Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort
Authors:   RISC-19-ICU Investigators, Wendel Garcia Pedro D. , Aguirre-Bermeo Hernán , Buehler Philipp K. , Alfaro-Farias Mario , Yuen Bernd , David Sascha , Tschoellitsch Thomas , Wengenmayer Tobias , Korsos Anita , Fogagnolo Alberto , Kleger Gian-Reto , Wu Maddalena A. , Colombo Riccardo , Turrini Fabrizio , Potalivo Antonella , Rezoagli Emanuele , Rodríguez-García Raquel , Castro Pedro , Lander-Azcona Arantxa , Martín-Delgado Maria C. , Lozano-Gómez Herminia , Ensner Rolf , Michot Marc P. , Gehring Nadine , Schott Peter , Siegemund Martin , Merki Lukas , Wiegand Jan , Jeitziner Marie M. , Laube Marcus , Salomon Petra , Hillgaertner Frank , Dullenkopf Alexander , Ksouri Hatem , Cereghetti Sara , Grazioli Serge , Bürkle Christian , Marrel Julien , Fleisch Isabelle , Perez Marie-Helene , Baltussen Weber Anja , Ceruti Samuele , Marquardt Katharina , Hübner Tobias , Redecker Hermann , Studhalter Michael , Stephan Michael , Selz Daniela , Pietsch Urs , Ristic Anette , Heise Antje , Meyer zu Bentrup Friederike , Franchitti Laurent Marilene , Fodor Patricia , Gaspert Tomislav , Haberthuer Christoph , Colak Elif , Heuberger Dorothea M. , Fumeaux Thierry , Montomoli Jonathan , Guerci Philippe , Schuepbach Reto A. , Hilty Matthias P. , Roche-Campo Ferran 
Published: May 2021

Abstract
Background
Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates.

Methods
Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups.

Results
Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016).

Conclusion
In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk.