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Observational Study
. 2020 Oct 1;180(10):1345-1355.
doi: 10.1001/jamainternmed.2020.3539.

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

Giacomo Grasselli  1   2 , Massimiliano Greco  3   4 , Alberto Zanella  1   2 , Giovanni Albano  5 , Massimo Antonelli  6   7 , Giacomo Bellani  8   9 , Ezio Bonanomi  10 , Luca Cabrini  11 , Eleonora Carlesso  2 , Gianpaolo Castelli  12 , Sergio Cattaneo  13 , Danilo Cereda  14 , Sergio Colombo  15 , Antonio Coluccello  16 , Giuseppe Crescini  16 , Andrea Forastieri Molinari  17 , Giuseppe Foti  8   9 , Roberto Fumagalli  8   18 , Giorgio Antonio Iotti  19   20 , Thomas Langer  8   18 , Nicola Latronico  13   21 , Ferdinando Luca Lorini  10 , Francesco Mojoli  19   20 , Giuseppe Natalini  22 , Carla Maria Pessina  23 , Vito Marco Ranieri  24 , Roberto Rech  25 , Luigia Scudeller  26 , Antonio Rosano  22 , Enrico Storti  27 , B Taylor Thompson  28 , Marcello Tirani  14   29 , Pier Giorgio Villani  27 , Antonio Pesenti  1   2 , Maurizio Cecconi  3   4 ; COVID-19 Lombardy ICU Network
Collaborators, Affiliations
Observational Study

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

Giacomo Grasselli et al. JAMA Intern Med. .

Erratum in

  • Addition of Group Members Supplement.
    [No authors listed] [No authors listed] JAMA Intern Med. 2021 Jul 1;181(7):1021. doi: 10.1001/jamainternmed.2021.1229. JAMA Intern Med. 2021. PMID: 33843945 Free PMC article. No abstract available.

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.

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Conflict of interest statement

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.

Figures

Figure.
Figure.. Kaplan-Meier Analysis of Survival of Patients Admitted to the Intensive Care Unit
Survival is reported for the overall group and stratified by median age (<64 or ≥64 years).
See this image and copyright information in PMC

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References

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