PMID- 32667669 OWN - NLM STAT- MEDLINE DCOM- 20201103 LR - 20220103 IS - 2168-6114 (Electronic) IS - 2168-6106 (Print) IS - 2168-6106 (Linking) VI - 180 IP - 10 DP - 2020 Oct 1 TI - Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy. PG - 1345-1355 LID - 10.1001/jamainternmed.2020.3539 [doi] AB - 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. FAU - Grasselli, Giacomo AU - Grasselli G AD - Dipartimento di Anestesia, Rianimazione e Emergenza-Urgenza, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. AD - Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. FAU - Greco, Massimiliano AU - Greco M AD - Department of Anaesthesia and Intensive Care Medicine, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy. AD - Department of Biomedical Sciences, Humanitas University, Milan, Italy. FAU - Zanella, Alberto AU - Zanella A AD - Dipartimento di Anestesia, Rianimazione e Emergenza-Urgenza, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. AD - Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. FAU - Albano, Giovanni AU - Albano G AD - Humanitas Gavazzeni, Bergamo, Italy. FAU - Antonelli, Massimo AU - Antonelli M AD - Department of Anesthesiology, Intensive Care and Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. AD - Dipartimento di Scienze biotecnologiche di base, cliniche intensivologiche e perioperatorie, Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Bellani, Giacomo AU - Bellani G AD - Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. AD - Department of Anesthesia and Intensive Care Medicine, Azienda Socio Sanitaria Territoriale (ASST) Monza-Ospedale San Gerardo, Monza, Italy. FAU - Bonanomi, Ezio AU - Bonanomi E AD - Department of Anaesthesia and Intensive Care, ASST Papa Giovanni XXIII, Bergamo, Italy. FAU - Cabrini, Luca AU - Cabrini L AD - Universita degli Studi dell'Insubria, Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi, Varese, Italy. FAU - Carlesso, Eleonora AU - Carlesso E AD - Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. FAU - Castelli, Gianpaolo AU - Castelli G AD - Department of Anesthesiology and Intensive Care, ASST Mantova-Ospedale Carlo Poma, Mantova, Italy. FAU - Cattaneo, Sergio AU - Cattaneo S AD - Department of Anaesthesiology, Intensive Care and Perioperative Medicine, Spedali Civili University Hospital, Brescia, Italy. FAU - Cereda, Danilo AU - Cereda D AD - Direzione Generale (DG) Welfare, Lombardy Region, Milan, Italy. FAU - Colombo, Sergio AU - Colombo S AD - Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. FAU - Coluccello, Antonio AU - Coluccello A AD - Department of Anesthesiology and Intensive Care, ASST Cremona-Ospedale di Cremona, Cremona, Italy. FAU - Crescini, Giuseppe AU - Crescini G AD - Department of Anesthesiology and Intensive Care, ASST Cremona-Ospedale di Cremona, Cremona, Italy. FAU - Forastieri Molinari, Andrea AU - Forastieri Molinari A AD - Department of Anesthesiology and Intensive Care, ASST Lecco-Ospedale di Lecco, Lecco, Italy. FAU - Foti, Giuseppe AU - Foti G AD - Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. AD - Department of Anesthesia and Intensive Care Medicine, Azienda Socio Sanitaria Territoriale (ASST) Monza-Ospedale San Gerardo, Monza, Italy. FAU - Fumagalli, Roberto AU - Fumagalli R AD - Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. AD - Dipartimento di Anestesia e Rianimazione, Grande Ospedale Metropolitano Niguarda, Milan, Italy. FAU - Iotti, Giorgio Antonio AU - Iotti GA AD - Department of Intensive Medicine, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. AD - Department of Clinical-Diagnostic, Surgical and Pediatric Sciences, University of Pavia, Pavia, Italy. FAU - Langer, Thomas AU - Langer T AD - Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. AD - Dipartimento di Anestesia e Rianimazione, Grande Ospedale Metropolitano Niguarda, Milan, Italy. FAU - Latronico, Nicola AU - Latronico N AD - Department of Anaesthesiology, Intensive Care and Perioperative Medicine, Spedali Civili University Hospital, Brescia, Italy. AD - Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy. FAU - Lorini, Ferdinando Luca AU - Lorini FL AD - Department of Anaesthesia and Intensive Care, ASST Papa Giovanni XXIII, Bergamo, Italy. FAU - Mojoli, Francesco AU - Mojoli F AD - Department of Intensive Medicine, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. AD - Department of Clinical-Diagnostic, Surgical and Pediatric Sciences, University of Pavia, Pavia, Italy. FAU - Natalini, Giuseppe AU - Natalini G AD - Department of Anesthesia and Intensive Care, Fondazione Poliambulanza Hospital, Brescia, Italy. FAU - Pessina, Carla Maria AU - Pessina CM AD - Department of Anesthesia and Intensive Care, ASST Rhodense-Presidio di Rho, Milano, Italy. FAU - Ranieri, Vito Marco AU - Ranieri VM AD - Anesthesia and Intensive Care Medicine, Policlinico di Sant'Orsola, Alma Mater Studiorum University of Bologna, Bologna, Italy. FAU - Rech, Roberto AU - Rech R AD - Department of Anesthesiology and Intensive Care, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Polo Universitario, University of Milan, Milan, Italy. FAU - Scudeller, Luigia AU - Scudeller L AD - Direzione Scientifica, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Rosano, Antonio AU - Rosano A AD - Department of Anesthesia and Intensive Care, Fondazione Poliambulanza Hospital, Brescia, Italy. FAU - Storti, Enrico AU - Storti E AD - Dipartimento Emergenza Urgenza, Unita Operativa Complessa (UOC) Anestesia e Rianimazione, ASST, Lodi, Italy. FAU - Thompson, B Taylor AU - Thompson BT AD - Division of Pulmonary and Critical Medicine, Massachusetts General Hospital, Boston. FAU - Tirani, Marcello AU - Tirani M AD - Direzione Generale (DG) Welfare, Lombardy Region, Milan, Italy. AD - Health Protection Agency of Pavia, Pavia, Italy. FAU - Villani, Pier Giorgio AU - Villani PG AD - Dipartimento Emergenza Urgenza, Unita Operativa Complessa (UOC) Anestesia e Rianimazione, ASST, Lodi, Italy. FAU - Pesenti, Antonio AU - Pesenti A AD - Dipartimento di Anestesia, Rianimazione e Emergenza-Urgenza, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. AD - Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. FAU - Cecconi, Maurizio AU - Cecconi M AD - Department of Anaesthesia and Intensive Care Medicine, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy. AD - Department of Biomedical Sciences, Humanitas University, Milan, Italy. CN - COVID-19 Lombardy ICU Network LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Intern Med JT - JAMA internal medicine JID - 101589534 SB - IM EIN - JAMA Intern Med. 2021 Jul 1;181(7):1021. PMID: 33843945 MH - Betacoronavirus/isolation & purification MH - COVID-19 MH - COVID-19 Testing MH - COVID-19 Vaccines MH - Clinical Laboratory Techniques/methods/statistics & numerical data MH - *Coronavirus Infections/diagnosis/mortality/therapy MH - *Critical Illness/mortality/therapy MH - Female MH - Hospital Mortality MH - Hospitalization/*statistics & numerical data MH - Humans MH - Intensive Care Units/*statistics & numerical data MH - Italy/epidemiology MH - Male MH - Middle Aged MH - Mortality MH - *Pandemics MH - *Pneumonia, Viral/mortality/therapy MH - Respiration, Artificial/*statistics & numerical data MH - Retrospective Studies MH - Risk Factors MH - SARS-CoV-2 PMC - PMC7364371 COIS- Conflict of Interest Disclosures: Dr Grasselli reported receiving personal fees from Getinge Group, Biotest, Draeger Medical Systems, Inc, Thermo Fisher Scientific, and Fisher & Paykel outside the submitted work. Dr Zanella reported holding patents to WO2016189427 and WO2015IB55837 (licensed). Dr Bellani reported receiving grants and personal fees from Draeger Medical Systems, Inc, and Dimar SRL and personal fees from Hamilton Medical Products, Inc, Getinge Group, GE Healthcare, and Intersurgical outside the submitted work. Dr Iotti reported receiving personal fees from Hamilton Medical Products, Inc, Intersurgical, Maquet Italia, Cinisello Balsamo Eurosets, and Burke & Burke outside the submitted work. Dr Mojoli reported receiving fees for lectures from Hamilton Medical Products, Inc, GE Healthcare, and Seda SpA and a consultancy agreement between University of Pavia and Hamilton Medical Products, Inc. Dr Thompson reported receiving personal fees from Bayer AG outside the submitted work. Dr Pesenti reported receiving personal fees from Maquet Italia, Novalung/Xenios AG, Baxter International, Inc, and Boehringer Ingelheim outside the submitted work. Dr Cecconi reported receiving personal fees from Edwards Lifesciences, Directed Systems, and Cheetah Medical, Inc, outside the submitted work. No other disclosures were reported. 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