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      Delirium Incidence, Duration, and Severity in Critically Ill Patients With Coronavirus Disease 2019

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          Abstract

          Supplemental Digital Content is available in the text.

          Abstract

          Objectives:

          To determine delirium occurrence rate, duration, and severity in patients admitted to the ICU with coronavirus disease 2019.

          Design:

          Retrospective data extraction study from March 1, 2020, to June 7, 2020. Delirium outcomes were assessed for up to the first 14 days in ICU.

          Setting:

          Two large, academic centers serving the state of Indiana.

          Patients:

          Consecutive patients admitted to the ICU with positive severe acute respiratory syndrome coronavirus 2 nasopharyngeal swab polymerase chain reaction test from March 1, 2020, to June 7, 2020, were included. Individuals younger than 18 years of age, without any delirium assessments, or without discharge disposition were excluded.

          Measurements and Main Results:

          Primary outcomes were delirium rates and duration, and the secondary outcome was delirium severity. Two-hundred sixty-eight consecutive patients were included in the analysis with a mean age of 58.4 years ( sd, 15.6 yr), 40.3% were female, 44.4% African American, 20.7% Hispanic, and a median Acute Physiology and Chronic Health Evaluation II score of 18 (interquartile range, 13–25). Delirium without coma occurred in 29.1% of patients, delirium prior to coma in 27.9%, and delirium after coma in 23.1%. The first Confusion Assessment Method for the ICU assessment was positive for delirium in 61.9%. Hypoactive delirium was the most common subtype (87.4%). By day 14, the median number of delirium/coma-free were 5 days (interquartile range, 4–11 d), and median Confusion Assessment Method for the ICU-7 score was 6.5 (interquartile range, 5–7) indicating severe delirium. Benzodiazepines were ordered for 78.4% of patients in the cohort. Mechanical ventilation was associated with greater odds of developing delirium (odds ratio, 5.0; 95% CI, 1.1–22.2; p = 0.033) even after adjusting for sedative medications. There were no between-group differences in mortality.

          Conclusions:

          Delirium without coma occurred in 29.1% of patients admitted to the ICU. Delirium persisted for a median of 5 days and was severe. Mechanical ventilation was significantly associated with odds of delirium even after adjustment for sedatives. Clinical attention to manage delirium duration and severity, and deeper understanding of the virus’ neurologic effects is needed for patients with coronavirus disease 2019.

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          Most cited references36

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          Neurologic Features in Severe SARS-CoV-2 Infection

          To the Editor: We report the neurologic features in an observational series of 58 of 64 consecutive patients admitted to the hospital because of acute respiratory distress syndrome (ARDS) due to Covid-19. The patients received similar evaluations by intensivists in two intensive care units (ICUs) in Strasbourg, France, between March 3 and April 3, 2020. Six patients were excluded because of paralytic neuromuscular blockade when neurologic data were collected or because they had died without a neurologic examination having been performed. In all 58 patients, reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays of nasopharyngeal samples were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The median age of the patients was 63 years, and the median Simplified Acute Physiology Score II at the time of neurologic examination was 52 (interquartile range, 37 to 65, on a scale ranging from 0 to 163, with higher scores indicating greater severity of illness). Seven patients had had previous neurologic disorders, including transient ischemic attack, partial epilepsy, and mild cognitive impairment. The neurologic findings were recorded in 8 of the 58 patients (14%) on admission to the ICU (before treatment) and in 39 patients (67%) when sedation and a neuromuscular blocker were withheld. Agitation was present in 40 patients (69%) when neuromuscular blockade was discontinued (Table 1). A total of 26 of 40 patients were noted to have confusion according to the Confusion Assessment Method for the ICU; those patients could be evaluated when they were responsive (i.e., they had a score of −1 to 1 on the Richmond Agitation and Sedation Scale, on a scale of −5 [unresponsive] to +4 [combative]). Diffuse corticospinal tract signs with enhanced tendon reflexes, ankle clonus, and bilateral extensor plantar reflexes were present in 39 patients (67%). Of the patients who had been discharged at the time of this writing, 15 of 45 (33%) had had a dysexecutive syndrome consisting of inattention, disorientation, or poorly organized movements in response to command. Magnetic resonance imaging (MRI) of the brain was performed in 13 patients (Figs. S1 through S3 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). Although these patients did not have focal signs that suggested stroke, they underwent MRI because of unexplained encephalopathic features. Enhancement in leptomeningeal spaces was noted in 8 patients, and bilateral frontotemporal hypoperfusion was noted in all 11 patients who underwent perfusion imaging. Two asymptomatic patients each had a small acute ischemic stroke with focal hyperintensity on diffusion-weighted imaging and an overlapping decreased apparent diffusion coefficient, and 1 patient had a subacute ischemic stroke with superimposed increased diffusion-weighted imaging and apparent diffusion coefficient signals. In the 8 patients who underwent electroencephalography, only nonspecific changes were detected; 1 of the 8 patients had diffuse bifrontal slowing consistent with encephalopathy. Examination of cerebrospinal fluid (CSF) samples obtained from 7 patients showed no cells; in 2 patients, oligoclonal bands were present with an identical electrophoretic pattern in serum, and protein and IgG levels were elevated in 1 patient. RT-PCR assays of the CSF samples were negative for SARS-CoV-2 in all 7 patients. In this consecutive series of patients, ARDS due to SARS-CoV-2 infection was associated with encephalopathy, prominent agitation and confusion, and corticospinal tract signs. Two of 13 patients who underwent brain MRI had single acute ischemic strokes. Data are lacking to determine which of these features were due to critical illness–related encephalopathy, cytokines, or the effect or withdrawal of medication, and which features were specific to SARS-CoV-2 infection.
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            Covid-19 in Critically Ill Patients in the Seattle Region — Case Series

            Abstract Background Community transmission of coronavirus 2019 (Covid-19) was detected in the state of Washington in February 2020. Methods We identified patients from nine Seattle-area hospitals who were admitted to the intensive care unit (ICU) with confirmed infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Clinical data were obtained through review of medical records. The data reported here are those available through March 23, 2020. Each patient had at least 14 days of follow-up. Results We identified 24 patients with confirmed Covid-19. The mean (±SD) age of the patients was 64±18 years, 63% were men, and symptoms began 7±4 days before admission. The most common symptoms were cough and shortness of breath; 50% of patients had fever on admission, and 58% had diabetes mellitus. All the patients were admitted for hypoxemic respiratory failure; 75% (18 patients) needed mechanical ventilation. Most of the patients (17) also had hypotension and needed vasopressors. No patient tested positive for influenza A, influenza B, or other respiratory viruses. Half the patients (12) died between ICU day 1 and day 18, including 4 patients who had a do-not-resuscitate order on admission. Of the 12 surviving patients, 5 were discharged home, 4 were discharged from the ICU but remained in the hospital, and 3 continued to receive mechanical ventilation in the ICU. Conclusions During the first 3 weeks of the Covid-19 outbreak in the Seattle area, the most common reasons for admission to the ICU were hypoxemic respiratory failure leading to mechanical ventilation, hypotension requiring vasopressor treatment, or both. Mortality among these critically ill patients was high. (Funded by the National Institutes of Health.)
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              Autopsy Findings and Venous Thromboembolism in Patients With COVID-19

              Background: The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. Objective: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. Design: Prospective cohort study. Setting: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction–confirmed diagnosis of COVID-19. Patients: The first 12 consecutive COVID-19–positive deaths. Measurements: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS–CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. Limitation: Limited sample size. Conclusion: The high incidence of thromboembolic events suggests an important role of COVID-19–induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19–related death, as well as possible therapeutic interventions to reduce it. Primary Funding Source: University Medical Center Hamburg-Eppendorf.
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                Author and article information

                Journal
                Crit Care Explor
                Crit Care Explor
                CC9
                Critical Care Explorations
                Lippincott Williams & Wilkins (Hagerstown, MD )
                2639-8028
                25 November 2020
                December 2020
                : 2
                : 12
                : e0290
                Affiliations
                [1 ]Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.
                [2 ]IU Center of Aging Research, Regenstrief Institute, Indianapolis, IN.
                [3 ]Indiana University Center of Health Innovation and Implementation Science, Indianapolis, IN.
                [4 ]Indiana University School of Nursing, Indianapolis, IN.
                [5 ]Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN.
                [6 ]Lebanese American University, Beirut, Lebanon.
                [7 ]Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN.
                [8 ]Division of General Medicine, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
                [9 ]Division of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
                [10 ]Division of Geriatrics and General Internal Medicine, Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, IN.
                [11 ]Sandra Eskenazi Center for Brain Care Innovation, Eskenazi Hospital, Indianapolis, IN.
                Author notes
                For information regarding this article, E-mail: sikhan@ 123456iu.edu
                Article
                00009
                10.1097/CCE.0000000000000290
                7690767
                33251519
                3a79d58f-0c74-49b6-85ca-fa558e0ae7ab
                Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
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                Observational Study
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                brain diseases,coma,coronavirus disease 2019,critical illness,delirium,respiratory insufficiency

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