Hypoxemia is the most common complication of endotracheal intubation in the critically ill and the strongest risk factor for periprocedural cardiac arrest and death. The traditional approach to avoiding desaturation during intubation is preoxygenation. However, in critically ill patients, acute physiologic abnormalities render preoxygenation less effective. Apneic oxygenation is the delivery of supplemental oxygen to the nasopharynx in the absence of ventilation. By increasing the fraction of oxygen in the gas moving from the nasopharynx to the lungs, apneic oxygenation aims to prevent arterial desaturation. There are significant differences between intubating electively in the operating room (benefit of apneic ox has been proven in anesthesia literature) and urgently in out-of operating room settings. Despite studies suggesting benefit for apneic oxygenation in out-of-operating room intubations, the effectiveness of apneic oxygenation in this context remains unclear.

Clinical Question

Does apneic oxygenation prevent clinically important desaturation during the peri-intubation period?


Medical ICU patients at Vanderbilt 18+ years old intubated by a pulmonary/critical care medicine fellow (from February 13, 2014 to February 11, 2015)


Apneic oxygenation using a high-flow nasal cannula set to 15 L/min flow of 100% oxygen


Usual care pre-oxygenation without supplemental/apneic oxygenation during intubation


Primary Outcome: Lowest arterial oxygen saturation measured by continuous pulse oximetry (SpO2) between induction and 2 minutes after successful endotracheal tube placement
Secondary Outcomes:
Efficacy Outcomes: Incidence of hypoxemia (SpO2 ,90%), severe hypoxemia (SpO2 ,80%), desaturation (decrease in SpO2 .3%), and change in saturation from baseline.
Safety outcomes: Cormack-Lehane grade of glottis view (24), incidence of successful intubation on the first laryngoscopy attempt (placement of an endotracheal tube in the trachea during the first insertion of the laryngoscope into the oral cavity without the use of any other devices), number of laryngoscopy attempts, time from induction to intubation, need for additional airway equipment or operators, and incidence of nonhypoxemia complications.


Single-center, open-label, randomized controlled trial with an intention to treat analysis


Patients with planned awake intubation, intubation was emergent (no time for randomization) or if clinicians felt intra-procedural oxygenation or a specific laryngoscope device was mandated for safety

Primary Results

  • 150 patients randomized
    • Apneic O2: 77 patients
    • Usual Care: 73 patients

Critical Results

  • Lowest SpO2 between induction + 2 minutes post intubation (Primary Outcome)
    • Apneic ox group 92% (IQR, 8499%)
    • Usual care group 90% (IQR, 8096%)
    • P = 0.16
  • Secondary Outcomes: Apneic oxygenation did not impact the proportion of patients who experienced an oxygen saturation less than 90%, less than 80%, or a desaturation greater than 3% during the procedure.
  • Tertiary Outcomes: There were no differences in duration of mechanical ventilation, ICU length of stay, or in-hospital mortality.


  • First randomized trial comparing apneic oxygenation with usual care during intubations outside the operating room and is five times larger than any prior trial
  • The primary outcome, lowest arterial oxygen saturation during intubation, is of interest to clinicians; has been used in prior airway management trials; and is linked to patient-centered outcomes, such as cardiac arrest and death
  • Collection of study endpoints by an independent observer and contemporaneous validation of these data by the primary investigators reduces potential for observer bias
  • The limited exclusion criteria and relatively small number excluded patients promote generalizability


  • A standardized intubation protocol or a highly uniform group of operators might have reduced practice-related variation in lowest arterial oxygen saturation (ex time from induction to laryngoscopy or variation in paralytic agent), making any effect of apneic oxygenation easier to detect
  • The study was powered to detect the 5% difference in lowest arterial oxygen saturation, but a smaller difference might have been missed
  • Although not observed in the analyses, benefit in specific subgroups of patients (e.g., severe hypoxic respiratory failure, preserved pulmonary function) cannot be excluded
  • The study was not blinded which may introduce bias to the results. Blinding may have been difficult to achieve
  • High likelihood of selection bias due to difficult airways/sicker patients being excluded from the trial.
  • True emergency intubations were excluded where the benefit may be most important. 75% of intubations were rated as easy (a group that may have less benefit)
  • Lack of external validity due to the single center nature of the study as well as exclusion of patients deemed by the clinician to require apneic oxygenation or a specific laryngoscopic device
  • Most patients in both arms were not truly apneic prior to laryngoscopy
    • Approximately 70% of the patients in both arms received either bag-valve mask ventilation or bi-level positive pressure ventilation (BPAP) during the period between induction and laryngoscopy, with only a small minority of patients (30%) truly left to their own ventilatory devices.
    • This is a critical flaw – these patients are less likely to benefit from ‘apneic oxygenation’ as they are being ventilated
    • This does not reflect standard ED practice
  • A study powered to detect differences in reaching critical desaturation, rather than absolute difference on SpO2, may be more clinically relevant
  • Lack of generalizability to the ED: Most patients were intubated for respiratory failure (not traumatic, hemodynamic, or neurologic conditions as in the ED)
  • The accuracy of waveform pulse oximetry suffers once the oxygenation saturation drops below 90%. In these cases the value of the patient’s true PaO2 can vary wildly from what is recorded on the monitor. As such it is hard to place a hierarchical value to the pulse oximetry at levels less than 90%. To say that an oxygen saturation of 53% holds a greater clinical value than a value of 35% is inaccurate.

Author's Conclusions

“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 the routine use of apneic oxygenation during endotracheal intubation of critically ill adults.”

Our Conclusions

This single ICU study did not demonstrate a benefit to apneic O2 in critically ill patients undergoing intubation when positive pressure ventilation was provided throughout the intubation process

Potential Impact To Current Practice

Due to limitations in applicability to ED practice, this study should not influence the use of apneic oxygenation in the ED for emergency intubations.

Bottom Line

Apneic oxygenation is a low cost, low risk intervention that may increase safe apneic times during intubation. This study does not inform ED practice and additional ED based research is needed.

Read More

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REBEL EM: The FELLOW Trial: An End to Apneic Oxygenation?

EM Lit of Note: More Futility: Apneic Oxygenation?