Secondary Logo

Journal Logo

Featured Articles

A Narrative Review of Oxygenation During Pediatric Intubation and Airway Procedures

Else, Scott D. N. MD*; Kovatsis, Pete G. MD

Author Information
doi: 10.1213/ANE.0000000000004403


See Article, p 828

Providing oxygenation is an essential component 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 contribute to short apnea times that are dependent on age.4,5 Predictably, hypoxemia is the most common complication 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 desaturation 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 intervention 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 anesthesia for the use of apneic oxygenation and oxygen supplementation during endotracheal intubation and airway procedures.


Physiology of Apneic Oxygenation

Figure 1.
Figure 1.:
Physiological conditions needed for effective apneic oxygenation. V/Q indicates ventilation to perfusion ratio.

Apneic oxygenation has long been described in the medical literature.14 This technique delays the onset of hypoxemia after cessation of ventilation via continued oxygen delivery and depends on the conditions 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 solubility 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 remaining intrapulmonary oxygen results in decreasing lung volume leading to shunt and hypoxemia. If the airways 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 reservoir 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

Table 1. - Demonstration of Effectiveness of Apneic Oxygenation in Clinical Studies in Children
Soneru et al20: Prospective, Observational Study in Elective Surgery
Summary Apneic oxygenation utilized during trainee intubations improved time to desaturation and decreased the frequency of attending intervention.
Median apnea time until desaturation to 95% (seconds)
median (95% CI)
Patient age group No apneic oxygenation Nasal cannula at 5 L/min
0–8 y 158 (152–168) >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, confidence interval; 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.

The clinical application of apneic oxygenation during airway management is intuitive. During a classic rapid sequence induction, patients are left apneic until muscle 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 children 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 during intubation or airway procedures. A retrospective study by Vukovic et al18 looking at rates of hypoxemia during intubation in a pediatric emergency department before and after instituting apneic oxygenation as the standard of care found that the rate of hypoxemia was reduced from 50% to <25%. Conversely, in a similar setting using a retrospective, video-based, observational design, Overmann et al19 showed no difference in the incidence, depth, or duration of desaturation with apneic oxygenation. Controlled studies in the operating room have consistently shown the ability of apneic oxygenation to prolong the time to desaturation in pediatric patients during intubation for elective surgery (Table 1).5,20–23 These studies have prompted authors to suggest that apneic oxygenation should be the standard of care in any anticipated difficult or prolonged tracheal intubation in children.6,24 This also may extend to intubations by trainees20 or for any infants and children who are not anticipated difficult intubations but are at risk for rapid desaturation due to very young age4 or comorbid conditions. One caveat to this recommendation is that during emergency intubation of critically ill patients, specifically those with intrapulmonary disease and shunting, the physiological conditions required for effective apneic oxygenation (Figure 1) may be precluded.25 Additionally, those patients in whom adequate preoxygenation followed by rapid laryngoscopy and intubation is achievable, the observed rate of hypoxemia is expected to be very low, thus, requiring a larger sample size to detect an effect. Even if the number of patients needed to treat is high, no study has shown direct adverse effects or patient discomfort with apneic oxygenation using nasal cannula.26 Thus, there appears minimal, if any, downside to apneic oxygenation when CO2 rise is limited.


Over the last decade, humidified, high-flow nasal oxygenation systems (H2FNOS) have been utilized for apneic oxygenation or oxygen supplementation during intubations and airway interventions. These high-flow systems are composed of an oxygen blender that connects to high-pressure oxygen and air inputs allowing for accurate titration of the fraction of inspired oxygen (Fio2) at flows up to 80 L/min, a heater-humidifier, a circuit, and high-flow nasal cannula or nasal mask in a range of sizes. These systems generate flow-dependent, positive airway pressure resulting in increases in end-transpulmonary pressure, alveolar pressures, and airway caliber.27,28 This flow-dependent effect also flushes CO2 out from the oronasopharyngeal dead space.29 The potential benefits of utilizing these systems include improved oxygenation, reduction in work of breathing, and respiratory rate with an increase of both end-expiratory lung volume and tidal volume.30,31 The focus herein when discussing these systems is their use in the operating room for apneic oxygenation and oxygen supplementation during airway management and airway procedures.

Transnasal Humidified Rapid Insufflation Ventilatory Exchange in Adults

Table 2. - Clinical Studies Describing Rate of Rise of CO2 During Apnea in THRIVE and Standard Care in Children and Adults
Rate of Rise of CO2 (mm Hg/min)
Control THRIVE
 Riva et al,34 median (range) None 3.84 (1.50–5.95)
 Riva et al,21 median (interquartile range) 4.13 (3.15–4.58) 4.5 (3.45–5.18)
 Humphreys et al,5 mean (range) 2.4 (0.2–3.9) 2.4 (0.2–3.9)
 Lyons and Callaghan,35 mean (SD) None 1.58 (0.60)
 Gustafsson et al,36 mean (SD) None 1.80 (0.38)
 Patel and Nouraei33 None 1.13 ± 0.15a
Previously published rates of rise of CO2 in adults during apnea have been estimated between 3 and 8 mm Hg/min with studies measuring longer periods of apnea having lower rates.14,16
Abbreviations: CO2, carbon dioxide; SD, standard deviation; THRIVE, transnasal humidified rapid insufflation ventilatory exchange.
aCalculated from linear regression equation derived by authors from data as follows: CO2 (in kPa) = (5.2 ± 0.5) + (0.15 ± 0.02) × apnea time.33

A limitation of apneic oxygenation has been the lack of CO2 clearance leading to profound respiratory acidosis. Early animal and human studies demonstrated long apnea times without desaturation as well as the development of cardiovascular complications due to hypercapnia.14,32 In 2015, Patel and Nouraei33 reported a study of apneic oxygenation in adults with difficult airways using a H2FNOS. None of the patients experienced oxygen saturations <90%, and no complications suggestive of CO2 toxicity were reported. This publication was novel in that CO2 clearance appeared to have occurred while using the H2FNOS. The authors named the technique: transnasal humidified rapid insufflation ventilatory exchange (THRIVE). Similar results for prolonged saturation during apnea and decreased CO2 rise were replicated in the adult literature and are summarized in Table 2.35,36 This has generated great interest to use THRIVE as a sole technique for airway management during airway surgery35 and other endoscopic and radiological procedures.

THRIVE in Children

Humphreys et al5 performed a randomized controlled trial using THRIVE in infants and children up to 10 years of age (Table 1). In contrast to adult THRIVE 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 subsequent 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

Table 3. - Estimated Appropriate Flow Rates for THRIVE in Children and Infants Using Allometric Scaling
70 kg Adult (Reference) 60 kg Teenager 40 kg Child 20 kg Child 10 kg Toddler 5 kg Infant 3 kg Neonate
Humphreys et al,5 Flow (L/min) 70 50 40 35 20 10 6
Flow (L/min) using allometric scalinga 70 62 46 38 22 13 9
Abbreviations: THRIVE, transnasal humidified rapid insufflation ventilatory exchange; VCo2, rate of production of carbon dioxide.
aAllometric scaling was done applying Brody's constant of kg3/4 multiplied by a constant of 11 for infants and children up to 20 kg and a constant of 8 for children and adults above 20 kg to mirror the relationship of VCo2 across different ages and weights.38,39 Using this technique suggests higher flow rates should be used, particularly in children <10 kg.

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 physiological 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 microventilation.37 Simultaneous cardiogenic oscillations cause small volumes of air to be flushed between the turbulent 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 during 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 production as described in 1984 by Lindahl et al39 to determine appropriate flow rates shows that, particularly in small children and infants, the rates used by Humphreys et al5 and Riva et al21 are not equivalent 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 minute of apnea, the rise of arterial CO2 tension is rapid (13–18 mm Hg) and mostly related to the equilibration 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 (<10 minutes) versus adult studies (15–60 minutes), it is possible that the average rate of rise of CO2 is overrepresented by the early phase of CO2 accumulation.16 Finally, the adult THRIVE studies have not had a control group meaning that the findings may not result from THRIVE as purported. Instead, the low observed rate of rise of CO2 may reflect the very long apnea time minimizing the contribution of the initial rapid rise of CO2 that occurs in the first minute. Further investigations of the possible mechanisms for this gas exchange as well as the use of higher-flow rates and longer apnea times are needed to clarify this difference in CO2 clearance between children and adults.


Techniques of Ventilation and Oxygenation

In addition to the benefits of oxygen supplementation during endotracheal intubation to prolong safe apnea time, another application is during invasive airway procedures. Children undergo many types of diagnostic and therapeutic airway interventions. Most proceduralists prefer to do these without an ETT to maximize visualization of the anatomic structures and allow access for their instruments. These procedures often require spontaneous respiration to allow for dynamic examination of the airway. This presents unique challenges to the anesthesiologist because they must sustain oxygenation and ventilation as well as maintain a deep level of anesthesia while sharing the airway with the proceduralist. Many different methods of oxygenation and ventilation have been described in the literature including various techniques of intermittent apnea, jet ventilation, and spontaneous respiration with oxygen supplementation.12,13,40 With apneic techniques, the operative time in each cycle is limited by the patient’s safe apnea time, which in turn, tends to further decline with additional cycles if FRC decreases. This becomes more significant with decreasing patient age.4 Many practitioners remain hesitant to utilize jet ventilation in pediatrics due to a concern of barotrauma, particularly in infants; however, it is an acceptable technique with the necessary expertise and equipment.41 Spontaneous ventilation is the most commonly used technique in pediatric airway examination and surgery. This avoids the potential harm associated with jet ventilation while providing sufficient oxygenation and acceptable ventilation for long periods with an open, uninstrumented airway for unobstructed dynamic assessment and intervention of the airway. The key challenge is achieving a depth of anesthesia that maintains an adequate drive for effective spontaneous ventilation while allowing the patient to tolerate the procedure without coughing or breath holding.

Another challenge of the spontaneous breathing technique is maintaining oxygenation. Children and infants are prone to desaturation when spontaneously breathing under general anesthesia as increasing anesthetic depth leads to hypoventilation followed by atelectasis and decreasing FRC.3 In addition to high-flow systems, other options for oxygen supplementation include simple nasal cannula, a ventilating bronchoscope, 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 nasopharyngeal 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 techniques 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 children with abnormal airways during total intravenous anesthesia (TIVA). The cases were separated into 4 categories: tubeless airway surgery, flexible bronchoscopy, 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 minutes. 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 including tracheal dilation and debridement, laser debridement, supraglottoplasty, and laryngeal cleft repair. High-flow nasal oxygen was delivered at flow rates of 4 L/kg/min for patients <5 kg or 2 L/kg/min for patients over 5 kg with 100% Fio2 unless a laser was used in which case the Fio2 was reduced to 30%. The investigators reported clinically relevant, longer apnea times in all cases without observed complications in the perioperative period. The median CO2 rise was 3.84 mm Hg/min, (range, 1.50–5.95 mm Hg/min) and was considered the limiting clinical factor.


Table 4. - Advantages and Disadvantages of Different Oxygenation Techniques Used During Invasive Airway Procedures
Technique Humidified High-Flow Nasal Oxygenation System Traditional Low-Flow Nasal Cannulae Modified Nasopharyngeal Airway42 O2 Catheter in Pharynxa Laryngoscope Side-Port Ventilating Bronchoscope
Advantages Continuous delivery of O2 throughout procedure
Ability to maintain inspired O2 concentration at or near 100% during spontaneous respiration
Accurate titration of Fio 2
May be used for preoxygenation45
Possible CO2 clearance (not shown in pediatrics)33,35,36
May provide continuous positive airway pressure when mouth closed27,28
Continuous delivery of O2 throughout procedure
Readily available
Low cost
Minimal interference with mask ventilation26
Continuous delivery of O2 throughout procedure
Readily available
Low cost
Aides mask ventilation
May help in children with obstructive upper airway pathology
Attaches directly to anesthesia circuit
May provide continuous positive airway pressure when mouth closed42
Continuous delivery of O2 throughout the procedure
Readily available
Low cost
Depending on type of catheter utilized, may not interfere with mask ventilation
Continuous delivery of low-flow O2 when instrument in place
Ability to provide jet ventilation
Continuous delivery of low-flow O2 when instrument in place
Ability to provide jet ventilation
Ability to provide positive-pressure ventilation
Delivery of O2 when glottis obstructed by bronchoscope
Disadvantages Ineffective if glottis is obstructed by airway instrumentation or in children with obstructive upper airway pathology
More complex set up and the equipment requires additional space
Higher cost
Interference with mask ventilation
Ineffective in children with obstructive upper airway pathology
Ineffective if glottis is obstructed by airway instrumentation or in children with obstructive upper airway pathology
Low Fio 2 during spontaneous ventilation
Lack of humidification
Inability to titrate Fio 2
No CO2 clearance
Ineffective in children with obstructive upper airway pathology
Ineffective if glottis is obstructed by airway instrumentation
Lack of humidification unless using low flows via anesthesia circuit
Minimal ability to titrate Fio 2 unless mouth and contralateral nares are closed
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 Fio 2 during spontaneous ventilation
Lack of humidification
Inability to titrate Fio 2
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 Fio 2 during spontaneous ventilation
Lack of humidification
Inability to titrate Fio 2
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 Fio 2 during spontaneous ventilation
Lack of humidification
Inability to titrate Fio 2
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.

Considering the pros and cons of the different methods of oxygenation during intubation and airway procedures as described in Table 4, our opinion is that the delivery of oxygen via nasal cannulas offers greater advantages. This technique provides continuous delivery of oxygen independent from and without interfering in the surgical technique. It also decreases the risks of nasopharyngeal bleeding or gastric insufflation that may occur with an oxygen catheter or a modified nasopharyngeal airway. Therefore, when considering nasal cannulas for oxygen supplementation during airway procedures or for apneic oxygenation during intubation of normal and difficult airways, a provider would choose between using low-flow or high-flow options.

During Airway Procedures

Although currently unverified when using H2FNOS with spontaneously breathing techniques in infants and children, these systems, at the properly calculated flow rate, could enhance ventilation as exhibited in an adult, observational, retrospective study of airway procedures with H2FNOS supporting spontaneous ventilation.49 Another advantage is the ability to deliver humidified oxygen that avoids the potential desiccation of the airway conferring an advantage by preserving respiratory mucosal function and integrity.43,44 Adult literature also supports H2FNOS as an alternative method of preoxygenation before induction.45 Finally, H2FNOS with an oxygen blender allows delivery of a specific Fio2 which is advantageous 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 preserving denitrogenation. When spontaneously breathing with low-flow nasal oxygen, a considerable amount of room air is entrained into the inhaled gas reversing 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 continued adequate oxygenation during hypoventilation or even unintentional apnea that may be encountered during the procedure. However, the provider may err on the side of a deeper plane of anesthesia thereby optimizing surgical conditions and avoiding 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 beneficial for the longer duration of procedures which can occur while spontaneous ventilation is supported with H2FNOS.

During Intubations

Figure 2.
Figure 2.:
Suggested procedure to create conditions for effective apneic oxygenation in the operating room during airway management in children. In cooperative children 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, consider using a high-flow, humidified oxygenation system. IV indicates intravenous; O2, oxygen; PEEP, positive end expiratory pressure; V/Q, ventilation to perfusion ratio.

The primary goal of oxygen supplementation while intubating is to prolong the time from onset of apnea until desaturation. Generally, the time until intubation 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 available 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 spontaneously 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.


Current literature on the clinical effectiveness of different 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 foundation and support to develop prospective, randomized trials in these high-risk patients. If further investigations continue verifying the utility to support the safety of H2FNOS, perhaps, these systems could even be built into the anesthetic workstation.


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 prolong time until desaturation in infants, children, and adults. The efficacy of apneic oxygenation in intubation of critically ill patients is up for debate particularly 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 management 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 significant difference in time until desaturation. Using H2FNOS may have an advantage during spontaneously 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 complications 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 management when difficulty is anticipated or in patients susceptible to rapid desaturation. The goal is to minimize the chance of a clinically significant desaturation 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 management 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 investigations are essential both to compare the 2 methods and to uncover any potential complications. Additional research studying higher-flow rates and longer apnea times with high-flow nasal oxygen systems during apnea in children to clarify the ventilatory effects, if any, are also needed.


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.



    1. Schibler A, Hall GL, Businger F, et al. Measurement of lung volume and ventilation distribution with an ultrasonic flow meter in healthy infants. Eur Respir J. 2002;20:912–918.
    2. Bancalari E, Clausen J. Pathophysiology of changes in absolute lung volumes. Eur Respir J. 1998;12:248–258.
    3. Humphreys S, Pham TM, Stocker C, Schibler A. The effect of induction of anesthesia and intubation on end-expiratory lung level and regional ventilation distribution in cardiac children. Paediatr Anaesth. 2011;21:887–893.
    4. Patel R, Lenczyk M, Hannallah RS, McGill WA. Age and the onset of desaturation in apnoeic children. Can J Anaesth. 1994;41:771–774.
    5. Humphreys S, Lee-Archer P, Reyne G, Long D, Williams T, Schibler A. Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) in children: a randomized controlled trial. Br J Anaesth. 2017;118:232–238.
    6. Fiadjoe JE, Nishisaki A, Jagannathan N, et al. Airway management complications in children with difficult tracheal intubation from the Pediatric Difficult Intubation (PeDI) registry: a prospective cohort analysis. Lancet Respir Med. 2016;4:37–48.
    7. Parker MM, Nuthall G, Brown C III, et al.; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Relationship between adverse tracheal intubation associated events and PICU outcomes. Pediatr Crit Care Med. 2017;18:310–318.
    8. Graciano AL, Tamburro R, Thompson AE, Fiadjoe J, Nadkarni VM, Nishisaki A. Incidence and associated factors of difficult tracheal intubations in pediatric ICUs: a report from National Emergency Airway Registry for Children: NEAR4KIDS. Intensive Care Med. 2014;40:1659–1669.
    9. Sawyer T, Foglia EE, Ades A, et al. Incidence, impact and indicators of difficult intubations in the neonatal intensive care unit: a report from the National Emergency Airway Registry for neonates. Arch Dis Child Fetal Neonatal Ed. 2019;104:F461–F466.
    10. Cook-Sather SD, Tulloch HV, Cnaan A, et al. A comparison of awake versus paralyzed tracheal intubation for infants with pyloric stenosis. Anesth Analg. 1998;86:945–951.
    11. Park RS, Rattana-arpa S, Peyton J, et al. Risk of hypoxemia by induction technique among infants and neonates undergoing pyloromyotomy. Anesth Analg. 2019 [Epub ahead of print].
    12. Ferrari LR, Zurakowski D, Solari J, Rahbar R. Laryngeal cleft repair: the anesthetic perspective. Paediatr Anaesth. 2013;23:334–341.
    13. Jaquet Y, Monnier P, Van Melle G, Ravussin P, Spahn DR, Chollet-Rivier M. Complications of different ventilation strategies in endoscopic laryngeal surgery: a 10-year review. Anesthesiology. 2006;104:52–59.
    14. Frumin MJ, Epstein RM, Cohen G. Apneic oxygenation in man. Anesthesiology. 1959;20:789–798.
    15. McNamara MJ, Hardman JG. Hypoxaemia during open-airway apnoea: a computational modelling analysis. Anaesthesia. 2005;60:741–746.
    16. Eger EI, Severinghaus JW. The rate of rise of PaCO2 in the apneic anesthetized patient. Anesthesiology. 1961;22:419–425.
    17. Baillard C, Boubaya M, Statescu E, et al. Incidence and risk factors of hypoxaemia after preoxygenation at induction of anaesthesia. Br J Anaesth. 2019;122:388–394.
    18. Vukovic AA, Hanson HR, Murphy SL, Mercurio D, Sheedy CA, Arnold DH. Apneic oxygenation reduces hypoxemia during endotracheal intubation in the pediatric emergency department. Am J Emerg Med. 2019;37:27–32.
    19. Overmann KM, Boyd SD, Zhang Y, Kerrey BT. Apneic oxygenation to prevent oxyhemoglobin desaturation during rapid sequence intubation in a pediatric emergency department. Am J Emerg Med. 2018;37:1416–1421.
    20. Soneru CN, Hurt HF, Petersen TR, Davis DD, Braude DA, Falcon RJ. Apneic nasal oxygenation and safe apnea time during pediatric intubations by learners. Paediatr Anaesth. 2019;29:628–634.
    21. Riva T, Pedersen TH, Seiler S, et al. Transnasal humidified rapid insufflation ventilatory exchange for oxygenation of children during apnoea: a prospective randomised controlled trial. Br J Anaesth. 2018;120:592–599.
    22. Steiner JW, Sessler DI, Makarova N, et al. Use of deep laryngeal oxygen insufflation during laryngoscopy in children: a randomized clinical trial. Br J Anaesth. 2016;117:350–357.
    23. Windpassinger M, Plattner O, Gemeiner J, et al. Pharyngeal oxygen insufflation during airTraq laryngoscopy slows arterial desaturation in infants and small children. Anesth Analg. 2016;122:1153–1157.
    24. Fiadjoe JE, Litman RS. Oxygen supplementation during prolonged tracheal intubation should be the standard of care. Br J Anaesth. 2016;117:417–418.
    25. Semler MW, Janz DR, Lentz RJ, et al.; FELLOW Investigators; Pragmatic Critical Care Research Group. Randomized trial of apneic oxygenation during endotracheal intubation of the critically Ill. Am J Respir Crit Care Med. 2016;193:273–280.
    26. Brown DJ, Carroll SM, April MD. Face mask leak with nasal cannula during noninvasive positive pressure ventilation: a randomized crossover trial. Am J Emerg Med. 2018;36:942–948.
    27. Parke RL, Bloch A, McGuinness SP. Effect of very-high-flow nasal therapy on airway pressure and end-expiratory lung impedance in healthy volunteers. Respir Care. 2015;60:1397–1403.
    28. Parke RL, McGuinness SP. Pressures delivered by nasal high flow oxygen during all phases of the respiratory cycle. Respir Care. 2013;58:1621–1624.
    29. Hernández G, Roca O, Colinas L. High-flow nasal cannula support therapy: new insights and improving performance. Crit Care. 2017;21:62.
    30. Papazian L, Corley A, Hess D, et al. Use of high-flow nasal cannula oxygenation in ICU adults: a narrative review. Intensive Care Med. 2016;42:1336–1349.
    31. Corley A, Caruana LR, Barnett AG, Tronstad O, Fraser JF. Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients. Br J Anaesth. 2011;107:998–1004.
    32. Fraioli RL, Sheffer LA, Steffenson JL. Pulmonary and cardiovascular effects of apneic oxygenation in man. Anesthesiology. 1973;39:588–596.
    33. Patel A, Nouraei SA. Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways. Anaesthesia. 2015;70:323–329.
    34. Riva T, Theiler L, Jaquet Y, Giger R, Nisa L. Early experience with high-flow nasal oxygen therapy (HFNOT) in pediatric endoscopic airway surgery. Int J Pediatr Otorhinolaryngol. 2018;108:151–154.
    35. Lyons C, Callaghan M. Apnoeic oxygenation with high-flow nasal oxygen for laryngeal surgery: a case series. Anaesthesia. 2017;72:1379–1387.
    36. Gustafsson IM, Lodenius Å, Tunelli J, Ullman J, Jonsson Fagerlund M. Apnoeic oxygenation in adults under general anaesthesia using Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) - a physiological study. Br J Anaesth. 2017;118:610–617.
    37. Laviola M, Das A, Chikhani M, Bates DG, Hardman JG. Computer simulation clarifies mechanisms of carbon dioxide clearance during apnoea. Br J Anaesth. 2019;122:395–401.
    38. Brody S. Bioenergetics and Growth. 1945.New York, NY: Reinhold.
    39. Lindahl SG, Hulse MG, Hatch DJ. Metabolic correlates in infants and children during anaesthesia and surgery. Acta Anaesthesiol Scand. 1984;28:52–56.
    40. Benjamin B. Anesthesia for laryngoscopy. Ann Otol Rhinol Laryngol. 1984;93:338–342.
    41. Mausser G, Friedrich G, Schwarz G. Airway management and anesthesia in neonates, infants and children during endolaryngotracheal surgery. Paediatr Anaesth. 2007;17:942–947.
    42. Yoon U, Yuan I. Modified nasal trumpet for airway management. Anesthesiology. 2016;125:596.
    43. Omori C, Schofield BH, Mitzner W, Freed AN. Hyperpnea with dry air causes time-dependent alterations in mucosal morphology and bronchovascular permeability. J Appl Physiol (1985). 1995;78:1043–1051.
    44. Williams R, Rankin N, Smith T, Galler D, Seakins P. Relationship between the humidity and temperature of inspired gas and the function of the airway mucosa. Crit Care Med. 1996;24:1920–1929.
    45. Lodenius Å, Piehl J, Östlund A, Ullman J, Jonsson Fagerlund M. Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) vs facemask breathing pre-oxygenation for rapid sequence induction in adults: a prospective randomised non-blinded clinical trial. Anaesthesia. 2018;73:564–571.
    46. Yao HT MV, McNally C, Smith M, Usatoff V. Gastric rupture following nasopharyngeal oxygen delivery - a report of two cases. Anaesth Intensive Care. 2015;43:244–248.
    47. Grude O, Solli HJ, Andersen C, Oveland NP. Effect of nasal or nasopharyngeal apneic oxygenation on desaturation during induction of anesthesia and endotracheal intubation in the operating room: a narrative review of randomized controlled trials. J Clin Anesth. 2018;51:1–7.
    48. Humphreys S, Rosen D, Housden T, Taylor J, Schibler A. Nasal high-flow oxygen delivery in children with abnormal airways. Paediatr Anaesth. 2017;27:616–620.
    49. Booth AWG, Vidhani K, Lee PK, Thomsett CM. SponTaneous Respiration using IntraVEnous anaesthesia and Hi-flow nasal oxygen (STRIVE Hi) maintains oxygenation and airway patency during management of the obstructed airway: an observational study. Br J Anaesth. 2017;118:444–451.
    50. Park R, Peyton JM, Fiadjoe JE, et al.; PeDI Collaborative Investigators; PeDI collaborative investigators. The efficacy of GlideScope® videolaryngoscopy compared with direct laryngoscopy in children who are difficult to intubate: an analysis from the paediatric difficult intubation registry. Br J Anaesth. 2017;119:984–992.
    Copyright © 2019 International Anesthesia Research Society