Preoxygenation and apneic oxygenation in emergency airway management

Article information

Clin Exp Emerg Med. 2024;11(2):136-144
Publication date (electronic) : 2024 January 29
doi :
1Department of Emergency Medicine, The University of Arizona College of Medicine, Tucson, AZ, USA
2Division of Pulmonary, Allergy, Critical Care, and Sleep, Department of Medicine, The University of Arizona College of Medicine, Tucson, AZ, USA
Correspondence to: Alexandra Barbosa Department of Emergency Medicine, 1501 North Campbell Ave, Tucson, AZ 85724, USA Email:
Received 2023 July 12; Revised 2023 November 11; Accepted 2023 November 12.


Preoxygenation during the peri-intubation period is now considered a critical aspect of rapid sequence intubation and an important skill for emergency medicine and critical care providers. Peri-intubation hypoxemia carries significant risk, including cardiac arrest, and care must be taken for appropriate management including through apnea and initiation of laryngoscopy. Appropriate selection of preoxygenation devices should depend on underlying physiology to optimize oxygenation prior to intubation attempts. A PubMed MEDLINE search was completed with selection of articles from March 2008 to March 2023 describing various techniques for preoxygenation for intubation in the critical care and operating room setting with pregnant and obese patient populations included. Prehospital and pediatric populations were excluded in this review. This review provides an overview of methods of preoxygenation with their clinical indications as well as methods for determining end points to preoxygenation and apneic oxygenation. An overview of approaches to preoxygenation was included for patients considered to have a physiologically difficult airway and obese and pregnant patient populations.


Emergency airway management is considered an essential skill in critical care settings (prehospital, emergency departments, intensive care units [ICUs]), but carries an inherent risk of critical hypoxemia and other major adverse events and complications reported in up to 40% to 45% of cases [13]. Hypoxemia before intubation, or significant desaturation during intubation, pose a risk peri-intubation cardiac arrest that occurs in up to one in 25 critically ill patients [3]. Recent studies indicate that peri-intubation hypoxemia and absence of preoxygenation carry significantly increased risk of intubation related cardiac arrest [4,5]. All patients require appropriate preoxygenation, positioning and hemodynamic optimization to allow for appropriate rapid sequence intubation (RSI), but patients with obesity, late term pregnancy, pediatric patients, and patients with acute hypoxemic respiratory failure are at particular risk of rapid desaturation and often require special attention or modifications to preoxygenation and/or intubation strategy.

Traditional RSI requires rapid successive administration of a sedative/hypnotic agent and a neuromuscular blocking agent without subsequent positive pressure ventilation before laryngoscopy. This requires adequate preoxygenation to provide an apnea time long enough for drug onset, laryngoscopy, and tube placement; a difficult task to achieve in patients with profound hypoxemia [6]. Preoxygenation should span the entire peri-intubation period to maximize oxygen reserve and account for continued oxygen consumption during the hypopneic and apneic periods [7]. Induction medications may take up to 90 seconds to optimize intubating conditions, and preoxygenation can be lost after five breaths following oxygen source removal [8]. Thus, optimizing preoxygenation includes continuing oxygen administration up until the period of apnea and often even during apnea to reduce the risk of cardiovascular collapse due to hypoxemia with intubation [8,9]. The differences in patient presentation and underlying physiology complicate planning a preoxygenation strategy. This review seeks to describe the methods for preoxygenation, appropriate endpoints to preoxygenation and the potential use of apneic oxygenation in patients undergoing rapid sequence intubation.


A MEDLINE search strategy using PubMed (US National Library of Medicine) was used with the following search terms from March 2008 to March of 2023: “rapid sequence intubation” OR “hypoxia” OR “intubation” OR “bag mask ventilation” OR “pregnancy critical care” OR “obesity critical care” OR “obesity intubation” OR “preoxygenation.” The search was conducted over a 4-month period from February to May of 2023. Articles related to the emergency department, ICU, and operating room, and physiologic studies, where appropriate, were included. Non-English articles, those related to pediatric patients (<18 years of age), and animal models were excluded. Articles related to prehospital airway management were excluded due to differences in availability of equipment and setting. Other exclusion criteria included: case reports/series, supraglottic airways for preoxygenation, studies primarily pertaining to analysis of video laryngoscopy, fiberoptic intubation or direct laryngoscopy, and those related to COVID-19 viruses.

This search resulted in an extensive list of resources, of 30,993 results. Following a search of the best matches and articles meeting the above criteria, an initial 10,000 articles were reviewed for evaluation of inclusion criteria with 298 further isolated out of this subgroup based on appropriate criteria, such as discussion of preoxygenation specifically in the emergency department. In the case of meta-analyses frequently referencing the same primary sources, with five or more common articles referenced between sources, attempts were made to select the article with the most recent publication or with inclusion of more randomized controlled trials or other sources. There were limited studies found on pregnancy related randomized controlled trials (RCTs) and meta-analysis and reviews were considered adequate sources as this is a special patient population less likely to be subject to RCTs. The final articles selected are included in Table 1 [1,5,6,1027].

Articles pertaining to preoxygenation prior to intubation


Preoxygenation prior to RSI is the standard of care, but strategies have evolved since RSI was first described [11]. RSI requires preoxygenation with set endpoints based on available equipment and oxygenation values to increase the time to desaturation after induction. The time to desaturation, or “safe apnea time” is traditionally considered the time from administration of RSI medications until the saturation reaches 90%, and the fundamental goal of preoxygenation is to prolong this time interval. Methods for preoxygenation, ranging from a standard nasal cannula to positive pressure ventilation, are summarized in Table 2 [6,22,25,2833].

Methods for preoxygenation prior to induction agents


As part of the preoxygenation strategy, the plan should include thresholds for adequate preoxygenation. In the emergency department, peripheral oxygen saturation (SpO2) is frequently used with goal saturations of 100% for preoxygenation, and <90% often considered the stopping point for reoxygenation before severe desaturation (<80%) occurs [14]. Other traditionally common end points include absolute time or duration of tidal breathing (3 minutes) or vital capacity breaths of 100% oxygen (typically eight), although it has limitations in the critically ill [29]. End-tidal oxygen (EtO2) in combination with other parameters, such as SpO2, the partial pressure of oxygen in arterial blood (PaO2), allows for granular evaluation of the underlying physiology to optimize preoxygenation methods [29]. EtO2 has been more closely studied in anesthesia literature due to availability in the operating room with additional note of fraction of expired oxygen <85% shown to be inadequate for intubation attempts [13]. In the presence of shunt physiology or uncertain reliability of oxygen monitoring devices, PaO2 provides a direct way to assess oxygenation of the blood and acts a gauge for the amount of gas exchange in the alveolar capillary beds [6,29]. The advantages and limitations of these methods are discussed in Table 3 [6,13,29].

Endpoints to preoxygenation


Continuous nasal oxygen throughout the intubation period after induction, termed “apneic oxygenation,” can augment preoxygenation and potentially prolong the safe apnea time. The literature on apneic oxygenation is mixed and plagued with confounders. Gleason et al. [10], showed decreased desaturation when adding apneic oxygenation, except for patients with primary respiratory failure. In contrast, Semler et al. [21] demonstrated no difference in lowest arterial oxygen saturation in patients intubated in the ICU setting, though it should be noted that most patients were intubated for primary respiratory failure. An additional study by Caputo et al. [20] showed no benefit when applying a standard nasal cannula (NC) at flow rates >15 L/min after preoxygenation with bag valve mask (BVM), nonrebreathing masks, or noninvasive positive pressure ventilation. McQuade et al. [28] found an increase in EtO2 with NC at rates >15 L/min, deleterious effect with <5 L/min, and no benefit when an adequate seal was achieved with BVM alone, as the addition of NC disrupted the mask seal, potentially explaining the study results by Caputo et al. [20]. Yet, in cases of a mask leak, there was benefit from adding a nasal cannula [28]. Russotto et al. [14] found that apneic oxygenation with low flow or high flow nasal cannula decreased desaturation.

A 2016 study by Sakles et al. [27] demonstrated increased first pass success without hypoxia in patients with apneic oxygenation, though it should be noted that these patients were primarily intubated for airway protection and traumatic injuries. In a 2017 meta-analysis, obesity, elective surgery, and those intubated emergently for nonpulmonary causes had improved oxygen saturations with apneic oxygenation further emphasizing the potential benefit from apneic oxygenation [24]. Cabrini et al. [12] and White et al. [24] demonstrated that there is likely no benefit from high flow NC (HFNC) administration during the apneic period which contrasts with operating room data showing prolonged safe apnea time and potential benefits in select patient populations. An additional study by Sakles et al. [34] from 2016 demonstrated decreased desaturation when apneic oxygenation was used for intubation.

While apneic oxygenation can be quite helpful in some patients, such as those intubated for primary neurologic injury or airway protection, and should be used, it is less likely to prevent desaturation in some patients with acute hypoxemic respiratory failure. In these patients, the underlying physiology presents significant challenges to preoxygenation, especially in patients with severe hypoxemic respiratory failure. Underlying pathophysiology must be considered when selecting the best preoxygenation strategy for a given patient. These include optimizing denitrogenation in all patients, maximizing functional residual capacity in at risk patients, reducing shunt physiology in high-risk patients, and recognizing failed preoxygenation in refractory patients.


Denitrogenation is the rate limiting step for preoxygenation in healthy patients, and at times in critically ill patients [11]. Thus, traditional preoxygenation with tidal breathing of 100% oxygen for 3 minutes or eight vital capacity breaths with a tight fitting mask is, in actuality, denitrogenation [29,35]. Methods of denitrogenation all involve overcoming nitrogen from ambient air with high flows of 100% oxygen to “washout” alveolar nitrogen, leaving only oxygen, water vapor, and CO2. The nonrebreathing masks commonly used in the ED do not achieve a tight mask seal, thus room air is entrained around the mask with each inspiration [29,33]. This reduces the effective fraction of inspired oxygen (FiO2) despite delivering 100% oxygen from the nonrebreather reservoir [33]. Groombridge et al. [33] and Mosier et al. [29] showed improved preoxygenation (measured by the fractional of exhaled oxygen) by adding a nasal cannula to attenuate the poor mask seal, but it does not completely compensate for the leak. Alternative methods for complete denitrogenation include using high flow nasal oxygen at flow rates greater than the inspiratory flow rate, or noninvasive positive pressure with a tight fitting mask [33]. EtO2 is a relatively easy measure to obtain, either with a single breath, or continuous monitoring, and can be helpful to objectively evaluate when adequate denitrogenation has been achieved (EtO2 >85%–90%) [7,8]. Fully denitrogenating the alveoli will result in a large alveolar oxygen tension, as the only other gasses available in the alveoli after denitrogenation would be water vapor and carbon dioxide as dictated by the alveolar gas equation.

Following denitrogenation, renitrogenation can rapidly occur when the oxygen source is removed before apnea [7,8]. West et al. [7] demonstrated renitrogenation may occur as quickly as 160 seconds, and Mosier et al. [8] found renitrogenation occurs after about five breaths once the oxygen source is removed in healthy patients. Gentle mask ventilation after induction can prevent renitrogenation, and has been shown to reduce the risk of severe hypoxemia [1].


The functional residual capacity (FRC) provides the lung volume for oxygen available during apnea. Denitrogenating an optimized FRC will provide the largest alveolar oxygen reservoir [8,10]. However, FRC is often reduced, either externally by compression from the chest wall, abdominal contents, pneumothorax/hemothorax or pleural effusion; or internally, by loss of functional airspace from pneumonia, edema, etc. [6]. Optimizing the FRC in at-risk patients involves upright positioning, draining relevant thoracic contents (effusions, hemothorax/pneumothorax), and recruiting lung units.

In patients where FRC is reduced because of body habitus, the dependent portions of the lung are compressed by the chest wall or abdomen, such as obesity. Upright positioning alone can improve FRC in these patients, with De Jong et al. [16] recommending reverse Trendelenburg positioning in combination with noninvasive ventilation for preoxygenation. Decreased FRC in pregnancy presents difficulties from the fixed compression of the gravid uterus on the chest cavity as well as on the inferior vena cava, specific positioning to overcome a decreased FRC includes ramped positioning with a left tilt [18]. Positioning, combined with preoxygenation with positive pressure ventilation can be quite advantageous in these patients [6,16]. For patients where external compression is due to body cavity fluids or air, such as ascites, hemothoraces, pleural effusions, or pneumothraces, drainage in parallel with preoxygenation can improve FRC and thus reduce ventilation/perfusion (V/Q) mismatch.

Given that positioning has an outsized role in improving FRC, a logical workflow would be to preoxygenate all patient in an upright position when able [6,11,29]. These patients can be repositioned after induction for the desired laryngoscopy position and to avoid increased intubation attempts with ramped positioning as stated by Cabrini et al. [12] and De Jong et al. [16]. There is potential for atelectasis by attempting nitrogen washout with 100% FiO2, a potential threat to the FRC [5,29]. Delay et al. [15] demonstrated that positive end-expiratory pressure during preoxygenation resulted in higher EtO2, a surrogate maker for denitrogenation, compared to spontaneous breathing and is likely a way to overcome the atelectasis of 100% FiO2 administration and maintain the FRC.


The most modifiable way to improve V/Q mismatch is via increasing the FRC, though in some patients with severe disease may still have intrapulmonary shunt significant enough to limit the effectiveness of preoxygenation [29]. In these patients, EtO2 may be appropriately high, yet that reservoir of oxygen does not sufficiently interface with the pulmonary blood flow to resaturate hemoglobin [29]. This is the final hurdle for some critically ill patients. Shunt fraction is on one extreme end of V/Q mismatch. However, unlike V/Q mismatch, shunt is refractory to both improving FRC and maximizing denitrogenation [5,29]. Shunt occurs when deoxygenated blood is not reoxygenated due to decreased alveolar-capillary gas exchange in the lung and will lead to further hypoxemia when the deoxygenated blood returns to the heart and the peripheral circulation [5].

When shunt is the rate limiting step for an adequate safe apnea time in a patient where RSI is the planned strategy, high flow nasal oxygen (HFNO) or noninvasive positive pressure ventilation (NIPPV) should be first-line for preoxygenation to maximize denitrogenation and reduce V/Q mismatch to the greatest possible degree through improved alveolar recruitment [5,6,29]. Fong et al. [25] and Mosier et al. [5] demonstrated that patients with acute hypoxemic respiratory failure receiving NIPPV had a decreased incidence of desaturation during intubation compared to conventional methods and HFNC, likely secondary to increased alveolar recruitment and gas exchange and thus potentially decreased shunt. In cases of shunt, PaO2 may be helpful compared to EtO2 and SpO2 to determine the degree of shunt and if safe apnea time is possible or if alternative intubated strategies should be considered [6,29]. In the setting of a fully denitrogenated patient, if the PaO2 is low, the shunt fraction is large and desaturation will occur quickly.

Patients with refractory shunt propose a unique challenge for preoxygenation management. Even with appropriate preoxygenation, they often do not tolerate periods of apnea with RSI [6]. In these patients, awake intubation may be preferred to maintain spontaneous breathing while still utilizing HFNO or nasal NIPPV during the procedure [5,6].



Obesity and pregnancy require consideration of the FRC and modification through positioning, recruitment maneuvers and carefully optimizing preoxygenation. Supine positioning in obesity will decrease FRC by up to 21% as body habitus compresses the chest cavity [15]. Reverse Trendelenburg and upright positioning improve chest compliance in these patients and should be used in the absence of clear contraindications [15,16]. Without improvement in the FRC of obese patients, the atelectatic portion of the lung, commonly the dependent portions receiving the most blood flow, will contribute to increased V/Q mismatch [6]. This is thought to be the primary cause of hypoxemia following an initial hypercarbia from decreased ventilation [15]. The addition of positive end-expiratory pressure can prevent end-expiratory collapse of airways in these patients. NIPPV allows for increased alveolar recruitment and EtO2 compared to standard ventilation in both operating room and ICU studies [15,16].

HFNO also provides similar physiological benefit of increased end-expiratory lung volume and FRC [15,36]. HFNO has been shown to prolong safe apnea time in noncritically ill obese patients based on operating room data [23,24]. Despite this data, De Jong et al. [16], Caputo et al. [13], and Delay et al. [15] emphasizes that standard of therapy for obese patients requiring preoxygenation should be NIPPV. While a potential rescue method in other populations, BVM may not be able to overcome central airway collapse in these patients with a preferred method including recruitment maneuvers with positioning [15].


Increased chest compression and reduction in FRC is also seen in pregnancy due to increase in the intrabdominal compartment from the gravid uterus as well as due to potential weight gain and breast enlargement [18]. Despite the decreased FRC, increased alveolar ventilation and hypocapnia are seen due to increased respiratory rate and comprise the baseline respiratory state during pregnancy. Zieleskiewicz et al. [18] emphasize that uterine compression of the IVC may lead to decreased preload, and left lateral decubitus positioning or ramped positioning with a 15° tilt to the left may relieve this compression, allowing for improved hemodynamic stability. Increased metabolic demand also leads to increased oxygen consumption and likely a decrease in safe apnea time. Preoxygenation of the pregnant patient may be performed with HFNO, nonrebreather mask, or NIPPV, though each has limitations.

Data is limited on preoxygenation techniques in pregnant populations. NC delivers oxygen at a lower rate and may not keep up with the higher oxygen consumption of late term pregnancy and should not be used [18,19]. Zhou et al. [19] demonstrated statistically significant elevated PaO2 and EtO2 of pregnant patient with high flow nasal oxygen compared to the standard face mask, though both are still used for preoxygenation. Zieleskiewicz et al. [18] note the risk of decreased venous return in pregnancy and delayed gastric emptying due to progesterone, which in theory could both be exacerbated by noninvasive ventilation via increased intrathoracic pressure and increased gastric filling.

Due to the potential for these complications and the demonstrated efficacy of HFNO, HFNC may present the best option for preoxygenation and apneic oxygenation, though NIPPV should still be considered in cases of profound hypoxemia due to increased metabolic demand in pregnancy. Hypercapnia and hypoxemia should be avoided as much as possible, even in the setting of acute respiratory distress due to the unique physiology of pregnancy and implications to mother and fetus [18].


Preoxygenation remains a necessary step in all intubations and should include apneic oxygenation. Selecting the optimal preoxygenation method requires considering the underlying physiology and optimizing the FRC, reducing shunt and achieving maximal denitrogenation. Positioning is equally important, and critical in certain populations such as obesity and pregnancy. Utilizing the right preoxygenation strategy tailored to the patient’s anatomy, underlying physiology, and intubation plan will improve intubation safety in critically ill patients. In the most severe cases of refractory hypoxemia, preoxygenation may not be possible despite optimizing preoxygenation.


Author contributions

Conceptualization: all authors; Formal analysis: all authors; Investigation: all authors; Writing–original draft: all authors; Writing–review & editing: all authors.

All authors read and approved the final manuscript.

Conflicts of interest

Jarrod M. Mosier is the National Course Director for The Difficult Airway Course: Critical Care and has received travel support from Fisher & Paykel. The authors have no other conflicts of interest to declare.


The authors received no financial support for this study.

Data availability

Data sharing is not applicable as no new data were created or analyzed in this study.


1. Casey JD, Janz DR, Russell DW, et al. Bag-mask ventilation during tracheal intubation of critically ill adults. N Engl J Med 2019;380:811–21.
2. Simpson GD, Ross MJ, McKeown DW, Ray DC. Tracheal intubation in the critically ill: a multi-centre national study of practice and complications. Br J Anaesth 2012;108:792–9.
3. Russotto V, Myatra SN, Laffey JG, et al. Intubation practices and adverse peri-intubation events in critically ill patients from 29 countries. JAMA 2021;325:1164–72.
4. De Jong A, Rolle A, Molinari N, et al. Cardiac arrest and mortality related to intubation procedure in critically ill adult patients: a multicenter cohort study. Crit Care Med 2018;46:532–9.
5. Mosier JM, Joshi R, Hypes C, Pacheco G, Valenzuela T, Sakles JC. The physiologically difficult airway. West J Emerg Med 2015;16:1109–17.
6. Mosier JM, Sakles JC, Law JA, Brown CA, Brindley PG. Tracheal intubation in the critically ill. where we came from and where we should go. Am J Respir Crit Care Med 2020;201:775–88.
7. West JR, Levine R, Raggi J, et al. Time to renitrogenation after maximal denitrogenation in healthy volunteers in the supine and sitting positions. West J Emerg Med 2022;23:926–30.
8. Mosier J, Reardon RF, DeVries PA, et al. Time to loss of preoxygenation in emergency department patients. J Emerg Med 2020;59:637–42.
9. Binks MJ, Holyoak RS, Melhuish TM, Vlok R, Bond E, White LD. Apneic oxygenation during intubation in the emergency department and during retrieval: a systematic review and meta-analysis. Am J Emerg Med 2017;35:1542–6.
10. Gleason JM, Christian BR, Barton ED. Nasal cannula apneic oxygenation prevents desaturation during endotracheal intubation: an integrative literature review. West J Emerg Med 2018;19:403–11.
11. Pourmand A, Robinson C, Dorwart K, O'Connell F. Pre-oxygenation: implications in emergency airway management. Am J Emerg Med 2017;35:1177–83.
12. Cabrini L, Landoni G, Baiardo Redaelli M, et al. Tracheal intubation in critically ill patients: a comprehensive systematic review of randomized trials. Crit Care 2018;22:6.
13. Caputo ND, Oliver M, West JR, Hackett R, Sakles JC. Use of end tidal oxygen monitoring to assess preoxygenation during rapid sequence intubation in the emergency department. Ann Emerg Med 2019;74:410–5.
14. Russotto V, Cortegiani A, Raineri SM, Gregoretti C, Giarratano A. Respiratory support techniques to avoid desaturation in critically ill patients requiring endotracheal intubation: a systematic review and meta-analysis. J Crit Care 2017;41:98–106.
15. Delay JM, Sebbane M, Jung B, et al. The effectiveness of noninvasive positive pressure ventilation to enhance preoxygenation in morbidly obese patients: a randomized controlled study. Anesth Analg 2008;107:1707–13.
16. De Jong A, Wrigge H, Hedenstierna G, et al. How to ventilate obese patients in the ICU. Intensive Care Med 2020;46:2423–35.
17. Natt BS, Malo J, Hypes CD, Sakles JC, Mosier JM. Strategies to improve first attempt success at intubation in critically ill patients. Br J Anaesth 2016;117 Suppl 1:i60–8.
18. Zieleskiewicz L, Chantry A, Duclos G, et al. Intensive care and pregnancy: epidemiology and general principles of management of obstetrics ICU patients during pregnancy. Anaesth Crit Care Pain Med 2016;35 Suppl 1:S51–7.
19. Zhou S, Zhou Y, Cao X, et al. The efficacy of high flow nasal oxygenation for maintaining maternal oxygenation during rapid sequence induction in pregnancy: a prospective randomised clinical trial. Eur J Anaesthesiol 2021;38:1052–8.
20. Caputo N, Azan B, Domingues R, et al. Emergency department use of apneic oxygenation versus usual care during rapid sequence intubation: a randomized controlled trial (the ENDAO trial). Acad Emerg Med 2017;24:1387–94.
21. Semler MW, Janz DR, Lentz RJ, et al. Randomized trial of apneic oxygenation during endotracheal intubation of the critically ill. Am J Respir Crit Care Med 2016;193:273–80.
22. Guitton C, Ehrmann S, Volteau C, et al. Nasal high-flow preoxygenation for endotracheal intubation in the critically ill patient: a randomized clinical trial. Intensive Care Med 2019;45:447–58.
23. Wong DT, Dallaire A, Singh KP, et al. High-flow nasal oxygen improves safe apnea time in morbidly obese patients undergoing general anesthesia: a randomized controlled trial. Anesth Analg 2019;129:1130–6.
24. White LD, Melhuish TM, White LK, Wallace LA. Apnoeic oxygenation during intubation: a systematic review and meta-analysis. Anaesth Intensive Care 2017;45:21–7.
25. Fong KM, Au SY, Ng GWY. Preoxygenation before intubation in adult patients with acute hypoxemic respiratory failure: a network meta-analysis of randomized trials. Crit Care 2019;23:319.
26. Ferreyro BL, Angriman F, Munshi L, et al. Association of noninvasive oxygenation strategies with all-cause mortality in adults with acute hypoxemic respiratory failure: a systematic review and meta-analysis. JAMA 2020;324:57–67.
27. Sakles JC, Mosier JM, Patanwala AE, Arcaris B, Dicken JM. First pass success without hypoxemia is increased with the use of apneic oxygenation during rapid sequence intubation in the emergency department. Acad Emerg Med 2016;23:703–10.
28. McQuade D, Miller MR, Hayes-Bradley C. Addition of nasal cannula can either impair or enhance preoxygenation with a bag valve mask: a randomized crossover design study comparing oxygen flow rates. Anesth Analg 2018;126:1214–8.
29. Mosier JM, Hypes CD, Sakles JC. Understanding preoxygenation and apneic oxygenation during intubation in the critically ill. Intensive Care Med 2017;43:226–8.
30. Sjoblom A, Hedberg M, Lodenius A, Jonsson Fagerlund M. Pre-oxygenation using high-flow nasal oxygen vs. tight facemask during rapid sequence induction: a reply. Anaesthesia 2021;76:1277–8.
31. Kim TH, Hwang SO, Cha YS, et al. The utility of noninvasive nasal positive pressure ventilators for optimizing oxygenation during rapid sequence intubation. Am J Emerg Med 2016;34:1627–30.
32. Baillard C, Fosse JP, Sebbane M, et al. Noninvasive ventilation improves preoxygenation before intubation of hypoxic patients. Am J Respir Crit Care Med 2006;174:171–7.
33. Groombridge C, Chin CW, Hanrahan B, Holdgate A. Assessment of common preoxygenation strategies outside of the operating room environment. Acad Emerg Med 2016;23:342–6.
34. Sakles JC, Mosier JM, Patanwala AE, Dicken JM. Apneic oxygenation is associated with a reduction in the incidence of hypoxemia during the RSI of patients with intracranial hemorrhage in the emergency department. Intern Emerg Med 2016;11:983–92.
35. Tanoubi I, Drolet P, Donati F. Optimizing preoxygenation in adults. Can J Anaesth 2009;56:449–66.
36. 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.

Article information Continued


Capsule Summary

What is already known

Peri-intubation hypoxemia or desaturation during intubation attempts increase the risk of peri-intubation cardiac arrest. Preoxygenation may help mitigate these risks and extend the period of safe apnea.

What is new in this review

This review provides information on the current methods for preoxygenation, determination of endpoints to preoxygenation and provides information on the use of apneic oxygenation. Additionally, special consideration is given to limiting factors of preoxygenation, including shunt physiology and denitrogenation of the functional residual capacity, as well as specific management for obese and pregnant populations.

Table 1.

Articles pertaining to preoxygenation prior to intubation

Study Study design Outcome
Casey et al. [1] RCT BVM ventilation during intubation in the critically ill resulted in lower incidence of hypoxemia and higher oxygen saturation.
Mosier et al. [5] Review Apneic oxygenation should be considered in all critically ill patients.
NIPPV can be utilized in cases of shunt physiology for preoxygenation.
Evaluation of four parameters for optimization prior to intubation: hypoxemia, hypotension, severe metabolic acidosis, and right heart failure
Mosier et al. [6] Review Develop an intubation strategy based on physiologic derangement.
Develop a skilled team for intubation with appropriate equipment.
Recognize failed intubation attempts and achieve appropriate reoxygenation.
Gleason et al. [10] Review NC likely provides some benefit to prevent desaturation during apneic oxygenation in patients not affected by primarily respiratory failure.
Pourmand et al. [11] Review Positioning, FRC, hypoxemia, and delayed sequence intubation should all be evaluated as parts of the preoxygenation strategy for intubation of the critically ill.
Cabrini et al. [12] Systematic review Limited evidence supports benefit of NIV and HFNC for preoxygenation of the critically ill.
Ramped positioning increased the number of intubation attempts.
Caputo et al. [13] Prospective observational cohort study Observed EtO2 varied with preoxygenation techniques.
Most patients in the ED do not achieve FeO2 >85% during preoxygenation.
EtO2 is not commonly evaluated in the ED but may be an option for determination of the end point for preoxygenation prior to intubation.
Russotto et al. [14] Systematic review Apneic oxygenation is associated with higher SpO2 during the intubation procedure.
Delay et al. [15] Prospective randomized study EtO2 measured in the anesthesia circuit was higher in obese patients receiving NIPPV compared to spontaneous ventilation prior to anesthesia induction.
De Jong et al. [16] Narrative review NIV should be considered first-line therapy in obese patients with acute hypoxic respiratory failure.
Reverse Trendelenburg position may help relive atelectasis and decreased FRC due to body habitus.
Natt et al. [17] Review Strategies to improve first intubation attempt success include adequate preoxygenation, apneic oxygenation, appropriate device, and medication selection.
An individualized approach to a patient’s airway will optimize first-attempt success.
Zieleskiewicz et al. [18] Expert review All intubations during pregnancy should be considered potential difficult intubations due to physiology of pregnancy.
Permissive hypercapnia and hypoxemia should be avoided during pregnancy due to risk to the fetus.
Inherent physiology of pregnancy includes hypocapnia, increased respiratory rate, decreased FRC, and increased oxygen consumption.
Zhou et al. [19] RCT HFNO results in higher PaO2 and EtO2 immediately after intubation compared to standard face mask for preoxygenation in pregnant patients undergoing RSI.
Caputo et al. [20] RCT Apneic oxygenation with nasal cannula following preoxygenation by other methods versus no apneic oxygenation prior to RSI showed no difference in lowest oxygen saturation in the ED setting.
Semler et al. [21] RCT There was no difference in arterial oxygen saturation 2 minutes post-intubation with or without apneic oxygenation in the ICU.
Patients were primarily intubated for respiratory failure in this setting.
Guitton et al. [22] RCT Preoxygenation and apneic oxygenation with HFNC in the ICU compared to standard mask oxygenation did not improve lowest SpO2 during intubation in nonseverely hypoxemic patients.
Reduction seen in intubation related adverse events seen in patients administered HFNO.
Wong et al. [23] RCT HFNO during apnea increased the safe apnea time in obese patients intubated in the OR compared to no apneic oxygenation.
White et al. [24] Meta-analysis There is evidence for improved oxygen saturation, SpO2, with the application of apneic oxygenation in elective surgical patients, obese patients and emergency intubations with the exception of respiratory failure.
Fong et al. [25] Meta-analysis NIV reduced the incidence of desaturation to SpO2 <80% compared to HFNC or other conventional methods of preoxygenation.
The risk of aspiration, hemodynamic instability, and cardiac arrest was lower with NIV compared to other methods of preoxygenation.
Ferreyro et al. [26] Meta-analysis Helmet and face mask NIV were associated with a lower risk of mortality in patients with acute hypoxemic respiratory failure.
HFNC and NIV were associated with lower risk of intubation.
Sakles et al. [27] Cohort study Increased first pass success without hypoxemia in intubation without desaturation increased with the use of apneic oxygenation in a tertiary care center ED.
Patients were primarily intubated for airway protection and traumatic injuries in this setting with less patients being intubated for primary hypoxia.

RCT, randomized controlled trial; BVM, bag valve mask; NIPPV, noninvasive positive pressure ventilation; NC, nasal cannula; FRC, functional residual capacity; NIV, noninvasive ventilation; HFNC, high flow nasal cannula; EtO2, end-tidal oxygen; ED, emergency department; FeO2, fraction of expired oxygen; SpO2, peripheral oxygen saturation; HFNO, high flow nasal oxygen; PaO2, partial pressure of oxygen in arterial blood; RSI, rapid sequence intubation; ICU, intensive care unit; OR, operating room.

Table 2.

Methods for preoxygenation prior to induction agents

Method Advantage Disadvantage
NC (<10 L/min) Readily available. No positive pressure even at higher flow rate.
Can combine with other methods, such as BVM, in the case of mask leak. Dependent on nasal breathing.
Can be used during apneic oxygenation and may have benefit in intubation due to causes other than primary respiratory failure [28]. Will create an improper seal in many cases when used with NRB or BVM if there was a seal initially.
NRB (flush >15 L/min) Readily available. FeO2 reached not above 80% when used alone in the critically ill [29].
Flush rate with fitted mask can allow for FiO2 of 70% [29]. Must be removed during period of intubation.
Decreased effect with increased minute ventilation (such as increased RR in high metabolic demand states).
HFNO (15–60 L/min) Provides some continuous positive pharyngeal pressure at higher rates. Mixed data on prevention of desaturation when used in isolation during apneic oxygenation.
Can be used during apneic oxygenation and during intubation period.
Titratable flow and FiO2.
May have same benefit as facemask in preventing desaturation based on anesthesia emergency surgery data [30].
May decrease RR by increasing end-expiratory lung volumes [25].
May lead to fewer intubation related events in the nonseverely hypoxemic [22].
NIPPV (CPAP and BiPAP) Ability to administer PEEP to improve alveolar recruitment. Should avoid in patients with altered mentation or who are obtunded.
Also assists with ventilation to improve hypercarbia. Patient discomfort.
Improves denitrogenation of the FRC and may increase FRC. Gastric distension.
May achieve FeO2 >90% with appropriate mask seal. Absolute contraindications: respiratory or cardiac arrest.
Options for full face or nasal mask.
Nasal mask can be used during apnea time with intubation [31].
May help improve oxygenation in patients with shunt physiology, such as pulmonary edema, or obesity [6].
Potentially more effective than BVM for reducing arterial hemoglobin desaturation when used for preoxygenation [32].
BVM Allows for administration of PEEP and improved denitrogenation as well as continued ventilation during the apneic period. Should avoid in patients who are not obtunded.
Must be removed prior to intubation attempts. Gastric distension.
May achieve similar FeO2 to NIPPV use when correctly applied. Using with a NC will disrupt the seal and decrease the effectiveness of denitrogenation
Shown to be comparable to the anesthesia circuit for preoxygenation [33].

NC, nasal cannula; BVM, bag valve mask; NRB, nonrebreather; FiO2, fraction of inspired oxygen; FeO2, fraction of expired oxygen; RR, respiratory rate; HFNO, high-flow nasal oxygen; NIPPV, noninvasive positive pressure ventilation; CPAP, continuous positive airway pressure; BiPAP, bilevel positive airway pressure; PEEP, positive end-expiratory pressure; FRC, functional residual capacity.

Table 3.

Endpoints to preoxygenation

Method Advantage Disadvantage
EtO2 Set parameters established for likely denitrogenation to proceed with intubation FeO2 >85%. Potentially misleading in shunt physiology due to impaired gas exchange in alveoli.
Potentially expensive and not available in all critical care settings [13].
Absolute duration/tidal breathing Provides established minimum requirement for preoxygenation based on literature in healthy patients [29]. Limited use in critically ill patients due to variability in presentation.
SpO2 Easily accessible in emergency departments. Misleading in the setting of profound hypoxemia.
Does not gauge the level of denitrogenation.
Does not provide information on the degree of shunt.
PaO2 Provides direct measurement of arterial oxygen. Invasive.
Can imply degree of impaired gas exchange if significantly low in the setting of adequate preoxygenation with normal EtO2 [6,13].

EtO2, end-tidal oxygen; FeO2, fraction of expired oxygen; SpO2, oxygen saturation by pulse oximetry; PaO2, partial pressure of oxygen in arterial blood.