Broadening the Berlin definition of ARDS to patients receiving high-flow nasal oxygen: an observational study in patients with acute hypoxemic respiratory failure due to COVID-19
Authors: van der Ven Fleur-Stefanie L. I. M. , Valk Christel M. A. , Blok Siebe , Brouwer Michelle G. , Go Dai Ming , Lokhorst Amanda , Swart Pien , van Meenen David M. P. , Paulus Frederique , Schultz Marcus J. ,   for the PRoAcT–COVID study investigators, Aydeniz E , van de Berg P , Bergmans D C , Bevers M , den Boer S , Boers L S , Bos L D , Botta M , Buiteman-Kruizinga L A , Coene W , Delmte M , Di Leo Vincenzo , Dongelmans D A , Dormans T P , Elting L M , Esmeijer A A , Abreu M G de , Girbes A R , de Graaff M J , Go D M , Goossen R L , Hansen H J , Haringman J J , Hol L , Hollmann M W , van der Heiden P L , Horn J , van Ingen L E , Juffermans N P , Kuiper M A , Kuipers L J , Koornstra E , Lokhorst A , Nijbroek S G , Martin-Loeches I , van Meenen D M , Mazzinari G , Myatra S , Paulus F , Offermans M , Pisters T , Prins A , van Oosten P , Pillay J , Purmer I M , Rezaee A S , Rettig T C D , Roca O , Rosenberg N M , Schavemaker N , Sciascera A A , Schultz M J , Serpa Neto A , Shrestha G , Sleeswijk M E , Stilma W , Strang A C , Spronk A C , Tuinman P R , Tsonas A M , Valk C M A , Verboom M , Vlaar A P , van der Ven W H , van Velzen P , Verhoef E J , Vermeulen T D , van Vliet P , Voorham J J , van der Voort P H , van der Woude M , Weiner  , Yaali N , Zandvliet J M , van Zanten A R , van Zijl T Z , Zonneveld S A 
Published: July 2023

Abstract
Background
High-flow nasal oxygen (HFNO) is increasingly used in patients with acute hypoxemic respiratory failure. It is uncertain whether a broadened Berlin definition of acute respiratory distress syndrome (ARDS), in which ARDS can be diagnosed in patients who are not receiving ventilation, results in similar groups of patients receiving HFNO as in patients receiving ventilation.

Methods
We applied a broadened definition of ARDS in a multicenter, observational study in adult critically ill patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19), wherein the requirement for a minimal level of 5 cm H2O PEEP with ventilation is replaced by a minimal level of airflow rate with HFNO, and compared baseline characteristics and outcomes between patients receiving HFNO and patients receiving ventilation. The primary endpoint was ICU mortality. We also compared outcomes in risk for death groups using the PaO2/FiO2 cutoffs as used successfully in the original definition of ARDS. Secondary endpoints were hospital mortality; mortality on days 28 and 90; need for ventilation within 7 days in patients that started with HFNO; the number of days free from HFNO or ventilation; and ICU and hospital length of stay.

Results
Of 728 included patients, 229 patients started with HFNO and 499 patients with ventilation. All patients fulfilled the broadened Berlin definition of ARDS. Patients receiving HFNO had lower disease severity scores and lower PaO2/FiO2 than patients receiving ventilation. ICU mortality was lower in receiving HFNO (22.7 vs 35.6%; p = 0.001). Using PaO2/FiO2 cutoffs for mild, moderate and severe arterial hypoxemia created groups with an ICU mortality of 16.7%, 22.0%, and 23.5% (p = 0.906) versus 19.1%, 37.9% and 41.4% (p = 0.002), in patients receiving HFNO versus patients receiving ventilation, respectively.

Conclusions
Using a broadened definition of ARDS may facilitate an earlier diagnosis of ARDS in patients receiving HFNO; however, ARDS patients receiving HFNO and ARDS patients receiving ventilation have distinct baseline characteristics and mortality rates.
Trial registration: The study is registered at ClinicalTrials.gov (identifier NCT04719182).