Noninvasive Ventilation May Beat Standard Oxygen for AHRF, Study Shows

Troy Brown, RN

June 12, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Helmet or face mask noninvasive ventilation (NIV) may help patients survive acute hypoxemic respiratory failure (AHRF) or avoid endotracheal intubation, a new study shows. One expert would like to see access to these technologies expanded to include outpatients as well.

"There are multiple alternatives to standard oxygen which seem to be better," lead author Bruno L. Ferreyro, MD, from the University of Toronto and Sinai Health System and University Health Network, Toronto, Canada, told Medscape Medical News.

"All of these interventions could be effective, but clinicians need to know that none of these interventions should delay timely intubation. Patients who need to be intubated need to be intubated.... [Delaying intubation] has been shown to be harmful for patients," he continued.

Ferreyro and colleagues' findings were published online on June 4 in JAMA.

"The current coronavirus disease 2019 (COVID-19) pandemic has further highlighted the importance of understanding the best approach to providing respiratory support for patients with respiratory failure," the authors write.

The researchers conducted a systematic review and network meta-analysis of 25 randomized clinical trials involving 3804 participants. The primary outcome was all-cause mortality, which was measured at the longest time point during the first 90 days after randomization.

The secondary outcome was endotracheal intubation up to 30 days. Other secondary outcomes were "patient comfort, dyspnea scores, intensive care unit and hospital lengths of stay, and 6-month mortality," the authors explain.

Treatment with helmet NIV (risk ratio [RR], 0.40; absolute risk difference, –0.19; low certainty) and face mask NIV (RR, 0.83; absolute risk difference, –0.06; moderate certainty) were linked to a lower risk for mortality compared with standard oxygen therapy (21 studies; 3370 patients).

High-flow nasal oxygen (RR, 0.87; absolute risk difference, –0.04; moderate certainty), however, was not linked to a significantly lower risk for death in comparison with standard oxygen.

Compared with high-flow nasal oxygen (RR, 0.46; absolute risk difference, –0.15; low certainty) and face mask NIV (RR, 0.48; absolute risk difference, –0.13; low certainty), helmet NIV was associated with significantly decreased mortality.

"In the case of face mask, we saw a very small marginal benefit in mortality, and that is a little bit against most recent trials, like the Frat trial," Ferreyro said. "That association did not stand in multiple scenarios, for example, in patients with more severe respiratory states."

The risk for endotracheal intubation was lower among those who received helmet NIV (RR, 0.26; absolute risk difference, –0.32; low certainty), face mask NIV (RR, 0.76; absolute risk difference, –0.12; moderate certainty), and high-flow nasal oxygen (RR, 0.76; absolute risk difference, –0.11; moderate certainty) (25 studies; 3804 patients) in comparison with standard oxygen.

The risk for bias resulting from lack of blinding for intubation was determined to be high.

Helmet NIV was linked to reduced risk for endotracheal intubation compared with high-flow nasal oxygen (RR, 0.35; absolute risk difference, −0.20; low certainty) and face mask NIV (RR,0.35; absolute risk difference, −0.20; low certainty).

There was no significant difference in the risk for endotracheal intubation with face mask NIV vs high-flow nasal oxygen (RR, 1.01; absolute risk difference, −0.00; low certainty).

Regarding concerns that these technologies could harm patients, "There is all upside and no downside" to using them, Lisa F. Wolfe, MD, associate professor of medicine (pulmonary and critical care), Northwestern University, Chicago, Illinois, told Medscape Medical News.

"There have been concerns that if we use this advanced technology, it might in some way harm patients by slowing down their access to intubation and mechanical ventilation," but the meta-analysis shows the technology does not harm patients, she added.

Which Patients Benefit Remains Unclear

"Questions remain for clinicians regarding when and for which patients these various noninvasive oxygen support strategies fit into the algorithm of AHRF management and specifically for patients with COVID-19," Bhakti K. Patel, MD, Section of Pulmonary and Critical Care Medicine, Pritzker School of Medicine, University of Chicago, Illinois, and colleagues write in an accompanying editorial.

"Although some have argued that the risk of spontaneous breathing should preclude any noninvasive oxygen support, the data from the analysis by Ferreyro et al indicate that it is a reasonable approach to spare a subset of patients with AHRF invasive mechanical ventilation and its inherent complications," Patel and colleagues continue.

The included studies make it difficult to determine which individual patients might benefit the most from NIV, Wolfe said. The most common diagnoses of the included patients were pneumonia and chronic obstructive pulmonary disease, she explained. She noted that there is a need for additional research to explore these questions.

"Given this is a network meta-analysis of aggregated data, we could not explore in detail which individual patient factors make them more likely to respond to any of these interventions," Ferreyro said.

"There's still a struggle to identify which specific patients will likely benefit from each of these strategies," he added.

Patel and colleagues caution against using a "one-size-fits-all" approach to NIV. They recommend "a precision-based approach that matches a given strategy to the observed phenotype of AHRF coupled with incorporating clinician experience and comfort with each technology.

"Although further studies are needed, the meta-analysis by Ferreyro et al has provided a useful summary of the available data to help inform clinicians as they determine locally the best way to choose wisely among several options for care of patients with AHRF, especially in the wave of patients with COVID-19 currently being encountered. Future clinical trials comparing these strategies should not focus on declaring a 'winner' per se but rather on identifying the patient phenotypes that stand to benefit from each noninvasive oxygenation support method. In the management of heterogeneous syndromes like AHRF, it is better to have multiple options than to focus on limiting clinical practice to a single choice," Patel and colleagues write.

Patients with interstitial lung disease and other conditions also experience hypoxemia, Wolfe said, adding, "The 'next evolution' of this is going to be expanding access to these types of support devices in the outpatient arena because hypoxemia is seen in COPD in outpatients" as well as inpatients.

Study coauthor Ferguson has received personal fees from Xenios and Getinge. The other coauthors have disclosed no relevant financial relationships. Editorialist Patel has received grants from the Parker B. Francis Foundation outside the submitted work. The remaining coauthors have disclosed no relevant financial relationships. Wolfe has disclosed no relevant financial relationships.

JAMA. Published online June 4, 2020. Full text, Editorial


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