A. Schibler
T. M. T. Pham
K. R. Dunster
K. Foster
A. Barlow
K. Gibbons
J. L. Hough
Reduced intubation rates for infants
after introduction of high-flow nasal
prong oxygen delivery
Received: 26 July 2010
Accepted: 17 January 2011
Published online: 3 March 2011
Ó Copyright jointly held by Springer and
ESICM 2011
A. Schibler T. M. T. Pham
K. R. Dunster J. L. Hough (
)
)
Paediatric Critical Care Research Group,
Paediatric Intensive Care Unit, Mater
Health Services, South Brisbane,
QLD 4101, Australia
e-mail: judith.hough@mater.org.au
Tel.: ?61-7-31631143
Fax: ?61-7-31631652
K. Foster A. Barlow
Paediatric Intensive Care Unit,
Mater Health Services, South Brisbane,
QLD, Australia
K. Gibbons J. L. Hough
Mater Medical Research Institute,
Mater Health Services, South Brisbane,
QLD, Australia
Abstract Purpose: To describe
the change in ventilatory practice in a
tertiary paediatric intensive care unit
(PICU) in the 5-year period after the
introduction of high-flow nasal prong
(HFNP) therapy in infants
\24 months of age. Additionally, to
identify the patient subgroups on
HFNP requiring escalation of therapy
to either other non-invasive or inva-
sive ventilation, and to identify any
adverse events associated with HFNP
therapy. Methods: The study was a
retrospective chart review of infants
\24 months of age admitted to our
PICU for HFNP therapy. Data was
also extracted from both the local
database and the Australian New
Zealand paediatric intensive care
(ANZPIC) registry for all infants
admitted with bronchiolitis. Results:
Between January 2005 and December
2009, a total of 298 infants
\24 months of age received HFNP
therapy. Overall, 36 infants (12%)
required escalation to invasive venti-
lation. In the subgroup with a primary
diagnosis of viral bronchiolitis
(n = 167, 56%), only 6 (4%) required
escalation to invasive ventilation. The
rate of intubation in infants with viral
bronchiolitis reduced from 37% to
7% over the observation period cor-
responding with an increase in the use
of HFNP therapy. No adverse events
were identified with the use of HFNP
therapy. Conclusion: HFNP therapy
has dramatically changed ventilatory
practice in infants \24 months of age
in our institution, and appears to
reduce the need for intubation in
infants with viral bronchiolitis.
Keywords High-flow nasal cannula
Oxygen delivery Infant
Introduction
Respiratory distress and hypoxaemia in infants are treated
with various forms of non-invasive respiratory therapy
[1]. In addition to oxygen therapy, continuous positive
airway pressure (CPAP) is used to reduce the work of
breathing and improve functional residual capacity, since
regional atelectasis of the lung is a common feature in
infants breathing near their closing volume [2, 3]. CPAP
can be delivered via nasopharyngeal tube or face mask
and generated by a water column (bubble CPAP) or a
dedicated CPAP driver [4, 5]. Recently high-flow nasal
prong (HFNP) therapy has been introduced to provide
respiratory support in preterm and term infants [6–8].
HFNP therapy has many possible advantages over other
forms of oxygen therapy: the inspired gas mixture can be
heated and humidified to reduce damage to the upper
airway mucosa; the inspired oxygen concentration can be
titrated to the patient’s need; anecdotally, it is better tol-
erated by the patient; and potentially, CPAP can be
delivered [9–12]. Studies in neonates have shown that the
amount of CPAP delivered by HFNP depends on the flow
Intensive Care Med (2011) 37:847–852
DOI 10.1007/s00134-011-2177-5
PEDIATRIC ORIGINAL
(relative to the size of the patient) and on the leak around
the nasal cannula [13]. Most studies of HFNP therapy
have been performed in neonates, and little clinical
experience is reported in older children [6].
HFNP therapy was introducedin our paediatric intensive
care unit (PICU) in 2005 and a subsequent significant change
has been observed in the care of infants with respiratory
distress with a suspected reduction in invasive ventilation.
This retrospective analysis aimed to describe: our 5-year
institutional experience of HFNP therapy in infants
\24 months of age; the subgroups of patients requiring
HFNP; the need for escalation of respiratory support from
HFNP to other forms of non-invasive or invasive ventilation;
the incidence of complications associated with HFNP ther-
apy; our ventilatory practice in comparison with the
subgroup of infants with bronchiolitis in all other PICUs in
Australia and New Zealand.
Methods
Study design
The study was a retrospective analysis of all infants
admitted to the PICU and treated with HFNP therapy
between 2005 and 2009. Demographic and physiological
real-time data were extracted from the unit’s clinical
information system (CIS). Informed consent from parents
or guardians was waived by the local ethics committee.
Setting
The PICU is a 19-bed tertiary mixed surgical/cardiac/med-
ical unit with approximately 1,100 admissions per year.
Definition of patient disease groups
The database was queried for all infants \24 months of
age who were treated with HFNP therapy within their first
24 h of admission to the PICU. These infants were allo-
cated to six disease groups using the Australian New
Zealand Paediatric Intensive Care (ANZPIC) registry
coding criteria [14]: clinically defined viral bronchiolitis
with or without a positive test for respiratory syncytial
virus (RSV), adenovirus, metapneumovirus or influenza
(BRONCH); lung disease without peripheral airway
obstruction (LD); upper airway obstruction (UAO); neu-
romuscular conditions (NM); cardiac conditions
(CARDIAC); and other (OTHER). Within the BRONCH
disease group, preexisting risk factors such as prematu-
rity, or underlying cardiac or neurological disorders were
also identified. Criteria for admission to the PICU for
respiratory distress is an oxygen requirement of more than
2 l/min and the need for respiratory support additional to
supplemental oxygen.
Definition of respiratory support subgroups
Infants within each disease group were then divided into
respiratory support subgroups, as follows: HFNP only
(HF), HFNP followed by other non-invasive ventilation
(HF ? N), HFNP followed by other non-invasive, fol-
lowed by invasive ventilation (HF ? N ? I), or HFNP
followed by invasive ventilation (HF ? I).
HFNP system
A humidified high-flow system was used with a low-resis-
tance paediatric binasal cannula (BC3780 and RT329;Fisher
& Paykel Healthcare, Auckland, NewZealand).The inspired
oxygen concentration was titrated to achieve pulse oximeter
oxygen saturations (SpO
2
)of[94%. The flow rate used was
generally set at 8 l/min at the beginning of the HFNP treat-
ment and then weaned at the discretion of the attending
consultant, most commonly down to 6 or 4 l/min. Failure of
HFNP therapy was defined as the need for escalation of
therapy to either non-invasive ventilation with a face mask,
or invasive ventilation with an endotracheal tube delivered
by the ventilator (Evita XL; Draeger, Lubeck, Germany).
Discontinuation of HFNP therapy was based on reduced
oxygen requirement (generally inspired oxygen fraction
\0.4), and clinical improvement in the work of breathing,
respiratory rate (RR) and heart rate (HR).
Patient parameters
Body weight, age at admission, length of stay (LOS), and
paediatric index of mortality risk of death (PIM2 ROD)
score were recorded [15]. Additionally, LOS and intuba-
tion rate of all infants with viral bronchiolitis admitted to
all PICUs in Australia and New Zealand were extracted
from the most recent ANZPIC data registry and compared
to our dataset [16].
Continuous physiological variables
Ventilatory parameters and physiological variables, such
as HR, RR, SpO
2
, inspired oxygen fraction (FiO
2
, value
when initially started on HFNP therapy) and SpO
2
/FiO
2
ratio were downloaded every 30 min. Data were extracted
from 4 h prior to initiation of HFNP therapy and contin-
ued for 24 h. All data were extracted from the unit’s CIS
(Critical Care Manager; PICIS, Wakefield, MA). Data
were either automatically downloaded from monitors and
validated or manually entered by the bedside nurse.
848
Adverse outcomes
A system for prospectively coding complications is
included in the CIS. These fields and the clinical notes
were screened for adverse events such as cardiac and
respiratory arrest, pneumothorax, gastric distension and
mucosal injury due to cannula position. The number of
failed HFNP treatments in respect of the need for other
non-invasive and invasive ventilation was recorded.
Comparison with ANZPIC registry
To investigate the change in ventilator practice over time
in our unit, case records were extracted from the local
ICU database for all children admitted during the study
period with bronchiolitis. In addition, case records were
extracted from the ANZPIC Registry [14] for patients
with bronchiolitis admitted during 2008. Intubation rate
and LOS in our unit in 2009 were compared to the
ANZPIC Registry patients in 2008.
Statistical analysis
Study groups, including the ANZPIC dataset, were com-
pared using Fisher’s exact test for categorical variables
and variables presented as percentages. Wilcoxon’s rank-
sum test was used to compare admission parameters and
LOS. Data are presented as medians and interquartile
ranges unless otherwise stated. To determine whether
there was an impact of underlying disease or time since
initiation of treatment on the change in the physiological
variables, a linear mixed model was used. HR, RR, SpO
2
and SpO
2
/FiO
2
ratio were used as dependent variables,
patient group and HFNP therapy sequence as factors, and
time as a covariate.
Results
Between January 2005 and December 2009 a total of 298
infants received HFNP therapy in our PICU. Table 1
presents the distribution by disease group and respiratory
support mode. Overall, 56 (19%) infants receiving HFNP
therapy needed escalation to other non-invasive and 36
(12%) to invasive ventilation. Of the infants with a pri-
mary diagnosis of viral bronchiolitis, only 6 (4%)
required escalation to invasive ventilation. There was a
significantly greater incidence of invasive ventilation in
the CARDIAC (n = 12, 50%) and OTHER (n = 7, 41%)
groups compared with the BRONCH (n = 6, 4%) and LD
(n = 8, 12%) groups (p \ 0.05). Most of the cardiac
infants needed intubation for a cardiac surgical procedure
or cardiac failure.
Table 2 shows the admission parameters and LOS of
infants with viral bronchiolitis only. Significant differ-
ences were found between the HF group and the infants
requiring escalation to other non-invasive ventilation for
PIM2 ROD score, admission FiO
2
and LOS (p \ 0.01).
There were no differences found between the therapy
groups in terms of age. Although PIM2 ROD score and
LOS were higher in the HF ? N ? I and HF ? I groups
compared to the HF group, statistical comparison was not
applicable due to the low number of infants in each group.
Table 3 shows the increased use of HFNP therapy in
our PICU for viral bronchiolitis over the study period. In
comparison to Table 1, all patients intubated at admission
were included. In 2005, 52 infants were admitted with
only 7 infants receiving HFNP therapy, whereas in 2009,
44 of 67 infants with bronchiolitis were started on HFNP
Table 1 Disease groups and respiratory support mode
Group HF HF ? NHF? N ? IHF? I All
HF
BRONCH 120 (72%) 41 (25%) 4 (2%) 2 (2%) 167
LD 55 (76%) 9 (13%) 4 (6%) 4 (6%) 72
UAO 6 (75%) 0 (0%) 1 (13%) 1 (13%) 8
NM 8 (80%) 1 (10%) 0 (0%) 1 (10%) 10
CARDIAC 11 (46%) 1 (4%) 0 (0%) 12 (50%) 24
OTHER 6 (35%) 4 (24%) 1 (6%) 6 (35%) 17
Total 206 (69%) 56 (19%) 10 (9%) 26 (3%) 298
Table 2 Admission parameters
of infants with bronchiolitis
(medians and interquartile
ranges)
Parameter HF
(n = 120)
HF ? N
(n = 41)
HF ? N ? I
(n = 4)
HF ? I
(n = 2)
All HF
(n = 167)
PIM2 ROD score (%) 0.17 0.70 0.72 1.49 0.21
0.16–0.23
#
0.59–0.87
#
0.60–0.83 – 0.16–0.59
FiO
2
0.50 0.60 0.60 0.45 0.50
0.40–0.60
$
0.50–0.70
$
0.55–0.70 – 0.4–0.6
LOS (days) 1.83 3.75 9.35 16.9 2.33
1.44–2.75
&
3.0–6.0
&
6.81–12.81 – 1.6–3.5
Age (months) 2.75 3.11 5.87 4.4 2.98
1.43–7.62 1.31–7.87 4.11–6.85 – 1.4–7.9
Weight (kg) 5.50 5.20 6.10 6.15 5.46
3.97–7.95 3.90–7.70 5.35–6.83 – 3.96–7.85
#, $, &
p \ 0.01
849
therapy and only 5 (7%) required intubation and venti-
lation. The overall intubation rate in our unit dropped
from 37% in 2005 to 7% in 2009 whereas, in 2008, the
ANZPIC data registry reported an overall intubation rate
of 28%.
The median LOS in the 2008 ANZPIC registry for
bronchiolitic infants was 2.42 compared to 2.33 in our
study (p = ns).
Table 4 shows admission parameters for infants with
LD. There were significant differences between the HF
and HF ? N groups with lower PIM2 ROD score and
FiO
2
and shorter LOS (p \ 0.001) in the HF group. Sta-
tistical comparison for the HF ? N and HF ? N ? I
groups was not applicable due to low numbers.
Analysis of continuous physiological variables
In all infants there was a significant reduction in RR and
HR after initiation of HFNP therapy (p \ 0.001). There
was a significant interaction between disease group and
HR and RR as well as between HFNP therapy and HR and
RR (mixed linear model, p \ 0.001). The patients with
viral bronchiolitis had the greatest change in HR and RR
after initiation of HFNP therapy (Figs. 1 and 2). After
90 min the mean RR and mean HR had both decreased by
more than 20% of the baseline (mean decrease in RR was
7.0 breaths/min, 95% CI 4.2–9.8, p \ 0.05, and mean
decrease in HR was 13 beats/min, 95% CI 9.25–16.75,
p \ 0.05) in the HF group whereas the in HF ? N group
similar rapid decreases in RR and HR could not be
demonstrated (mean decrease in RR was 5.0 breaths/min,
95% CI 0–10, and mean decrease in HR was 6 beats/min,
95% CI 0.6–11.4). There was no significant interaction
between HFNP therapy and SpO
2
or SpO
2
/FiO
2
ratio.
Adverse effects
There were two in-hospital respiratory arrests and one in-
hospital cardiac arrest identified in the database, all three
of which occurred before admission to the PICU and
before the start of HFNP. No pneumothorax, gastric or
abdominal distension or mucosal injuries were identified.
Discussion
In this retrospective analysis we showed that since the
introduction of HFNP therapy in our PICU, the need for
intubation and mechanical ventilation in infants with viral
bronchiolitis decreased significantly over the 5-year per-
iod, from 37% in 2005 to 7% in 2009. A similar reduction
in intubation rate for bronchiolitic patients has also been
reported in a retrospective study by McKiernan et al. [6].
They reported a reduction from 23% to 9%, but did not
report whether non-invasive ventilation with a face mask
was used in their unit. This reduction reported in our unit
is unlikely to be explained by an overall improved stan-
dard of care across time, as the ANZPIC registry data for
2008 still reported a comparatively higher ventilation rate
for infants with bronchiolitis in a PICU [16]. As with any
retrospective analysis, it is always difficult to demonstrate
a cause and effect relationship, but there are some
important findings in our retrospective analysis that may
have been related to the reduced intubation rate.
The most common reason for non-elective admission
to a PICU in Australia is viral bronchiolitis which
imposes a significant financial burden on the hospital
[16]. In our retrospective analysis, infants with viral
bronchiolitis comprised the largest proportion of infants
receiving HFNP therapy, followed by infants with lung
disease. Similar to respiratory care of the preterm infant in
the NICU [8], there has been an increasing trend toward
the use of non-invasive ventilation in the PICU in order to
reduce the risks associated with invasive ventilation. In
our 5-year observation period, the proportion of infants
Table 3 Infants with viral bronchiolitis listed by year
Year Total
BRONCH
HF and HF ? N Total intubated
2005 52 7 (13%) 19 (37%)
2006 72 32 (44%) 21 (29%)
2007 49 23 (46%) 15 (31%)
2008 90 56 (62%) 12 (13%)
2009 67 44 (66%) 5 (7%)
Total 330 161 (49%) 72 (22%)
Table 4 Admission parameters
for infants with lung disease
(medians and interquartile
ranges)
Parameter HF
(n = 55)
HF ? N
(n = 9)
HF ? N?I
(n = 4)
HF ? I
(n = 4)
All HF
(n = 72)
PIM2 ROD score (%) 0.83 3.61 3.23 1.77 0.91
0.39–1.06
#
1.14–4.42
#
2.41–7.34 0.61–6.58 0.75–1.22
FiO
2
0.5 0.6 0.58 0.55 0.5
0.4–0.6
$
0.6–0.8
$
0.51–0.60 0.50–0.63 0.4–0.6
LOS (days) 1.42 7.83 25.56 11.46 1.83
0.88–2.69
&
5.42–16.46
&
20.69–42.02 9.68–14.88 0.96–4.31
#, $, &
p \ 0.01
850
with viral bronchiolitis treated with HFNP increased from
13% to 66%, while those requiring intubation decreased
proportionately. The admission criteria did not change
during this observational study. Our standard admission
practice was that infants with respiratory distress and an
increased oxygen requirement of[2 l/min were reviewed
by a PICU consultant or senior registrar either in the
emergency department, paediatric ward or during retrie-
val from a referring hospital. Infants were only admitted
to the PICU if respiratory support additional to supple-
mental oxygen was considered necessary.
Escalation of therapy to other non-invasive ventilation
occurred in one-quarter of infants with bronchiolitis
within the first 24 h of admission. The mean HR and
mean RR discriminated between responders and non-
responders to HFNP therapy. Responders showed a 20%
decrease in RR and HR within 90 min of the start of
HFNP therapy, whereas non-responders showed little
change in RR and HR. Infants who required escalation of
treatment to other non-invasive ventilation had a higher
PIM2 ROD score and FiO
2
when HFNP therapy was
started on admission.
Did the introduction of HFNP lead to longer LOS?
The median LOS for all infants with bronchiolitis in our
unit was no different from that reported in the ANZPIC
registry data for 2008 [16]. With the increased experience,
indications for HFNP were broadened and HFNP therapy
was initiated in infants with causes of respiratory distress
other than viral bronchiolitis. Infants with LD who needed
escalation to other non-invasive ventilation were gener-
ally sicker on admission, demonstrating a higher PIM2
ROD score and FiO
2
and had a longer LOS. In infants
with cardiac disease the intubation rate was 50% within
the first 24 h of admission suggesting that HFNP therapy
was not as effective in this population of infants. This was
due to the fact that these infants were intubated for a
cardiac procedure or severe cardiac failure.
This study was limited to a single institution without a
control group, and clinical practice changed over the
study period. A multicentre randomized controlled trial
comparing HFNP therapy with standard care is needed to
assess and prove the efficacy of HFNP therapy.
In conclusion, HFNP therapy provided efficient
respiratory support and oxygen delivery in infants with
respiratory distress in our PICU, and its introduction
coincided with a significant reduction in the need for
intubation of infants with viral bronchiolitis. Further
research is required to establish safety and efficacy of
HFNP definitively.
Acknowledgment We are grateful to the Preston James Fund and
Golden Casket for support of this study.
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4. Klein M, Reynolds LG (1986) Relief of
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Infants with Viral Bronchiolitis: Heart Rate
140
145
150
155
160
165
170
175
180
-90 -60 -30
0
30 60 90 120 150 180 210 240 270 300 330 360
time [min]
heart rate per minute
HF_N
HF_only
start HF therapy
Fig. 1 HR in infants with viral bronchiolitis 90 min before and 6 h
after the start of HFNP therapy. HR decreased significantly in the
HF group (linear mixed model, p \ 0.001). Successfully treated
infants in the HF group showed a significantly lower HR 90 min
after the start of HFNP therapy than those in the HF ? N group
(p \ 0.05). The data are presented as means and 95% CI
Infants with Viral Bronchiolitis: Respiratory Rate
35
40
45
50
55
60
65
70
75
-90 -60 -30 0 30 60 90 120 150 180 210 240 270 300 330 360
time [min]
respiratory rate per minute
start HF therapy
HF_only
HF_N
Fig. 2 RR of infants with viral bronchiolitis 90 min before and 6 h
after the start of HFNP therapy. RR decreased significantly in the
HF group (linear mixed model, p \ 0.001). Successfully treated
infants in the HF group showed a significantly lower RR 90 min
after start of HFNP therapy than those the HF ? N group
(p \ 0.05). The data are presented as means and 95% CI
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