Fellow: Brandon Palmer, MD, Children’s Hospital Los Angeles, Los Angeles, CA
Article: Durand P, Guiddir T, Kyheng C, et al. A Randomised Trial of High-Flow Nasal Cannula in Infants with Moderate Bronchiolitis [published online ahead of print, 2020 May 7]. Eur Respir J. 2020;1901926. doi:10.1183/13993003.01926-2019
Summary: Routine High-Flow nasal cannula (HFNC) use in bronchiolitis has gained popularity in the US and internationally. However, there have not been randomized controlled trials that test if early or pre-emptive support with HFNC is superior to low-flow oxygen to reduce the rate of treatment failure leading to escalation of care. This multicenter randomized controlled trial of infants aged 7 days to 6 months with a first episode of hospitalization for bronchiolitis sought to determine whether HFNC use compared to low-flow oxygen therapy would reduce the rate of treatment failure requiring escalating care with noninvasive or invasive ventilation within 7 days following randomization. Data was gathered on 268 block randomized patients during two successive bronchiolitis seasons from 2016 to 2017. The study spanned 17 tertiary and non-tertiary hospitals throughout Paris, France. Patients were randomized within 48 hours of admission. The patients received either standard low-flow oxygen therapy up to 2L/min to maintain SpO2 at 94% or higher (control group) or HFNC therapy at 3L/kg/min with FiO2 adjusted to maintain a similar SpO2 target. Bronchiolitis severity was determined using the modified Wood clinical asthma score (m-WCAS), with patients included with a m-WCAS of 2 to 5 (indicating moderate bronchiolitis). Treatment failure was described as FiO2 requirement on HFNC >40% or nasal cannula >2L/min, elevated m-WCAS by 1 point or more at hour 6 or any score >5, refractory apnea episodes or increasing PaCO2 or above 60mmHg at hour 6. The study found that HFNC use did NOT result in statistically significant improvement in rate of treatment failure, as failure occurred in 14% of patients in the HFNC group, compared to 20% in the control group (OR 0.66, p=0.21). HFNC use also did not result in statistically significant reduced risk of admission to the ICU (OR 0.78, p=0.45). There were three cases of pneumothoraces in the HFNC group, with no complications in the control group.
Key Strengths: This is one of the first randomized controlled trials to assess the utility of HFNC in reducing the rate of treatment failure and escalation of care in infants with moderate bronchiolitis. Two previous RCTs have shown no benefit of HFNC over standard oxygen therapy to reduce duration of oxygen therapy or length of stay. This study was unique in that HFNC was used as routine therapy rather than rescue therapy, and the primary outcome assessed rate of treatment failure, which is clinically relevant. The study highlights the lack of evidence for routine HFNC use in bronchiolitis, and along with the findings of the two previous RCTs highlights a potential need for de-implementation.
Limitations: The study was performed across 17 institutions, many of which were non-tertiary institutions and most of which did not utilize HFNC prior to the study. This may have led to a lack of comfort with HFNC and respiratory insufficiency, leading to an increased rate of treatment failure in those patients. Also, the SpO2 limit chosen (94%) was higher than the threshold established by the AAP, and the majority of treatment failure in the HFNC group was due to an elevated m-WCAS score, which is of unknown clinical significance, limiting the generalizability of the study. Lastly, there was an absence of a PICU in all but one recruiting center, potentially leading to inclusion and evaluation bias.
Main Takeaway: Routine High Flow Nasal Cannula use in moderate bronchiolitis to prevent respiratory failure is not evidence-based. This study, as well as two other RCTs, have not shown a significant benefit of HFNC compared to standard oxygen therapy to reduce rates of treatment failure, duration of oxygen therapy or length of stay. This study highlights the need for further RCTs on HFNC use in bronchiolitis.
Impact on Practice: Routine use of HFNC in moderate bronchiolitis to prevent treatment failure is not evidence-based and may lead to increased costs and adverse events. Similar to previous interventions utilized in bronchiolitis, such as steroids, ribavirin and hypertonic saline, it may be time to discuss de-implementation of the routine use of HFNC in bronchiolitis.
Article: Durand P, Guiddir T, Kyheng C, et al. A Randomised Trial of High-Flow Nasal Cannula in Infants with Moderate Bronchiolitis [published online ahead of print, 2020 May 7]. Eur Respir J. 2020;1901926. doi:10.1183/13993003.01926-2019
Summary: Routine High-Flow nasal cannula (HFNC) use in bronchiolitis has gained popularity in the US and internationally. However, there have not been randomized controlled trials that test if early or pre-emptive support with HFNC is superior to low-flow oxygen to reduce the rate of treatment failure leading to escalation of care. This multicenter randomized controlled trial of infants aged 7 days to 6 months with a first episode of hospitalization for bronchiolitis sought to determine whether HFNC use compared to low-flow oxygen therapy would reduce the rate of treatment failure requiring escalating care with noninvasive or invasive ventilation within 7 days following randomization. Data was gathered on 268 block randomized patients during two successive bronchiolitis seasons from 2016 to 2017. The study spanned 17 tertiary and non-tertiary hospitals throughout Paris, France. Patients were randomized within 48 hours of admission. The patients received either standard low-flow oxygen therapy up to 2L/min to maintain SpO2 at 94% or higher (control group) or HFNC therapy at 3L/kg/min with FiO2 adjusted to maintain a similar SpO2 target. Bronchiolitis severity was determined using the modified Wood clinical asthma score (m-WCAS), with patients included with a m-WCAS of 2 to 5 (indicating moderate bronchiolitis). Treatment failure was described as FiO2 requirement on HFNC >40% or nasal cannula >2L/min, elevated m-WCAS by 1 point or more at hour 6 or any score >5, refractory apnea episodes or increasing PaCO2 or above 60mmHg at hour 6. The study found that HFNC use did NOT result in statistically significant improvement in rate of treatment failure, as failure occurred in 14% of patients in the HFNC group, compared to 20% in the control group (OR 0.66, p=0.21). HFNC use also did not result in statistically significant reduced risk of admission to the ICU (OR 0.78, p=0.45). There were three cases of pneumothoraces in the HFNC group, with no complications in the control group.
Key Strengths: This is one of the first randomized controlled trials to assess the utility of HFNC in reducing the rate of treatment failure and escalation of care in infants with moderate bronchiolitis. Two previous RCTs have shown no benefit of HFNC over standard oxygen therapy to reduce duration of oxygen therapy or length of stay. This study was unique in that HFNC was used as routine therapy rather than rescue therapy, and the primary outcome assessed rate of treatment failure, which is clinically relevant. The study highlights the lack of evidence for routine HFNC use in bronchiolitis, and along with the findings of the two previous RCTs highlights a potential need for de-implementation.
Limitations: The study was performed across 17 institutions, many of which were non-tertiary institutions and most of which did not utilize HFNC prior to the study. This may have led to a lack of comfort with HFNC and respiratory insufficiency, leading to an increased rate of treatment failure in those patients. Also, the SpO2 limit chosen (94%) was higher than the threshold established by the AAP, and the majority of treatment failure in the HFNC group was due to an elevated m-WCAS score, which is of unknown clinical significance, limiting the generalizability of the study. Lastly, there was an absence of a PICU in all but one recruiting center, potentially leading to inclusion and evaluation bias.
Main Takeaway: Routine High Flow Nasal Cannula use in moderate bronchiolitis to prevent respiratory failure is not evidence-based. This study, as well as two other RCTs, have not shown a significant benefit of HFNC compared to standard oxygen therapy to reduce rates of treatment failure, duration of oxygen therapy or length of stay. This study highlights the need for further RCTs on HFNC use in bronchiolitis.
Impact on Practice: Routine use of HFNC in moderate bronchiolitis to prevent treatment failure is not evidence-based and may lead to increased costs and adverse events. Similar to previous interventions utilized in bronchiolitis, such as steroids, ribavirin and hypertonic saline, it may be time to discuss de-implementation of the routine use of HFNC in bronchiolitis.