Factors influencing liberation from mechanical ventilation in coronavirus disease 2019: multicenter observational study in fifteen Italian ICUs
Authors: Gamberini Lorenzo , Tonetti Tommaso , Spadaro Savino , Zani Gianluca , Mazzoli Carlo Alberto , Capozzi Chiara , Giampalma Emanuela , Bacchi Reggiani Maria Letizia , Bertellini Elisabetta , Castelli Andrea , Cavalli Irene , Colombo Davide , Crimaldi Federico , Damiani Federica , Fogagnolo Alberto , Fusari Maurizio , Gamberini Emiliano , Gordini Giovanni , Laici Cristiana , Lanza Maria Concetta , Leo Mirco , Marudi Andrea , Nardi Giuseppe , Ottaviani Irene , Papa Raffaella , Potalivo Antonella , Russo Emanuele , Taddei Stefania , Volta Carlo Alberto , Ranieri V. Marco ,   the ICU-RER COVID-19 Collaboration, Tartaglione Marco , Chiarini Valentina , Buldini Virginia , Coniglio Carlo , Moro Federico , Cilloni Nicola , Giuntoli Lorenzo , Bellocchio Angela , Matteo Emanuele , Pizzilli Giacinto , Siniscalchi Antonio , Tartivita Chiara , Matteo Francesco , Marchio Annalisa , Bacchilega Igor , Bernabé Laura , Guarino Sonia , Mosconi Elena , Bissoni Luca , Viola Lorenzo , Meconi Tommaso , Pavoni Vittorio , Pagni Aline , Pompa Cleta Patrizia , Cavagnino Marco , Malfatto Anna , Adduci Angelina , Pareschi Silvia , Melegari Gabriele , Maccieri Jessica , Marinangeli Elisa , Racca Fabrizio , Verri Marco , Falò Giulia , Marangoni Elisabetta , Boni Francesco , Felloni Giulia , Baccarini Federico Domenico , Terzitta Marina , Maitan Stefano , Imbriani Michele , Orlandi Paolo , Dalpiaz Giorgia , Golfieri Rita , Ciccarese Federica , Poerio Antonio , Muratore Francesco , Ferrari Fabio , Mughetti Martina , Franchini Loredana , Neziri Ersenad , Miceli Marco , Minguzzi Maria Teresa , Mellini Lorenzo , Piciucchi Sara 
Published: October 2020

Abstract
Background
A large proportion of patients with coronavirus disease 2019 (COVID-19) develop severe respiratory failure requiring admission to the intensive care unit (ICU) and about 80% of them need mechanical ventilation (MV). These patients show great complexity due to multiple organ involvement and a dynamic evolution over time; moreover, few information is available about the risk factors that may contribute to increase the time course of mechanical ventilation.
The primary objective of this study is to investigate the risk factors associated with the inability to liberate COVID-19 patients from mechanical ventilation. Due to the complex evolution of the disease, we analyzed both pulmonary variables and occurrence of non-pulmonary complications during mechanical ventilation. The secondary objective of this study was the evaluation of risk factors for ICU mortality.

Methods
This multicenter prospective observational study enrolled 391 patients from fifteen COVID-19 dedicated Italian ICUs which underwent invasive mechanical ventilation for COVID-19 pneumonia. Clinical and laboratory data, ventilator parameters, occurrence of organ dysfunction, and outcome were recorded. The primary outcome measure was 28 days ventilator-free days and the liberation from MV at 28 days was studied by performing a competing risks regression model on data, according to the method of Fine and Gray; the event death was considered as a competing risk.

Results
Liberation from mechanical ventilation was achieved in 53.2% of the patients (208/391). Competing risks analysis, considering death as a competing event, demonstrated a decreased sub-hazard ratio for liberation from mechanical ventilation (MV) with increasing age and SOFA score at ICU admission, low values of PaO2/FiO2 ratio during the first 5 days of MV, respiratory system compliance (CRS) lower than 40 mL/cmH2O during the first 5 days of MV, need for renal replacement therapy (RRT), late-onset ventilator-associated pneumonia (VAP), and cardiovascular complications.
ICU mortality during the observation period was 36.1% (141/391). Similar results were obtained by the multivariate logistic regression analysis using mortality as a dependent variable.

Conclusions
Age, SOFA score at ICU admission, CRS, PaO2/FiO2, renal and cardiovascular complications, and late-onset VAP were all independent risk factors for prolonged mechanical ventilation in patients with COVID-19.

Trial registration
NCT04411459