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April 2020 • Volume 130 • Number 4 www.anesthesia-analgesia.org 831
DOI: 10.1213/ANE.0000000000004403
GLOSSARY
CO2 = carbon dioxide; ETT = endotracheal tube; Fio2 = fraction of inspired oxygen; FRC = functional 
residual capacity; H2FNOS = humidified, high-flow nasal oxygenation systems; NEAR4KIDS = 
National Emergency Airway Registry for Children; NEAR4NEOS = National Emergency Airway 
Registry for Neonates; O2 = oxygen; PeDI-R = Pediatric Difficult Intubation Registry; THRIVE = 
transnasal humidified rapid insufflation ventilatory exchange; TIVA = total intravenous anesthetic
Providing oxygenation is an essential compo-
nent of anesthetic care, yet hypoxemia remains 
an all too familiar complication in the pediatric 
operating room. Children have a high rate of oxygen 
consumption for body mass as compared to adults.1,2 
They also have a propensity to alveolar collapse and 
reduction in functional residual capacity (FRC) under 
anesthesia.3 These physiological differences contrib-
ute to short apnea times that are dependent on age.4,5 
Predictably, hypoxemia is the most common compli-
cation during pediatric airway management.6–9 The 
rate of hypoxemia in intubation of infants— typically 
otherwise healthy patients—with pyloric stenosis 
has been reported at 20%–40%.10,11 In an analysis of 
the Pediatric Difficult Intubation Registry (PeDI-R), 
Fiadjoe et al6 found that hypoxemia occurred in 9% of 
difficult intubations. The National Emergency Airway 
Registry for Children (NEAR4KIDS) reported a desat-
uration rate of 13% in all intubations and in almost half 
of the difficult intubations.7,8 The National Emergency 
Airway Registry for Neonates (NEAR4NEOS) 
reported an even higher rate of hypoxemia during 
intubation with an incidence of 42% in nondifficult 
intubations and 75% in difficult intubations.9 As 
expected, all cases of cardiac arrest were preceded by 
hypoxemia in the PeDI-R cohort.6 Parallel problems 
arise during endoscopic evaluation and surgical inter-
vention of the airway. These procedures often require 
a significant depth of anesthesia with an unsecured 
airway leading to periods of hypoventilation or apnea 
and predisposing the patient to hypoxemia.12,13
As hypoxemia is a common occurrence which can 
lead to serious adverse events, continued efforts must 
be directed to reduce the incidence of hypoxemia. This 
review will discuss current trends in pediatric anes-
thesia for the use of apneic oxygenation and oxygen 
Hypoxemia is a common complication in the pediatric operating room during endotracheal intu-
bation and airway procedures and is a precursor to serious adverse events. Small children and 
infants are at greater risk of hypoxemia due to their high metabolic requirements and propensity 
to alveolar collapse during general anesthesia. To improve the care and safety of this vulnerable 
population, continued efforts must be directed to mitigate hypoxemia and the risk of subsequent 
serious adverse events. Apneic oxygenation has been shown to significantly prolong the safe apnea 
time until desaturation in infants, children, and adults and may reduce the incidence of desaturation 
during emergency intubation of critically ill patients. Successful apneic oxygenation depends on ade-
quate preoxygenation, patent upper and lower airways, and a source of continuous oxygen delivery. 
Humidified, high-flow nasal oxygenation systems have been shown to provide excellent conditions 
for effective apneic oxygenation in adults and children and have the added benefit of providing some 
carbon dioxide clearance in adults; although, this latter benefit has not been shown in children. 
Humidified, high-flow nasal oxygenation systems may also be useful during spontaneous ventilation 
for airway procedures in children by minimizing room air entrainment and maintaining adequate oxy-
genation allowing for a deeper anesthetic. The use of apneic oxygenation and humidified, high-flow 
nasal oxygenation systems in the pediatric operating room reduces the incidence of hypoxemia and 
may be effective in decreasing related complications. (Anesth Analg 2020;130:831–40)
A Narrative Review of Oxygenation During Pediatric 
Intubation and Airway Procedures
Scott D. N. Else, MD,* and Pete G. Kovatsis, MD†
See Article, p 828
From the *Department of Anesthesiology and Pain Medicine, Stollery 
Children’s Hospital, Edmonton, Alberta, Canada; and †Department of 
Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, 
Harvard Medical School, Boston, Massachusetts.
S. D. N. Else is currently affiliated with the Department of Anesthesiology, 
Perioperative and Pain Medicine, Alberta Children’s Hospital, Cumming 
School of Medicine, University of Calgary, Calgary, AB, Canada.
Accepted for publication July 23, 2019.
Funding: None.
Conflicts of Interest: See Disclosures at the end of the article.
Reprints will not be available from the authors.
Address correspondence to Scott D. N. Else, MD, Department of Anes-
thesiology, Perioperative and Pain Medicine, Alberta Children’s Hos-
pital, 28 Oki Dr, Calgary, AB, Canada T3B 6AC. Address e-mail to 
scott.else@ahs.ca.
Copyright © 2019 International Anesthesia Research Society
E NARRATIVE REVIEW ARTICLE
Pediatric Anesthesiology
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mailto:scott.else@ahs.ca
Copyright © 2019 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
832 www.anesthesia-analgesia.org ANESTHESIA & ANALGESIA
Oxygenation During Pediatric Airway Procedures
supplementation during endotracheal intubation and 
airway procedures.
APNEIC OXYGENATION
Physiology of Apneic Oxygenation
Apneic oxygenation has long been described in the 
medical literature.14 This technique delays the onset 
of hypoxemia after cessation of ventilation via con-
tinued oxygen delivery and depends on the condi-
tions described in Figure 1. Adequate preoxygenation 
minimizes the partial pressure of nitrogen in the 
alveoli thereby maximizing the driving pressure for 
the movement of oxygen from the airspace into the 
blood.15 After the onset of apnea, oxygen uptake from 
the alveoli continues in proportion to the patient’s 
metabolic requirements as long as the oxygen tension 
in the alveoli is maintained. Due to the high solubil-
ity in blood and a low driving gradient for diffusion, 
carbon dioxide (CO2) is excreted into the alveoli at a 
significantly lower rate than the rate at which oxygen 
is absorbed.16 This increased flow of oxygen from the 
alveoli and into the blood relative to the excretion of 
CO2 into the alveoli creates a pressure gradient along 
which gasses flow from the upper airway into the 
alveoli. If the airways do not remain patent, no gas 
will flow and the continued absorption of the remain-
ing intrapulmonary oxygen results in decreasing lung 
volume leading to shunt and hypoxemia. If the air-
ways remain patent but the patient is left exposed 
to room air, the oxygen in the alveoli is replaced by 
nitrogen and CO2 leading to exhaustion of the alveolar 
oxygen gradient and hypoxemia. If, however, a reser-
voir of oxygen is created in the upper passageways 
by insufflation, the alveolar oxygen gradient will be 
maintained, and the patient may remain oxygenated 
for a prolonged period of time.
Clinical Application of Apneic Oxygenation
The clinical application of apneic oxygenation during 
airway management is intuitive. During a classic rapid 
sequence induction, patients are left apneic until mus-
cle relaxation is achieved, an adequate laryngoscopic 
view is obtained, and an endotracheal tube (ETT) is 
placed. After adequate preoxygenation,the amount of 
time that passes before desaturation ensues, or the safe 
apnea time, is more than sufficient in healthy patients 
with normal airways. However, in obese or small chil-
dren and in patients with cardiopulmonary illness, the 
safe apnea time is reduced. Similarly, this time frame 
is challenged in patients with difficult laryngoscopy 
and intubation due to a prolonged total apnea time.17 
These conditions increase the risk of hypoxemia. 
Unfortunately, there are very limited clinical studies 
in the pediatric literature looking at the effectiveness 
of apneic oxygenation in preventing hypoxemia dur-
ing intubation or airway procedures. A retrospective 
study by Vukovic et al18 looking at rates of hypoxemia 
during intubation in a pediatric emergency depart-
ment before and after instituting apneic oxygenation 
as the standard of care found that the rate of hypox-
emia was reduced from 50% to 277
Riva et al21: Randomized Controlled Trial in Elective Surgery
Summary Low-flow O2 with nasal prongs had comparable apnea times to THRIVE 100%. THRIVE 30% had significantly 
shorter apnea times than the other 2 groups. There was no difference in the rate of rise of transcutaneous 
CO2 among the 3 groups (median, 4.28 mm Hg/min).
 Apnea time until desaturation to 95% (s), 
median (interquartile range)
Patient age group THRIVE 30% O2 (2.0 L/kg/min) THRIVE 100% O2 (2.0 L/kg/min) Low-flow 100% O2 (0.2 L/kg/min)
 1–6 y 180 (144–222) 456 (372–546) 414 (342–468)
Humphreys et al5: Randomized Controlled Trial in Elective Surgery
Summary THRIVE was effective in significantly delaying the onset of hypoxia during apnea but had no effect on CO2 
clearance.
 Apnea time until desaturation to 92% or double the published age-specific apnea times (seconds)
Patient age group Published apnea time,4 mean (SD) Control, mean (95% CI) THRIVEa
 0–6 mo 96 (12.7) 109.2 (28.8) 192
 6–25 mo 118 (9.0) 147.3 (18.9) 236
 2–5 y 160 (30.7) 190.5 (15.3) 320
 6–10 y 215 (34.9) 260.8 (37.3) 430
Steiner et al22: Randomized Controlled Trial in Elective Surgery
Summary Time to desaturation in apneic oxygenation group more than doubled the apnea time in standard care group
 Apnea time until 1% O2 desaturation (seconds)
Data are given as 25th percentile (95% confidence limits)
Patient age group Standard care O2 insufflation during video 
laryngoscopy
O2 insufflation during direct 
laryngoscopy
 1–17 y 30 (23–39) 67 (35–149) 75 (37–122)
Windpassinger et al23: Blinded, Randomized Controlled Trial in Elective Surgery
Summary Insufflation of O2 during intubation prolonged measured time to desaturation by 35 s.
 Mean apnea time until desaturation to 95% (seconds ± SD)
Patient age group Control O2 insufflation during laryngoscopy
 0–2 y 131 ± 39 166 ± 47
Abbreviations: CI, confidenceinterval; CO2, carbon dioxide; O2, oxygen; SD, standard deviation; THRIVE, transnasal humidified rapid insufflation ventilatory 
exchange.
aNo statistical measures are reported because in the THRIVE arm, the study was terminated when double the published apnea time was reached which occurred 
in all patients. O2 was delivered at weight-dependent flow rates of 0–15 kg at 2 L/kg/min, 15–30 kg at 35 L/min, 30–50 kg at 40 L/min, and >50 kg at 50 L/min.
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Copyright © 2019 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
834 www.anesthesia-analgesia.org ANESTHESIA & ANALGESIA
Oxygenation During Pediatric Airway Procedures
studies, Humphreys et al5 found no difference in the 
rate of CO2 rise between the 2 groups (Table 2). This 
lack of a ventilatory effect was confirmed in a sub-
sequent randomized controlled trial by Riva et al21 
(Tables 1–2). The current evidence would suggest that 
while THRIVE can greatly prolong apnea time until 
desaturation in children, it has no effect on ventilation.
Physiology of CO2 Clearance in THRIVE: Adults 
Versus Children
Given the conflicting data from these studies, why is 
there an apparent CO2 clearance in adults but not in 
children? This may be explained by the physiologi-
cal and anatomical differences between children and 
adults: children have higher metabolic rates, smaller 
airways, and experience a greater decrease in FRC 
with supine positioning and during anesthesia. The 
proposed mechanism for CO2 clearance in adults is 
a cascading vortex of flows and has been modeled in 
computer simulations by Laviola et al.37 High flows 
in the upper airway introduce a turbulent vortex of 
100% oxygen in the supraglottic region leading to 
pharyngeal pressure variations and microventila-
tion.37 Simultaneous cardiogenic oscillations cause 
small volumes of air to be flushed between the turbu-
lent vortex and the intrathoracic airways eventually 
leading to the exchange of CO2 from the alveoli.37 
This reliance on turbulent flow may underpin the 
reason that this technique has not proven effective 
in children and infants. The small airway caliber in 
children results in much higher resistance to flow 
which may limit the propagation of the turbulent 
vortex into the alveoli. Children are also more prone 
to airway and alveolar collapse under anesthesia, 
causing further decreases in FRC and resulting in 
less lung volume available for gas exchange dur-
ing apnea.3 Another possible explanation is that 
higher flows than utilized to date may be necessary 
to achieve a ventilatory effect in children. Using 
Brody’s number38 for allometric scaling of CO2 pro-
duction as described in 1984 by Lindahl et al39 to 
determine appropriate flow rates shows that, partic-
ularly in small children and infants, the rates used 
by Humphreys et al5 and Riva et al21 are not equiva-
lent to 70 L/min in adults (Table  3). Additionally, 
THRIVE studies in children may not have allowed 
an adequate apneic time to reach a steady state of 
CO2 accumulation and clearance. In the initial min-
ute of apnea, the rise of arterial CO2 tension is rapid 
(13–18 mm Hg) and mostly related to the equili-
bration of arterial and venous CO2. After this first 
minute, the rate of rise of arterial CO2 slows and 
reaches a constant.16 With the shorter apnea times 
used in the pediatric studies (and 
infants are prone to desaturation when spontaneously 
breathing under general anesthesia as increasing anes-
thetic depth leads to hypoventilation followed by atel-
ectasis and decreasing FRC.3 In addition to high-flow 
systems, other options for oxygen supplementation 
include simple nasal cannula, a ventilating broncho-
scope, a laryngoscopic side port, or the positioning of an 
ETT or other oxygen catheter in the pharynx. Another 
option described in the literature is to modify a naso-
pharyngeal airway by inserting the 15-mm connector 
from an ETT into the proximal end of the airway so that 
it may be connected to an oxygen supply.42 These tech-
niques are feasible for oxygen supplementation during 
airway procedures or for apneic oxygenation during 
intubation. The advantages and disadvantages of these 
techniques are described in Table 4.43–47
Clinical Application of H2FNOS for Airway 
Procedures
Given the anesthetic challenges presented by airway 
procedures, there has been growing interest in the 
use of H2FNOS. In a prospective observational study, 
Humphreys et al48 reported on their experience of 
using H2FNOS in 20 spontaneously breathing chil-
dren with abnormal airways during total intravenous 
anesthesia (TIVA). The cases were separated into 4 
categories: tubeless airway surgery, flexible bronchos-
copy, management of difficult airways, and patients 
who were at increased risk of respiratory issues due 
to comorbidities. The average lowest saturation 
observed in the study was 96%. The lowest saturation 
value was 77% in a 5-day-old infant with obstructing 
upper airway pathology which, as detailed, would 
make H2FNOS less effective. This was also the only 
patient who required interruption of the procedure 
for rescue oxygenation and intubation after 3 min-
utes. The authors concluded that a high-flow oxygen 
system was a safe and effective method to provide 
oxygenation to spontaneously breathing infants and 
children. In another prospective observational study, 
Riva et al34 reported on the use of H2FNOS under 
apneic conditions for endoscopic treatment of upper 
airway obstructive surgery. In this study, 6 patients 
underwent a total of 14 endoscopic procedures includ-
ing tracheal dilation and debridement, laser debride-
ment, supraglottoplasty, and laryngeal cleft repair. 
High-flow nasal oxygen was delivered at flow rates 
of 4 L/kg/min for patientsclosed
No CO2 clearance
Attaching circuit 
may partially 
obstruct airway 
procedure and 
additional weight 
may accidentally 
remove nasal 
airway
Nasal placement 
risks nasal 
bleeding
Risk of barotrauma 
such as gastric 
distension 
or rupture if 
misplaced46,47
Ineffective if glottis 
is obstructed 
by airway 
instrumentation 
or in children 
with obstructive 
upper airway 
pathology
Low Fio2 during 
spontaneous 
ventilation
Lack of 
humidification
Inability to titrate 
Fio2
No CO2 clearance
Nasal placement 
risk nasal 
bleeding
Risk of barotrauma 
such as gastric 
distension 
or rupture if 
misplaced46,47
Inability to deliver 
O2 if glottis 
is obstructed 
by airway 
instrumentation
Periods without O2 
delivery during 
placement and 
removal
Low Fio2 during 
spontaneous 
ventilation
Lack of 
humidification
Inability to titrate 
Fio2
No CO2 clearance
Periods without O2 
delivery during 
placement and 
removal or when 
luminal access 
port is open 
to atmosphere 
while exchanging 
intraluminal 
equipment
Low Fio2 during 
spontaneous 
ventilation
Lack of 
humidification
Inability to titrate 
Fio2
No CO2 clearance
Abbreviations: CO2, carbon dioxide; Fio2, fraction of inspired oxygen; O2, oxygen.
aCatheters include endotracheal tubes and nonstandard catheters such as suction catheters or feeding tubes.
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 E NARRATIVE REVIEW ARTICLE
April 2020 • Volume 130 • Number 4 www.anesthesia-analgesia.org 837
induction.45 Finally, H2FNOS with an oxygen blender 
allows delivery of a specific Fio2 which is advanta-
geous if laser or cautery is utilized.
The main disadvantages of the H2FNOS are higher 
cost and complexity requiring time and familiarity to 
use. Another disadvantage is that while simple nasal 
cannulas provide minimal interference with bag mask 
ventilation26 or, at the very least, are quick to add and 
remove, the larger size of the high-flow cannula is 
not conducive to effective mask ventilation given the 
more complex apparatus and is not as easy to rapidly 
replace.
As spontaneous breathing is often utilized during 
invasive airway procedures, H2FNOS may have the 
added advantage in this setting of better preserv-
ing denitrogenation. When spontaneously breathing 
with low-flow nasal oxygen, a considerable amount 
of room air is entrained into the inhaled gas revers-
ing the effects of preoxygenation. If the patient 
becomes apneic and the physiological conditions 
needed for effective apneic oxygenation (Figure  1) 
are not met, the patient will desaturate quickly. The 
ability of H2FNOS to deliver oxygen at flow rates 
which are higher than the patient generates during 
normal tidal breathing means that minimal room 
air, if any, is entrained allowing the Fio2 to remain 
near 100%. This preserves a high oxygen tension in 
the alveoli akin to preoxygenation, allowing contin-
ued adequate oxygenation during hypoventilation 
or even unintentional apnea that may be encoun-
tered during the procedure. However, the provider 
may err on the side of a deeper plane of anesthesia 
thereby optimizing surgical conditions and avoid-
ing complications associated from initiating reactive 
airway reflexes. To reiterate, the air-oxygen blender 
in high-flow systems allows for accurate delivery of 
a reduced oxygen concentration during airway laser 
surgery, and H2FNOS provide humidification benefi-
cial for the longer duration of procedures which can 
occur while spontaneous ventilation is supported 
with H2FNOS.
During Intubations
The primary goal of oxygen supplementation while 
intubating is to prolong the time from onset of apnea 
until desaturation. Generally, the time until intuba-
tion is not long enough to be clinically concerned with 
the accumulation of CO2. Therefore, even in situations 
where a ventilation effect is possible with H2FNOS, 
this benefit is clinically irrelevant except in the most 
at-risk patients such as those with critical pulmonary 
or intracranial hypertension. Given that both high-
flow and low-flow nasal oxygenation equally prolong 
the time until desaturation occurs during apnea,21 
intubation with a simple nasal cannula is favored in 
most clinical situations when considering the added 
benefits of decreased expense, less interference with 
bag mask ventilation, and a simple setup that is avail-
able easily and everywhere an intubation may occur. 
A stepwise approach to apneic oxygenation during 
intubation is described in Figure 2.
During Difficult Intubations
H2FNOS may have the advantage in the patient with 
an expected difficult airway because these intubations 
may be prolonged and are often done using spontane-
ously breathing techniques. In these situations, such 
as a challenging flexible fiberscopic intubation or the 
added complexity of a difficult airway and advanced 
cardiopulmonary disease, the advantages described 
above of preserving denitrogenation and possible 
CO2 clearance could safely add additional time that 
may be essential for a successful intubation.
Figure 2. Suggested procedure to create 
conditions for effective apneic oxygenation 
in the operating room during airway man-
agement in children. In cooperative chil-
dren and in high-risk intubations, consider 
placing nasal cannula as the first step and 
performing steps 2–4 before induction of 
anesthesia. In higher-risk patients, con-
sider using a high-flow, humidified oxygen-
ation system. IV indicates intravenous; O2, 
oxygen; PEEP, positive end expiratory pres-
sure; V/Q, ventilation to perfusion ratio.
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Copyright © 2019 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
838 www.anesthesia-analgesia.org ANESTHESIA & ANALGESIA
Oxygenation During Pediatric Airway Procedures
FUTURE DIRECTIONS
Current literature on the clinical effectiveness of dif-
ferent oxygen supplementation techniques in children 
is limited, and there has not been a demonstrated CO2 
clearance effect for H2FNOS during apnea. Future 
studies of apneic oxygenation designed using higher-
flow rates (Table  3) and longer apnea times may be 
useful in exploring this issue further. Computer 
simulations, such as those done in adults,37 could 
be run using various pediatric models to attempt to 
elucidate the reasons for the lack of CO2 clearance. 
Furthermore, it would be interesting to study how 
H2FNOS performs in other tubeless anesthetics such 
as for gastroenterology, pulmonology, and radiology. 
Prospective randomized studies analyzing the use of 
these methods in higher-risk pediatric patients in the 
operating rooms are nonexistent. Such prospective 
studies would be very challenging to pursue. Instead, 
utilizing large databases (eg, PeDI-R, NEAR4KIDS, 
and NEAR4NEOS) to analyze high-flow versus low-
flow systems on hypoxemia and other complications 
may be instructive and provide the necessary founda-
tion and support to develop prospective, randomized 
trials in these high-risk patients. If further investi-
gations continue verifying the utility to support the 
safety of H2FNOS, perhaps, these systems could even 
be built into the anesthetic workstation.
CONCLUSIONS
Apneic oxygenation is a technique that has long been 
described in the literature but has only recently begun 
to gain significant traction in pediatric anesthesiology. 
Apneic oxygenation has been shown to significantly 
prolongtime until desaturation in infants, children, 
and adults. The efficacy of apneic oxygenation in 
intubation of critically ill patients is up for debate par-
ticularly in patients with pulmonary air-space disease 
and significant shunting. Overall, apneic oxygenation 
is likely to be more efficacious in the operating room 
setting. With H2FNOS, apneic oxygenation has shown 
ventilatory effects during apnea in adults, but this has 
not been shown in infants and children. Thus, while 
H2FNOS may have a role as the sole airway manage-
ment technique for tubeless airway surgery in apneic 
adults, it is not clinically equivalent in apneic children 
at the currently published flow rates.
In children, using high flow versus low flow for 
apneic oxygenation has not been shown to have a sig-
nificant difference in time until desaturation. Using 
H2FNOS may have an advantage during spontane-
ously breathing tubeless airway surgery in children 
by allowing delivery of 100% Fio2, titrating to a lower 
Fio2 when appropriate, and providing humidification. 
The main disadvantages of these systems are cost, 
complexity, and interference with mask ventilation.
In summary, although no high-quality, adequately 
powered, pediatric, randomized controlled studies 
on both the ventilation effects and potential com-
plications have been published making any clinical 
recommendations regarding apneic oxygenation 
preliminary, in our opinion, apneic oxygenation with 
simple nasal cannula at a flow rate of at least 0.2 L/
kg/min21 should be considered during airway man-
agement when difficulty is anticipated or in patients 
susceptible to rapid desaturation. The goal is to min-
imize the chance of a clinically significant desatura-
tion leading to premature abortion of an attempt or 
a serious adverse event and hopefully improving 
intubation success rate and patient safety.6,50 Apneic 
oxygenation is also useful during airway manage-
ment with trainees allowing more time, reducing 
the stress on the trainee and the supervisor while 
maintaining the saturation and hopefully the safety 
of the patient.20 H2FNOS during spontaneously 
breathing tubeless airway surgery are advantageous 
in patients at higher risk of desaturation events 
and during longer operations to prevent drying of 
the mucosa. Apneic oxygenation and supplemental 
oxygenation during pediatric airway management 
and airway procedures have a nascent foundation in 
science. To fully support the use of either high-flow 
or low-flow methods of oxygenation, further inves-
tigations are essential both to compare the 2 meth-
ods and to uncover any potential complications. 
Additional research studying higher-flow rates and 
longer apnea times with high-flow nasal oxygen sys-
tems during apnea in children to clarify the ventila-
tory effects, if any, are also needed. E
DISCLOSURES
Name: Scott D. N. Else, MD.
Contribution: This author helped review the literature, write 
large portions of the text, and review and edit the manuscript.
Conflicts of Interest: None.
Name: Pete G. Kovatsis, MD.
Contribution: This author helped review the literature, write 
large portions of the text, and review and edit the manuscript.
Conflicts of Interest: P. G. Kovatsis is a medical advisor to 
Verathon.
This manuscript was handled by: James A. DiNardo, MD, 
FAAP.
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Copyright © 2019 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
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840 www.anesthesia-analgesia.org ANESTHESIA & ANALGESIA
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