group. Furthermore, there were no differences in over-
cidence of treatment failure in bronchiolitis.1 However, all duration of hospital stay or duration of oxygen therapy
treatment failure in the standard cannula group univer- between groups.
sally led to crossover to HFNC in the 2 relevant trials2,3; While both trials had the stated purpose of compar-
thus, a potentially more accurate representation of the ing low-flow with high-flow oxygen, owing to therapeu-
trials to date would be that they compare early vs res- tic crossover both trials really evaluated early vs rescue
cue use of HFNC. Furthermore, key findings in both trials use of high flow. It is worth noting that the original title
were that there were no differences in overall duration of the study by Franklin et al, as evidenced by the pub-
of oxygen use, transfer to the intensive care unit (ICU), lished protocol, was “Early High Flow Nasal Cannula
hospital length of stay, or adverse events between Therapy in Bronchiolitis: A Prospective Randomized Con-
groups. A layman’s summary of the current literature trol Trial (protocol).”4 Thus, an accurate interpretation
would be this: if you start HFNC early in bronchiolitis, you of this evidence is that the 2 strategies (early vs rescue)
can avoid needing to start it later, although it will not appear equivalent in terms of outcomes. Furthermore,
really alter the overall hospital course either way. If you it has also been pointed out that a large proportion of
find this situation a little confusing, you are likely not patients in the standard care arms (77% in Franklin et al
alone. and 68% in Kepreotes et al) were successfully treated
A closer look at the details of the 2 trials comparing without escalation of care.5 Finally, the available eco-
standard cannula therapy with HFNC for patients with nomic analysis suggests HFNC costs 16 times as much
moderate bronchiolitis may provide clarity. Kepreotes as standard care.2 Thus, another reasonable conclu-
et al2 studied 201 children younger than 24 months with sion from these data might be that early initiation of
moderate bronchiolitis in a single Australian hospital. The HFNC is the inferior choice since it involves providing a
primary outcome of the trial was time receiving oxygen costly therapy to a large number of children who will not
therapy, for which there was no difference (20 hours in benefit from it.
the HFNC group vs 24 hours in the standard cannula Given the reality of the situation represented by the
group; hazard ratio, 0.9; 95% CI, 0.7-1.2). There were dif- observational literature, what can we do with the press-
ferences in initial treatment failure rates between the 2 ing clinical question about how to more appropriately use
groups (14 patients [14%] receiving HFNC vs 33 pa- this ubiquitous therapy? An Australian pediatric emer-
tients [33%] receiving standard cannula therapy); how- gency medicine research collaborative recently pro-
ever, all 32 children in the standard cannula group were posed that HFNC in patients with bronchiolitis should be
deemed to have treatment failures and were switched limited to use as rescue therapy for infants with hypox-
to receive HFNC. Of those, 20 were successfully res- emia in whom standard cannula therapy has failed.6 This
Corresponding cued and 12 transferred to the ICU. In the HFNC group, suggestion seems appropriate since there is no evi-
Author: Shawn L. the same proportion (14 patients) were deemed to have dence that a patient would have any different outcome
Ralston, MD, MS, treatment failures and transferred to an ICU; thus, the or be placed at increased risk by delaying the use of
Division of Quality and
Safety, Department of
final outcome was equivalent for both groups. HFNC. The suggestion also highlights a large gap in the
Pediatrics, Johns Franklin et al3 studied 1472 infants younger than 12 existing literature: there are no clear initiation criteria for
Hopkins Children’s months in 17 hospitals in Australia and New Zealand and when to start HFNC for patients with bronchiolitis.
Center, 1800 N
used a flow rate of 2 L/kg, thus, younger infants and One possible strategy would be to use the treat-
Orleans St, Baltimore,
MD 21287 (sralsto3@ higher flow rates than the study by Kepreotes et al.2 ment failure criteria in the existing randomized trials as
jhmi.edu). Treatment failure was chosen as the primary outcome, initiation criteria for HFNC. The definition of treatment

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failure in the Kepreotes et al trial included a heart rate or respira- HFNC, whereas some hospitals do not allow feeding while HFNC is
tory rate in the “red zone” for age-based norms or an oxygen satu- in use. Other adverse effects include a risk of pneumothorax, par-
ration below 90% (while receiving a maximum flow rate of 2 L/min ticularly at higher flow rates.7 Taken together, the 2 randomized trials
with a standard nasal cannula), or a respiratory distress score in the suggest that, if we apply HFNC early in the course of bronchiolitis,
severe range as well as a concurrent assessment by the treating cli- we can expect approximately 70% of that use will be unnecessary.
nician. Treatment failure in the trial by Franklin et al required 2 of the It is sometimes exceptionally difficult for us to understand small
following 4 criteria: (1) heart rate or respiratory rate remaining un- harms applied to large populations as a meaningful concern when
changed or increased from admission, (2) failure to maintain oxy- we are hoping to help a single patient in the moment. However, it is
gen saturations above 92% (or 94% at some sites) despite maxi- highly likely that the liberal application of HFNC oxygen in bronchi-
mal therapy, (3) triggering of the hospital early warning tool, as well olitis is doing more harm than good at the population level.
as (4) physician determination or confirmation of treatment fail- Given the risk of harm and the strong suggestion that we are
ure. While these are notably distinct sets of criteria, the fact that treat- wasting resources with our current use of HFNC, we urgently need
ment failure rates were so similar in each trial would suggest that prospective research to define the appropriate population in whom
either set of criteria would be reasonable. to use this therapy. Until then, limiting the use of HFNC to rescue
Finally, it is important to remember the potential for a down- therapy by protocolizing treatment failure criteria for standard, low-
side to HFNC other than the significantly increased cost. Infants of- flow nasal cannula in the treatment of bronchiolitis is likely to do the
ten experience gastric distention and poor feeding while receiving most good with the least harm.

ARTICLE INFORMATION randomised controlled trial. Lancet. 2017;389 Sirens. JAMA Pediatr. 2019;173(2):125-126. doi:10.
Published Online: March 23, 2020. (10072):930-939. doi:10.1016/S0140-6736(17) 1001/jamapediatrics.2018.3831
doi:10.1001/jamapediatrics.2020.0040 30061-2 6. O’Brien S, Craig S, Babl FE, Borland ML, Oakley
Conflict of Interest Disclosures: None reported. 3. Franklin D, Babl FE, Schlapbach LJ, et al. A E, Dalziel SR; Paediatric Research in Emergency
randomized trial of high-flow oxygen therapy in Departments International Collaborative (PREDICT)
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