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High Flow Nasal Oxygen

4 Dec, 15 | by BMJ Clinical Evidence

Ken Milne

By Ken Milne

Case: A 55-year-old woman presents to the emergency department with a 48-hour history of cough, fever and increasing shortness of breath. She has no history of chronic respiratory problems. On examination, she febrile, tachycardic, tachypneic, and her oxygen saturation is 88% despite facemask oxygen. You wonder if you should try out the new high flow nasal oxygen (HFNO) machine?

Non-invasive positive pressure ventilation (NIPPV) has shown benefit in patients with respiratory distress. HFNO is another option to provide oxygenation that has gained popularity in pediatrics for the treatment of severe bronchiolitis and is now being used in adult patients. It humidifies and heats air to make flows of up to 60 liters a minute safe and tolerable.

A recent paper was published in NEJM. It asked whether HFNO reduced intubation rates and improved outcomes for adult intensive care patients (ICU) patients with acute hypoxic respiratory failure.

This study included 310 patients and used NIPPV and HFNO to treat acute hypoxic respiratory failure and compared it to standard facemask oxygen therapy. Their primary outcome was the proportion of patients intubated at day 28. They had a number of secondary outcomes including all-cause mortality in the ICU, mortality at 90 days, duration of ICU stay and number of ventilator free days at day 28.

The primary result showed no statistical difference in the rate of intubation at 28 days. However, they did find an ICU mortality difference at 90 days: standard 23%, HFNO 12% and NIPVV 28%.

So how does this help us with our clinical decision? Whether HFNO can successfully oxygenate patients, avoid intubation and decrease mortality is an important question to ask. However, there were a number of issues with the study that limit the authors conclusions.

The first issue is the large number of patients they saw with acute respiratory failure admitted to the ICU that did not qualify because of their inclusion and exclusion criteria. They had almost 5,000 patients with acute respiratory failure but only 313 ultimately underwent randomization with 310 included in the analysis.

The study, while being multicentered, was an open-label trial. A lack of blinding can always introduce some bias into how the patients were treated. Bias can be defined as a systematic way of moving the results away from the “truth”.

A third issue is the high level of crossover between the groups. The treating physicians were allowed to use NIPPV for the standard group or the HFNO group if the patient appeared worse. The contamination of the groups because of crossover could have impacted the intention to treat analysis.

Another important point to remember is that although they failed to show a significant difference between the interventions compared to the control group for the primary outcome, the study was powered to detect a 20% difference in intubation rate. So we cannot conclude there was no difference between the groups, only that there was not a 20% superiority of the intervention when compared to standard care assuming a baseline intubation rate of 60%.

The final issue is about their secondary outcome of ICU mortality at 90 days. This result was highlighted in their paper. However, if you search for their original protocol it only lists ICU morbidity at day 28 (not mortality) and mechanical ventilation-free to day 28. This issue should make us more skeptical of the mortality results because it was not an original secondary outcome. However, it is an important and interesting finding and should generate a hypothesis for a future HFNO study.

Thank you to Dr. Justin Morgenstern from for helping with this review. 

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

Dr. Milne is the Chief of Staff at South Huron Hospital in Exeter, Ontario, Canada. He has been doing research for over 30 years publishing on a variety of topics. He is passionate about skepticism, medical education and evidence based medicine. He is the creator of the knowledge translation project, The Skeptics’ Guide to Emergency Medicine. When not working he is trying hard to be an endurance athlete. Dr. Milne is married to Barb and has three amazing children.

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