Cerebral Autoregulation, Cerebral Hemodynamics, and Injury Biomarkers, in Patients with COVID-19 Treated with Veno-Venous Extracorporeal Membrane Oxygenation

Abstract

Background This study aimed to describe the cerebrovascular dynamics, in particular cerebral autoregulation (CA), and cerebral biomarkers as neuron-specific enolase (NSE) in patients with a diagnosis of coronavirus disease 2019 and acute respiratory distress syndrome as well as undergoing veno-venous extracorporeal membrane treatment. Methods This was a single center, observational study conducted in the intensive care unit of the University Hospital in Wroclaw from October 2020 to February 2022. Transcranial Doppler recordings of the middle cerebral artery conducted for at least 20 min were performed. Cerebral autoregulation (CA) was estimated by using the mean velocity index (Mxa), calculated as the moving correlation coefficient between slow-wave oscillations in cerebral blood flow velocity and arterial blood pressure. Altered CA was defined as a positive Mxa. Blood samples for the measurement of NSE were obtained at the same time as transcranial Doppler measurements. Results A total of 16 patients fulfilled the inclusion criteria and were enrolled in the study. The median age was 39 (34–56) years. Altered CA was found in 12 patients, and six out of seven patients who died had altered CA. A positive Mxa was a significant predictor of mortality, with a sensitivity of 85.7%. We found that three out of five patients with pathological changes in brain computed tomography and six out of ten patients with neurological complications had altered CA. NSE was a significant predictor of mortality (cutoff value: 28.9 µg/L); area under the curve = 0.83, p = 0.006), with a strong relationship between increased level of NSE and altered CA, χ2 = 6.24; p = 0.035; φ = 0.69. Conclusions Patients with coronavirus disease 2019–related acute respiratory distress syndrome, requiring veno-venous extracorporeal membrane treatment, are likely to have elevated NSE levels and altered CA. The CA was associated with NSE values in this group. This preliminary analysis suggests that advanced neuromonitoring and evaluation of biomarkers should be considered in this population.

Cerebrospinal Fluid and Serum Biomarker Insights in Aneurysmal Subarachnoid Haemorrhage: Navigating the Brain–Heart Interrelationship for Improved Patient Outcomes

“…PRx was correlated with NSE and GFAP; therefore, impaired cerebral autoregulation (indicated by a higher PRx) was associated with increased levels of NSE and GFAP. This observation is consistent with our previous research, where we found a positive relationship between NSE and cerebral autoregulation [81]. Previous studies have also indicated that cerebral autoregulation is related to inflammation-related blood biomarkers [82].…”

Increased impairment of cerebral autoregulation in COVID-19 associated pulmonary failure requiring extracorporeal membrane oxygenation

“…In this study, we observed an equal incidence of cerebral pathologies in both groups. Impaired cerebral autoregulation has been proposed previously in SARS-CoV-2 infection in single cases and small series ( 4 , 7 ). Schramm et al ( 16 ) showed that severe sepsis is associated with impaired cerebral autoregulation using a transcranial doppler sonography-derived autoregulation index.…”

“…Similar results are reported by Crippa et al ( 17 ), showing that 50% of patients with sepsis exhibit impaired cerebral autoregulation which is associated with brain dysfunction. Burzynska et al ( 7 ) reported in a series of 16 SARS-CoV-2 patients with ARDS undergoing vv-ECMO therapy that these patients are likely to experience both elevated biomarkers of cerebral damage and impairment of cerebral autoregulation. We can essentially confirm these findings with the additional finding that there is a difference in cerebral autoregulation between SARS-CoV-2 and non SARS-CoV-2 patients.…”

“…In patients with severe SARS-CoV-2 infections, both ischemic and hemorrhagic stroke have been reported in the early stages of the pandemic ( 6 ). Cerebral autoregulation has been shown to be impaired in a small series of patients with ECMO due to SARS-CoV-2 ( 7 ). Brain endothelial cells as well as the blood–brain barrier have been demonstrated to be affected by the virus ( 8–11 ).…”

Anti-PD-L1 therapy altered inflammation but not survival in a lethal murine hepatitis virus-1 pneumonia model

“…At day 5, 26 proteins were differentially expressed with respect to the overall virus effect that were not altered at day 2. Some of these proteins were associated with adhesion [Clmp: Coxsackie- And Adenovirus Receptor-Like Membrane Protein ( 44 ); Itgb6, integrin subunit beta 6; Itgb1bp2, integrin subunit beta 1 binding protein 2; Mia, melanoma inhibitory activity protein ( 45 ); Matn2, matrilin 2 ( 46 )], cardiac function [Fstl3, follistatin like 3 ( 47 ); Tnni3, troponin I type 3 cardiac], and neurological function [Eno2, enolase 2/neuron-specific enolase ( 48 ); Gdnf, glial cell-derived neurotrophic factor; Ntf3, neurotrophin 3; Gfra1, glial cell-derived neurotrophic factor (GDNF) family receptor alpha 1 ( 49 ); Clmp ( 44 ); and Matn2 ( 46 )].…”