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Long B, Gottlieb M. Noninvasive respiratory support for pediatric acute hypoxemic respiratory failure. Academic Emergency Medicine. 2026;33(1):e70221. doi:10.1111/acem.70221

Study Population: 8163 participants <18 years from 30 trials with acute hypoxemic respiratory failure receiving any modality of NRS or SOT

Efficacy Endpoints

Reduced risk of IMV, treatment failure, need for pediatric intensive care unit admission, duration of oxygen therapy, mortality

Harm Endpoints

Duration of noninvasive respiratory support (NRS), risk of pressure injury, serious adverse events, length of stay, sedation use, abdominal distension

Narrative

Acute hypoxemic respiratory failure (AHRF) has various etiologies and is a common cause of pediatric cardiac arrest1. In the pediatric intensive care unit (PICU) setting, approximately 75% of pediatric patients receive some form of respiratory support2. This may include standard oxygen therapy (SOT), noninvasive respiratory support (NRS) such as high-flow nasal cannula (HFNC) or continuous positive airway pressure (CPAP), and endotracheal intubation with invasive mechanical ventilation (IMV)2^,3^,4. NRS has become an effective means of managing AHRF, with guidelines recommending NRS in adults3^,4. In pediatric patients, guidelines regarding the mode of NRS vary and are vague regarding specific types of therapy5^,6^,7.

The network meta-analysis summarized here included randomized controlled trials (RCTs) of participants <18 years with AHRF receiving any modality of NRS or SOT which reported mortality rate, need for IMV, treatment failure rate (intubation, escalation/crossover to another NRS node, or according to individual study definition), and serious adverse events (SAEs)8. The systematic review excluded studies of patients with neuromuscular, oncologic, or chronic respiratory disease; those in the postoperative or post-extubation setting; and those with more than 50% of participants being neonates. The primary outcomes summarized here included in-hospital mortality, IMV requirement, and treatment failure. Secondary outcomes include serious adverse events (SAE; e.g., pneumothorax, unexpected emergency intubation, respiratory or cardiac arrest), PICU and hospital length of stay (LOS), PICU admission rate, duration of NRS and oxygen use, ventilation intolerance, sedation use, pressure injuries, and abdominal distension.

The review included 30 trials (n = 8163 participants) published between 2008 and 20248. Trial settings included the PICU (12 trials), general ward (8 trials), emergency department (5 trials), and multiple settings (5 trials)8. One trial compared CPAP, HFNC, and SOT, and the other trials compared 2 treatment arms (16 trials SOT versus HFNC, 8 trials HFNC versus CPAP, 3 trials SOT versus CPAP, and 2 trials SOT versus bilevel positive airway pressure [BPAP]). Sixteen trials evaluated AHRF due to bronchiolitis, 5 trials evaluated those with pneumonia, and 3 trials evaluated those with asthma, while 6 trials did not restrict the cause of AHRF.

CPAP reduced risk of IMV compared to SOT (risk ratio [RR]: 0.61; 95% confidence interval [CI]: 0.38 to 0.97; risk difference [RD]: −1.3%; number needed to treat [NNT]: 77), as did noninvasive ventilation (BPAP) (RR: 0.47; 95% CI: 0.23 to 0.96; risk difference [RD]: −1.7%; NNT: 59), but HFNC did not. Both CPAP (RR: 0.52; 95% CI: 0.28 to 0.99; RD: −9.5%; NNT: 11) and HFNC (RR: 0.52; 95% CI: 0.33 to 0.80; RD: −9.5%; NNT: 11) reduced the risk of treatment failure.

HFNC increased the risk of PICU admission (RR: 1.29; 95% CI: 1.03 to 1.61; RD: 2.6%; number needed to harm [NNH]: 39), though CPAP did not. Compared to SOT, CPAP (RR: 30.57; 95% CI: 4.71 to 198.63; RD: 8.9%; NNH: 11) and HFNC (RR: 10.12; 95% CI: 1.79 to 57.31; RD: 2.7%; NNH: 37) were harder for patients to tolerate, and CPAP was associated with intolerance when compared to HFNC (RR: 3.02; 95% CI: 1.08 to 8.45; RD: 14.1%; NNH: 7). HFNC reduced the total duration of respiratory support compared with SOT (mean difference: 6.26 h fewer; 95% CI: 11.07 to 1.45 h fewer), and CPAP increased the duration of respiratory support compared to SOT (mean difference: 6.37 h more; 95% CI: 1.66 to 11.08 h more) or HFNC (mean difference: 4.95 h more; 95% CI: 0.51 to 9.38 h more). CPAP increased risk of pressure injuries compared with HFNC (RR: 2.41; 95% CI: 1.30 to 4.47; RD: 3.1%; NNH: 32). CPAP and HFNC did not reduce mortality compared to SOT or when compared to each other, and they did not reduce hospital and PICU LOS.

Caveats

The included trials span different settings (PICU, non-PICU, low- and middle-income countries) and different underlying etiologies of respiratory failure. This variability complicates pooling and comparison of results across trials. The meta-analysis attempted to mitigate this by performing several subgroup or sensitivity analyses, but residual confounding likely remains. A network meta-analysis requires that the trials are sufficiently similar so that the indirect comparisons are valid. Given heterogeneity in settings, populations, and protocols, that assumption may not be the case here. Inconsistencies or violation of transitivity may distort estimates in comparisons with no direct head-to-head trials. The evidence supporting some of the pairwise comparisons such as BPAP relative to SOT was rated as very low certainty. Trials differed in design, blinding, and other methodological features. Some may have had high or unclear risk of bias, which undermines confidence in effect estimates. While primary outcomes (e.g., mortality, need for invasive ventilation, treatment failure) are addressed, the differences in secondary outcomes (e.g., length of stay, sedation requirements, adverse events) were often nonsignificant or underpowered. Therefore, it is likely that the adverse events (serious adverse events, pressure injuries, abdominal distension) may have been underreported or inadequately captured. Lastly, respiratory support strategies, device technology, and supportive care evolve over time. Some older trials may not align with current clinical practice, which could affect the relevance of pooled estimates.

In summary, the review summarized here found CPAP reduced IMV and risk of treatment failure, while also increasing the risk of intolerance and prolonging the duration of NRS. HFNC was also effective but was associated with increased risk of PICU admission. Thus, we have assigned a color recommendation of Green (benefit>harm) for NRS including CPAP and HFNC for pediatric AHRF, though further study is needed evaluating BPAP and patients with severe AHRF. Clinicians must consider available equipment, resources, and local demand on the care team including nursing when selecting NRS, as these factors play a significant role in the efficacy of NRS.

The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.

Author

Brit Long, MD; Michael Gottlieb, MD
Supervising Editors: Shahriar Zehtabchi, MD

Published/Updated

January 29, 2026