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Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy.
JAMA Intern Med. 2020 10 01; 180(10):1345-1355.JIM

Abstract

Importance

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

Objective

To evaluate the independent risk factors associated with mortality of patients with COVID-19 requiring treatment in ICUs in the Lombardy region of Italy.

Design, Setting, and Participants

This retrospective, observational cohort study included 3988 consecutive critically ill patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinating center (Fondazione IRCCS [Istituto di Ricovero e Cura a Carattere Scientifico] Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network from February 20 to April 22, 2020. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by real-time reverse transcriptase-polymerase chain reaction assay of nasopharyngeal swabs. Follow-up was completed on May 30, 2020.

Exposures

Baseline characteristics, comorbidities, long-term medications, and ventilatory support at ICU admission.

Main Outcomes and Measures

Time to death in days from ICU admission to hospital discharge. The independent risk factors associated with mortality were evaluated with a multivariable Cox proportional hazards regression.

Results

Of the 3988 patients included in this cohort study, the median age was 63 (interquartile range [IQR] 56-69) years; 3188 (79.9%; 95% CI, 78.7%-81.1%) were men, and 1998 of 3300 (60.5%; 95% CI, 58.9%-62.2%) had at least 1 comorbidity. At ICU admission, 2929 patients (87.3%; 95% CI, 86.1%-88.4%) required invasive mechanical ventilation (IMV). The median follow-up was 44 (95% CI, 40-47; IQR, 11-69; range, 0-100) days; median time from symptoms onset to ICU admission was 10 (95% CI, 9-10; IQR, 6-14) days; median length of ICU stay was 12 (95% CI, 12-13; IQR, 6-21) days; and median length of IMV was 10 (95% CI, 10-11; IQR, 6-17) days. Cumulative observation time was 164 305 patient-days. Hospital and ICU mortality rates were 12 (95% CI, 11-12) and 27 (95% CI, 26-29) per 1000 patients-days, respectively. In the subgroup of the first 1715 patients, as of May 30, 2020, 865 (50.4%) had been discharged from the ICU, 836 (48.7%) had died in the ICU, and 14 (0.8%) were still in the ICU; overall, 915 patients (53.4%) died in the hospital. Independent risk factors associated with mortality included older age (hazard ratio [HR], 1.75; 95% CI, 1.60-1.92), male sex (HR, 1.57; 95% CI, 1.31-1.88), high fraction of inspired oxygen (Fio2) (HR, 1.14; 95% CI, 1.10-1.19), high positive end-expiratory pressure (HR, 1.04; 95% CI, 1.01-1.06) or low Pao2:Fio2 ratio (HR, 0.80; 95% CI, 0.74-0.87) on ICU admission, and history of chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.28-2.19), hypercholesterolemia (HR, 1.25; 95% CI, 1.02-1.52), and type 2 diabetes (HR, 1.18; 95% CI, 1.01-1.39). No medication was independently associated with mortality (angiotensin-converting enzyme inhibitors HR, 1.17; 95% CI, 0.97-1.42; angiotensin receptor blockers HR, 1.05; 95% CI, 0.85-1.29).

Conclusions and Relevance

In this retrospective cohort study of critically ill patients admitted to ICUs in Lombardy, Italy, with laboratory-confirmed COVID-19, most patients required IMV. The mortality rate and absolute mortality were high.

Authors+Show Affiliations

Dipartimento di Anestesia, Rianimazione e Emergenza-Urgenza, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.Department of Anaesthesia and Intensive Care Medicine, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy. Department of Biomedical Sciences, Humanitas University, Milan, Italy.Dipartimento di Anestesia, Rianimazione e Emergenza-Urgenza, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.Humanitas Gavazzeni, Bergamo, Italy.Department of Anesthesiology, Intensive Care and Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Dipartimento di Scienze biotecnologiche di base, cliniche intensivologiche e perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy.Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. Department of Anesthesia and Intensive Care Medicine, Azienda Socio Sanitaria Territoriale (ASST) Monza-Ospedale San Gerardo, Monza, Italy.Department of Anaesthesia and Intensive Care, ASST Papa Giovanni XXIII, Bergamo, Italy.Università degli Studi dell'Insubria, Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi, Varese, Italy.Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.Department of Anesthesiology and Intensive Care, ASST Mantova-Ospedale Carlo Poma, Mantova, Italy.Department of Anaesthesiology, Intensive Care and Perioperative Medicine, Spedali Civili University Hospital, Brescia, Italy.Direzione Generale (DG) Welfare, Lombardy Region, Milan, Italy.Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.Department of Anesthesiology and Intensive Care, ASST Cremona-Ospedale di Cremona, Cremona, Italy.Department of Anesthesiology and Intensive Care, ASST Cremona-Ospedale di Cremona, Cremona, Italy.Department of Anesthesiology and Intensive Care, ASST Lecco-Ospedale di Lecco, Lecco, Italy.Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. Department of Anesthesia and Intensive Care Medicine, Azienda Socio Sanitaria Territoriale (ASST) Monza-Ospedale San Gerardo, Monza, Italy.Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. Dipartimento di Anestesia e Rianimazione, Grande Ospedale Metropolitano Niguarda, Milan, Italy.Department of Intensive Medicine, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Department of Clinical-Diagnostic, Surgical and Pediatric Sciences, University of Pavia, Pavia, Italy.Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. Dipartimento di Anestesia e Rianimazione, Grande Ospedale Metropolitano Niguarda, Milan, Italy.Department of Anaesthesiology, Intensive Care and Perioperative Medicine, Spedali Civili University Hospital, Brescia, Italy. Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.Department of Anaesthesia and Intensive Care, ASST Papa Giovanni XXIII, Bergamo, Italy.Department of Intensive Medicine, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Department of Clinical-Diagnostic, Surgical and Pediatric Sciences, University of Pavia, Pavia, Italy.Department of Anesthesia and Intensive Care, Fondazione Poliambulanza Hospital, Brescia, Italy.Department of Anesthesia and Intensive Care, ASST Rhodense-Presidio di Rho, Milano, Italy.Anesthesia and Intensive Care Medicine, Policlinico di Sant'Orsola, Alma Mater Studiorum University of Bologna, Bologna, Italy.Department of Anesthesiology and Intensive Care, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Polo Universitario, University of Milan, Milan, Italy.Direzione Scientifica, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.Department of Anesthesia and Intensive Care, Fondazione Poliambulanza Hospital, Brescia, Italy.Dipartimento Emergenza Urgenza, Unità Operativa Complessa (UOC) Anestesia e Rianimazione, ASST, Lodi, Italy.Division of Pulmonary and Critical Medicine, Massachusetts General Hospital, Boston.Direzione Generale (DG) Welfare, Lombardy Region, Milan, Italy. Health Protection Agency of Pavia, Pavia, Italy.Dipartimento Emergenza Urgenza, Unità Operativa Complessa (UOC) Anestesia e Rianimazione, ASST, Lodi, Italy.Dipartimento di Anestesia, Rianimazione e Emergenza-Urgenza, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.Department of Anaesthesia and Intensive Care Medicine, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy. Department of Biomedical Sciences, Humanitas University, Milan, Italy.No affiliation info available

Pub Type(s)

Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32667669

Citation

Grasselli, Giacomo, et al. "Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy." JAMA Internal Medicine, vol. 180, no. 10, 2020, pp. 1345-1355.
Grasselli G, Greco M, Zanella A, et al. Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy. JAMA Intern Med. 2020;180(10):1345-1355.
Grasselli, G., Greco, M., Zanella, A., Albano, G., Antonelli, M., Bellani, G., Bonanomi, E., Cabrini, L., Carlesso, E., Castelli, G., Cattaneo, S., Cereda, D., Colombo, S., Coluccello, A., Crescini, G., Forastieri Molinari, A., Foti, G., Fumagalli, R., Iotti, G. A., ... Cecconi, M. (2020). Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy. JAMA Internal Medicine, 180(10), 1345-1355. https://doi.org/10.1001/jamainternmed.2020.3539
Grasselli G, et al. Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy. JAMA Intern Med. 2020 10 1;180(10):1345-1355. PubMed PMID: 32667669.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy. AU - Grasselli,Giacomo, AU - Greco,Massimiliano, AU - Zanella,Alberto, AU - Albano,Giovanni, AU - Antonelli,Massimo, AU - Bellani,Giacomo, AU - Bonanomi,Ezio, AU - Cabrini,Luca, AU - Carlesso,Eleonora, AU - Castelli,Gianpaolo, AU - Cattaneo,Sergio, AU - Cereda,Danilo, AU - Colombo,Sergio, AU - Coluccello,Antonio, AU - Crescini,Giuseppe, AU - Forastieri Molinari,Andrea, AU - Foti,Giuseppe, AU - Fumagalli,Roberto, AU - Iotti,Giorgio Antonio, AU - Langer,Thomas, AU - Latronico,Nicola, AU - Lorini,Ferdinando Luca, AU - Mojoli,Francesco, AU - Natalini,Giuseppe, AU - Pessina,Carla Maria, AU - Ranieri,Vito Marco, AU - Rech,Roberto, AU - Scudeller,Luigia, AU - Rosano,Antonio, AU - Storti,Enrico, AU - Thompson,B Taylor, AU - Tirani,Marcello, AU - Villani,Pier Giorgio, AU - Pesenti,Antonio, AU - Cecconi,Maurizio, AU - ,, PY - 2021/07/15/pmc-release PY - 2020/7/16/pubmed PY - 2020/11/4/medline PY - 2020/7/16/entrez SP - 1345 EP - 1355 JF - JAMA internal medicine JO - JAMA Intern Med VL - 180 IS - 10 N2 - Importance: Many patients with coronavirus disease 2019 (COVID-19) are critically ill and require care in the intensive care unit (ICU). Objective: To evaluate the independent risk factors associated with mortality of patients with COVID-19 requiring treatment in ICUs in the Lombardy region of Italy. Design, Setting, and Participants: This retrospective, observational cohort study included 3988 consecutive critically ill patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinating center (Fondazione IRCCS [Istituto di Ricovero e Cura a Carattere Scientifico] Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network from February 20 to April 22, 2020. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by real-time reverse transcriptase-polymerase chain reaction assay of nasopharyngeal swabs. Follow-up was completed on May 30, 2020. Exposures: Baseline characteristics, comorbidities, long-term medications, and ventilatory support at ICU admission. Main Outcomes and Measures: Time to death in days from ICU admission to hospital discharge. The independent risk factors associated with mortality were evaluated with a multivariable Cox proportional hazards regression. Results: Of the 3988 patients included in this cohort study, the median age was 63 (interquartile range [IQR] 56-69) years; 3188 (79.9%; 95% CI, 78.7%-81.1%) were men, and 1998 of 3300 (60.5%; 95% CI, 58.9%-62.2%) had at least 1 comorbidity. At ICU admission, 2929 patients (87.3%; 95% CI, 86.1%-88.4%) required invasive mechanical ventilation (IMV). The median follow-up was 44 (95% CI, 40-47; IQR, 11-69; range, 0-100) days; median time from symptoms onset to ICU admission was 10 (95% CI, 9-10; IQR, 6-14) days; median length of ICU stay was 12 (95% CI, 12-13; IQR, 6-21) days; and median length of IMV was 10 (95% CI, 10-11; IQR, 6-17) days. Cumulative observation time was 164 305 patient-days. Hospital and ICU mortality rates were 12 (95% CI, 11-12) and 27 (95% CI, 26-29) per 1000 patients-days, respectively. In the subgroup of the first 1715 patients, as of May 30, 2020, 865 (50.4%) had been discharged from the ICU, 836 (48.7%) had died in the ICU, and 14 (0.8%) were still in the ICU; overall, 915 patients (53.4%) died in the hospital. Independent risk factors associated with mortality included older age (hazard ratio [HR], 1.75; 95% CI, 1.60-1.92), male sex (HR, 1.57; 95% CI, 1.31-1.88), high fraction of inspired oxygen (Fio2) (HR, 1.14; 95% CI, 1.10-1.19), high positive end-expiratory pressure (HR, 1.04; 95% CI, 1.01-1.06) or low Pao2:Fio2 ratio (HR, 0.80; 95% CI, 0.74-0.87) on ICU admission, and history of chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.28-2.19), hypercholesterolemia (HR, 1.25; 95% CI, 1.02-1.52), and type 2 diabetes (HR, 1.18; 95% CI, 1.01-1.39). No medication was independently associated with mortality (angiotensin-converting enzyme inhibitors HR, 1.17; 95% CI, 0.97-1.42; angiotensin receptor blockers HR, 1.05; 95% CI, 0.85-1.29). Conclusions and Relevance: In this retrospective cohort study of critically ill patients admitted to ICUs in Lombardy, Italy, with laboratory-confirmed COVID-19, most patients required IMV. The mortality rate and absolute mortality were high. SN - 2168-6114 UR - https://www.unboundmedicine.com/medline/citation/32667669/Risk_Factors_Associated_With_Mortality_Among_Patients_With_COVID_19_in_Intensive_Care_Units_in_Lombardy_Italy_ L2 - https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2020.3539 DB - PRIME DP - Unbound Medicine ER -