[Source: JAMA Internal Medicine, full page: (LINK). Abstract, edited.]
Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy
Giacomo Grasselli, MD1,2; Massimiliano Greco, MD3,4; Alberto Zanella, MD1,2; Giovanni Albano, MD5; Massimo Antonelli, MD6,7; Giacomo Bellani, MD, PhD8,9; Ezio Bonanomi, MD10; Luca Cabrini, MD11; Eleonora Carlesso, MS2; Gianpaolo Castelli, MD12; Sergio Cattaneo, MD13; Danilo Cereda, MD14; Sergio Colombo, MD15; Antonio Coluccello, MD16; Giuseppe Crescini, MD16; Andrea Forastieri Molinari, MD17; Giuseppe Foti, MD8,9; Roberto Fumagalli, MD8,18; Giorgio Antonio Iotti, MD19,20; Thomas Langer, MD8,18; Nicola Latronico, MD13,21; Ferdinando Luca Lorini, MD10; Francesco Mojoli, MD19,20; Giuseppe Natalini, MD22; Carla Maria Pessina, MD23; Vito Marco Ranieri, MD24; Roberto Rech, MD25; Luigia Scudeller, MD26; Antonio Rosano, MD22; Enrico Storti, MD27; B. Taylor Thompson, MD28; Marcello Tirani, MD14,29; Pier Giorgio Villani, MD27; Antonio Pesenti, MD1,2; Maurizio Cecconi, MD3,4; for the COVID-19 Lombardy ICU Network
Author Affiliations: 1 Dipartimento di Anestesia, Rianimazione e Emergenza-Urgenza, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 2 Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; 3 Department of Anaesthesia and Intensive Care Medicine, Humanitas Clinical and Research Center–IRCCS, Rozzano, Italy; 4 Department of Biomedical Sciences, Humanitas University, Milan, Italy; 5 Humanitas Gavazzeni, Bergamo, Italy; 6 Department of Anesthesiology, Intensive Care and Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; 7 Dipartimento di Scienze biotecnologiche di base, cliniche intensivologiche e perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy; 8 Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; 9 Department of Anesthesia and Intensive Care Medicine, Azienda Socio Sanitaria Territoriale (ASST) Monza–Ospedale San Gerardo, Monza, Italy; 10 Department of Anaesthesia and Intensive Care, ASST Papa Giovanni XXIII, Bergamo, Italy; 11 Università degli Studi dell’Insubria, Azienda Ospedaliera Ospedale di Circolo e Fondazione Macchi, Varese, Italy; 12 Department of Anesthesiology and Intensive Care, ASST Mantova–Ospedale Carlo Poma, Mantova, Italy; 13 Department of Anaesthesiology, Intensive Care and Perioperative Medicine, Spedali Civili University Hospital, Brescia, Italy; 14 Direzione Generale (DG) Welfare, Lombardy Region, Milan, Italy; 15 Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; 16 Department of Anesthesiology and Intensive Care, ASST Cremona–Ospedale di Cremona, Cremona, Italy; 17 Department of Anesthesiology and Intensive Care, ASST Lecco–Ospedale di Lecco, Lecco, Italy; 18 Dipartimento di Anestesia e Rianimazione, Grande Ospedale Metropolitano Niguarda, Milan, Italy; 19 Department of Intensive Medicine, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 20 Department of Clinical-Diagnostic, Surgical and Pediatric Sciences, University of Pavia, Pavia, Italy; 21 Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy; 22 Department of Anesthesia and Intensive Care, Fondazione Poliambulanza Hospital, Brescia, Italy; 23 Department of Anesthesia and Intensive Care, ASST Rhodense–Presidio di Rho, Milano, Italy; 24 Anesthesia and Intensive Care Medicine, Policlinico di Sant’Orsola, Alma Mater Studiorum University of Bologna, Bologna, Italy; 25 Department of Anesthesiology and Intensive Care, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Polo Universitario, University of Milan, Milan, Italy; 26 Direzione Scientifica, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 27 Dipartimento Emergenza Urgenza, Unità Operativa Complessa (UOC) Anestesia e Rianimazione, ASST, Lodi, Italy; 28 Division of Pulmonary and Critical Medicine, Massachusetts General Hospital, Boston; 29 Health Protection Agency of Pavia, Pavia, Italy
JAMA Intern Med. Published online July 15, 2020. doi:10.1001/jamainternmed.2020.3539
- Question – What are the risk factors associated with mortality among critically ill patients with laboratory-confirmed coronavirus disease 2019 admitted to intensive care units in Lombardy, Italy?
- Findings – In this cohort study that involved 3988 critically ill patients admitted from February 20 to April 22, 2020, the hospital mortality rate as of May 30 was 12 per 1000 patient-days after a median observation time of 70 days. In the subgroup of the first 1715 patients, 865 (50.4%) had been discharged from the intensive care unit, 836 (48.7%) had died in the intensive care unit, and 14 (0.8%) were still in the intensive care unit; 915 patients died in the hospital for overall hospital mortality of (53.4%).
- Meaning – This study found that most critically ill patients with coronavirus disease 2019 in the intensive care unit required invasive mechanical ventilation, and mortality rate and absolute mortality rate were high.
Many patients with coronavirus disease 2019 (COVID-19) are critically ill and require care in the intensive care unit (ICU).
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.
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.
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.
Keywords: SARS-CoV-2; COVID-19; Intensive Care; Italy.