Delirium and encephalopathy in severe COVID-19: a cohort analysis of ICU patients

Abstract

Background: Neurotropism of SARS-CoV-2 and its neurological manifestations have now been confirmed. We aimed at describing delirium and neurological symptoms of COVID-19 in ICU patients.

Methods: We conducted a bicentric cohort study in two French ICUs of Strasbourg University Hospital. All the 150 patients referred for acute respiratory distress syndrome due to SARS-CoV-2 between March 3 and May 5, 2020, were included at their admission. Ten patients (6.7%) were excluded because they remained under neuromuscular blockers during their entire ICU stay. Neurological examination, including CAM-ICU, and cerebrospinal fluid analysis, electroencephalography, and magnetic resonance imaging (MRI) were performed in some of the patients with delirium and/or abnormal neurological examination. The primary endpoint was to describe the incidence of delirium and/or abnormal neurological examination. The secondary endpoints were to describe the characteristics of delirium, to compare the duration of invasive mechanical ventilation and ICU length of stay in patients with and without delirium and/or abnormal neurological symptoms.

Results: The 140 patients were aged in median of 62 [IQR 52; 70] years old, with a median SAPSII of 49 [IQR 37; 64] points. Neurological examination was normal in 22 patients (15.7%). One hundred eighteen patients (84.3%) developed a delirium with a combination of acute attention, awareness, and cognition disturbances. Eighty-eight patients (69.3%) presented an unexpected state of agitation despite high infusion rates of sedative treatments and neuroleptics, and 89 (63.6%) patients had corticospinal tract signs. Brain MRI performed in 28 patients demonstrated enhancement of subarachnoid spaces in 17/28 patients (60.7%), intraparenchymal, predominantly white matter abnormalities in 8 patients, and perfusion abnormalities in 17/26 patients (65.4%). The 42 electroencephalograms mostly revealed unspecific abnormalities or diffuse, especially bifrontal, slow activity. Cerebrospinal fluid examination revealed inflammatory disturbances in 18/28 patients, including oligoclonal bands with mirror pattern and elevated IL-6. The CSF RT-PCR SARS-CoV-2 was positive in one patient. The delirium/neurological symptoms in COVID-19 patients were responsible for longer mechanical ventilation compared to the patients without delirium/neurological symptoms. Delirium/neurological symptoms could be secondary to systemic inflammatory reaction to SARS-CoV-2.

Conclusions and relevance: Delirium/neurological symptoms in COVID-19 patients are a major issue in ICUs, especially in the context of insufficient human and material resources.

Trial registration: NA.

Keywords: COVID-19; Delirium; Encephalopathy; ICU; MRI.

Fig. 1

Flow chart. Asterisk indicates CAM-ICU was performed in 122/140 patients (87.1%). Four patients could not be evaluated because they did not speak French and 14 patients died without being scored (RASS − 4/− 5). CSF, cerebrospinal fluid; EEG, electroencephalogram; MRI, magnetic resonance imaging

Fig. 2

Axial SWI (a–e), axial diffusion (f), apparent diffusion coefficient (ADC) (g), coronal (h), and sagittal (i) FLAIR-weighted MR images: multiple infra and supratentorial white matter microhemorrhages (arrows), associated with FLAIR (cross) and diffusion (star) hyperintensities

Fig. 3

Axial, sagittal, and coronal FLAIR (a, c, d) and axial post-contrast T1 (b)-weighted MR images: extensive white matter confluent FLAIR hyperintensities (arrow), with small foci of contrast enhancement (arrow head)