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COVID-19 patients with severe disease were significantly less likely to require mechanical ventilation when treated with high-flow oxygen therapy compared to conventional oxygen therapy, based on data from 220 adults.
Arterial hypoxemia is a signature feature of severe COVID-19 and should be managed with oxygen supplementation, but mechanical ventilation has been associated with increased mortality in these patients, write Gustavo A. Ospina-Tascón, MD, of Fundación Valle del Lili, Cali, Columbia, and colleagues.
Data from previous studies suggest a reduced need for intubation if patients with acute hypoxemic respiratory failure receive high-flow oxygen therapy through a nasal cannula; however, the effect of high-flow oxygen therapy vs conventional oxygen therapy has in severe COVID-19 patients has not been explored, they say.
In a study published in JAMA, the researchers randomized 109 adults with severe COVID-19 to high-flow oxygen therapy and 111 to conventional therapy. All patients in the open-label study had baseline respiratory distress and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of less than 200. The patients were treated in three centers between August 2020 and January 2021, with a final follow-up on February 10, 2021. The median age of the patients was 60 years, and 33% were women. The primary outcomes were the need for intubation and the time to clinical recovery until day 28.
A total of 34 patients in the high-flow group and 51 patients in the conventional oxygen group required intubation (hazard ratio, 0.62; P = .03). Patients in the high-flow group also had a significantly shorter time to clinical recovery within 28 days compared to the conventional group (11 days vs 14 days). Rates of bacterial pneumonia and bacteremia also were lower in the high-flow oxygen group compared to the conventional group (13.1% vs 17.0%, respectively, and 7.1% vs 11.0%, respectively).
The study also examined eight secondary outcomes, including risk of intubation at 7 and 14 days, and median ventilator-free days in the first 28 days. For these outcomes, compared to conventional oxygen, high-flow oxygen was significantly associated with lower risk of intubation at day 7 (31.3% vs 50%) and day 14 (34.3% vs 51.0%), and more ventilator-free days (28 days vs 24 days). Other secondary outcomes, including the need for kidney replacement therapy, length of in-hospital and ICU stay, and the proportion of adverse events, were not significantly different between groups. The hazard ratio for death at day 28 was not significantly different between groups (0.49; P = .11).
“Avoiding systematic intubation in COVID-19 could prevent complications related to invasive mechanical ventilation, sedation, delirium, and neuromuscular paralysis,” and prevention of intubation could conserve resources in pandemic conditions, the researchers note in their discussion.
The study findings were limited by several factors, including the open-label design, small sample size, and inclusion of patients from only three centers in one country, which could limit generalizability, the researchers note. In addition, the use of two primary endpoints could increase the potential for error, they say.
However, the results were strengthened by the consistent randomization and similarity to studies of respiratory failure from other causes, they write. The data suggest that “[I]mprovement of respiratory mechanics and limitation of lung injury could reduce time to clinical recovery, assuming that part of such injury might appear as a consequence of increased respiratory load that is inadequately supported during spontaneous breathing,” the researchers state.
Data Highlight the Value of Reducing Ventilator Use
“Mortality in acute respiratory distress syndrome varies with the severity of ARDS,” said Setu Patolia, MD, of Saint Louis University School of Medicine, in an interview. “Severe ARDS has mortality rate of 45%, and ventilator-induced lung injury has been implicated as one of the important causes of increased mortality in severe ARDS,” he noted. “Intubation and placing a patient on ventilator support is a double-edged sword. On one side, not intubating somebody who needs the intubation because of respiratory distress itself leads to the death. However, by placing somebody on ventilator support in a heterogeneously injured lung from ARDS carries the risk of injuring the normal lung ─ so called ‘baby lung,’ ” Patolia explained.
The COVID-19 pandemic has highlighted the need for more research in ARDS, said Patolia. “Treating ARDS-related primary lung injury while preventing further ventilator-induced secondary lung injury is the main goal of ARDS therapies. Preventing intubation while supporting patients appropriately serves this purpose,” thus, the current study is especially relevant. “Also, the COVID-19 pandemic has highlighted the importance of resource management, particularly in the developing countries,” Patolia emphasized. “Intubated patients need ICU care, and in many parts of the world, ICU care is limited or nonexistent,” therefore, finding safe and effective alternatives to avoid intubations and ICU care should be the priorities in ARDS research, he added.
Patolia said that he found some aspects of the study findings surprising, but others not surprising. In 2015, the FLORALI trial randomized patients with ARDS to high-flow nasal canula, nasal canula, or noninvasive ventilation. The primary outcome was intubation at 28 days, and overall, there was no difference between three arms, he said. However, in that study, “patients with PaO2/FIO2 of less than 200 (moderate-severe ARDS), high-flow nasal canula was associated with decreased intubation rate compared to the two other arms,” and 90-day mortality favored the use of high-flow nasal canula, he said. The results of the current study are comparable to the primary outcome from the FLORALI trial, he added.
Mortality was not significantly different in the current study, but this may be related to sample size, Patolia noted.
The current study findings suggest that “high-flow nasal canula is an important tool in the treatment of COVID-19 ARDS patients,” Patolia said. “Along with oxygen support, it provides positive end-expiratory pressure, decreased muscle workload, and provides comfort through humidified oxygen,” and it decreases intubation rate, he said.
As for future research, high-flow nasal cannula oxygenation could have an impact on mortality and should be studied with a larger sample size to address this question, Patolia noted.
“Also, based on the subgroup analysis, it seems that younger patients (age <60) and patients with low interleukin-6 levels (<100 pg/mL) had more benefit from high-flow nasal canula use. These subgroups need to be explored in future studies,” he emphasized.
The study was supported by the Centro de Investigaciones Clínicas, Fundación Valle del Lili, Cali, Colombia. Ospina-Tascón and Patolia have disclosed no relevant financial relationships.
JAMA. Published online December 7, 2021. Abstract
Heidi Splete is a freelance medical journalist with 20 years of experience.
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