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Reference:  George S, et al. Effectiveness of nasal high-flow oxygen during apnoea on hypoxaemia and intubation success in paediatric emergency and ICU settings: a randomised, controlled, open-label trial. Lancet Respir Med. March 2025

Date: July 10, 2025

Guest Skeptic: Dr. Spyridon Karageorgos is a Pediatric Chief Resident at Aghia Sophia Children’s Hospital, Athens, Greece and faculty of the Pediatric Emergency Medicine MSc at Queen Mary University in London. Dr. Spyridon Karageorgos

Case: A two-year-old boy presents in the emergency department (ED) with severe respiratory distress and hypoxemia. You attempt to use some non-invasive forms of respiratory support, but he continues to have significant work of breathing and retractions. His mental status begins to decline, and he appears much sleepier than before. The team makes the decision to intubate him. You follow the steps of the pre-intubation checklist and pre-oxygenate him with 100% FiO2. As the sedative and paralytic for intubation are given, the respiratory therapist asks, “Do you also want to use nasal high flow (NHF) for apneic oxygenation during intubation?”

 Background: Managing hypoxia in pediatric patients in EDs and intensive care units (ICUs) remains a challenge. Hypoxia can arise from various causes, including bronchiolitis, pneumonia, asthma, or undifferentiated respiratory failure. Ensuring timely and effective oxygenation is critical to stabilizing these patients and preventing progression to respiratory failure or cardiac arrest.

 NHF oxygenation has gained traction as a respiratory support modality in both ED and ICU settings. NHF delivers humidified and heated oxygen at high flow rates, which typically exceed the patient’s inspiratory flow through nasal cannula. This mechanism not only improves oxygenation but can also help reduce the work of breathing by flushing anatomical dead space and providing some degree of positive end-expiratory pressure (PEEP). The use of NHF is considered less invasive than continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) or mechanical ventilation. It is usually better tolerated, especially by children.

The use of NHF has expanded into general pediatric practice, especially for treating conditions like bronchiolitis and other forms of acute respiratory distress. But, its comparative efficacy to standard oxygen therapy in various clinical settings and patient populations remains a subject of ongoing investigation.

While we would always prefer a controlled intubation, sometimes the patients we see in the ED are unstable and need to be intubated emergently. We often try to pre-oxygenate prior to intubating to maximize oxygen reserves. Previous studies have suggested that the use of NHF may reduce the risk of hypoxemia and improve first-attempt intubation . However, randomized controlled trials evaluating this practice in the pediatric population are limited.

Clinical Question: In children requiring emergency intubation, does the use of nasal high-flow oxygen for apneic oxygenation reduce hypoxemia and increase the rate of successful first-attempt intubation compared to standard care?

Reference:  George S, et al. Effectiveness of nasal high-flow oxygen during apnoea on hypoxaemia and intubation success in paediatric emergency and ICU settings: a randomised, controlled, open-label trial. Lancet Respir Med. March 2025

  • Population: Children aged 1 month to 15 years with acute hypoxic respiratory failure (SpO₂ <92% on room air) requiring emergency endotracheal intubation in EDs and pediatric and neonatal ICUs across Australia, New Zealand, and Switzerland.
    • Exclusion: Primary nasal intubation, blocked nasal airways, elective endotracheal tube change, intubation required immediately for loss of cardiac output or respiratory arrest, location of intubation outside of ED or ICU, death
  • Intervention: Nasal high-flow oxygen at 2L/kg/min during the apneic phase of intubation.
  • Weight HFNC rate
    0-12 kg 2L/kg/min (max 25 L/min)
    13-15 kg 30L/min
    15-30 kg 35L/min
    30-50 kg 40L/min
    >50 kg 50L/min
  • Comparison: Standard care
  • Outcome:
    • Primary Outcomes: Hypoxemia (SpO2 ≤90% or difference of ≥10% if they were unable to achieve a pre-intubation saturation of 100% or the patient had cyanotic congenital heart disease with a right to left shunt) and first-attempt intubation success without hypoxemia
    • Secondary Outcomes: Total intubation attempts, re-oxygenation needs, duration of ventilation, lowest oxygen saturation throughout intubation period, length of stay, mortality, adverse events.
  • Trial: Randomized controlled, open-label, pragmatic multicenter trial

Dr. Shane George

Guest Author: Dr. Shane George is a paediatric emergency and critical care physician at Gold Coast University Hospital, Australia. That’s right he’s trained in both emergency medicine and paediatric intensive care. He’s the lead for children’s critical care research for Gold Coast Health which is affiliated with the University of Queensland and Vice Chair of the Paediatric Research in Emergency Departments International Collaborative (PREDICT)

 Authors’ Conclusions: The use of NHF during emergency intubation in children did not result in a reduction in hypoxaemic events or an increase in the frequency of successful intubation on the first attempt. However, in per-protocol analysis, there were fewer hypoxaemic events but no difference in successful intubation without hypoxaemia on first attempt. Barriers to the application of NHF during emergency intubation and the reasons for abandoning intubation attempts before physiological compromise should be further investigated to inform future research and recommendations for intubation guidelines and clinical practice.

Quality Checklist for Randomized Clinical Trials:

  1. The study population included or focused on those in the emergency department. No
  2. The patients were adequately randomized. Yes
  3. The randomization process was concealed. Yes
  4. The patients were analyzed in the groups to which they were randomized. Yes
  5. The study patients were recruited consecutively (i.e. no selection bias). Unsure
  6. The patients in both groups were similar with respect to prognostic factors. Yes
  7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No
  8. All groups were treated equally except for the intervention. Unsure
  9. Follow-up was complete (i.e. at least 80% for both groups). Yes
  10. All patient-important outcomes were considered. Yes
  11. The treatment effect was large enough and precise enough to be clinically significant. Unsure
  12. Financial conflicts of interest. The funders (Fisher & Paykel Healthcare) provided equipment that was used during the trial but did not have a role in study design, data collection, data analysis, data interpretation, or writing of manuscript. Three of the authors reported consultancy fees, travel, and accommodations by the same company.

Results: They included 969 children with 535 assigned to NHF and 534 assigned to the standard care group.

Key Results: There was no statistical difference in hypoxemic events or first attempt intubation success among patients who received nasal high flow compared to standard care.

Primary Outcome:

Hypoxemia occurred in 61 (12.8%) of the NHF group compared to 77 (16.2%) of the standard care group (aOR 0.74; 97.5% CI 0.46-1.18, p=0.15).

First attempt successful intubation without desaturation occurred in 300 (63%) of the NHF group compared to 280 (59.1%) of the standard care group (aOR 1.13; 97.5% CI 0.79-1.62, p=0.43).

They also did a per protocol analysis where 45 of the intubations were removed.

Hypoxemia occurred in 48 (10.8%) of the NHF group compared to 77 (16.7%) of the standard care group (aOR 0.59; 97.5% CI 0.36-0.97, p=0.017).

First attempt successful intubation without desaturation occurred in 284 (64%) of the NHF group compared to 268 (58.1%) of the standard care group (aOR 1.22; 97.5% CI 0.87-1.71, p=0.19).

Secondary Outcomes: 

 There were no statistical differences in intubation attempts, need for re-oxygenation in between intubation attempts, duration of mechanical ventilation, length of ICU or hospital stay.

The rates of minor and major adverse events were similar as well.

Tune in to the podcast to hear Dr. George answer our questions.

Biases

In this study, approximately 14% of eligible patients were not approached for inclusion due to the treating clinician’s discretion. This is separate from those who were not approached for social or compassionate reasons. Another 14% were missed for unknown reasons. This could have introduced selection bias.

  • Do you have any insights on why the treating clinicians chose not to approach certain patients? How do you think this may have impacted the study results?
  • The open-label design (lack of masking) meant neither clinicians nor evaluators were blinded, introducing potential performance and detection bias. What impact to you think that may have had on the trial?

Standard Care

When we looked at the protocol deviations in the study. It looks like there was more non-compliance in the NHF group, with most of the reasons being that clinicians seemed to have forgotten to put on the NHF.

  • Did you happen to collect data on what “standard care” meant to clinicians involved in the study?

Modified Intention-to-Treat (mITT) vs Per-Protocol (PP) Analysis

 You performed two different analyses for the data: Modified Intention-to-Treat (mITT) and Per-Protocol (PP) analysis. Each type of analysis has some strengths and weaknesses.

  • Why did you not perform a pure ITT?

Your team did find a statistical difference in the rate of hypoxemia between the two groups based on the analysis performed with the per protocol analysis favoring the use of NHF.

  • How would you guide people in interpreting the results of this study given differences based on the type of analysis?

MOOs vs POOs

In this study, one of the primary outcomes, hypoxemia, is a monitor-oriented outcome (MOO). We looked at this recently in SGEM #447, another intubation critical appraisal comparing preoxygenation before intubation with non-invasive positive ventilation vs facemask in adults. It’s unclear whether or not these episodes of oxygen desaturation had a meaningful clinical impact on the patients.

If we look at just the numbers, we see that the NHF group had less episodes of hypoxemia compared to the standard care group. But the rates of major adverse events don’t really differ.

  • Do you think the use of NHF has a clinically significant impact on patient-oriented outcomes?

Abandoned Intubations

Around 17% of intubations in both groups were abandoned without significant desaturation. This finding may also explain why this study had a lower frequency of severe desaturation (SpO2 < 80%) when compared to other large multicentre studies.

  • Can you provide any potential explanations behind this finding?

Bonus Question: Who would benefit the most from NHF for apneic oxygenation?

In the subgroup analyses, the use of NHF did reduce rates of hypoxaemia in the NICU group (aOR 0.19, 97.5% CI 0.04-0.87), those younger than 1 year (aOR 0.49, 97.5% CI 0.26-0.91) and for junior operators (aOR 0.54, 97.5% CI 0.31-0.96). However, the p-values did not reach level of statistical significance.

  • Was it because the study was underpowered for these subgroups?
  • Do you think there’s a specific patient population that may benefit the most from the use of NHF for apneic intubation?

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusion.

SGEM Bottom  : In critically ill children requiring emergency intubation, nasal high-flow oxygen during apnea modestly reduces hypoxemia without significantly improving first-attempt intubation success.

Case Resolution: After you pre-oxygenate the boy prior to intubation to an oxygen saturation of 100% and administer RSI medications, you take a look with your laryngoscope and successfully intubate him on the first attempt. You confirm endotracheal tube placement and place him on a vent. He is transported up to the ICU shortly afterward.

Clinical Application:

Tune in to hear Dr. George’s response.

What do I tell the respiratory therapist? 

Thanks for the suggestion. It looks like we don’t have any NHF set up at the moment, and he’s been well pre-oxygenated. I am comfortable just intubating rather than taking additional time to get NHF set up. In the future, if we have NHF set up prior to intubating, we can use it.

 Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

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