The FELLOW Trial: An End to Apneic Oxygenation?

Background: Every year there are a handful of “game changing” publications that truly change how we care for our patients. One such paper was a paper by Scott Weingart and Richard Levitan in the Annals of Emergency Medicine in 2011 on the topics of preoxygenation and apneic oxygenation (This paper was already reviewed on REBEL EM – Preoxygenation and Apneic Oxygenation). As many of us know, one of the most common and feared complications dealt with in critically ill patients requiring endotracheal intubation is hypoxemia. Hypoxemia can subsequently lead to cardiac arrest and death. Since the advent of apneic oxygenation this common complication seems to have decreased in occurrence, but is apneic oxygenation effective in all settings?

 The Facilitating EndotrachealL intubation by Laryngoscopy technique and apneic Oxygenation Within the intensive care unit (FELLOW) Trial

What They Did:

  • Randomized, Open-label, Pragmatic trial of 150 adults undergoing endotracheal intubation in a medical ICU at Vanderbilt
  • Determine if apneic oxygenation actually increases arterial oxygen saturations in patients undergoing endotracheal intubation in an ICU
  • Randomized to:
    • Apneic Oxygenation = 15L/min of 100% O2 via high-flow nasal cannula during laryngoscopy
    • Usual Care = No supplemental oxygen during laryngoscopy


  • Primary: Lowest arterial oxygen saturation between induction and two minutes after completion of intubation measured by pulse oximetry (SpO2)
  • Secondary Efficacy Outcomes:
    • Incidence of hypoxemia (SpO2 < 90%)
    • Incidence of Severe hypoxemia (SpO2 <80%)
    • Desaturation (decrease in SpO2 >3%)
    • Change in saturation from baseline
  • Secondary Safety Outcomes:
    • Cormack-Lehane Grade of Glottic View
    • Incidence of Successful Intubation on first Laryngoscopy Attempt (Placement of ETT in trachea)
    • Number of Laryngoscopy Attempts
    • Time from Induction to Intubation
    • Need for Additional Airway Equipment or Operators
    • Incidence of Non-Hypoxemia Complications
  • Tertiary Outcomes:
    • Duration of Mechanical Ventilation
    • ICU Length of Stay
    • In-Hospital Mortality


  • 150 patients randomized
    • 77 patients apneic oxygenation
    • 73 patients usual care
  • Median lowest arterial oxygen saturation:
    • 92% with apneic oxygenation
    • 90% with usual care
    • 95% CI 1.6 – 7.5%; p = 0.16
  • No difference in incidence of oxygen saturation <90%
    • 44.7% vs 47.2% (p = 0.87)
  • No difference in incidence of oxygen saturation <80%
    • 15.8% vs 25.0% (p = 0.22)
  • No difference in incidence of decrease in oxygen saturation >3%
    • 53.9% vs 55.6% (p = 0.87)
  • There was no statistical difference between duration of mechanical ventilation, ICU length of stay, and in-hospital mortality between groups


  • 1st randomized controlled trial to evaluate apneic oxygenation vs usual care
  • Largest trial to date evaluating apneic oxygenation vs usual care
  • Trial occurred outside the operating room setting where intubations are elective and patients may be healthier than patients in the ED or ICU
  • Patients randomized in a 1:1 fashion for intervention and control in sealed envelopes
  • Data collection during intubation was performed by independent observers not aware of the study hypothesis or involved in the procedure itself
  • To confirm accuracy of data collection by independent observes, the primary investigators also collected data for 10% of intubations


  • This is a single center study of one medical ICU of an academic center and may not generalize to community settings or ED settings
  • Excluded patients requiring emergent intubation due to inability to randomize patients. Also patients were excluded if providers wanted a specific approach to oxygenation. Both of these lead to a selection bias with the sickest patients being removed from the study.
  • In the apneic oxygenation group HFNC was used prior to induction, but unclear for how long before the procedure
  • After enrollment clinicians and study personnel no longer blinded to study group assignments
  • This study was powered to detect 5% differences in lowest arterial oxygen saturation, so smaller differences may have been missed
  • Patient requiring prolonged intubation times or abnormal upper airway anatomy were excluded from this trial
  • Patientts were randomized to DL vs VL. There is no real data published on this for us to review, but time to intubation could play a role in Ap Ox.


  • Pre-oxygenation and apneic oxygenation is fairly cheap and easy way to maintain oxygen saturation. Additionally, nasal canula is widely used in preoxygenation so it’s already on the patient at the time of induction. This study did not show increase in harm by using apneic oxygenation.
  • Looking at the supplemental material some interesting stats:
    • Induction agent was etomidate in >90% of cases in both arms
    • Paralytic agent was Rocuronium >50% of cases in both arms
    • The difficulty of the intubation was rated easy in >75% of intubations
  • A majority of patients were not left apneic prior to intubation. For example BPAP was used in approximately 1/3 of patients and another 40% of patients BVM was used prior to and as induction medications were pushed up to laryngoscopy which defeats the purpose of the apneic portion of apneic oxygenation.
  • 1/3 of patients had BiPAP so tidal volumes could be observed for airway patency, but in the other 2/3 of patients airway patency could not be confirmed which is essential for apneic oxygenation to work.

Thoughts from the Twitterverse:

The FELLOW Trial

The FELLOW Trial 1

The FELLOW Trial 2

Author Conclusion: Apneic Oxygenation does not appear to increase lowest arterial oxygen saturation during endotracheal intubation of critically ill patients compared to usual care. These findings do not support routine use of apneic oxygenation during endotracheal intubation of critically ill adults

Clinical Take Home Point: In critically ill patients requiring intubation, if  you use BPAP or BVM during the pre-oxygenation period, you may not get as much benefit from apneic oxygenation.  However, it is important to remember that apneic oxygenation is cheap, low risk (no risk) intervention, with no proven harms to date.


  1. 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

For More Thoughts on This Topic Checkout:

Post Peer Reviewed By: Anand Swaminathan (Twitter: @EMSwami) and Matt Astin (Twitter: @mastinmd)

Cite this article as: Salim Rezaie, "The FELLOW Trial: An End to Apneic Oxygenation?", REBEL EM blog, October 12, 2015. Available at:

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