• Preoxygenation is the administration of oxygen to a patient prior to intubation to extend ‘the safe apnoea time’.
  • The primary mechanism is ‘denitrogenation’ of the lungs, however maximal preoxygenation is achieved when the alveolar, arterial, tissue, and venous compartments are all filled with oxygen.
  • Safe apnoea time is the duration of time following cessation of breathing/ventilation until critical arterial desaturation occurs (typically considered SaO2 88% to 90% in clinical settings)
  • Denitrogenation involves using oxygen to wash out the nitrogen contained in lungs after breathing room air, resulting in a larger alveolar oxygen reservoir
  • Oxygen consumption during apnea is approximately 200-250 mL/min (~3 mL/kg/min) in healthy adults


The main goal is to extend the ‘safe apnoea time’ (see below), which is more likely if these physiological objectives are met:

  • denitrogenation of the lungs
    • the lungs serve as a large oxygen reservoir during apnea
    • when breathing room air (79% nitrogen) ~450 mL of oxygen is present in the lungs of an average healthy adult
    • when a patient breathes 100% oxygen, this washes out the nitrogen, increasing the oxygen in the lungs to ~3,000 mL
  • achieve as close to SaO2 100% as possible
    • this maximises oxygen content of the blood by ensuring haemoglobin is fully saturated
  • oxygenate the plasma
    • of little importance due to the low solubility of oxygen in blood

End tidal O2 (ETO2) monitoring is the gold standard test in clinical practice for assessing denitrogenation of the lungs during preoxygenation:

  • ETO2 is typically used in the operating theatre setting and is rarely available elsewhere
  • optimal preoxygenation is achieved when ETO2 = 90%
  • an ETO2 of 90% may not be achievable in some critically ill patients regardless of the means of preoxygenation


Safe apnoea time is the duration of time until critical arterial desaturation (SaO2 88% to 90%) occurs following cessation of breathing/ventilation

  • an alternative term in use is ‘duration of apnoea without desaturation’ (DAWD)
  • SaO2 88% to 90% marks the upper inflection point on the oxygen-haemoglobin dissociation curve beyond which further decreases in PaO2 leads to a rapid decline in SaO2 (~ 30% every minute)
  • In a healthy preoxygenated patient the safe apnea time is up to 8 minutes, compared to ~1 min if they were breathing room air
  • In some critically ill patients critical desaturation may occur immediately despite attempts at preoxygenation

Factors that decrease safe apnoea time include:

  • critical illness
  • inadequate preoxygenation
  • obesity
  • pregnancy
  • shunt physiology
  • airway occlusion
  • increased oxygen consumption (e.g. high metabolic rate, fasciculations from suxamethonium)
  • anaemia or dyshaemoglobinaemia

In patients who develop airway occlusion, desaturation will occur more rapidly due to loss of functional residual capacity (FRC)

  • FRC will decrease in a healthy adult patient by about 250 mL during the first minute after airway occlusion
  • This occurs due to resorption atelectasis as oxygen transfers from the lungs into the pulmonary circulation
  • Pulmonary shunting (blood flow to the non-oxygenated, collapsed lung units) then occurs resulting in much more rapid desaturation than otherwise predicted — even if pre-oxygenation is performed

Apnoeic oxygenation and safe apnoea time

  • Oxygenation can be further optimised by performing apnoeic oxygenation in addition to preoxygenation
  • in critical care settings apnoeic oxygenation is most commonly with 15L/min via nasal prongs
  • In some cases, instead of apnoeic oxygenation, the benefits of ongoing ventilation to avoid apnoea and hypoxia may outweigh the risk of aspiration
  • Airway patency must be maintained throughout preoxygenation and apnoeic oxygenation
  • Apnoeic oxygenation is merely an adjunct, it cannot compensate for ineffective preoxygenation
  • see apnoeic oxygenation and delayed sequence intubation


Outside of the operating theatre, this approach is effective for preoxygenation:

  • Perform standard monitoring for emergency intubation
  • Position the patient ‘head up’ at 30 degrees (or more), with auditory meatus above the jugular notch
    • this increases functional residual capacity and thus the oxygen reservoir of the lungs
  • Ensure the patient has a patent airway
  • Place standard nasal cannula (at 15 L/min oxygen) prior to placement of the preoxygenation device if apnoeic oxygenation will be used once the patient is sedated (also serves as a preoxygenation adjunct)
  • Choose preoxygenation device based on the patient’s SpO2:
    • if SpO2 >95% use:
      • bag-valve-mask (BVM) with PEEP valve and a good seal at 15+ L/min O2 or more, or
      • non-rebreather (NRB) mask and a good seal at 15 L/min O2 or more
    • if SpO2 <95%:
      • BVM with PEEP valve and a good seal at 15+ L/min O2 or more
  • if adequate respiratory drive, preoxygenate by:
    • at least 3 minutes of tidal ventilations, or
    • 8 breaths with full inspiration/ expiration to achieve vital capacity in <60 seconds (requires patient cooperation)
  • if inadequate respiratory drive, preoxygenate by:
    • positive pressure ventilation (e.g. assisted breaths with BVM or NIV) at 15+ L/min O2 or more

Ensure a patent airway and effective mask seal during the entire period of preoxygenation and subsequent apnoeic oxygenation


Equipment/ procedural factors

  • insufficient time used for preoxygenation
  • inadequate FiO2
    • FiO2 <1.0 will lead to ineffective denitrogenation and suboptimally fill the lung reservoir with oxygen
    • the most common reason for this is poor mask seal, although inadequate oxygen flow rate and failure of oxygen connection are also important (see below)
  • oxygen not connected
    • check by following oxygen tubing from ‘connection-to-connection’, i.e. from flow meter to mask/ cannula
  • poor mask seal or leaks
    • results in a lower FiO2 during preoxygenation due to air entrainment at high inspiratory flow rates
    • if oxygen is provided at a rate greater than the maximum inspiratory flow rate then leaks are not a concern
    • suspect if
      • bag in the circuit does not stay inflated
      • if gas can be felt to escape around the face mask
      • if poor ETCO2 trace
      • if FEO2 plateaus in the 50–80% range
    • if a poor seal is difficult to correct a cooperative patient may be able to apply his/her mouth directly around the circuit connector
  • inadequate oxygen flow rate
    • inspiratory flow rates may reach ~30 L/min during quiet breathing
    • low oxygen flow rate may:
      • cause rebreathing of CO2
      • exacerbate the effect of leaks and poor mask seal (more air is entrained during inspiration)

Patient factors

  • non-cooperative or agitated patient
    • consider sedation and delayed sequence intubation approach
  • poor respiratory reserve, e.g. low FRC
    • use NIV for preoxygenation
  • airway obstruction
    • perform airway opening manoeuvres, reposition patient, remove foreign bodies, suction, treat APO, consider LMA
    • may require surgical airway/ front-of-neck access (FONA) if unable to correct
  • shunt physiology
    • when the shunt fraction exceeds 30%, the increased dissolved oxygen content in the nonshunted blood cannot compensate for the relative lack of bound oxygen content in the shunted blood
    • has an even greater effect if anaemic or increased oxygen consumption (resulting in lower SvO2)


  • hyperoxia is associated with harms in certain settings (e.g. stroke, post-arrest)
  • minor haemodynamic effects of oxygen
    • mild increase in systemic vascular resistance
    • mild decrease in cardiac output and heart rate
  • hyperventilation and hypocapnia (if using the 8 deep breaths breaths in 60 seconds)
  • atelectasis due to oxygen resorption
  • adverse effects associated with the devices used for preoxygenation
    • e.g. aspiration from vomiting into a CPAP mask


Monitoring during preoxygenation

  • Ideally use ETO2 monitoring, however this is typically only available in operating theatres
  • An SpO2 of 100% on pulse oximetry does not indicate optimal preoxygenation
    • hemoglobin becomes 100% saturated at a PaO2 only slightly above that provided by room air
    • it does not indicate how effectively the lungs have been denitrogenated/ filled with oxygen; nor less important compartmentes (e.g. tissue and venous)
  • Remember that there is an inherent lag time with pulse oximetry (SpO2)
    • in critically ill patients this may be > 90 seconds
    • this is due to the time delay for redistribution of oxygenated blood from the central to the peripheral circulation and prolonged signal averaging times
  • Use continuous ETCO2 monitoring:
    • confirms that it functions prior to intubation and confirmation of endotracheal tube position
    • helps to detect leaks/ poor mask seal
    • helps to identify inadequate ventilation and shunt

Duration of preoxygenation

  • A common dilemma when intubating hypoxic critically ill patients is whether to extend the period of preoxygenation if the SpO2 fails to rise adequately
  • Mort et al (2010) found that oxygenation benefits were marginalin a small cohort of critically ill patients when the preoxygenation period was extended from 4 to 8 minutes, and in some patients desaturation occurred
  • A reasonable approach is to ensure the optimal available means of preoxygenation is being used, and if there is no improvement after 3-4 minutes to proceed with intubation

Rate of oxygenation (from Benumof, 1999)

  • The half-time for exponential change in FAO2with a step change in FIO2is 0.693 × VFRC/V̇A for a non-rebreathing system
    • With VFRC equal to 2.5 l, the half-time is 26s and 13s when V̇A= 4.0 and 8.0 l/min, respectively
  • Thus, most of the oxygen that can be stored in the alveolar and arterial spaces can be brought in by hyperventilation with FIO2= 1.0 for a short period of time
  • this is the basis for the 4-deep-breath-within-30-seconds method of preoxygenation (aka the “4DB/30 sec method”)
  • However the4DB/30 sec method still submaximally preoxygenates and leads to more rapid desaturation because:
    • it does not allow enough time to maximally oxygenate tissue and venous compartments, and
    • FiO2 may be decreased if the oxygen flow rate is insufficient for the rate of alveolar ventilation (due to entrained air)

Nasal cannulae

  • Nasal cannulae are used primarily for apnoeic oxygenation rather than preoxygenation
  • Previous recommendations were to place nasal cannula with an initial oxygen flow rate of 4 L/min, then increase to 15L/min to provide apneic oxygenation once the patient is sedated
  • Brainard et al (2015) have shown that awake patients can comfortably tolerate the short-term administration of 15L/min via standard nasal cannula during preoxygenation
  • If used during pre-oxygenation, ensure that an effective seal is maintained with whatever face mask device is used otherwise air may be entrained leading to ineffective preoxygenation
  • If nasal cannulae compromise the seal of the face mask, they can be placed above the face mask until just prior to attempting laryngoscopy, at which point they are placed in the nares to facilitate apnoeic oxygenation
  • the additional flow rate provided my nasal cannula may be a useful preoxygenation adjunct if a non-rebreather mask or BVM is used for preoxygenation (see below)

Non-rebreather (NRB) masks

  • Standard NRB masks deliver only 60% to 70% FiO2 at oxygen flow rates of 15 L/min
  • The FiO2 can be improved by connecting the NRB to 30-60 L/min oxygen flows
    • This can often be achieved by over dialing a standard wall oxygen rotameter (flow meter)
    • Driver et al (2016) demonstrated that a NRB with wall oxygen flow rates increased to maximum levels, rather than the standard 15L/min, provided end-tidal O2 (ET-O2) levels similar to an anesthesia circuit
  • NRB are potentially limited in patients with high inspiratory flow rates as FiO2 may be decreased due to the entrainment of air through valves and a poor face mask seal
  • Performance varies with NRB design (e.g. seal, valve function)
    • some devices with effective seals and valves will collapse onto the patient’s face at high inspiratory flow rates causing transient airway obstruction (e.g. Mayo NRM #2014)
  • Preoxygenation may be improved by providing supplemental oxygen flow (15 L/min) with nasal cannulae placed under the face mask
    • Supplemental nasal cannula oxygen improved nonrebreather face mask preoxygenation both with and without a mask leak (Hayes-Bradley et al, 2016)
    • However, NRB masks +/- nasal cannulae still performed poorly for pre-oxygenation in healthy volunteers in a small emergency department study by Groombridge et al (2015)


  • CPAP or PEEP improves oxygenation by increasing FRC thus preventing atelectasis and by reversing ‘shunt physiology’ through the recruitment of poorly ventilated lung units
  • NIV was found to be more effective than face mask for preoxygenation in critically ill hypoxic patients in a small RCT (Baillard et al, 2006)
  • If used during apnoea, apnoea alarms and back up functions may need to be disabled

BVM devices

  • In ideal circumstances, depending on the device, the effectiveness of a BVM may approximate an anaesthesia circuit for preoxygenation (Hayes-Bradley et al, 2016)
  • BVM devices vary in performance according to:
    • type of BVM device
    • spontaneous ventilation versus positive pressure ventilation
    • presence of a PEEP valve / expiratory port valve
  • During spontaneous ventilation the patient must produce sufficient negative inspiratory pressures to activate the inspiratory valve
    • this pressure varies with different devices
    • this increases work of breathing to some extent
    • the negative pressures generated within the mask may lead to entrainment of room air (e.g. through the expiratory port) and lower FiO2 during preoxygenation (e.g. FiO2 40-50%, similar to a Hudson mask)
    • does not impair performance during positive pressure ventilation (e.g. FiO2 >95% expected with most types) or if there is an expiratory port valve
  • FiO2 will fall regardless of whether the patient is spontaneously breathing or being delivered positive pressure ventilations if used to hyperventilate a patient in excess of the oxygen flow delivered
    • this occurs due to entrainment of air through valves or around the mask
  • Performance can be optimised during spontaneous breathing by:
    • using high flow oxygen
    • use a PEEP valve (expiratory port valve)
    • providing supplemental oxygen flow (15 L/min) with nasal cannulae placed under the face mask
      • improves ETO2 in healthy volunteers with a BVM mask leak (Hayes-Bradley et al, 2016)
      • may be beneficial if minute ventilation exceeds BVM oxygen flow
    • assisting spontaneous ventilations with positive pressure ventilations in synchrony with patient’s spontaneous inspiratory efforts

High flow nasal cannulae (HNFC)

  • High flow nasal cannulae (HFNC) were found to be more effective than a non-rebreather mask for preoxygenation in ICU patients by Miguel-Montanes et al, 2015. HFNC have also been shown to be effective in the THRIVE study (Patel and Nouraei, 2015)
  • It is unclear how the use of HFNC compares with preoxygenation using a combination of standard nasal cannula and a non-rebreather mask
  • It is also unclear how HFNC compare to the combination of standard nasal cannula and use of a bag-valve-mask (BVM) with a PEEP valve for apnoeic oxygenation
  • Different HFNC achieve different maximal FiO2 values — those that cannot generate high FiO2 are not suitable for preoxygenation
  • In summary, if a patient is already on HFNC these are a potentially effective option for preoxygenation and apnoiec oxygenation. However, they are not essential and do not need to be used for patients who are not already using HFNC prior to intubation

References and Links


Journal articles and textbooks

  • Baillard C, Fosse JP, Sebbane M. Noninvasive ventilation improves preoxygenation before intubation of hypoxic patients. American journal of respiratory and critical care medicine. 174(2):171-7. 2006. [pubmed]
  • Benumof JL. Preoxygenation: best method for both efficacy and efficiency. Anesthesiology. 91(3):603-5. 1999. [pubmed]
  • Brainard A, Chuang D, Zeng I, Larkin GL. A Randomized Trial on Subject Tolerance and the Adverse Effects Associated With Higher- versus Lower-Flow Oxygen Through a Standard Nasal Cannula. Ann Emerg Med. 2015 Apr;65(4):356-61. PMID: 25458980.
  • Delay JM, Sebbane M, Jung B. The effectiveness of noninvasive positive pressure ventilation to enhance preoxygenation in morbidly obese patients: a randomized controlled study. Anesthesia and analgesia. 107(5):1707-13. 2008. [pubmed]
  • Dixon BJ, Dixon JB, Carden JR. Preoxygenation is more effective in the 25 degrees head-up position than in the supine position in severely obese patients: a randomized controlled study. Anesthesiology. 102(6):1110-5; discussion 5A. 2005. [pubmed]
  • Driver BE, Prekker ME, Kornas RL, Cales EK, Reardon RF. Flush Rate Oxygen for Emergency Airway Preoxygenation. Annals of emergency medicine. 2016. [pubmed]
  • Hayes-Bradley C, Lewis A, Burns B, Miller M. Efficacy of Nasal Cannula Oxygen as a Preoxygenation Adjunct in Emergency Airway Management. Annals of emergency medicine. 68(2):174-80. 2016. [pubmed]
  • Kwei P, Matzelle S, Wallman D, Ong M, Weightman W. Inadequate preoxygenation during spontaneous ventilation with single patient use self-inflating resuscitation bags. Anaesthesia and intensive care. 34(5):685-6. 2006. [pubmed]
  • Leibowitz AB. Persistent preoxygenation efforts before tracheal intubation in the intensive care unit are of no use: who would have guessed? Critical care medicine. 37(1):335-6. 2009. [pubmed]
  • Lumb AB. Just a little oxygen to breathe as you go off to sleep…is it always a good idea? Br J Anaesth. 2007 Dec;99(6):769-71. PubMed PMID: 18006527. [Free Full Text]
  • Miguel-Montanes R, Hajage D, Messika J, Bertrand F, Gaudry S, Rafat C, Labbé V, Dufour N, Jean-Baptiste S, Bedet A, Dreyfuss D, Ricard JD. Use of High-Flow Nasal Cannula Oxygen Therapy to Prevent Desaturation During Tracheal Intubation of Intensive Care Patients With Mild-to-Moderate Hypoxemia*. Crit Care Med. 2015 Mar;43(3):574-83. PubMed PMID: 25479117.
  • Mort TC, Waberski BH, Clive J. Extending the preoxygenation period from 4 to 8 mins in critically ill patients undergoing emergency intubation. Critical care medicine. 37(1):68-71. 2009. [pubmed]
  • Nimmagadda U, Salem MR, Joseph NJ. Efficacy of preoxygenation with tidal volume breathing. Comparison of breathing systems. Anesthesiology. 93(3):693-8. 2000. [pubmed]
  • 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 Mar;70(3):323-9. doi: 10.1111/anae.12923. Epub 2014 Nov 10. PubMed PMID: 25388828.
  • Russell T, Ng L, Nathan E, Debenham E. Supplementation of standard pre-oxygenation with nasal prong oxygen or machine oxygen flush during a simulated leak scenario. Anaesthesia. 2014 Oct;69(10):1133-7. doi: 10.1111/anae.12630. Epub 2014 Jun 14. PubMed PMID: 24931923.
  • Sirian R, Wills J. Apnoea and the benefits of preoxygenation. Contin Educ Anaesth Crit Care Pain 2009; 9 (4): 105-108 [Free Full Text]
  • Tanoubi I, Drolet P, Donati F. Optimizing preoxygenation in adults. Can J Anesth 2009;56:449-66. [pubmed] [Free full text]
  • Weingart SD. Preoxygenation, reoxygenation, and delayed sequence intubation in the emergency department. J Emerg Med. 2011 Jun;40(6):661-7. Epub 2010 Apr 8. Review. PubMed PMID: 20378297. [Free Full Text]
  • Weingart SD, Levitan RM. Preoxygenation and prevention of desaturation during emergency airway management. Ann Emerg Med. 2012 Mar;59(3):165-75.e1. Epub 2011 Nov 3. Review. PubMed PMID: 22050948. [Free Full Text]

FOAM and web resources

CCC 700 6

Critical Care


Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

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