Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study.


Journal

The Lancet. Respiratory medicine
ISSN: 2213-2619
Titre abrégé: Lancet Respir Med
Pays: England
ID NLM: 101605555

Informations de publication

Date de publication:
03 2021
Historique:
received: 01 10 2020
revised: 14 11 2020
accepted: 17 11 2020
pubmed: 12 1 2021
medline: 20 3 2021
entrez: 11 1 2021
Statut: ppublish

Résumé

To date, 750 000 patients with COVID-19 worldwide have required mechanical ventilation and thus are at high risk of acute brain dysfunction (coma and delirium). We aimed to investigate the prevalence of delirium and coma, and risk factors for delirium in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirium and associated sequelae. This multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries. We included all patients (aged ≥18 years) admitted to participating ICUs with severe acute respiratory syndrome coronavirus 2 infection before April 28, 2020. Patients who were moribund or had life-support measures withdrawn within 24 h of ICU admission, prisoners, patients with pre-existing mental illness, neurodegenerative disorders, congenital or acquired brain damage, hepatic coma, drug overdose, suicide attempt, or those who were blind or deaf were excluded. We collected de-identified data from electronic health records on patient demographics, delirium and coma assessments, and management strategies for a 21-day period. Additional data on ventilator support, ICU length of stay, and vital status was collected for a 28-day period. The primary outcome was to determine the prevalence of delirium and coma and to investigate any associated risk factors associated with development of delirium the next day. We also investigated predictors of number of days alive without delirium or coma. These outcomes were investigated using multivariable regression. Between Jan 20 and April 28, 2020, 4530 patients with COVID-19 were admitted to 69 ICUs, of whom 2088 patients were included in the study cohort. The median age of patients was 64 years (IQR 54 to 71) with a median Simplified Acute Physiology Score (SAPS) II of 40·0 (30·0 to 53·0). 1397 (66·9%) of 2088 patients were invasively mechanically ventilated on the day of ICU admission and 1827 (87·5%) were invasively mechanical ventilated at some point during hospitalisation. Infusion with sedatives while on mechanical ventilation was common: 1337 (64·0%) of 2088 patients were given benzodiazepines for a median of 7·0 days (4·0 to 12·0) and 1481 (70·9%) were given propofol for a median of 7·0 days (4·0 to 11·0). Median Richmond Agitation-Sedation Scale score while on invasive mechanical ventilation was -4 (-5 to -3). 1704 (81·6%) of 2088 patients were comatose for a median of 10·0 days (6·0 to 15·0) and 1147 (54·9%) were delirious for a median of 3·0 days (2·0 to 6·0). Mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day (all p≤0·04), whereas family visitation (in person or virtual) was associated with a lower risk of delirium (p<0·0001). During the 21-day study period, patients were alive without delirium or coma for a median of 5·0 days (0·0 to 14·0). At baseline, older age, higher SAPS II scores, male sex, smoking or alcohol abuse, use of vasopressors on day 1, and invasive mechanical ventilation on day 1 were independently associated with fewer days alive and free of delirium and coma (all p<0·01). 601 (28·8%) of 2088 patients died within 28 days of admission, with most of those deaths occurring in the ICU. Acute brain dysfunction was highly prevalent and prolonged in critically ill patients with COVID-19. Benzodiazepine use and lack of family visitation were identified as modifiable risk factors for delirium, and thus these data present an opportunity to reduce acute brain dysfunction in patients with COVID-19. None. For the French and Spanish translations of the abstract see Supplementary Materials section.

Sections du résumé

BACKGROUND
To date, 750 000 patients with COVID-19 worldwide have required mechanical ventilation and thus are at high risk of acute brain dysfunction (coma and delirium). We aimed to investigate the prevalence of delirium and coma, and risk factors for delirium in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirium and associated sequelae.
METHODS
This multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries. We included all patients (aged ≥18 years) admitted to participating ICUs with severe acute respiratory syndrome coronavirus 2 infection before April 28, 2020. Patients who were moribund or had life-support measures withdrawn within 24 h of ICU admission, prisoners, patients with pre-existing mental illness, neurodegenerative disorders, congenital or acquired brain damage, hepatic coma, drug overdose, suicide attempt, or those who were blind or deaf were excluded. We collected de-identified data from electronic health records on patient demographics, delirium and coma assessments, and management strategies for a 21-day period. Additional data on ventilator support, ICU length of stay, and vital status was collected for a 28-day period. The primary outcome was to determine the prevalence of delirium and coma and to investigate any associated risk factors associated with development of delirium the next day. We also investigated predictors of number of days alive without delirium or coma. These outcomes were investigated using multivariable regression.
FINDINGS
Between Jan 20 and April 28, 2020, 4530 patients with COVID-19 were admitted to 69 ICUs, of whom 2088 patients were included in the study cohort. The median age of patients was 64 years (IQR 54 to 71) with a median Simplified Acute Physiology Score (SAPS) II of 40·0 (30·0 to 53·0). 1397 (66·9%) of 2088 patients were invasively mechanically ventilated on the day of ICU admission and 1827 (87·5%) were invasively mechanical ventilated at some point during hospitalisation. Infusion with sedatives while on mechanical ventilation was common: 1337 (64·0%) of 2088 patients were given benzodiazepines for a median of 7·0 days (4·0 to 12·0) and 1481 (70·9%) were given propofol for a median of 7·0 days (4·0 to 11·0). Median Richmond Agitation-Sedation Scale score while on invasive mechanical ventilation was -4 (-5 to -3). 1704 (81·6%) of 2088 patients were comatose for a median of 10·0 days (6·0 to 15·0) and 1147 (54·9%) were delirious for a median of 3·0 days (2·0 to 6·0). Mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day (all p≤0·04), whereas family visitation (in person or virtual) was associated with a lower risk of delirium (p<0·0001). During the 21-day study period, patients were alive without delirium or coma for a median of 5·0 days (0·0 to 14·0). At baseline, older age, higher SAPS II scores, male sex, smoking or alcohol abuse, use of vasopressors on day 1, and invasive mechanical ventilation on day 1 were independently associated with fewer days alive and free of delirium and coma (all p<0·01). 601 (28·8%) of 2088 patients died within 28 days of admission, with most of those deaths occurring in the ICU.
INTERPRETATION
Acute brain dysfunction was highly prevalent and prolonged in critically ill patients with COVID-19. Benzodiazepine use and lack of family visitation were identified as modifiable risk factors for delirium, and thus these data present an opportunity to reduce acute brain dysfunction in patients with COVID-19.
FUNDING
None.
TRANSLATIONS
For the French and Spanish translations of the abstract see Supplementary Materials section.

Identifiants

pubmed: 33428871
pii: S2213-2600(20)30552-X
doi: 10.1016/S2213-2600(20)30552-X
pmc: PMC7832119
pii:
doi:

Substances chimiques

Hypnotics and Sedatives 0

Types de publication

Journal Article Multicenter Study Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

239-250

Subventions

Organisme : NCATS NIH HHS
ID : UL1 TR000445
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM120484
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061161
Pays : United States
Organisme : NIA NIH HHS
ID : R24 AG054259
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135144
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG058639
Pays : United States
Organisme : NIA NIH HHS
ID : K76 AG054864
Pays : United States

Investigateurs

Jacques Creteur (J)
Elisa Govea Bogossian (EG)
Lorenzo Peluso (L)
Felipe González-Seguel (F)
Viviane Hidalgo-Calibin (V)
Pablo Carreño-Montenegro (P)
Verónica Rojas (V)
Eduardo Tobar (E)
Antonio Ramírez-Palma (A)
Karen Herrera-Davis (K)
Alexis Ferré (A)
Stéphane Legriel (S)
Thomas Godet (T)
Ugo Fraisse (U)
Bruno Gonçalves (B)
Aurélien Mazeraud (A)
Myrto Tzimou (M)
Frank Rasulo (F)
Silvia Beretta (S)
Mattia Marchesi (M)
Chiara Robba (C)
Denise Battaglini (D)
Paolo Pelosi (P)
Anna Teresa Mazzeo (AT)
Alberto Noto (A)
Giuseppe Servillo (G)
Annachiara Marra (A)
Salvatore Lucio Cutuli (SL)
Gabriele Pintaudi (G)
Eleonora Stival (E)
Eloisa Sofia Tanzarella (ES)
Erik Roman-Pognuz (E)
Chiara Maria Concetta Massaro (CM)
Muhammed Elhadi (M)
Lisa Smit (L)
Theresa Olasveengen (T)
Isabel Jesus Pereira (IJ)
Carla Margarida Teixeira (CM)
Alice Santos (A)
Miguel Valente (M)
Cristina Granja (C)
Rita Pereia (R)
João Silva (J)
Blanca Furquet (B)
Mónica García Simón (M)
Daniel A Godoy Torres (DA)
Berta Monleón (B)
Esteban Morcillo (E)
Nekane Romero (N)
Ainhoa Serrano (A)
Sara Torrico Sánchez (S)
Francisco Luis Pérez Caballero (FL)
Isabel Peña Luna (I)
Ignacio Baeza Gómez (I)
Milagros Calizaya Vargas (M)
Jordi Morillas Pérez (J)
Genís Carrasco Gómez (G)
Ricard Molina Latorre (R)
Sheila Moya Gutiérrez (S)
Irene Patricia Barón Barrera (IP)
Cristina Delgado Palacios (C)
Beatriz García Góngora (B)
Laura Labrador Romero (L)
Laura Galarza (L)
Ignacio Catalán-Monzón (I)
Enver Rodriguez-Martínez (E)
Cristina Murcia Gubianas (C)
Ariadna Bellès (A)
María Esther Rodriguez Delgado (ME)
Jesús Caballero (J)
Dulce Morales (D)
Andrés Pujol (A)
Jorge Rubio (J)
Eva Álvarez Torres (E)
Estefanía Carvajal Revuelta (E)
Isabel de la Calle Gil (I)
Blanca Fernández Tomás (B)
Berta Gallego Rodríguez (B)
Matilde González Serrano (M)
Paloma LaTorre Andreu (P)
Aris Pérez Lucendo (A)
Elena Abril Palomares (E)
Elena González González (E)
María Cruz Martín Delgado (MC)
Carlos Muñoz De Cabo (C)
Pablo T Aznar (PT)
Carlos A Calvo (CA)
Ignacio Garutti (I)
Fernando Higuero (F)
David Martínez-Gascueña (D)
Emilio Maseda (E)
Itziar Insausti (I)
Ana Montero Feijoo (A)
Alejandro Suarez-de-la-Rica (A)
Beatriz Del Moral Barbudo (B)
Yago García Blanco-Traba (Y)
Maria Claudia Giménez Santamarina (MC)
Alba Gonzalo Millán (A)
Sergio Llorente Damas (S)
David Pestaña Lagunas (D)
Isabel Reyes García (I)
Alejandro Ruiz Perea (A)
Álvaro Ortega Guerrero (Á)
María Jesús Mármol Cubillo (MJ)
David Díaz Muñoz (D)
Silvia García de Castrillón I Ramal (S)
Xavier Andorrà Sunyer (X)
María de Las Nieves Noci Moreno (MLN)
Rosa María Pérez Manrique (RM)
Emilio Del Campo Molina (E)
María Elena Martínez Quintana (ME)
Sol Fernandez-Gonzalo (S)
Gemma Gomà Fernández (G)
Guillem Navarra-Ventura (G)
Anna Baró Serra (A)
Cristina Fuster (C)
Oriol Plans Galván (O)
Diana Gil-Castillejos (D)
Mario Dalorzo González (M)
Francisco Javier Morán Gallego (FJ)
Irene Paredes Borrachero (I)
Patricia Rodríguez Villamizar (P)
Juan Romeu Prieto (J)
María José Sánchez Carretero (MJ)
Susana Gallardo Sánchez (S)
Filadelfo Bustos Molina (F)
María Luisa García Pérez (ML)
Paula Castello-Mora (P)
Jaume Puig (J)
María Rosa Sanchis-Martin (MR)
Carmen Andrea Sanchis-Veryser (CA)
María Pilar Vicente-Fernández (MP)
Rafael Zaragoza (R)
Laura Lizama (L)
Irene Torres (I)
Cristina Álvarez (C)
Paula Ramírez (P)
Meri Martin Cerezuela (M)
María Jesús Montero (MJ)
Jose García Cantos (J)
Paola Valls (P)
Nerea Aretxabala Cortajarena (N)
Pablo García Domelo (P)
Laura González Cubillo (L)
Marta Martín Martínez (M)
Inés Pérez Francisco (I)
Yolanda Poveda Hernández (Y)
Amaia Quintano Rodero (A)
César Rodriguez Nuñez (C)
Martin Siegemund (M)
Anna Estermann (A)
Núria Zellweger (N)
Imen Ben Saida (I)
Mohamed Boussarsar (M)
Figen Esen (F)
Perihan Ergin Özcan (P)
Christopher Berkey (C)
Christine Harb (C)
Morgan H Tandy (MH)
Ellis Morgan (E)
Karen Shephard (K)
Robert C Hyzy (RC)
Michael Kenes (M)
Kristine Nelson (K)
Robert E Hosse (RE)
Katie M Vance (KM)
C Adrian Austin (CA)
Aaron Lerner (A)
Emily Sanders (E)
Robert A Balk (RA)
David A Bennett (DA)
Andrew R Vogel (AR)
Lucia Chowdhury (L)
Kiran Devulapally (K)
Michelle Woodham (M)
Sarah Cohen (S)
Nihal Patel (N)
Catherine M Kuza (CM)
Mandeep Sing (M)
Spencer Roberson (S)
Kelly Drumright (K)
Sameep Sehgal (S)
Sara C LaHue (SC)
Vanja C Douglas (VC)
Aarti Sarwal (A)

Commentaires et corrections

Type : CommentIn
Type : ErratumIn

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Auteurs

Brenda T Pun (BT)

Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Rafael Badenes (R)

Department of Anesthesiology and Surgical-Trauma Intensive Care, Hospital Clínico Universitario de Valencia, Valencia, Spain; Department of Surgery, University of Valencia, Valencia, Spain; INCLIVA Health Research Institute, Valencia, Spain. Electronic address: rafaelbadenes@gmail.com.

Gabriel Heras La Calle (G)

Proyecto HU-CI, Hospital Comarcal Santa Ana, Motril, Spain; Universidad Francisco de Vitoria, Madrid, Spain.

Onur M Orun (OM)

Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.

Wencong Chen (W)

Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.

Rameela Raman (R)

Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN, USA; Center for Health Services Research, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.

Beata-Gabriela K Simpson (BK)

Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Stephanie Wilson-Linville (S)

Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Borja Hinojal Olmedillo (B)

Department of Anesthesiology and Surgical Critical Care, Hospital Universitario Ramón y Cajal, Madrid, Spain.

Ana Vallejo de la Cueva (A)

Department of Intensive Care, Hospital Universitario de Alava, Vitoria Gasteiz, Spain.

Mathieu van der Jagt (M)

Department of Intensive Care Adults, Erasmus MC University Medical Center, Rotterdam, Netherlands.

Rosalía Navarro Casado (R)

Department of Anesthesiology and Surgical Critical Care, Hospital Universitario 12 de Octubre, Madrid, Spain.

Pilar Leal Sanz (P)

Department of Intensive Care Complejo Hospitalario de Toledo -Virgen de la Salud Hospital, Toledo, Spain.

Günseli Orhun (G)

Department of Anesthesiology and Intensive Care, Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Carolina Ferrer Gómez (C)

Department of Anesthesiology and Critical Care, Consorcio Hospital General Universitario, Valencia, Spain.

Karla Núñez Vázquez (K)

Department of Intensive Care, Hospital de Barcelona, Barcelona, Spain.

Patricia Piñeiro Otero (P)

Department of Anesthesiology and Intensive Care Medicine, Hospital Universitario Gregorio Marañón, Madrid, Spain.

Fabio Silvio Taccone (FS)

Department of Intensive Care, Hopital Erasme, Brussels, Belgium.

Elena Gallego Curto (E)

Department of Intensive Care, Hospital Universitario San Pedro de Alcántara, Cáceres, Spain.

Anselmo Caricato (A)

Neuro Intensive Care Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

Hilde Woien (H)

Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway.

Guillaume Lacave (G)

Medical-Surgical Intensive Care Unit, Centre Hospitalier de Versailles, Le Chesnay, France.

Hollis R O'Neal (HR)

Pulmonary and Critical Care Medicine, Our Lady of the Lake Regional Medical Center, Baton Rouge, LA, USA.

Sarah J Peterson (SJ)

Department of Clinical Nutrition and Department of Pulmonary and Critical Care Medicine, Rush University Medical Center, Chicago, IL, USA.

Nathan E Brummel (NE)

Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Timothy D Girard (TD)

Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Critical Care Medicine, Clinical Research, Investigations, and Systems Modeling of Acute illness Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

E Wesley Ely (EW)

Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN, USA; Center for Health Services Research, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Geriatric Research, Education and Clinical Center, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA.

Pratik P Pandharipande (PP)

Critical Illness, Brain Dysfunction, and Survivorship Center, Vanderbilt University Medical Center, Nashville, TN, USA; Center for Health Services Research, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Anesthesiology, Division of Anesthesiology Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

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