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Randomized Trial of Apneic Oxygenation during Endotracheal Intubation of the Critically Ill

Semler. Am J Respire Care Med; published online first 1st October 2015.

Clinical Question

  • In Intensive Care patients undergoing intubation does apneic oxygenation during laryngoscopy increase the lowest arterial oxygen saturation experienced by patients


  • Single-centre, randomised controlled trial
  • Permuted block generated by computerized algorithm
  • Allocation concealment; sequentially-numbered opaque envelopes
  • Treating clinicians non-blinded. Data collection during intubation by independent observers unaware of the study hypothesis
  • Pragmatic design with other treatments left to treating physicians
  • Sample size of 150 patients calculated to give 80% power to detect a mean lowest arterial oxygen saturation difference of 4.6%
  • Intention to treat analysis


  • Medical ICU at Vanderbilt University Medical Center
  • Feb 2014 to Feb 2015
  • Baseline characteristics similar in both groups


  • Inclusion: Patients 18 years or older being intubated by a pulmonary and critical care medicine fellow in the ICU
  • Exclusion: Patients undergoing awake intubation, patients who required intubation so urgently that randomization could not be achieved, or if a specific approach to intra-procedural oxygenation or a specific laryngoscopy device was mandated safe for intubation (as part of a comparison of VL and DL in the same cohort).
  • 196 patients met inclusion criteria: 150 underwent randomisation (73 to usual care, 77 to apneic oxygenation). 46 were excluded (23 required intubation too urgently, 18 were felt to require video or FO intubation, 1 was felt to require direct laryngoscopy, 1 was felt to require apneic oxygenation, 3 excluded for unknown reasons)


  • For patients in the apneic oxygenation group, a high-flow nasal cannula set to 15L/min of 100% O2 was placed in the patient’s nares prior to induction and kept in place until intubation was complete. Patients could be delivered additional oxygen up until the time of laryngoscopy: NRBM (32.5%), bipap (29.9%), BVM (42.9%), standard nasal cannula at 6L/min (7.8%)


  • The clinical team made decisions regarding airway management. Patients could be delivered oxygen right up until the time of laryngoscopy by NRBM (43.8%), Bipap (31.5%), BVM (42.5%) or standard nasal cannula 6L/min (2.7%)

Management common to both groups

  • Approach to pre-oxygenation, patient positioning, medications for induction & neuromuscular blockade, ventilation between induction and laryngoscopy, choice of laryngoscope blade and use of airway equipment were at the discretion of the intubating team.


  • Primary outcome: No difference in the lowest arterial oxygen saturation measured by continuous pulse oximetry (SpO2) between induction and two minutes after successful ETT placement. The median lowest SpO2 was 92% (IQR 84-99%) [usual care] vs 90% (IQR 80-96%) [apneic O2] p=0.16
  • Secondary outcome: [usual vs apneic O2] No difference in:
    • Incidence of hypoxemia (SpO2 <90%) [47.2% vs 44.7% p=0.87]
    • Incidence of severe hypoxemia (SpO2 <80%) [25% vs 15.8% p=0.22]
    • Incidence of desaturation (decrease in SpO2 > 3%) [55.6% vs53.9% p= 0.87]
    • Change in saturation from baseline. [4.5% vs 4% p=0.6]
  • Tertiary outcome: [usual vs apneic O2]
    • Duration of mechanical ventilation (3 vs 3 days p= 0.73)
    • ICU length of stay (7 vs 4 days p=0.24)
    • In-hospital mortality (49% vs 35% p=0.1)
    • Time from induction to secured airway 150 seconds vs 132 seconds (p=0.31)

Authors’ Conclusions

  • Apneic oxygenation does not appear to increase lowest arterial oxygen saturation during endotracheal intubation of critically ill patients compared to usual care


  • Well designed, pragmatic study that examines a low cost and potentially effective intervention that has been widely adopted but only tested in small randomised controlled trials in the operating room and not in a critical care setting.
  • The pragmatic design meant patients could receive other forms of oxygenation up until the time of laryngoscopy. This is an accurate reflection of what happens in the real world of critical care intubations.
  • The patient’s were unwell and primarily intubated for respiratory failure which is exactly the right group to test this intervention in
  • Statistical analysis plan was made publicly available prior to enrolment.
  • Intention to treat analysis of the primary outcome
  • Results were consistent after a multivariate linear regression analysis
  • The lowest saturation between induction and two minutes after successful ETT placement takes into account a lag for the SpO2 to fall following successful intubation
  • The data collectors were unaware of the study hypothesis so probably free of bias


  • A small trial with a surrogate primary outcome. A much larger trial would be required to detect a clinical outcome such as hypoxemic arrest in the peri-intubation period
  • One of the exclusion criteria was ‘felt to require video or fibreoptic intubation’. This is because the trial was trying to answer two questions at once. I worry that the 18 patients excluded due to this reason were perhaps sicker or deemed difficult intubations – again this is the group of patients that apneic oxygenation would be most useful.
  • Single centred, medical ICU limiting external validity
  • The intubators were fellows, so presumably quite adept, as is reflected in the very brief times to intubation. This intervention cannot be discounted if the operator is less experienced.
  • The lag in decrease in SpO2 may be longer than 2 minutes following intubation in some cases
  • The majority of patients received some form of supplemental oxygen from time of induction to laryngoscopy, so this trial does not answer the question for those patients where this is contraindicated. (73% received Bipap or BVM)
  • The median highest FiO2 in the preceding 6 hours was 40%. Apneic oxygenation would be expected to assist if the patient had a high FiO2 at the time of intubation and this may explain why a treatment effect has not been observed in this study as profoundly hypoxemic patients are underrepresented.

The Bottom Line

  • In this medical ICU, where patients were being intubated by experienced fellows, and where the operator did not think that video laryngoscopy was essential, apneic oxygenation did not increase lowest arterial oxygen saturation compared to usual care. No harm was demonstrated.

External Links


Summary author: @CeliaBradford
Summary date: 14 October 2015
Peer-review editor: @DavidSlessor

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