To the Editor:
We read with great interest the article by Bellani and colleagues, “Noninvasive Ventilatory Support of Patients with COVID-19 outside the Intensive Care Units (WARd-COVID),” published in AnnalsATS (1). Without a doubt, this prospective study is one of the most important and largest published studies on the effectiveness of noninvasive ventilation (NIV) in coronavirus disease (COVID-19)–associated acute hypoxemic respiratory failure (AHRF). Bellani and colleagues demonstrated that NIV is feasible outside the intensive care unit (ICU) in COVID-19–associated AHRF, with an overall success rate of 65% and a 60-day mortality rate of 25%. The authors also showed that lower arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2) ratio, higher CRP (C-reactive protein) concentrations, and lower platelet counts were independently associated with an increased risk of NIV failure.
However, we believe that using the PaO2/FiO2 ratio is a rather questionable means of predicting NIV failure. First, PaO2/FiO2 values are inherently inaccurate because the FiO2 in a nonintubated patient is quite difficult to determine (2). And this is especially true in the context of non-ICU departments when using free-flow systems under the condition of a gas leak around the mask or helmet. Second, the PaO2/FiO2 threshold of 150 mm Hg is also rather controversial. In a study by Franco and colleagues (3), there were no differences in the 30-day mortality rate between patients with COVID-19 with baseline PaO2/FiO2 values of 101–150 mm Hg and patients with COVID-19 with baseline PaO2/FiO2 values of 151–200 mm Hg (24% and 26%, respectively). Third, in two other studies (4, 5) conducted outside the ICU, the mortality rates of patients with COVID-19 with even lower baseline PaO2/FiO2 values during NIV were better than that in the study by Bellani and colleagues: the rate was 17% in a study by Brusasco and colleagues (initial median PaO2/FiO2 of 119 mm Hg) (4), and the rate was 21% in a study by Nightingale and colleagues (initial median PaO2/FiO2 of 122 mm Hg) (5).
In our recent study, in patients with COVID-19 receiving NIV outside the ICU, the baseline PaO2/FiO2 index also did not differ between the success and failure groups, but we found that patients who experienced NIV failure had higher minute ventilation on the first day of NIV (due to a slightly higher tidal volume and a higher respiratory rate) (6), which, of course, may increase the risk of self-inflicted lung injury. These findings are in line with Bellani and colleagues’ data, which also showed that the patients experiencing NIV failure had lower arterial carbon dioxide pressure levels. However, we must admit that today in non-ICU settings, it is rather difficult to identify robust markers of possible self-inflicted lung injury.
Bellani and colleagues also identified elevated levels of CRP as an independent predictor of NIV failure. Interestingly, in our study, an elevated D-dimer level was an indicator of the increased possibility of NIV failure (6). Both high CRP levels and high D-dimer levels are associated with the progression of COVID-19 and a higher mortality rate. So, progressive underlying processes in COVID-19 might need prolonged respiratory support and can be associated with NIV failure.
In conclusion, because the appropriate patient selection is the key to the successful application of NIV, further research is needed to identify reliable predictors of NIV failure in COVID-19–associated AHRF.
Footnotes
Author disclosures are available with the text of this letter at www.atsjournals.org.
References
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