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      Effect of timing of intubation on clinical outcomes of critically ill patients with COVID-19: a systematic review and meta-analysis of non-randomized cohort studies

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          Abstract

          Background

          Although several international guidelines recommend early over late intubation of patients with severe coronavirus disease 2019 (COVID-19), this issue is still controversial. We aimed to investigate the effect (if any) of timing of intubation on clinical outcomes of critically ill patients with COVID-19 by carrying out a systematic review and meta-analysis.

          Methods

          PubMed and Scopus were systematically searched, while references and preprint servers were explored, for relevant articles up to December 26, 2020, to identify studies which reported on mortality and/or morbidity of patients with COVID-19 undergoing early versus late intubation. “Early” was defined as intubation within 24 h from intensive care unit (ICU) admission, while “late” as intubation at any time after 24 h of ICU admission. All-cause mortality and duration of mechanical ventilation (MV) were the primary outcomes of the meta-analysis. Pooled risk ratio (RR), pooled mean difference (MD) and 95% confidence intervals (CI) were calculated using a random effects model. The meta-analysis was registered with PROSPERO (CRD42020222147).

          Results

          A total of 12 studies, involving 8944 critically ill patients with COVID-19, were included. There was no statistically detectable difference on all-cause mortality between patients undergoing early versus late intubation (3981 deaths; 45.4% versus 39.1%; RR 1.07, 95% CI 0.99–1.15, p = 0.08). This was also the case for duration of MV (1892 patients; MD − 0.58 days, 95% CI − 3.06 to 1.89 days, p = 0.65). In a sensitivity analysis using an alternate definition of early/late intubation, intubation without versus with a prior trial of high-flow nasal cannula or noninvasive mechanical ventilation was still not associated with a statistically detectable difference on all-cause mortality (1128 deaths; 48.9% versus 42.5%; RR 1.11, 95% CI 0.99–1.25, p = 0.08).

          Conclusions

          The synthesized evidence suggests that timing of intubation may have no effect on mortality and morbidity of critically ill patients with COVID-19. These results might justify a wait-and-see approach, which may lead to fewer intubations. Relevant guidelines may therefore need to be updated.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13054-021-03540-6.

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          Most cited references26

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          Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy

          Many patients with coronavirus disease 2019 (COVID-19) are critically ill and require care in the intensive care unit (ICU).
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            Management of COVID-19 Respiratory Distress

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              Case characteristics, resource use, and outcomes of 10 021 patients with COVID-19 admitted to 920 German hospitals: an observational study

              Summary Background Nationwide, unbiased, and unselected data of hospitalised patients with COVID-19 are scarce. Our aim was to provide a detailed account of case characteristics, resource use, and outcomes of hospitalised patients with COVID-19 in Germany, where the health-care system has not been overwhelmed by the pandemic. Methods In this observational study, adult patients with a confirmed COVID-19 diagnosis, who were admitted to hospital in Germany between Feb 26 and April 19, 2020, and for whom a complete hospital course was available (ie, the patient was discharged or died in hospital) were included in the study cohort. Claims data from the German Local Health Care Funds were analysed. The data set included detailed information on patient characteristics, duration of hospital stay, type and duration of ventilation, and survival status. Patients with adjacent completed hospital stays were grouped into one case. Patients were grouped according to whether or not they had received any form of mechanical ventilation. To account for comorbidities, we used the Charlson comorbidity index. Findings Of 10 021 hospitalised patients being treated in 920 different hospitals, 1727 (17%) received mechanical ventilation (of whom 422 [24%] were aged 18–59 years, 382 [22%] were aged 60–69 years, 535 [31%] were aged 70–79 years, and 388 [23%] were aged ≥80 years). The median age was 72 years (IQR 57–82). Men and women were equally represented in the non-ventilated group, whereas twice as many men than women were in the ventilated group. The likelihood of being ventilated was 12% for women (580 of 4822) and 22% for men (1147 of 5199). The most common comorbidities were hypertension (5575 [56%] of 10 021), diabetes (2791 [28%]), cardiac arrhythmia (2699 [27%]), renal failure (2287 [23%]), heart failure (1963 [20%]), and chronic pulmonary disease (1358 [14%]). Dialysis was required in 599 (6%) of all patients and in 469 (27%) of 1727 ventilated patients. The Charlson comorbidity index was 0 for 3237 (39%) of 8294 patients without ventilation, but only 374 (22%) of 1727 ventilated patients. The mean duration of ventilation was 13·5 days (SD 12·1). In-hospital mortality was 22% overall (2229 of 10 021), with wide variation between patients without ventilation (1323 [16%] of 8294) and with ventilation (906 [53%] of 1727; 65 [45%] of 145 for non-invasive ventilation only, 70 [50%] of 141 for non-invasive ventilation failure, and 696 [53%] of 1318 for invasive mechanical ventilation). In-hospital mortality in ventilated patients requiring dialysis was 73% (342 of 469). In-hospital mortality for patients with ventilation by age ranged from 28% (117 of 422) in patients aged 18–59 years to 72% (280 of 388) in patients aged 80 years or older. Interpretation In the German health-care system, in which hospital capacities have not been overwhelmed by the COVID-19 pandemic, mortality has been high for patients receiving mechanical ventilation, particularly for patients aged 80 years or older and those requiring dialysis, and has been considerably lower for patients younger than 60 years. Funding None.
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                Author and article information

                Contributors
                isiempos@yahoo.com
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                25 March 2021
                25 March 2021
                2021
                : 25
                : 121
                Affiliations
                [1 ]GRID grid.5216.0, ISNI 0000 0001 2155 0800, First Department of Critical Care Medicine and Pulmonary Services, Evangelismos Hospital, , National and Kapodistrian University of Athens Medical School, ; 45-47 Ipsilantou Street, 10676 Athens, Greece
                [2 ]GRID grid.413734.6, ISNI 0000 0000 8499 1112, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medicine, , New York-Presbyterian Hospital-Weill Cornell Medical Center, ; New York, NY USA
                Author information
                http://orcid.org/0000-0003-0036-3322
                Article
                3540
                10.1186/s13054-021-03540-6
                7993905
                33766109
                ef15612e-a0da-4698-bcda-7756348fac27
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 6 January 2021
                : 8 March 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100013209, Hellenic Foundation for Research and Innovation;
                Award ID: 80-1/15.10.2020
                Award Recipient :
                Funded by: Hellenic Thoracic Society (GR)
                Award ID: 2019
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2021

                Emergency medicine & Trauma
                coronavirus,delayed,pneumonia,intensive care unit,acute respiratory failure,acute respiratory distress syndrome

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