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Outcomes in Patients With COVID-19 With Acute Encephalopathy and Coma: An International Prospective Study
Stephane Legriel1, Rafael Badenes2, Nicolas Engrand2
1From the Intensive Care Unit (S.L., G.J., A.F., M. Paul, M.-C.d.-C.), Centre Hospitalier de Versailles-Site André Mignot, Le Chesnay; University Paris-Saclay (S.L., G.J.), UVSQ, INSERM, CESP, Team « PsyDev », Villejuif; IctalGroup (S.L., P.S., J.C., M.L., G.P., G.J., A. Galbois, O.L., P. Bailly, P. Beuret, C.B., A.S., A.M.), Le Chesnay, France; Anesthesiology and Surgical-Trauma Intensive Care (R.B.), University Clinic Hospital, Valencia; Department of Surgery (R.B.), University of Valencia, Spain; Neuro-Intensive Care Unit (N.E.), Rothschild Foundation Hospital, Paris, France; Anesthesiology and Intensive Care (R.M.-T.), Hospital Regional de Alta Especilidad del Bajío, Leon, Mexico; Intensive Care Unit (P.S.), Groupe Hospitalier Sud Ile de France, Melun; Medical ICU (S.B.), Cochin Hospital, AP-HP, Paris, France; Departments of Neurology and Neurosurgery (M. Pizzi, C.M.), University of Florida College of Medicine, Gainesville; Department of Neurology (C.M.), Yale University School of Medicine, New Haven, CT; Department of Neurology (C.M.), University of Utah, Salt Lake City; Intensive Care Unit (J.C.), Centre Hospitalier Intercommunal Toulon La Seyne sur Mer; Intensive Care Unit (B.Z.), Hôpital Foch, Suresnes; Réanimation Médicale (M.L.), CHU Dijon; Service de Médecine Intensive Réanimation (G.P.), Centre Hospitalier d'Argenteuil; Intensive Care Unit (A. Galbois), Claude Galien Private Hospital, Quincy-sous-Senart, Île-de-France; Réanimation Chirurgicale (Y.L.), Département d'Anesthésie-Réanimation, Centre Hospitalier Universitaire de Rennes; Hospices Civils de Lyon (L.A.), Hôpital Edouard Herriot, Service de Médecine Intensive-Réanimation; Université de Lyon (L.A.), Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Est; Service de Réanimation (O.L.), Centre Hospitalier de la Rochelle, Nouvelle-Aquitaine; Intensive Care Unit (A. Guillon), Tours University Hospital; INSERM UMR 1100 (Research Center for Respiratory Diseases) (A. Guillon), University of Tours; Médecine Intensive Réanimation (P. Bailly), CHU de Brest; Service de Réanimation et Soins Continus (P. Beuret), Centre Hospitalier de Roanne, Rhône-Alpes; Polyvalent ICU (S. Siami), Centre Hospitalier Sud Essonne Dourdan-Etampes, Paris; Médecine Intensive Réanimation (D.B.), Centre Hospitalier Régional d'Orléans; Médecine Intensive Réanimation (G.C.), District Hospital Center, La Roche-sur-Yon, France; Centro de Investigación Clínica (L.G.), and Adult Intensive Care Unit (J.L.A., J.M.), Fundación Valle del Lili, University Hospital, Cali, Colombia; Service de Réanimation (C.B.), Groupe Hospitalier Paris Saint Joseph; Service de Réanimation (A.S.), Institut Gustave Roussy, Villejuif, France; Service de Réanimation (N.S.), Hôpital Fleyriat, Bourg en Bresse; Service de Médecine Intensive Réanimation (G.G.), Hôpital Universitaire Ambroise-Paré, APHP, Boulogne-Billancourt, France; Department of Neurology (D.S., Evie Sobczak, Emily Swafford, K.O.P., A.A.), University of Miami, FL; Service d'Anesthésie Réanimation Chirurgicale (A.M.), Hôpital Henri Mondor, Creteil, Île-de-France; Department of Anesthesiology and Critical Care (M.H.), Beaujon Hospital, DMU Parabol, AP-HP. Nord, Paris; Critical Care Unit (S. Silva), University Teaching Hospital of Purpan, Toulouse Cedex 9; Toulouse NeuroImaging Center (S. Silva), Toulouse University, UMR INSERM/UPS 1214, UPS, France; and Intensive Care Unit (M.J.A.d.C.), Hospital Nossa Senhora de Lourdes (Antigo Hospital Alfa), Recife, Pernambuco, Brazil. stephane.legriel@ictalgroup.org.
Background And Objectives:
To report the prevalence of acute encephalopathy and outcomes in patients with severe coronavirus disease 2019 (COVID-19) and to identify determinants of 90-day outcomes.
Methods:
Data from adults with severe COVID-19 and acute encephalopathy were prospectively collected for patients requiring intensive care unit management in 31 university or university-affiliated intensive care units in 6 countries (France, United States, Colombia, Spain, Mexico, and Brazil) between March and September of 2020. Acute encephalopathy was defined, as recently recommended, as subsyndromal delirium or delirium or as a comatose state in case of severely decreased level of consciousness. Logistic multivariable regression was performed to identify factors associated with 90-day outcomes. A Glasgow Outcome Scale-Extended (GOS-E) score of 1-4 was considered a poor outcome (indicating death, vegetative state, or severe disability).
Results:
Of 4,060 patients admitted with COVID-19, 374 (9.2%) experienced acute encephalopathy at or before the intensive care unit (ICU) admission. A total of 199/345 (57.7%) patients had a poor outcome at 90-day follow-up as evaluated by the GOS-E (29 patients were lost to follow-up). On multivariable analysis, age older than 70 years (odds ratio [OR] 4.01, 95% CI 2.25-7.15), presumed fatal comorbidity (OR 3.98, 95% CI 1.68-9.44), Glasgow coma scale score <9 before/at ICU admission (OR 2.20, 95% CI 1.22-3.98), vasopressor/inotrope support during ICU stay (OR 3.91, 95% CI 1.97-7.76), renal replacement therapy during ICU stay (OR 2.31, 95% CI 1.21-4.50), and CNS ischemic or hemorrhagic complications as acute encephalopathy etiology (OR 3.22, 95% CI 1.41-7.82) were independently associated with higher odds of poor 90-day outcome. Status epilepticus, posterior reversible encephalopathy syndrome, and reversible cerebral vasoconstriction syndrome were associated with lower odds of poor 90-day outcome (OR 0.15, 95% CI 0.03-0.83).
Discussion:
In this observational study, we found a low prevalence of acute encephalopathy at ICU admission in patients with COVID-19. More than half of patients with COVID-19 presenting with acute encephalopathy had poor outcomes as evaluated by GOS-E. Determinants of poor 90-day outcome were dominated by older age, comorbidities, degree of impairment of consciousness before/at ICU admission, association with other organ failures, and acute encephalopathy etiology.
Trial Registration Information:
The study is registered with ClinicalTrials.gov, number NCT04320472.
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