Preoxygenation and apneic oxygenation for airway management for anesthesia

INTRODUCTION — Preoxygenation, or administration of oxygen prior to induction of anesthesia, is an essential component of airway management. Preoxygenation is used to increase oxygen reserves in order to prevent hypoxemia during apnea. Preoxygenation and apneic oxygenation are particularly beneficial if manual ventilation after induction of anesthesia is undesirable (eg, during rapid sequence induction and intubation [RSII]), if difficulty with airway management is anticipated, and for patients who are expected to desaturate rapidly (eg, obese, pregnant, pediatric, or hypermetabolic patients).

Novel techniques have been developed that allow for preoxygenation and continued oxygenation during attempts to secure the airway, thereby preventing or delaying oxygen desaturation, and reducing time pressure during airway management.

This topic will discuss the principles and techniques for preoxygenation and for apneic oxygenation. Other aspects of airway management for anesthesia and outside the operating room are discussed separately in numerous topics. (See "Airway management for induction of general anesthesia" and "Rapid sequence intubation for adults outside the operating room" and "Rapid sequence induction and intubation (RSII) for anesthesia" and "Management of the difficult airway for general anesthesia in adults".)

GOALS FOR PREOXYGENATION — The functional goal for both preoxygenation and apneic oxygenation is to prolong the safe apnea time (or duration of apnea without desaturation [DAWD]). Safe apnea time is typically defined as the time from cessation of breathing or ventilation until the peripheral arterial oxygen saturation (SpO₂) declines to 90 percent, after which it falls precipitously [1-3]. (See 'Physiology of apnea' below.)

Arterial oxyhemoglobin desaturation is a dangerous event, with prolonged desaturation leading to dysrhythmias, hemodynamic decompensation, hypoxic brain injury, and ultimately death [4,5]. Preoxygenation delays desaturation by increasing oxygen reserves; preoxygenation to a fraction of expired oxygen (FEO₂) of 0.9 in a healthy patient prolongs the safe apnea time to eight minutes, compared with one minute in the same patient breathing room air [6,7]. Continued oxygenation during apnea prolongs the safe apnea time significantly further, depending on the apneic oxygenation technique and patient factors. (See 'Apneic oxygenation' below.)

The importance of preoxygenation both before intubation and before extubation has been emphasized in guidelines by the American Society of Anesthesiologists and other international anesthesia organizations, and it has become a minimum standard of care during induction and emergence from anesthesia [6,8-12].

Prolonging the time to desaturation after induction of anesthesia reduces the time pressure to secure an airway, thereby reducing anxiety and increasing operator performance [13].

OXYGEN STORAGE — Oxygen stored in the body is quickly depleted when oxygen supply and ventilation are interrupted. Effective preoxygenation will increase the total body stores of oxygen and thereby lengthen the time until depletion occurs. The largest stores of oxygen in the human body are in the blood and in the lungs (table 1). Optimal preoxygenation can increase lung oxygen stores approximately six times compared with breathing room air, depending on patient factors (figure 1 and table 1).

Oxygen storage in the lungs — Gas in the lungs is stored primarily in the lung space defined by functional residual capacity (FRC), which is the volume of the lungs at the end of a normal tidal breath. Factors affecting FRC include body size, sex, age, posture, ethnic origin, and body habitus.

The alveolar gas in a healthy patient breathing room air with normal tidal ventilation contains approximately 14 percent oxygen, 5 percent carbon dioxide, 6 percent water vapor, and 75 percent nitrogen. If the same patient breathes 100 percent oxygen, alveolar nitrogen is progressively "washed out" and replaced with oxygen. The process of preoxygenation involves this progressive replacement of nitrogen for oxygen in the lung space defined by the FRC. (See "Measures of oxygenation and mechanisms of hypoxemia", section on 'Alveolar-arterial (A-a) oxygen gradient'.)

A change in FRC can clearly have a significant impact on the size of the oxygen reservoir within the lungs, and therefore on the efficacy of preoxygenation. Thus, patients with reduced FRC (obese, pregnant, or pediatric patients) have reduced oxygen reserves and are at increased risk of desaturation during apnea (figure 2 and table 2). (See 'Efficacy' below.)

PHYSIOLOGY OF APNEA — After the onset of apnea, oxygen is consumed from the alveoli at a rate of approximately 250 mL per minute, while carbon dioxide is excreted into the alveoli at a rate of 20 mL per minute [14].

●Fall in oxygenation during apnea – During apnea, as the alveolar partial pressure of oxygen (PAO₂) falls there is a corresponding fall in the arterial partial pressure of oxygen (PaO₂). The oxyhemoglobin dissociation curve defines the relationship between the partial pressure of oxygen in the blood and the oxygen saturation of hemoglobin (figure 3). (See "Structure and function of normal hemoglobins".)

The sigmoid shaped curve is relatively flat above a PaO₂ of approximately 60 mmHg (8 kPa); this represents the point at which arterial oxygen saturation (SaO₂) is 90 percent. The flatness of the curve means that above a PaO₂ of 60 mmHg, the SaO₂ remains relatively constant even when there is variation in the pressure of inspired oxygen. Below a critical PaO₂ of 60 mmHg (which corresponds to SaO₂ of 90 percent) the oxyhemoglobin dissociation curve becomes a steep, almost vertical line, and small decreases in the PaO₂ result in a large corresponding fall in the SaO_2. The sigmoid shape of the curve, along with the signal averaging used by pulse oximeters, means that peripheral arterial oxygen saturation (SpO₂) is a late indicator of impending severe hypoxemia. (See "Pulse oximetry", section on 'Advantages and disadvantages'.)

●Increase in carbon dioxide during apnea – Carbon dioxide is 20 times more water soluble than oxygen. Once apnea occurs, carbon dioxide is excreted into the alveoli at approximately 20 mL per minute, while 90 percent of carbon dioxide remains dissolved in plasma and tissues. The arterial partial pressure of carbon dioxide (PaCO₂) rises approximately 8 to 16 mmHg per minute during the first minute of apnea, with a subsequent rise of approximately 3 mmHg per minute during continued apnea, ultimately causing hypercarbia and acidosis [14].

●Alveolar pressure during apnea – Initially during apnea, the difference between the amount of oxygen removed from the alveoli (approximately 250 mL/min) and the amount of carbon dioxide excreted into the alveoli (approximately 20 mL/min) creates a negative pressure gradient between the alveoli and the upper airway. Thus the gas in the oropharynx moves down the trachea into the alveoli. This phenomenon is the basis for apneic oxygenation. (See 'Apneic oxygenation' below.)

EFFICACY AND EFFICIENCY OF PREOXYGENATION — Preoxygenation can be defined in terms of efficiency and efficacy. Effective preoxygenation occurs when alveolar, arterial, tissue, and venous compartments are all maximally filled with oxygen. Efficiency is defined by the rate of decline in arterial oxygen saturation (SaO₂) [15-18]; the slower the rate of decline the more efficient the preoxygenation process is (table 2).

Efficacy — Efficacy has been defined in terms of alveolar oxygenation, alveolar denitrogenation, or the arterial partial pressure of oxygen (PaO₂) achieved by preoxygenation. In healthy patients preoxygenation typically increases the PaO₂ from approximately 80 mmHg to 400 mmHg [19]. In most clinical situations, the end-tidal oxygen concentration (EtO₂) is used to assess efficacy, with an EtO₂ of 90 percent considered an adequate target [6,15]. Importantly, EtO₂ can be considered an accurate endpoint for preoxygenation only if it is accompanied by a normal capnogram and appropriate movement of the reservoir bag during respiration. Absent these findings, the EtO₂ may reflect sampling of fresh gas flow, rather than true EtO₂ [20]. The SaO₂ may also be a misleading guide to the efficacy of preoxygenation. A SaO₂ of 100 percent may occur well before the lungs are adequately denitrogenated. Conversely, failure of SaO₂ to increase substantially during preoxygenation does not necessarily indicate failure of the technique; patients with substantial extrapulmonary shunting may achieve excellent pulmonary oxygen reservoirs while remaining hypoxemic [21].

The process of oxygen wash in and nitrogen wash out is an exponential function. As with all exponential functions the rate of this process is governed by a time constant (t). In this case, t is proportional to the functional residual capacity (FRC) and inversely proportional to alveolar ventilation (VA). The time required for preoxygenation will depend on the size of the FRC (the larger the FRC the longer time required for full preoxygenation) and the VA (increasing alveolar ventilation reduces the time needed for preoxygenation).

After 1T the oxygen concentration will be increased by approximately 63 percent of its original value; 86 percent after 2T; 93 percent after 3T; and to 98 percent after 4T [22].

The anesthesia circuit is a reservoir from which nitrogen must be removed or washed out. This is also an exponential function with the time constant dependent on the size of the circuit and oxygen flow [23,24]. Therefore, flushing with oxygen before attempting preoxygenation and selecting a flow rate of oxygen that eliminates rebreathing will minimize the time required to preoxygenate. The fraction of inspired oxygen (FiO₂) is influenced by the type of breathing, the duration of breathing, and the level of fresh gas flow [25]. (See 'Maximizing FiO2' below.)

Efficiency — The delay in desaturation during apnea after preoxygenation (ie, efficiency), is dependent on the efficacy of preoxygenation, the capacity for oxygen loading and the rate of oxygen consumption. Thus, the factors that affect efficiency include the volume of the FRC, PaO₂, the arterial oxygen content, cardiac output, and the rate of tissue oxygen consumption. Patients with reduced oxygen loading potential (primarily reduced FRC) or those with increased oxygen consumption will desaturate much faster during apnea [26-29]. The effect of FRC and oxygen consumption on the efficiency of preoxygenation is shown in a figure (figure 2). Oxygen delivery and consumption and abnormalities of these processes are discussed separately. (See "Oxygen delivery and consumption".)

PREOXYGENATION TECHNIQUES

General principles — Efficacy of preoxygenation can be optimized by maximizing the usable space of the lung reservoir for oxygen (ie, recruiting lung units by reducing atelectasis or consolidation) and maximizing the filling of the reservoir with oxygen (ie, using a fraction of inspired oxygen [FiO₂] of 100 percent and achieving an end-tidal oxygen [EtO₂] as high as possible) (figure 1).

Maximizing FiO2 — The main reasons for failure to achieve a fraction of inspired oxygen (FiO₂) of close to 1.0 are a leak under the face mask [17,30-33], rebreathing of exhaled gases, and use of systems incapable of delivering high FiO₂ [34].

●Prevent entrainment of air – Entrainment of room air from underneath a face mask will be reduced by choosing an appropriately sized mask and applying it tightly to the face. In one study, using gravity alone to keep a face mask in place allowed >20 percent entrainment of room air, with fresh gas flow of 10 L/minute [33]. The technique, including the importance of a tight fitting mask, should be explained to the patient in advance. A tight seal may be challenging in edentulous patients, those with facial hair, and those with a nasogastric tube in place. Applying a transparent occlusive dressing (eg, Tegaderm) to the beard or mustache area underneath the face mask may be helpful. Endpoints that indicate a good seal include appropriate movement of the reservoir bag during respiration, a normal capnogram and end-tidal carbon dioxide (EtCO₂), and expected expired oxygen concentration [17]. Where a good mask seal cannot be obtained or a patient is claustrophobic, he/she may breathe through a mouthpiece (eg, Entonox connector) connected to the anesthesia circuit with his/her nose occluded.

●Use high flow oxygen – Oxygen flow of at least 10 L/minute will prevent rebreathing of exhaled gases with most breathing circuits and assure maximal FiO₂ during preoxygenation.

●Denitrogenate the breathing circuit – Any reservoir bags should be emptied and the circuit should be flushed with oxygen prior to commencing preoxygenation. The purpose is to denitrogenate the breathing circuit.

●Avoiding self-inflating resuscitation bag for preoxygenation – Self-inflating resuscitation bags have been designed for positive pressure ventilation. They have variable characteristics when used for spontaneously breathing patients and often entrain room air in this situation [34,35]. The valve type and design may also increase the work of breathing.

Inspired and expired gas monitoring — Capnography and EtO₂ monitoring should always be used to assess efficacy during preoxygenation (see 'Efficacy' above). An EtO₂ of >94 percent cannot usually be achieved due to the presence of carbon dioxide and water vapor in the expired gases. Erroneously high EtO₂ readings can occur with small tidal volumes and reflects a sampling of the fresh gas flow or dead space gasses.

Positioning — Patients should be preoxygenated in the head up or reverse Trendelenburg position, unless they are at risk for hypotension with the head up position. The supine position reduces functional residual capacity (FRC) and increases dependent atelectasis, thereby shortening the safe apnea time, particularly in patients with obesity. (See "Anesthesia for the patient with obesity", section on 'Preoxygenation and apneic oxygenation'.)

The head up position improves the efficacy of preoxygenation and prolongs the safe apnea time when compared with the supine position, even in non-obese patients [36-38]. However, head up positioning may not increase the safe apnea time after preoxygenation in pregnant patients [39].

Breathing technique for routine preoxygenation — The breathing technique employed affects the speed and efficacy of preoxygenation. Preoxygenation is typically performed with tidal volume breathing (TVB) (ie, normal depth and rate of ventilation) for at least three minutes. For rapid preoxygenation using deeper breaths, optimal efficacy and efficiency can be achieved with eight vital capacity breaths over one minute (figure 4).

Tidal volume breathing — TVB preoxygenation requires at least three minutes for maximal denitrogenation, depending on patient factors. For a 70 kg person inhaling tidal volume breaths of approximately 490 mL (7 mL/kg), at a respiratory rate of 12 per minute, with anatomical dead space 140 mL (2 mL/kg), alveolar ventilation would be equal to 4200 mL per min. If the FRC is 3000 mL then the time constant for nitrogen wash out would be approximately 0.7 minutes, and 2.8 minutes (4 time constants) would be required to achieve 98 percent nitrogen washout. Because of interindividual variation in FRC and alveolar ventilation, preoxygenation with TVB should be performed for at least three minutes, and or optimally until the EtO₂ is >90 percent. Preoxygenation with tidal volume breaths occurs more rapidly in pregnant patients at term and can be reduced to two minutes for maximal increase in EtO₂ [40].

Efficiency, as measured by safe apnea time after preoxygenation with TVB for three minutes, has been reported at approximately 4 to 9 minutes in normal weight, nonpregnant adults [6,7]. Efficacy with this technique has been reported at 88 to 92 percent EtO₂ [25,41,42].

Deep breathing techniques — Preoxygenation techniques using vital capacity breaths were introduced to reduce the time required for efficacious preoxygenation. The increased minute ventilation achieved by deep breathing theoretically reduces the time constant for nitrogen washout and therefore increases the speed of preoxygenation.

Most studies have reported that preoxygenation with eight vital capacity breaths over the course of one minute is equally effective and efficient as three minutes of TVB, and that both techniques are superior to preoxygenation with four deep breaths over 30 seconds, including in older adult patients [1,7,16,25,41-43]. In one study, preoxygenation with eight deep breaths over one minute slowed the fall in oxygen saturation during apnea compared with both TVB and four deep breaths over 30 seconds (figure 4) [16]. Extending deep breathing to 1.5 or 2 minutes may further increase the likelihood of achieving an ETO₂ >90 percent [25].

Prior maximal exhalation — Maximal exhalation before preoxygenation with either deep breathing or TVB confers no additional benefit. Maximal exhalation results in a more rapid rise in ETO₂ in the first minute of preoxygenation, but does not affect the time required to reach ETO₂ >90 percent [44].

Positive airway pressure techniques during preoxygenation — Positive airway pressure techniques used during preoxygenation and during ventilation prior to intubation increase FRC [45], reduce atelectasis [46,47] and intrapulmonary shunting, and increase the safe apnea time. Options include continuous positive airway pressure (CPAP), positive end-expiratory pressure (PEEP), bilevel positive airway pressure (BPAP), and noninvasive positive pressure ventilation. (See 'High-risk patients' below.)

During preoxygenation PEEP is most easily applied by closing the adjustable pressure limiting (APL) valve on the anesthetic circuit and maintaining a tight face mask seal as the patient breathes spontaneously. After induction of anesthesia and prior to intubation, CPAP can be achieved by maintaining an open airway with PEEP during positive pressure mask ventilation.  

●Efficacy with positive airway pressure techniques – The efficacy of preoxygenation is increased when using positive airway pressure techniques. Preoxygenation utilizing noninvasive ventilation (NIV) or CPAP has been shown to increase the proportion of patients attaining the preoxygenation target of ETO₂ >90 percent in both obese and non-obese subjects [48]. NIV can also reduce time required to complete preoxygenation [49].

●Efficiency with positive airway pressure techniques – The use of CPAP during preoxygenation prior to induction of anesthesia has been shown to increase the safe apnea time in non-obese individuals [50,51]. For patients with obesity, the effect of positive pressure ventilation during preoxygenation may depend on the duration and level of positive pressure. In one study of patients with severe obesity who underwent rapid sequence induction and intubation (RSII), there was no difference in the time to desaturation to 90 percent in patients who were preoxygenated for three minutes with CPAP at 7.5 cm H₂O, compared with patients without CPAP [52]. In contrast, in another trial that included 30 patients with severe obesity, preoxygenation with PEEP of 10 cm H₂O, followed by mask ventilation with PEEP at 10 cm H₂O for another five minutes until intubation increased the safe apnea time by 50 percent (from 127 to 188 seconds) [53].

NIV for preoxygenation, with [54] or without [55] the use of high flow nasal cannulae, may reduce the incidence of severe oxygen desaturation during intubation of critically ill patients in the intensive care unit (ICU). (See "Rapid sequence intubation for adults outside the operating room", section on 'Right-to-left intrapulmonary shunting'.)

High flow nasal oxygen provides positive airway pressure along with apneic oxygenation. (See "Heated and humidified high-flow nasal oxygen in adults: Practical considerations and potential applications", section on 'General principles of application' and 'Heated humidified high flow nasal oxygen' below.)

Complications of preoxygenation — The most important potential complication of preoxygenation is resorption atelectasis. When breathing room air, alveoli contain a high concentration of nitrogen, which is poorly soluble in blood and remains largely in the alveoli, helping to stent them open. After preoxygenation (ie, denitrogenation), absorption of oxygen from alveoli into blood accentuates the atelectasis that results from general anesthesia, and shunting can occur. (See "Adverse effects of supplemental oxygen", section on 'Absorptive atelectasis'.)

Decreasing the FiO₂ during preoxygenation to 0.8 prevents atelectasis formation during general anesthesia [56], but it reduces the duration of safe apnea. In a study of women who were preoxygenated for general anesthesia, preoxygenation with FiO₂ of 0.8 desaturated to 90 percent in a mean of 303 seconds, compared with 411 seconds in patients who were preoxygenated with 100 percent oxygen [57]. The relative risk of atelectasis versus the risk of decreasing the safe apnea time must be assessed by the clinician. The use of CPAP or PEEP can offset the occurrence of atelectasis. (See 'Positive airway pressure techniques during preoxygenation' above.)

Since preoxygenation increases the safe apnea time, desaturation will be a late sign of airway compromise, including after esophageal intubation. Therefore, EtCO₂ monitoring and clinical assessment of ventilation are mandatory after intubation and extubation.

Oxygen toxicity can occur after administration of supplemental oxygen; there is not a well-defined FiO₂ or duration of exposure below which oxygen toxicity does not occur (see "Adverse effects of supplemental oxygen", section on 'Lung parenchymal injury'). Nonetheless, given the short duration of administration of oxygen for preoxygenation and apneic oxygenation for intubation, the unknown but likely very small risk of oxygen toxicity is probably far outweighed by the risk of hypoxemia that can suddenly develop when apnea occurs. For patients who have received bleomycin, prolonged administration of oxygen, as might occur during apneic oxygenation for laryngeal surgery, should probably be avoided. (See "Adverse effects of supplemental oxygen", section on 'Lung parenchymal injury'.)  

Use of positive airway pressure techniques during preoxygenation could theoretically insufflate air into the stomach and increase the risk of regurgitation and aspiration, though there is no evidence that this occurs. There is no reason to avoid PEEP or NIV during preoxygenation prior to RSII for anesthesia. In a randomized study of the use of NIV for preoxygenation for intubation in critically ill patients, there were no differences in regurgitation or new infiltrates on chest radiograph after intubation in patients who were preoxygenated with NIV, compared with patients with preoxygenation by face mask [55]. Positive pressure ventilation during RSII is discussed separately. (See "Rapid sequence induction and intubation (RSII) for anesthesia", section on 'Mask ventilation'.)

APNEIC OXYGENATION — Apneic oxygenation is a process by which oxygen moves by mass flow through the upper airways and into the alveoli in the absence of any respiratory effort. A pressure gradient is created by the differential rates of oxygen removal from and carbon dioxide diffusion into the lungs [58] (see 'Physiology of apnea' above). Apneic oxygenation during intubation may be particularly beneficial in patients who are at risk for rapid desaturation, and in patients for whom airway management may be difficult or prolonged. Apneic oxygenation techniques may also be used during upper airway surgery, to allow the surgeon access to airway structures unimpeded by the presence of an endotracheal tube or supraglottic airway.

Efficacy and efficiency of apneic oxygenation — The use of apneic oxygenation has become more widespread over the past decade. Studies have demonstrated its ability to reduce the incidence of critical desaturation in a variety of clinical settings [59-61]. As an example, a meta-analysis of eight randomized and observational studies (1837 patients) of intubation in the emergency department or intensive care unit (ICU) found that apneic oxygenation was associated with reduced odds of peri-intubation desaturation to peripheral arterial oxygen saturation (SpO₂) <93 percent (OR 0.66, 95% CI 0.52 to 0.85) and an increase in first-pass intubation success (OR 1.59, 95% CI 1.04 to 2.44) [62]. In the included studies, apneic oxygenation was performed with either a humidified high flow nasal oxygenation system or standard nasal cannulae (see 'Apneic oxygenation with standard nasal cannulae' below and 'Heated humidified high flow nasal oxygen' below). Two other meta-analyses published in 2017, including many of the same studies, reached similar conclusions [63,64].

Apneic oxygenation depends on maintaining a patent air passage between the lungs and oropharyngeal airspaces, and a continuous supply of oxygen to the nasopharyngeal and oropharyngeal reservoirs. Apneic oxygenation after preoxygenation can maintain arterial oxygen saturation (SaO₂) for a surprising length of time; SaO₂ has been maintained at over 90 percent for 100 minutes in some studies [65,66].

Optimal efficiency of apneic oxygenation requires maximal preoxygenation and delivery of 100 percent oxygen [67]. Computational modelling has shown that increasing the ambient oxygen fraction during apneic oxygenation from 0.9 to 1.0 more than doubles the time to desaturation compared with increasing the ambient oxygen fraction from 0.21 to 0.9 (figure 5) [67].  

The efficiency of apneic oxygenation is also affected by the ratio of functional residual capacity (FRC) to body weight [66]. Patients with a low FRC to bodyweight ratio (eg, patients with obesity) may therefore desaturate quickly, even during apneic oxygenation.

Apneic oxygenation techniques — Administration of oxygen via face mask provides minimal oxygen to apneic patients [68], and of course the mask must be removed for intubation. A variety of devices and techniques have therefore been developed to insufflate oxygen into the pharynx or trachea during intubation. Some devices that have been used for apneic oxygenation during intubation in children are shown in a figure (picture 1). Most of these devices have been used in adults as well.

The mechanisms and dynamics of oxygen flow when using apneic oxygenation techniques are the subject of continuing research. The location of delivery of oxygen insufflation and the flow rate will influence upper airway pressure, turbulence, and entrainment. The optimal location for delivery of oxygen into the airway (ie, tracheal, pharyngeal, or nasal) for apneic oxygenation has not been established. With respect to increasing the safety of airway management, the most beneficial methods of oxygen administration are those that can be started before airway manipulation, namely supplementary nasal oxygenation at low or high flows. Use of high flow nasal oxygen for preoxygenation and apneic oxygenation is discussed below. (See 'Heated humidified high flow nasal oxygen' below.)

Apneic oxygenation with nasopharyngeal catheter — Several small trials have reported prolongation of safe apnea time with administration of oxygen at 3 to 5 L/minute directly into the pharynx via a nasopharyngeal airway after preoxygenation.

●In one study of 30 patients who were preoxygenated with four deep breaths of oxygen before induction of anesthesia, patients who were randomly assigned to receive oxygen at 5 L/minute via a nasopharyngeal catheter after induction remained at SpO₂ 100 percent during six minutes of apnea, while patients who received no nasopharyngeal oxygen desaturated to 95 percent at a mean of 3.65 minutes [69].

●In another study, SpO₂ remained unchanged at 99 percent during 10 minutes of apnea in patients who received nasopharyngeal oxygen at 3 L/minute after preoxygenation, whereas the SpO₂ fell to 92 percent over approximately 7 minutes in patients who received no nasopharyngeal oxygen [70].  

●A randomized trial including 34 patients with severe obesity reported that SpO₂ was maintained at 100 percent during four minutes of apnea in 16 of 17 patients who received nasopharyngeal oxygen at 5 L/minute after preoxygenation, while SpO₂ fell to 95 percent in all patients who received no nasopharyngeal oxygen over a mean of 145 seconds [71].

Apneic oxygenation with standard nasal cannulae — A commonly used and readily available technique for apneic oxygenation involves the use of standard nasal cannulae. The patient is typically preoxygenated using nasal cannulae simultaneously with face mask oxygen, with nasal oxygen continued during intubation after the facemask is removed. Nasal oxygen is discontinued once the airway is secured.

Nasal oxygen during efforts at securing a tube (NO DESAT) was initially described for intubation in the emergency department [72]. Nasal oxygen flow rates up to 15 L/minute have been studied.

Apneic oxygenation with standard nasal cannula was used in a small randomized trial involving patients with severe obesity. Thirty patients were randomly assigned to receive 5 L/minute of oxygen via nasal prongs, or no oxygen via nasal prongs, during preoxygenation to end-tidal oxygen (EtO₂) >90 percent, and during apnea during simulated difficult intubation [60]. The time to desaturation to SpO₂ 95 percent was greater in patients who received nasal oxygen (mean 5.29 versus 3.49 minutes), and the minimum SpO₂ during apnea was higher in patients who received nasal oxygen (94.3 versus 87.7 percent).

Apneic oxygenation using nasal cannulae has not been shown to be of benefit during intubation in critically ill patients. As an example, in a randomized trial involving 150 critically ill patients who required intubation, there were no differences in the lowest SpO₂ or desaturation to <90 percent in patients who received 15 L/minute nasal oxygen during intubation and those who received no nasal oxygen [73].

Complications of apneic oxygenation — Carbon dioxide is not removed during apneic oxygenation and there is a consequential decrease in pH. If left unchecked cardiac arrest will ensue. The rate of rise of carbon dioxide has been shown to be approximately 3 to 4 mmHg per minute [14]. Therefore the safe limit of apneic oxygenation is estimated to be 15 minutes [66].

Oxygen is delivered via standard nasal cannulae as a cold dry gas, which has the effect of drying the nasal and respiratory mucosa. This can cause sinus pain, mucosal dehiscence and epistaxis. Flows above 4 L/minute via nasal cannula are rarely tolerated by patients for significant lengths of time. Further studies are required to assess long term outcomes (eg, length of stay in the hospital or ICU, sinusitis, upper respiratory tract infection, pneumonia) of various methods of apneic oxygenation in comparison with nasal low flow dry oxygen.

HEATED HUMIDIFIED HIGH FLOW NASAL OXYGEN — Heated humidified high flow oxygen (HFNO; >30 liters/minute) is highly effective for preoxygenation and apneic oxygenation, and has also been used as the primary airway technique for laryngeal surgery. The best available evidence suggests that HFNO does not clear carbon dioxide.

Low flow oxygen delivery devices are defined as those with which the fraction of inspired oxygen (FiO₂) varies with inspiratory flow. High flow devices are capable of delivering oxygen at flow rates that match peak inspiratory flow. At these high flows, the gas must be warmed and humidified both for patient comfort and to prevent damage to airway mucosa. The benefits of heated and humidified high flow nasal oxygen (HFNO) include pharyngeal dead space washout; reduction in the work of breathing; positive end-expiratory pressure (PEEP); a constant FiO₂; and improved mucociliary clearance. (See "Heated and humidified high-flow nasal oxygen in adults: Practical considerations and potential applications", section on 'Mechanisms of clinical benefit'.)

The use of apneic oxygenation (including HFNO) in children is discussed separately. (See "Management of the difficult airway for pediatric anesthesia", section on 'Apneic oxygenation'.)

HFNO for preoxygenation and apneic oxygenation — Advantages to the use of HFNO for preoxygenation and apneic oxygenation include the ability to deliver an FiO₂ of 100 percent without requiring a tight mask seal, and that it leaves the operator’s hands free. HFNO also allows a seamless transition from preoxygenation to apneic oxygenation and prolonged apnea time. However, HFNO cannot be performed simultaneously with face mask ventilation, so the operator cannot confirm the ability to achieve a mask seal or successfully ventilate by mask. End tidal gas sampling/capnography cannot be used with HFNO. Thus, for prolonged apneic oxygenation (ie, beyond 30 minutes) with HFNO, CO₂ should be monitored using transcutaneous CO₂, intermittent arterial blood gases, or intermittent ventilation with measurement of EtCO₂.

For preoxygenation with HFNO the initial oxygen flow rate is set to 30 L/minute. The patient is asked to take tidal volume breaths via nasal breathing, with the mouth closed [74-76] for three minutes. After induction of anesthesia, the flow rate is increased to 70 L/minute and maintained until the endotracheal tube is in place. Airway patency must be maintained via jaw thrust and an oropharyngeal airway, if necessary, while HFNO is used.

Multiple studies have found that the use of HFNO for preoxygenation and apneic oxygenation prolongs apnea time compared with face mask preoxygenation [58,77-82].

Ventilatory exchange with HFNO — When HFNO was initially used for apneic oxygenation during anesthesia, the term transnasal humidified rapid insufflation ventilatory exchange (THRIVE) was used. However, HFNO has not consistently been shown to slow the rate of rise of CO₂ compared with low flow apneic oxygenation techniques. Some studies have reported reduced rate of rise of CO₂ during apneic oxygenation with HFNO [58,77,83-86], while others have found no difference [87-89].

A single center trial assessed the rate of rise of CO₂ in 125 heathy surgical patients who were randomly assigned to receive apneic oxygenation at one of four oxygen flows after induction of anesthesia and paralysis (0.25 L/minute, 2 L/minute, 10 L/minute, 70 L/minute with jaw thrust, 70 L/minute with continuous video laryngoscopy) [89]. The rate of rise of CO₂ assessed by arterial blood gases every 2 minutes was similar across all groups and did not reach a predefined noninferiority threshold. In addition, the rate of oxygen desaturation over the 15-minute apneic period was similar across all groups.

Utility for special patient populations — Many studies have quantified the utility of HFNO for surgical anesthesia, and in different patient groups including those with severe obesity.

●Emergency intubation – Several studies suggest that HFNO may be beneficial for preoxygenation and apneic oxygenation for emergency intubation.

•In a small randomized trial that compared face mask preoxygenation with preoxygenation with HFNO for patients who underwent rapid sequence induction and intubation (RSII), there were no differences in arterial partial pressure of oxygen (PaO₂) or arterial partial pressure of carbon dioxide (PaCO₂) immediately after intubation, despite a significantly longer apnea time in the patients who were managed with HFNO (248 versus 123 seconds) [78].

•In another trial, 80 adults who underwent rapid sequence induction and intubation (RSII) for emergency surgery were randomly assigned to face mask preoxygenation or HFNO for preoxygenation and apneic oxygenation until intubation [79]. There were no differences in median lowest peripheral arterial oxygen saturation (SpO₂) until one minute after intubation, but five patients who received face mask preoxygenation desaturated to <93 percent, compared with none in the HFNO group. There were no episodes of aspiration or regurgitation.

•In a larger international randomized trial comparing HFNO for preoxygenation and apneic oxygenation with face mask preoxygenation for RSII in 350 patients who had emergency surgery, the number of patients who desaturated to SpO₂ <93 percent was similar in the two groups (five [2.9 percent] versus six [3.4 percent]) patients in the high-flow nasal oxygen and facemask group, respectively [80]. Although mean apnea time was longer in the HFNO group, first breath ETCO₂ was similar. This study demonstrates the feasibility of using HFNO as a primary means of preoxygenation in patients undergoing RSII.

Computed tomography assessment of gastric volume has shown that HFNO preoxygenation does not increase gastric volume as compared with traditional face mask preoxygenation and is unlikely to increase the risk of aspiration [90].

●Severe obesity – In one trial, 40 patients with severe obesity (body mass index [BMI] >40 kg/m²) who underwent general anesthesia for surgery were randomly assigned to preoxygenation and apneic oxygenation with HFNO, vs three minutes of conventional face mask preoxygenation [81]. Safe apnea time was longer (261.4 ± 77.7 vs 185.5 ± 52.9 seconds) and the minimum peri-intubation SpO₂ was higher (91.0 ± 3.5 vs 88.0 ± 4.8 percent) in the high-flow nasal oxygenation group.

●Elderly patients – In a randomized trial including 60 patients aged 65 to 80yrs without known pulmonary disease who underwent general anesthesia, safe apnea time was prolonged with the use of HFNO compared with face mask oxygenation, when either technique was used for preoxygenation and apneic oxygenation [82].

●Pregnancy – Preoxygenation and apneic oxygenation in pregnant patients is discussed separately. (See "Airway management for the pregnant patient".)

HFNO for preoxygenation before intubation in the intensive care unit (ICU) is discussed separately. (See "Heated and humidified high-flow nasal oxygen in adults: Practical considerations and potential applications", section on 'Intubation support'.)

HFNO for laryngologic surgery — HFNO may be used for apneic ventilation during laryngologic surgery that requires ventilation without an airway device in place. In this setting, HFNO is typically used for preoxygenation at a flow rate of 30 L/minute. After induction of anesthesia, HFNO is temporarily stopped to confirm the ability to ventilate by face mask. HFNO is then restarted at 70 L/minute and airway patency must be meticulously maintained until the surgical laryngoscope is inserted.

The maximum recommended duration of HFNO is 30 minutes unless PaCO₂ is measured. Since capnography is not possible while HFNO is in progress, transcutaneous carbon dioxide monitoring should be used where available, or arterial blood gases should be measured. If either of these modalities are not available and surgery needs to continue for longer than 30 minutes HFNO may be paused intermittently and EtCO₂ measured. This technique should be avoided in patients at risk of sequelae from hypercapnia (eg, brain injury, pulmonary hypertension).

Examples of studies of the use of HFNO for airway management during general anesthesia include the following:

●In a landmark study, 25 patients who had general anesthesia were preoxygenated with a HFNO system at 70 L/min, which was continued for apneic oxygenation [58]. The patients underwent a variety of surgical procedures, including laryngologic surgery, which required different methods for definitive airway management. No patient desaturated to <90 percent SpO₂ during apneic periods lasting 5 to 65 minutes. The rate of rise of EtCO₂ was 1.13 mmHg (or 0.15 kPa) per minute, lower than reported rates of 3 to 4.2 mmHg/minute with classic apneic oxygenation [14,65,66].

●In an observational study of 30 patients who underwent laryngologic surgery using HFNO with oxygen at 70 L/minute for up to 30 minutes of apnea, no patient had an SpO₂ <91 percent [85]. PaCO₂ rose at 1.8 mmHg/minute. In one patient, jet ventilation was started when the PaCO₂ reached 82.5 mmHg.

Use of HFNO in patients with COVID-19 — Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is thought to occur primarily through respiratory droplets and aerosols. Thus, there has been concern that use of HFNO may increase transmission of COVID-19. However, simulator studies using smoke have found that the dispersal distance using HFNO is similar to or less than other oxygen delivery devices including face mask, venturi masks, and non-rebreathing masks [91,92]. In addition, in a randomized control trial in critically ill patients with bacterial pneumonia, HFNO was not associated with increased environmental bacterial contamination, compared with a conventional oxygen mask [93]. Based on these findings, use of HFNO for anesthesia is unlikely to increase the risk of infectious contamination of the environment compared with other oxygenation techniques. Nonetheless, appropriate personal protective equipment should always be used when managing the airway in patients with COVID-19. Airway management in patients with COVID-19 and use of HFNO in COVID-19 patients in the ICU are discussed separately. (See "COVID-19: Perioperative risk assessment and anesthetic considerations, including airway management and infection control" and "COVID-19: Respiratory care of the nonintubated hypoxemic adult (supplemental oxygen, noninvasive ventilation, and intubation)", section on 'Noninvasive modalities'.)

OUR STRATEGIES FOR PREOXYGENATION AND APNEIC OXYGENATION — All patients should be preoxygenated prior to induction of general anesthesia. The technique chosen and the decision to use apneic oxygenation should be individualized, based on patient and clinical factors, and availability of resources and equipment. The choice of awake intubation rather than airway management after induction of anesthesia for patients with predicted difficult airways is discussed separately. (See "Management of the difficult airway for general anesthesia in adults", section on 'Timing of airway control'.)

Our approach to preoxygenation and apneic oxygenation is as follows:

Routine preoxygenation — For patients without risk factors for difficulty with airway management or rapid oxygen desaturation with apnea, we position the patients head up, and administer 100 percent oxygen via a tight fitting face mask for at least three minutes of tidal volume breathing (TVB; ie, normal depth and rate of respiration), or to an end-tidal oxygen concentration (EtO₂) of ≥90 percent, prior to induction of anesthesia. (See 'Positioning' above and 'Tidal volume breathing' above.)

After induction of anesthesia and before a definitive airway is inserted we apply positive end-expiratory pressure (PEEP) at approximately 5 cm H₂O using the adjustable pressure limiting (APL) valve. (See 'Positive airway pressure techniques during preoxygenation' above.)

Preoxygenation for emergency intubation — For emergency intubation in patients without risk factors for difficulty with airway management or rapid desaturation with apnea:

●Position the patient head up unless the patient is hypovolemic.

●Whenever possible, administer 100 percent oxygen at 10 to 12 L/minute via tight fitting face mask, and ask the patient to take eight maximal breaths over one minute prior to induction of anesthesia. (See 'Deep breathing techniques' above.)

●Apply PEEP of approximately 5 cm H₂O during preoxygenation by tightening the APL valve on the anesthesia circuit. (See 'Positive airway pressure techniques during preoxygenation' above.)

●After induction of anesthesia, use apneic oxygenation, maintain PEEP at 5 cm H₂O, and ventilate by mask with peak pressures <20 cm H₂O, even for rapid sequence induction and intubation (RSII). (See 'Apneic oxygenation' above.)  

High-risk patients — High-risk patients include those with anticipated difficulty with airway management, reduced functional residual capacity (FRC), increased oxygen consumption, and medical conditions with reduced oxygenation (table 2).

●Position the patient head up if the patient is hemodynamically stable.

●For hypoxic patients, use noninvasive ventilation for preoxygenation if time permits, and use apneic oxygenation after induction of anesthesia. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications".)

●For patients who are not hypoxic preoperatively, we prefer high flow nasal oxygen (HFNO) for preoxygenation and for apneic oxygenation after induction of anesthesia. We set the flow rate at 30 L/minute for preoxygenation, and turn it up to 70 L/minute after induction of anesthesia. (See 'HFNO for preoxygenation and apneic oxygenation' above.)

●If equipment for HFNO is unavailable and for emergency intubation in high-risk patients, administer oxygen via nasal cannulae at 15 L/minute in addition to oxygen at 10 to 12 L/minute via tight fitting face mask with PEEP at approximately 5 cm H₂O for preoxygenation (see 'Apneic oxygenation with standard nasal cannulae' above). We provide low pressure (<20 cm H₂O) mask ventilation after induction and before intubation.

Preoxygenation for laryngeal surgery — For laryngeal surgery that requires ventilation without an airway device in place, we select a preoxygenation technique according to the plan for intraoperative ventilation.

●If jet ventilation is used, we perform routine preoxygenation as described above, depending on patient factors.

●If HFNO will be used for apneic ventilation during surgery, we preoxygenate with HFNO at 30 L/minute, and turn the flow up to 70 L/minute after induction of anesthesia. (See 'HFNO for laryngologic surgery' above.),

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Airway management in adults" and "Society guideline links: COVID-19 – Index of guideline topics".)

SUMMARY AND RECOMMENDATIONS

●Effective preoxygenation will increase the total body stores of oxygen, primarily in the lungs, and thereby lengthen the time until depletion occurs during apnea (table 1). (See 'Oxygen storage' above.)

●The end-tidal oxygen concentration (EtO₂) is used to assess efficacy, with an EtO₂ of 90 percent considered an adequate target. Efficacy can be optimized by recruiting lung space as a reservoir for oxygen (eg, with head up positioning, use of positive end-expiratory pressure [PEEP]), and maximizing the fraction of inspired oxygen (FiO₂; eg, by using oxygen flow ≥10 L/minute and maintaining a tight mask seal) (table 1 and figure 1). (See 'Efficacy' above.)

●The efficiency of preoxygenation (ie, the delay in desaturation during apnea) is affected by patient factors, primarily the volume of the functional residual capacity (FRC) and rate of oxygen consumption, as well as the efficacy of preoxygenation (figure 2 and figure 5). (See 'Efficiency' above.)

●Preoxygenation is performed with tidal volume breathing (TVB) for at least three minutes, or with eight vital capacity breaths over one minute (figure 4). (See 'Breathing technique for routine preoxygenation' above.)

●Positive pressure techniques (ie, PEEP, continuous positive airway pressure [CPAP], bilevel positive airway pressure [BPAP]) during preoxygenation increases the safe apnea time. (See 'Positive airway pressure techniques during preoxygenation' above.)

●Apneic oxygenation prolongs the safe apnea time during attempts at airway management and can be used during airway surgery without the presence of an airway device. Options for low flow apneic oxygenation include standard nasal cannulae, and nasopharyngeal catheters. (See 'Apneic oxygenation' above.)

●High flow nasal oxygen (HFNO) can be used for preoxygenation, and for oxygenation and ventilation during laryngologic surgery. The rate of rise of CO₂ during HFNO is unpredictable. Therefore, for prolonged apneic oxygenation (ie, beyond 30 minutes) with HFNO, CO₂ should be monitored using transcutaneous CO₂, intermittent arterial blood gases, or intermittent ventilation with measurement of EtCO₂. (See 'Heated humidified high flow nasal oxygen' above.)

●For routine preoxygenation, we position patients head up, administer 100 percent oxygen via a tight fitting face mask for at least three minutes of TVB, or to an peripheral arterial oxygen saturation (SpO₂) of >90 percent, and we use PEEP during ventilation after induction of anesthesia. (See 'Routine preoxygenation' above.)

●For preoxygenation for emergency intubation in patients without risk factors for difficulty with airway management or rapid desaturation with apnea (table 2), we position hemodynamically stable patients head up, and administer 100 percent oxygen with PEEP at 5 cm H₂O via a tight fitting face mask during 8 maximal breaths over one minute. We ventilate by mask with peak pressures <20 cm H₂O after induction and prior to intubation. (See 'Preoxygenation for emergency intubation' above.)

●For patients with risk factors for rapid desaturation or anticipated difficulty with airway management, we position hemodynamically stable patients head up. For hypoxic patients, we use noninvasive ventilation (NIV) for preoxygenation and use apneic oxygenation after induction of anesthesia. For patients who are not hypoxic, we prefer to use HFNO for preoxygenation and apneic oxygenation after induction of anesthesia, or nasal cannulae in addition to face mask oxygen if HFNO is unavailable and ventilate by mask with peak pressures <20 cm H₂O after induction and prior to intubation. (See 'High-risk patients' above.)