14 research outputs found

    A Mechanistic Link to Peripheral Endothelial Dysfunction

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    Background: Sleep‐disordered breathing (SDB) after acute ischemic stroke is frequent and may be linked to stroke‐induced autonomic imbalance. In the present study, the interaction between SDB and peripheral endothelial dysfunction (ED) was investigated in patients with acute ischemic stroke and at 1‐year follow‐up. Methods and Results: SDB was assessed by transthoracic impedance records in 101 patients with acute ischemic stroke (mean age, 69 years; 61% men; median National Institutes of Health Stroke Scale, 4) while being on the stroke unit. SDB was defined by apnea‐hypopnea index ≥5 episodes per hour. Peripheral endothelial function was assessed using peripheral arterial tonometry (EndoPAT‐2000). ED was defined by reactive hyperemia index ≤1.8. Forty‐one stroke patients underwent 1‐year follow‐up (390±24 days) after stroke. SDB was observed in 57% patients with acute ischemic stroke. Compared with patients without SDB, ED was more prevalent in patients with SDB (32% versus 64%; P<0.01). After adjustment for multiple confounders, presence of SDB remained independently associated with ED (odds ratio, 3.1; [95% confidence interval, 1.2–7.9]; P<0.05). After 1 year, the prevalence of SDB decreased from 59% to 15% (P<0.001). Interestingly, peripheral endothelial function improved in stroke patients with normalized SDB, compared with patients with persisting SDB (P<0.05). Conclusions: SDB was present in more than half of all patients with acute ischemic stroke and was independently associated with peripheral ED. Normalized ED in patients with normalized breathing pattern 1 year after stroke suggests a mechanistic link between SDB and ED

    Diagnosis and treatment of neurogenic dysphagia - S1 guideline of the German Society of Neurology.

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    INTRODUCTION Neurogenic dysphagia defines swallowing disorders caused by diseases of the central and peripheral nervous system, neuromuscular transmission, or muscles. Neurogenic dysphagia is one of the most common and at the same time most dangerous symptoms of many neurological diseases. Its most important sequelae include aspiration pneumonia, malnutrition and dehydration, and affected patients more often require long-term care and are exposed to an increased mortality. Based on a systematic pubmed research of related original papers, review articles, international guidelines and surveys about the diagnostics and treatment of neurogenic dysphagia, a consensus process was initiated, which included dysphagia experts from 27 medical societies. RECOMMENDATIONS This guideline consists of 53 recommendations covering in its first part the whole diagnostic spectrum from the dysphagia specific medical history, initial dysphagia screening and clinical assessment, to more refined instrumental procedures, such as flexible endoscopic evaluation of swallowing, the videofluoroscopic swallowing study and high-resolution manometry. In addition, specific clinical scenarios are captured, among others the management of patients with nasogastric and tracheotomy tubes. The second part of this guideline is dedicated to the treatment of neurogenic dysphagia. Apart from dietary interventions and behavioral swallowing treatment, interventions to improve oral hygiene, pharmacological treatment options, different modalities of neurostimulation as well as minimally invasive and surgical therapies are dealt with. CONCLUSIONS The diagnosis and treatment of neurogenic dysphagia is challenging and requires a joined effort of different medical professions. While the evidence supporting the implementation of dysphagia screening is rather convincing, further trials are needed to improve the quality of evidence for more refined methods of dysphagia diagnostics and, in particular, the different treatment options of neurogenic dysphagia. The present article is an abridged and translated version of the guideline recently published online ( https://www.awmf.org/uploads/tx_szleitlinien/030-111l_Neurogene-Dysphagie_2020-05.pdf )

    Hypertonic saline for fluid resuscitation after cardiac surgery (HERACLES): study protocol for a preliminary randomised controlled clinical trial.

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    BACKGROUND Intraoperative and postoperative management of cardiac surgery patients is complex, involving the application of differential vasopressors and volume therapy. It has been shown that a positive fluid balance has a major impact on postoperative outcome. Today, the advantages and disadvantages of buffered crystalloid solutes are a topic of controversy, with no consensus being reached so far. The use of hypertonic saline (HS) has shown promising results with respect to lower total fluid balance and postoperative weight gain in critically ill patients in preliminary studies. However, collection of more data on HS in critically ill patients seems warranted. This preliminary study aims to investigate whether fluid resuscitation using HS in patients following cardiac surgery results in less total fluid volume being administered. METHODS In a prospective double-blind randomised controlled clinical trial, we aim to recruit 96 patients undergoing elective cardiac surgery for ischaemic and/or valvular heart disease. After postoperative admission to the intensive care unit (ICU), patients will be randomly assigned to receive 5 ml/kg ideal body weight HS (7.3% NaCl) or normal saline (NS, 0.9% NaCl) infused within 60 min. Blood and urine samples will be collected preoperatively and postoperatively up to day 6 to assess changes in renal, cardiac, inflammatory, acid-base, and electrolyte parameters. Additionally, we will perform renal ultrasonography studies to assess renal blood flow before, during, and after infusion, and we will measure total body water using preoperative and postoperative body composition analysis (bioimpedance). Patients will be followed up for 90 days. DISCUSSION The key objective of this study is to assess the cumulative amount of fluid administered in the intervention (HS) group versus control (NS) group during the ICU stay. In this preliminary, prospective, randomised controlled clinical trial we will test the hypothesis that use of HS results in less total fluids infused and less postoperative weight gain when compared to the standard of intensive care in cardiac surgery patients. TRIAL REGISTRATION ClinicalTrials.gov, NCT03280745 . Registered on 12 September 2017

    Clinical testing of immunological strategies for the therapy of patients with severe sepsis / septic shock

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    Das Krankheitsbild „schwere Sepsis/ septischer Schock“ ist durch eine steigende Inzidenz bei persistierend hoher Mortalität charakterisiert. Viele Patienten überleben heute die frühe „pro-inflammatorische“ Phase und sterben im Verlauf an sekundären Infektionen. Als Antwort auf eine initial gesteigerte Freisetzung pro-inflammatorischer Mediatoren kommt es im Verlauf häufig zu einer kompensatorischen „hyporesponsiven“ Phase mit kompromittierten zellulären Immunfunktionen. Obwohl die zugrundeliegenden Mechanismen der sepsis-assoziierten Immunsuppression nicht umfassend bekannt sind, weisen experimentelle Daten darauf hin, dass Störungen der zellulären Immunität eine zielgerichtete mikrobielle Abwehr verhindern. Neben experimentellen Untersuchungen wurden in der vorliegenden Arbeit zwei klinische Ansätze zur Rekonstitution der monozytären Immunfunktion mittels Immunstimulation (GM-CSF) und extrakorporaler Entfernung von inhibitorischen Mediatoren (Immunadsorption) untersucht. Wir haben erstmalig eine immunmonitoring- basierte randomisierte placebo-kontrollierte Studie durchgeführt und konnten zeigen, dass Immunstimulation mit GM-CSF zu einer Wiederherstellung der Zytokinfreisetzung aus Monozyten als auch der mHLA-DR Expression (als Marker für monozytäre Immunfunktion) führt. GM-CSF verminderte zudem die Aktivität der Indolamin-2,3-Dioxygenase (IDO) und senkte Kynurenin-Metabolite. Da Kynurenine die Apoptose von Immunzellen induzieren können, könnte deren Reduktion zu einer verminderten Suszeptibilität gegenüber Infektionen beitragen. Weiterhin konnten wir zeigen, dass GM-CSF Gabe bei Patienten mit sepsis-assoziierter Immunsuppression zu einer signifikanten Verkürzung der Beatmungszeit führt. Da die statistische Kraft der von uns durchgeführten Studie nicht ausreicht klinische Effekte abschließend zu beurteilen, wird in einer größeren Folgestudie nun untersucht, ob eine solche Intervention die hohe Sterblichkeitsrate bei Patienten mit Sepsis reduziert. Unsere Daten zeigen weiterhin, dass eine Rekonstitution monozytärer Immunfunktion auch mittels extrakorporaler Reduktion inhibitorischer Faktoren möglich ist. Unsere Pilotstudie zur LPS-, IL6- und C5a- Immunadsorption testete erstmals einen selektiven antikörper-basierten extrakorporalen Ansatz bei Patienten mit schwerer Sepsis und septischem Schock. Eine simultane LPS-, IL-6- und C5a- Immunadsorption führte zu einer signifikanten Zunahme der mHLA-DR Expression. Im Vergleich zur Kontrollgruppe wurde ein günstigerer klinischer Verlauf bei behandelten Patienten beobachtet. Ob eine solche interventionelle Therapie Einfluss auf klinische Endpunkte bei Patienten mit Sepsis hat, wird in einer größer angelegten Folgestudie untersucht.Severe sepsis and septic shock are characterized by a rising incidence and a persistent high mortality rate. Today, many patients survive the early “pro- inflammatory” phase of the disease and will die in the later course of sepsis as a consequence of severe secondary/ nosocomial infections. As a response to initially elevated levels of “pro-inflammatory” mediators, a compensatory “hypo-responsive“ immunological phase characterized by compromised cellular immune functions can often be observed. Nevertheless, although the underlying molecular mechanisms of sepsis-induced immunosupression are not completely understood, experimental data indicate that a state of defective cellular immunity prevents a target-oriented anti-microbial defense. Here, two different clinical approaches to reconstitute monocytic immune function were developed and tested in clinical trials. Reconstitution of monocytic immune function was achieved by means of immunostimulation (GM-CSF) as well as by extracorporeal removal of inhibitory factors (using LPS-, IL-6, C5a- Immunoadsorption). For the first time, we performed an immune-monitoring guided randomized placebo-controlled trial in sepsis and were able to demonstrate that immunostimulation using GM-CSF restores monocytic immunity (as defined by assessment of the monocytic HLA-DR expression and ex vivo monocytic cytokine release). Moreover, GM-CSF reduces the activity of indoleamine-2,3-dioxygenase (IDO) and thus reduces serum levels of kynurenines. As kynurenines are critically involved in immune cell apoptosis, reduction of kynurenines could contribute to a diminished susceptibility to infection. In addition, we could demonstrate that adjunctive therapy with GM- CSF significantly shortens the time of mechanical ventilation in critically ill patients with severe sepsis and septic shock. As the respective trial was not powered to assess clinical endpoints, a larger trial which investigates a potential impact on mortality is currently started. As an alternative to immunostimulation, reconstitution of monocytic immunity may also be achieved by extracorporeal removal of inhibitory factors. For the first time, we developed and tested a simultaneous and selective (antibody-based) extracorporeal immune intervention in patients with severe sepsis/ septic shock. Data from our pilot trial on LPS-, IL6- and C5a- immunoadsorption show that selective simultaneous extracorporeal removal of LPS, IL6 and C5a significantly restores initially suppressed levels of monocytic HLA-DR. A beneficial impact on the clinical course of respective patients receiving the intervention was observed. Whether such a therapy influences clinical endpoints in patients with sepsis is now investigated in larger follow-up trials

    Physiology education for intensive care medicine residents: A 15-minute interactive peer-led flipped classroom session.

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    INTRODUCTION In acute care medicine, knowledge of the underlying (patho)-physiology is of paramount importance. This may be especially relevant in intensive care medicine, where individual competence and proficiency greatly depend on knowledge and understanding of critical care physiology. In settings with time constraints such as intensive care units (ICUs), time allotted to education is often limited. We evaluated whether introduction of a short, interactive, peer-led flipped classroom session is feasible and can provide ICU residents with a better understanding of critical care physiology. MATERIALS AND METHODS Using the flipped classroom concept, we developed a 15-minute peer-led interactive "physiology education" session to introduce a total of 44 residents to critical care physiology. Using a nine-item electronic survey with open questions and a five-point Likert scale, we analysed the overall concept with regard to feasibility, motivation, and subjective learning of critical care physiology. RESULTS The overall rate of response to the survey was 70.5% (31/44). The residents reported that these sessions sparked their interest (p = 0.005, Chi square 10.52), and that discussion and interaction during these sessions had promoted their knowledge and understanding. Both novice and experienced residents reported that new knowledge was imparted (both p<0.0001, Chi-square 32.97 and 25.04, respectively). CONCLUSIONS In an environment with time constraints such as the ICU, a 15-minute, interactive, peer-led flipped classroom teaching session was considered feasible and generally appeared useful for teaching critical care physiology to ICU residents. Responses to questions on questionnaires indicated that teaching sessions sparked interest and increased motivation. This approach may theoretically induce a modification in professional behaviour and promote self-directed learning. We therefore support the use of peer-led flipped classroom training sessions in the ICU. Whether these sessions result in improved ICU care should be addressed in subsequent studies

    Dysphagia in the intensive care unit in Switzerland (DICE) - results of a national survey on the current standard of care.

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    INTRODUCTION Oropharyngeal dysphagia (OD) is often observed in critically ill patients. In most affected patients OD persists throughout hospital stay and negatively impacts on clinical outcomes. Here we systematically explore routine clinical practice standards for recognition/screening, diagnosis and treatment of OD in accredited Swiss ICUs. METHODS An online, 23-item questionnaire-based survey was performed to investigate current standards of care for OD in Switzerland (DICE). All (n = 49) accredited Swiss teaching hospitals providing specialist training for adult intensive care medicine were contacted. Senior intensivists were interviewed on how they would screen for, diagnose and treat OD in the ICU. RESULTS The total response rate was 75.5%, with information available on all tertiary care academic centres. 67.6% (25/37) of institutions stated that they have established standard operating procedures for OD using a mostly sequential diagnostic approach (86.5%, 32/37). In 75.7% (28/37) of institutions, OD confirmation is performed without the use of instrumental techniques such as flexible (or fibre-endoscopic) evaluation of swallowing (FEES). Presumed key risk factors for OD were admission for acute neurological illness, long-term mechanical ventilation, ICU-acquired weakness and pre-existing neurological disease. Reported presumed OD-related complications typically include aspiration-induced pneumonia, increased rates of both reintubation and tracheostomy and increased ICU readmission rates. CONCLUSIONS Many Swiss ICUs have established standard operating procedures, with most using sequential clinical approaches to assess ICU patients at risk of dysphagia. OD confirmation is mostly performed using non-instrumental techniques. In general, it appears that awareness of OD and ICU educational curricula can be further optimised

    Dysphagia in COVID-19 -multilevel damage to the swallowing network?

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    We read with great interest the article "COVID-19: what if the brain had a role in causing the deaths?" by Tassorelli and co-workers, in which the authors generate and summarize hypotheses how SARS-CoV-2 may enter the peripheral and central nervous system and cause life-threatening complications [1]. With this letter we would like to contribute to this discussion by highlighting how different complications of COVID-19 may result in damage to central and peripheral parts of the swallowing network leading to dysphagia in critically ill COVID-survivors

    Time to onset of gastrointestinal bleeding in the SUP-ICU trial: a preplanned substudy.

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    BACKGROUND The aetiology and risk factors for clinically important gastrointestinal bleeding (CIB) in adult ICU patients may differ according to onset of CIB, which could affect the balance between benefits and harms of stress ulcer prophylaxis (SUP). METHODS We assessed the time to CIB in the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. We assessed if associations between baseline characteristics including allocation to SUP and CIB changed during time in the ICU, specifically in the later (after day two) compared to the earlier (first two days) period, using Cox models adjusted for SAPS II and allocation to SUP. Additionally, we described baseline characteristics and CIB episodes stratified by earlier/later/no CIB and 90-day mortality status. RESULTS CIB occurred in 110/3291 (3.3%) patients after a median of 6 (interquartile range 2-13) days; 25.5% of the episodes occurred early. Higher SAPS II was consistently associated with increased risk of CIB (hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.05 in the earlier period vs HR 1.02, 95% CI 1.01-1.03 in the later period; P=0.37); university hospital admission was associated with decreased risk of earlier CIB (HR 0.30, 95% CI 0.14-0.63); this significantly increased in the later period (to HR 0.85, 95% CI 0.53-1.37; P=0.02). Patients with later compared to earlier CIB received more transfusions and had more diagnostic/therapeutic procedures for CIB. CONCLUSIONS CIB mostly occurred more than two days after randomisation. University hospital admission was associated with significantly decreased risk of CIB in the earlier period only. This article is protected by copyright. All rights reserved

    Sex-specific outcome disparities in very old patients admitted to intensive care medicine: a propensity matched analysis

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    Female and male very elderly intensive patients (VIPs) might differ in characteristics and outcomes. We aimed to compare female versus male VIPs in a large, multinational collective of VIPs with regards to outcome and predictors of mortality. In total, 7555 patients were included in this analysis, 3973 (53%) male and 3582 (47%) female patients. The primary endpoint was 30-day-mortality. Baseline characteristics, data on management and geriatric scores including frailty assessed by Clinical Frailty Scale (CFS) were documented. Two propensity scores (for being male) were obtained for consecutive matching, score 1 for baseline characteristics and score 2 for baseline characteristics and ICU management. Male VIPs were younger (83 ± 5 vs. 84 ± 5; p  4; 38% versus 49%; p < 0.001) but evidenced higher SOFA (7 ± 6 versus 6 ± 6 points; p < 0.001) scores. After propensity score matching, no differences in baseline characteristics could be observed. In the paired analysis, the mortality in male VIPs was higher (mean difference 3.34% 95%CI 0.92–5.76%; p = 0.007) compared to females. In both multivariable logistic regression models correcting for propensity score 1 (aOR 1.15 95%CI 1.03–1.27; p = 0.007) and propensity score 2 (aOR 1.15 95%CI 1.04–1.27; p = 0.007) male sex was independently associated with higher odds for 30-day-mortality. Of note, male gender was not associated with ICU mortality (OR 1.08 95%CI 0.98–1.19; p = 0.14). Outcomes of elderly intensive care patients evidenced independent sex differences. Male sex was associated with adverse 30-day-mortality but not ICU-mortality. Further research to identify potential sex-specific risk factors after ICU discharge is warranted
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