Aju tiheliiduste valkude ekspressioon sepsise korral lahangumaterjalis

Eesti Arst 2021; 100(8):45

The brain as an end organ in sepsis?

Abstract Delirium in intensive care is the main manifestation of sepsis-associated encephalopathy. In sepsis the brain acts as both a mediator of the immune response and as a target organ. Our aim was to evaluate sepsis-induced changes in the brain. In study I, retinal arterial filling time (RAFT) was measured in septic patients. Of 31 patients, 93% were in septic shock, 71% developed delirium, and 51.6% had retinal angiopathies. Patients with prolonged RAFT had a lower cardiac index before and during angiography, and more frequently had retinal abnormalities. Patients with prolonged RAFT had lower C-reactive protein and interleukin-6 levels than those with shorter RAFT. Study II included 22 patients with septic shock, who were assessed by CAM-ICU for the presence of delirium. Delirium was associated with an elevated protein S-100β concentration and with more severe organ dysfunction during the ICU stay. Study III examined adult patients deceased due to sepsis on the ICU. Patients were categorized as having blood-brain barrier (BBB) damage if there was no expression of occludin in the endothelium of cerebral microvessels. A damaged BBB was related to severe organ dysfunction and systemic inflammation. In Study IV, an overnight electroencephalogram (EEG) was recorded in ICU patients with hyperactive delirium and receiving dexmedetomidine. Night-time slow-wave activity in an EEG was evaluated with an offline calculation of the C-Trend® index. Both the EEG and clinical evaluation showed that the quality and depth of night-time sleep were poor in most patients with hyperactive delirium. In conclusion, retinal angiography detects disturbances in retinal blood flow and retinal microaneurysms in septic shock patients. S-100β concentration could be used in the diagnosis of delirium in sepsis. The blood brain barrier damage in sepsis is related to severe organ dysfunction and systemic inflammation. Offline calculation of the C-Trend® index might offer an objective method for sleep evaluation in patients with delirium.Tiivistelmä Delirium on tärkein sepsiksen yhteydessä tapahtuva aivojen toimintahäiriö. Aivot toimivat sekä immuunireaktion välittäjänä että kohde-elimenä. Tutkimuksen tavoitteena oli selvittää sepsiksen aiheuttamia muutoksia aivoissa. Ensin selvitettiin verkkokalvon verenvirtausta määrittämällä verkkokalvon valtimon täyttymisaika (RAFT). Sepsispotilaiden silmän sisäistä painetta, tulehdusta ja aivojen toimintaa kuvaavia biomerkkiaineita mitattiin. Verkkokalvon valtimon täyttymisaika oli pidentynyt, jos RAFT oli yli 8,3 sekuntia. Tutkimuksen 31 potilaasta 93 %:lla oli septinen sokki, 71 % kärsi deliriumista ja 52 %:lla oli verkkokalvolla verisuonipoikkeavuuksia. Jos potilailla oli pidentynyt RAFT, heillä oli alentunut sydämen minuuttivirtausindeksi. Heillä oli myös useammin verkkokalvomuutoksia. Seuraavaksi selvitettiin 22 septisestä sokista kärsivällä potilaalla deliriumin esiintymistä CAM-ICU-luokituksella. Kun septisen sokin yhteydessä potilailla todettiin delirium, heillä oli suurentunut proteiinin S-100β-pitoisuus (> 0,15 μg/L). Deliriumpotilailla oli myös tehohoitojakson aikana useammin vaikeita elintoimintojen häiriöitä kuin ei-deliriumpotilailla. Kolmanneksi selvitettiin sepsiksen vuoksi menehtyneiden tehopotilaiden ruumiinavauksen yhteydessä otettuja aivokudosnäytteitä immunohistokemiallisilla värjäyksillä. Jos verisuonten seinämässä ei todettu okkludiinia, se oli merkki veri-aivoesteen vauriosta. Näillä potilailla oli ollut vakavia elintoimintojen häiriöitä. Viimeisenä tutkittiin 15 hyperaktiivisesta deliriumista kärsivää teho-osaston potilasta, joille annettiin deksmedetomidiinia yöunen turvaamiseksi. Heidän aivosähkötoimintaansa seurattiin yön yli EEG:llä. Yönaikaista aivojen hidasaaltotoimintaa (SWA) arvioitiin C-Trend®-indeksillä. Sekä SWA:n että kliinisen arvion perusteella hyperakuutin deliriumin aikana yönaikaisen unen laatu ja syvyys olivat huonoja. Yhteenvetona voidaan todeta, että verkkokalvon valtimon täyttymisaika toimii kajoamattomana menetelmänä keskushermoston ja aivojen verenkierron arvioinnissa. S-100β:aa voidaan käyttää sepsispotilaiden deliriumin toteamisessa. Okkludiinin puuttuminen verisuonten endoteelista kuvastaa veri-aivoesteen vauriota, johon liittyi elämän aikana vaikeita elintoimintojen häiriöitä. C-Trend®-indeksin käyttö tarjoaa objektiivisen lähestymistavan deliriumpotilaiden unen arviointiin

Monitoring of nighttime EEG slow-wave activity during dexmedetomidine infusion in patients with hyperactive ICU delirium:an observational pilot study

Abstract Background: The disturbance of sleep has been associated with intensive care unit (ICU) delirium. Monitoring of EEG slow-wave activity (SWA) has potential in measuring sleep quality and quantity. We investigated the quantitative monitoring of night-time SWA and its association with the clinical evaluation of sleep in patients with hyperactive ICU delirium treated with dexmedetomidine. Methods: We performed overnight EEG recordings in 15 patients diagnosed with hyperactive delirium during moderate dexmedetomidine sedation. SWA was evaluated by offline calculation of the C-Trend Index, describing SWA in one parameter ranging 0 to 100 in values. Average and percentage of SWA values <50 were categorized as poor. The sleep quality and depth was clinically evaluated by the bedside nurse using the Richards-Campbell Sleep Questionnaire (RCSQ) with scores <70 categorized as poor. Results: Nighttime SWA revealed individual sleep structures and fundamental variation between patients. SWA was poor in 67%, sleep quality (RCSQ) in 67%, and sleep depth (RCSQ) in 60% of the patients. The category of SWA aligned with that of RCSQ-based sleep quality in 87% and RCSQ-based sleep depth in 67% of the patients. Conclusions: Both, SWA and clinical evaluation suggested that the quality and depth of nighttime sleep were poor in most patients with hyperactive delirium despite dexmedetomidine infusion. Furthermore, the SWA and clinical evaluation classifications were not uniformly in agreement. An objective mode such as practical EEG-based solution for sleep evaluation and individual drug dosing in the ICU setting could offer potential in improving sleep for patients with delirium

A correlation-driven mapping for deep learning application in detecting artifacts within the EEG

Abstract Objective: When developing approaches for automatic preprocessing of electroencephalogram (EEG) signals in non-isolated demanding environment such as intensive care unit (ICU) or even outdoor environment, one of the major concerns is varying nature of characteristics of different artifacts in time, frequency and spatial domains, which in turn causes a simple approach to be not enough for reliable artifact removal. Considering this, current study aims to use correlation-driven mapping to improve artifact detection performance. Approach: A framework is proposed here for mapping signals from multichannel space (regardless of the number of EEG channels) into two-dimensional RGB space, in which the correlation of all EEG channels is simultaneously taken into account, and a deep convolutional neural network (CNN) model can then learn specific patterns in generated 2D representation related to specific artifact. Main results: The method with a classification accuracy of 92.30% (AUC = 0.96) in a leave-three-subjects-out cross-validation procedure was evaluated using data including 2310 EEG sequences contaminated by artifacts and 2285 artifact-free EEG sequences collected with BrainStatus self-adhesive electrode and wireless amplifier from 15 intensive care patients. For further assessment, several scenarios were also tested including performance variation of proposed method under different segment lengths, different numbers of isoline and different numbers of channel. The results showed outperformance of CNN fed by correlation coefficients data over both spectrogram-based CNN and EEGNet on the same dataset. Significance: This study showed the feasibility of utilizing correlation image of EEG channels coupled with deep learning as a promising tool for dimensionality reduction, channels fusion and capturing various artifacts patterns in temporal-spatial domains. A simplified version of proposed approach was also shown to be feasible in real-time application with latency of 0.0181 s for making real-time decision

Automatic detection of artifacts in EEG by combining deep learning and histogram contour processing

Abstract This paper introduces a simple approach combining deep learning and histogram contour processing for automatic detection of various types of artifact contaminating the raw electroencephalogram (EEG). The proposed method considers both spatial and temporal information of raw EEG, without additional need for reference signals like ECG or EOG. The proposed method was evaluated with data including 785 EEG sequences contaminated by artifacts and 785 artifact-free EEG sequences collected from 15 intensive care patients. The obtained results showed an overall accuracy of 0.98, representing high reliability of proposed technique in detecting different types of artifacts and being comparable or outperforming the approaches proposed earlier in the literature

Retinal arterial blood flow and retinal changes in patients with sepsis: preliminary study using fluorescein angiography

Abstract Background Although tissue perfusion is often decreased in patients with sepsis, the relationship between macrohemodynamics and microcirculatory blood flow is poorly understood. We hypothesized that alterations in retinal blood flow visualized by angiography may be related to macrohemodynamics, inflammatory mediators, and retinal microcirculatory changes. Methods Retinal fluorescein angiography was performed twice during the first 5 days in the intensive care unit to observe retinal abnormalities in patients with sepsis. Retinal changes were documented by hyperfluorescence angiography; retinal blood flow was measured as retinal arterial filling time (RAFT); and intraocular pressure was determined. In the analyses, we used the RAFT measured from the eye with worse microvascular retinal changes. Blood samples for inflammation and cerebral biomarkers were collected, and macrohemodynamics were monitored. RAFT was categorized as prolonged if it was more than 8.3 seconds. Results Of 31 patients, 29 (93%) were in septic shock, 30 (97%) required mechanical ventilation, 22 (71%) developed delirium, and 16 (51.6%) had retinal angiopathies, 75% of which were bilateral. Patients with prolonged RAFT had a lower cardiac index before (2.1 L/kg/m2 vs. 3.1 L/kg/m2, P = 0.042) and during angiography (2.1 L/kg/m2 vs. 2.6 L/kg/m2, P = 0.039). They more frequently had retinal changes (81% vs. 20%, P = 0.001) and higher intraocular pressure (18 mmHg vs. 14 mmHg, P = 0.031). Patients with prolonged RAFT had lower C-reactive protein (139 mg/L vs. 254 mg/L, P = 0.011) and interleukin-6 (39 pg/ml vs. 101 pg/ml, P < 0.001) than those with shorter RAFT. Conclusions Retinal angiopathic changes were more frequent and cardiac index was lower in patients with prolonged RAFT, whereas patients with shorter filling times had higher levels of inflammatory markers

Brain tight junction protein expression in sepsis in an autopsy series

Abstract Background: Neuroinflammation often develops in sepsis along with increasing permeability of the blood-brain barrier (BBB), which leads to septic encephalopathy. The barrier is formed by tight junction structures between the cerebral endothelial cells. We investigated the expression of tight junction proteins related to endothelial permeability in brain autopsy specimens in critically ill patients deceased with sepsis and analyzed the relationship of BBB damage with measures of systemic inflammation and systemic organ dysfunction. Methods: The case series included all (385) adult patients deceased due to sepsis in the years 2007–2015 with available brain specimens taken at autopsy. Specimens were categorized according to anatomical location (cerebrum, cerebellum). The immunohistochemical stainings were performed for occludin, ZO-1, and claudin. Patients were categorized as having BBB damage if there was no expression of occludin in the endothelium of cerebral microvessels. Results: Brain tissue samples were available in 47 autopsies, of which 38% (18/47) had no expression of occludin in the endothelium of cerebral microvessels, 34% (16/47) developed multiple organ failure before death, and 74.5% (35/47) had septic shock. The deceased with BBB damage had higher maximum SOFA scores (16 vs. 14, p = 0.04) and more often had procalcitonin levels above 10 μg/L (56% vs. 28%, p = 0.045) during their ICU stay. BBB damage in the cerebellum was more common in cases with C-reactive protein (CRP) above 100 mg/L as compared with CRP less than 100 (69% vs. 25%, p = 0.025). Conclusions: In fatal sepsis, damaged BBB defined as a loss of cerebral endothelial expression of occludin is related with severe organ dysfunction and systemic inflammation

Retinal arterial blood flow and retinal changes in patients with sepsis:preliminary study using fluorescein angiography

Abstract Background: Although tissue perfusion is often decreased in patients with sepsis, the relationship between macrohemodynamics and microcirculatory blood flow is poorly understood. We hypothesized that alterations in retinal blood flow visualized by angiography may be related to macrohemodynamics, inflammatory mediators, and retinal microcirculatory changes. Methods: Retinal fluorescein angiography was performed twice during the first 5 days in the intensive care unit to observe retinal abnormalities in patients with sepsis. Retinal changes were documented by hyperfluorescence angiography; retinal blood flow was measured as retinal arterial filling time (RAFT); and intraocular pressure was determined. In the analyses, we used the RAFT measured from the eye with worse microvascular retinal changes. Blood samples for inflammation and cerebral biomarkers were collected, and macrohemodynamics were monitored. RAFT was categorized as prolonged if it was more than 8.3 seconds. Results: Of 31 patients, 29 (93%) were in septic shock, 30 (97%) required mechanical ventilation, 22 (71%) developed delirium, and 16 (51.6%) had retinal angiopathies, 75% of which were bilateral. Patients with prolonged RAFT had a lower cardiac index before (2.1 L/kg/m² vs. 3.1 L/kg/m², P = 0.042) and during angiography (2.1 L/kg/m² vs. 2.6 L/kg/m², P = 0.039). They more frequently had retinal changes (81% vs. 20%, P = 0.001) and higher intraocular pressure (18 mmHg vs. 14 mmHg, P = 0.031). Patients with prolonged RAFT had lower C-reactive protein (139 mg/L vs. 254 mg/L, P = 0.011) and interleukin-6 (39 pg/ml vs. 101 pg/ml, P &lt; 0.001) than those with shorter RAFT. Conclusions: Retinal angiopathic changes were more frequent and cardiac index was lower in patients with prolonged RAFT, whereas patients with shorter filling times had higher levels of inflammatory markers