HFNC for Apneic Oxygenation

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The Pre-brief

Apneic oxygenation gained attention in the last decade as a way to increase the time to desaturation during intubation and prevent critical desaturation.  Many studies now exist in the literature not only in the OR, as the original studies were performed, but as well as in the ED and ICU.  Early studies principally used a low flow oxygen via standard nasal prongs, then flush rate oxygen achieving flows such as 20-40lpm.  However, a growing body of evidence is now available utilizing high flow nasal cannula with flow rates of 50-60 LPM during the apneic period.  Should we be abandoning the standard flow cannula in lieu of higher flows?

What we already know:

  • Preoxygenation is KEY to a successful and safe intubation, whether it be by NRB, NIPPV, or BVM
  • Apneic oxygenation provides passive diffusion of oxygen from the alveoli into the bloodstream in an effort to prolong time to desaturation during intubation.
  • Apneic oxygenation with nasal cannula has been shown in a review and meta-analysis to:
    • Relative risk to any desaturation was RR = 0.76 with ApOx95% CI = 0.60 to 0.90, p = 0.002
    • Relative risk of critical desaturation was RR = 0.51, 95% CI = 0.30 to 0.87, p = 0.01
    • As well as increased first pass success RR = 1.09, 95% CI = 1.03 to 1.16, p = 0.004)
  • However! This review included retrospective and observational data.  Two well-performed RCTs (FELLOW and ENDAO Trial) did not demonstrate a difference between usual care and nasal cannula, confounding the topic.
  • These two studies begged the question, is apneic oxygenation completely futile??
  • Highflow nasal cannula offers benefits over nasal cannula such as PEEP, dead space washout, improved work of breathing and higher FiO2.
  • Many patients will already be on HFNC prior to intubation as a means of respiratory support.

The evidence for LFNC during apnea is limited and debated however many will argue that it is a cheap and harm-free intervention with perhaps some benefit. However, setting up a HFNC device takes a bit more effort and time. So we have to ask..

What high-quality evidence exists for HFNC during the apneic period?

Below we have 5 RCTs that all employed HFNC during the apneic period versus no oxygen support.  All studies were performed in ICUs suggesting some minimum degree of critical illness.  Note there is significant heterogeneity among pre-oxygenation techniques and the patient’s baseline oxygen requirement.  However, as we survey these studies, we definitely see a theme emerge despite their differences.

One of the earlier studies that looked at pre-selected hypoxic subpopulation (increased O2 requirement, increased work of breathing, PF <300) showing no difference in lowest oxygen saturation (91.5% vs 89.5%, p =0.44) when randomized to receive pre-ox with NRBM vs HFNC with HFNC during the apneic period.

This single-center study is the one-of-five showing a benefit for HFNC during the apneic period by a mean difference of 4% (100% vs 96%, p=0.02). They also demonstrated an absolute reduction (with p=0.05) in the number of desaturations below 80%.  The clinical significance of improved median desaturation is likely limited but prevention of critical desaturations is a patient-relevant outcome.

This single-site study again demonstrated no significant difference in mean lowest SpO2 or the number of patients with critical desaturations with SpO2<80%.  However, the HFNC group was able to see a higher mean SpO2 prior to intubation during pre-oxygenation.  However, without prevention of hypoxia during the apneic period, the utility of this is limited. 

This is the second study comparing BVM for pre-oxygenation with no apneic oxygenation versus HFNC preoxygenation with HFNC apneic oxygenation that demonstrated no significant difference in median lowest SpO2 (99% vs 100%, p=0.30).  This population compared to our other studies, was primarily intubated for altered mental status and did not have a significant oxygen deficit prior to intubation, which is reflected in the high median SpO2.  However, the authors’ secondary outcomes noted fewer desaturations below 95% (12% vs 23%, p=0.04) and significantly less composite of critical desaturations, hypotension, and cardiac arrest when utilizing HFNC.

This multi-center trial compared pre-ox and apneic oxygenation strategies in both hypoxic and severely hypoxic patients prior to intubation.  In the mildly hypoxic population, there was no difference identified in outcomes of critical desaturation or mean lowest SpO2.  However in the pre-defined severely hypoxic patients (PF ratio <200mmHg) there more critical desaturations (24% vs 35%, p=0.045) and lower mean SpO2 (86% vs 81%, p=0.02) when utilizing HFNC.  The first of the above studies suggesting harm when using HFNC, at least to preoxygenate.


So we have 4 of 5 studies, albeit with different pre-oxygenation techniques, demonstrating no significant difference in median SpO2 when using HFNC during the apneic period.  One small study demonstrated a benefit, while a larger, multicenter trial actually demonstrated harm.  Without a clear signal of benefit, is the cognitive and logistical load of placing a patient on HFNC prior to intubation worth it?  Furthermore, when we have a strong study showing the safety and efficacy of BVM during apnea, should our future directions be along the route of further clarifying the role of BVM for apneic support?


Further thoughts by Steve Haywood, CCN Editor:

These studies likely show a failure of HFNC to recruit alveoli in the pre-oxygenation process rather than a failure of HFNC for apneic oxygenation. While HFNC can generate some positive pressure, it is far less than what is possible with a BVM+PEEP Valve or NIPPV. The one study that used NIPPV in both arms for pre-oxygenation (Jaber et al) was also the study that displayed the benefit of using HFNC for ApOx.  

The Debrief

  • There does not exist strong evidence to support the routine use of HFNC during the apneic period. 
  • HFNC was not reported to complicate or impede intubation.
  • The subgroups that still need more investigation include those who are severely hypoxic at baseline, those with prolonged intubations, those who are morbidly obese.


  1. 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 Oct;35(10):1542-1546. doi: 10.1016/j.ajem.2017.06.046. Epub 2017 Jun 24. PMID: 28684195.
  2. Semler MW et al. Randomized Trial of Apneic Oxygenation During Endotracheal Intubation of the Critically Ill. Am J Respir Crit Care Med 2015 [Epub ahead of print] PMID: 26426458
  3. Caputo N 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. [epub ahead of print]. PMID: 28791755
  4. Vourc’h, M. et al. High-fow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomized controlled clinical trial. Intensive care medicine 41, 1538–1548, https://doi.org/10.1007/s00134-015-3796-z (2015).
  5. Jaber, S. et al. Apnoeic oxygenation via high-flow nasal cannula oxygen combined with non-invasive ventilation preoxygenation for intubation in hypoxaemic patients in the intensive care unit: the single-centre, blinded, randomized controlled OPTINIV trial.
  6. Simon, M. et al. High-Flow Nasal Cannula Versus Bag-Valve-Mask for Preoxygenation Before Intubation in Subjects With Hypoxemic Respiratory Failure. Respiratory care 61, 1160, https://doi.org/10.4187/respcare.04413 (2016).
  7. Guitton, C. et al. Nasal high-flow preoxygenation for endotracheal intubation in the critically ill patient: a randomized clinical trial. Intensive care medicine 45, 447–458, https://doi.org/10.1007/s00134-019-05529-w (2019).
  8. Frat, J. P. et al. Non-invasive ventilation versus high-fow nasal cannula oxygen therapy with apnoeic oxygenation for preoxygenation before intubation of patients with acute hypoxaemic respiratory failure: a randomised, multicentre, open-label trial. Te Lancet. Respiratory medicine 7, 303–312, https://doi.org/10.1016/s2213-2600(19)30048-7 (2019).


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