• Gianmaria Cammarota, Teresa Esposito, Danila Azzolina, Roberto Cosentini, Francesco Menzella, Stefano Aliberti, Andrea Coppadoro, Giacomo Bellani, Giuseppe Foti, Giacomo Grasselli, Maurizio Cecconi, Antonio Pesenti, Michele Vitacca, Tom Lawton, V Marco Ranieri, Sandro Luigi Di Domenico, Onofrio Resta, Antonio Gidaro, Antonella Potalivo, Giuseppe Nardi, Claudia Brusasco, Simonetta Tesoro, Paolo Navalesi, Rosanna Vaschetto, and Edoardo De Robertis.
• Department of Medicine and Surgery, University of Perugia, Piazza Università 1, 06123, Perugia, Italy. gmcamma@gmail.com.
• Crit Care. 2021 Jul 30; 25 (1): 268268.

BackgroundNoninvasive respiratory support (NIRS) has been diffusely employed outside the intensive care unit (ICU) to face the high request of ventilatory support due to the massive influx of patients with acute respiratory failure (ARF) caused by coronavirus-19 disease (COVID-19). We sought to summarize the evidence on clinically relevant outcomes in COVID-19 patients supported by NIV outside the ICU.MethodsWe searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials register, along with medRxiv and bioRxiv repositories for pre-prints, for observational studies and randomized controlled trials, from inception to the end of February 2021. Two authors independently selected the investigations according to the following criteria: (1) observational study or randomized clinical trials enrolling ≥ 50 hospitalized patients undergoing NIRS outside the ICU, (2) laboratory-confirmed COVID-19, and (3) at least the intra-hospital mortality reported. Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed. Data extraction was independently performed by two authors to assess: investigation features, demographics and clinical characteristics, treatments employed, NIRS regulations, and clinical outcomes. Methodological index for nonrandomized studies tool was applied to determine the quality of the enrolled studies. The primary outcome was to assess the overall intra-hospital mortality of patients under NIRS outside the ICU. The secondary outcomes included the proportions intra-hospital mortalities of patients who underwent invasive mechanical ventilation following NIRS failure and of those with 'do-not-intubate' (DNI) orders.ResultsSeventeen investigations (14 peer-reviewed and 3 pre-prints) were included with a low risk of bias and a high heterogeneity, for a total of 3377 patients. The overall intra-hospital mortality of patients receiving NIRS outside the ICU was 36% [30-41%]. 26% [21-30%] of the patients failed NIRS and required intubation, with an intra-hospital mortality rising to 45% [36-54%]. 23% [15-32%] of the patients received DNI orders with an intra-hospital mortality of 72% [65-78%]. Oxygenation on admission was the main source of between-study heterogeneity.ConclusionsDuring COVID-19 outbreak, delivering NIRS outside the ICU revealed as a feasible strategy to cope with the massive demand of ventilatory assistance.RegistrationPROSPERO, https://www.crd.york.ac.uk/prospero/ , CRD42020224788, December 11, 2020.© 2021. The Author(s).

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