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  • Hafner C, Soto-Gonzalez L, Wojta J, Tretter EV, Markstaller K, Klein KU
    Moderate Hyperoxia Induces Inflammation, Apoptosis and Necrosis and Human Umbilical Vein Endothelial Cells
    Abteilung für Anästhesie, Allgemeine Intensivmedizin und Schmerztherapie, Medizinische Universität Wien Goal of the study: Perioperative supplemental oxygen (O 2) therapy can cause hyperoxia with potential injury to the cardiovascular system and remote organs. The aim of this study was to investigate the effects ofmoderate constant and cyclic hyperoxia, on human umbilical vein endothelial cells (HUVEC) in comparison to different constant O2 concentrations using our developed bioreactor model, which allow exposure of cells to rapidly altered O 2-conditions. Methods HUVECs were exposed to constant hyperoxia (40% O 2), cyclic hyperoxia/anoxia (40%/0% O 2, average 20% O2), constant normoxia (21% O2) and constant anoxia (0% O2) using a cell culture bioreactor. Cell growth, viability and release of interleukin (IL)-6, IL-8 and macrophage migration inhibitory factor (MIF) were assessed at baseline and after 6, 12, 24 and 48h of treatment. A phosphokinase array was performed after 60 min of treatment to identify the cellular signalling pathways activated. Results and Discussion Constant hyperoxia and cyclic hyperoxia/anoxia impeded cell growth, reduced viability, triggered a pro-inflammatory response, as evidenced by IL-6, IL-8 and MIF reelase, and induced apoptosis and necrosis. The inflammatory and cytotoxicity responses were the highest in the constant hyperoxia group. Phosphokinase arrays revealed the different O2 concentrations activated distinct sets of cytoprotective and cell death-associated kinases, including mitogen-activated protein kinases (MAPKs), Src kinases, p53, Akt, mitogen- and stress-activated kinase (MSK), Lyn, Lck, p7056, signal transducers and activators of transcription (STATs) 5b and 6, glycogen synthase kinase (GSK) 3a/b and 5’AMP-activated protein kinases (AMPKs) 1/2. Conclusion Continous moderate hyperoxia as well as cyclic moderate hyperoxia/anoxia induced endothelial cell apoptosis and necrosis. Given the large surface of the vascular endothelium, elevated perioperative O2 may increase the risk of cardiovascular inflammation and injury.
  • Kietaibl C, Engel A, Puskas L, Klein KU, Erdoes G
    Extracorporeal Membrane Oxygenation (ECMO) in Intensive Care Patients is Associated with Gaseous Cerebral Microembolism: a Transcranial Doppler Study
    Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Austria Goal of the Study: Extracorporeal membrane oxygenation (ECMO) is frequently used in critically ill patients with cardiac or respiratory failure as a bridging option until organ recovery occurs. However, ECMO therapy may impair cerebral integrity by exposing patients to cerebral microemboli (ME).1 2 Our aim was to quantify (embolic load) and qualify (solid versus gaseous) cerebral ME in intensive care patients undergoing ECMO therapy. Methods: Sixteen patients under veno-arterial (VA) ECMO were investigated using transcranial Doppler ultrasound. Cerebral ME were detected as high-intensity transient signals in both middle cerebral arteries for 30 minutes in a period without any interventions (e.g. ECMO adjustment, change of syringe pumps). Statistical analyses were performed using the Wilcoxon signed-ranks test (median (25th; 75th percentile) and linear regression analysis. Results and Discussion: High-intensity transient signals were detected in all patients. The differentiation of ME primarily showed gaseous ME, while the number of solid ME was negligibly small (121.5 (41.75; 393.75) versus 2 (0; 7.25), p < 0.001). Emboli counts did neither correlate to blood flow (R2 = 0.025), gas flow (R2 = 0.033), or pump speed (R2 = 0.044) of VA ECMO, nor to the duration of VA ECMO therapy (R2 = 0.030). Our results reveal that, similarly to haemodialysis therapy3, gaseous ME pass common filter systems and enter the blood circulation. Conclusion: Critically ill patients under VA ECMO are exposed to a considerable load of gaseous cerebral ME. Individual patient factors (e.g. fluid infusions, intravenous catheters, comorbidities) may contribute to the embolic load, which may play a key role in adverse cerebral outcome. References: Zanatta P, Forti A, Bosco E, et al. Microembolic signals and strategy to prevent gas embolism during extracorporeal membrane oxygenation. J Cardiothorac Surg 2010; 5:5 Risnes I, Wagner K, Nome T, et al. Cerebral outcome in adult patients treated with extracorporeal membrane oxygenation. Ann Thorac Surg 2006; 81:1401-6 Erdoes G, Kietaibl C, Boehme S, et al. Cerebral Gaseous Microemboli are Detectable During Continuous Venovenous Hemodialysis in Critically Ill Patients: An Observational Pilot Study. J Neurosurg Anesthesiol 2016 [Epub ahead of print]
  • Tscherny K, Roth D, Herkner H
    Assessment tools for Health Related Quality of Life in Critical Care patients- an analysis based on Cochrane reviews
    Department of Emergency Medicine, Medical University of Vienna, Austria Goal of the study: Health-related quality of life (HRQoL), defined as "the functional effect of an illness and its treatment upon a patient as perceived by the patient"1, might provide better information about the actual impact of a therapy; detect less obvious or unexpected effects; and is among the most relevant outcomes for patients2. We aimed to evaluate the frequency of reporting of HRQoL in RCTs in critical care medicine, to analyse differences between studies reporting HRQoL and those not, and to evaluate HRQoL assessment instruments used for. Methods: The Cochrane Database of Systematic Reviews was searched for all reviews of RCTs on critical care published after 2000. Study characteristics such as sample size, type of intervention, disease-spectrum, ICU-setting, hospital-setting, funding, effect size, number and type of outcomes, risk of bias, were extracted. HRQoL-specific data included whether HRQoL was reported, and which instrument was used. These HRQoL instruments were then analysed for development, reliability and validity. Results and Discussion: 468 individual studies from 136 reviews representing 88,585 patients were included. 39 (8%) reported HRQoL as an outcome, 1 (0.2%) study as a primary outcome. 13 different assessment instruments were identified (See Table 1 for details). No differences in study characteristics were found between studies reporting HRQoL and those not. None of the instruments was developed on the basis of a HRQoL Model. The available data for quality criteria of the tools varied from numerous to marginal testing. Conclusion: Reporting HRQoL is uncommon in RCTs of critical care, with only 8% of studies including measures of HRQoL. Only one assessment tool (EuroQol) was able to depict the whole concept of HRQoL, despite the fact it was not developed on the basis of a model. All other tools represented only parts of the HRQoL concept. References 1. Acquadro C. Health-related quality of life in the Context of Cochrane reviews. In: 7th International Cochrane Colloquium 1999; Rome. 2. Patrick D, GH G. Cochrane Patient Reported Outcomes Methods Group. In: About The Cochrane Collaboration (Methods Groups), Issue 3; 2007. Table 1 Korrespondenzadresse: Katharina Tscherny Universitätsklinik für Notfallmedizin, Medizinische Universität Wien Währinger Gürtel 18-20 1090 Wien katharina_dorothea@yahoo.de
  • Köstenberger M, Likar R, Neuwersch S, Höfner E, Hamdy S, Weissmann H
    Pharyngeal Electrical Stimulation (PES) - a novel treatment for dysphagia in mechanically ventilated neuro-ICU patients
    Landeskrankenanstalten-Betriebsgesellschaft - KABEG, Klagenfurt am Wörthersee, Austria PHADER Chief Investigator; Centre for Gastrointestinal Sciences, University of Manchester, Manchester, UK Introduction: Dysphagia is a common symptom (incidence 50% to 70%) in patients admitted to ICU that significantly impacts on patient outcomes (Ajemian et al. 2001; Skoretz et al. 2010). Duration of mechanical ventilation is independently associated with post-extubation-dysphagia (93%) which is independently associated with longer hospital lengths of stay in patients with primary neurological disorders (Macht et al., 2013). Pharyngeal Electrical Stimulation (PES) has been shown to measurably improve swallowing function in dysphagic stroke patients in studies spanning over a decade and more recently has been shown to have significant benefits in airway protection in tracheotomised stroke patients weaned from mechanical ventilation (Suntrup et al. 2015). Aim: To evaluate the benefits of PES in ICU-admitted patients with neurogenic dysphagia due to multiple causes. Methods: Patients (n=17) admitted to our ICU who were intubated or tracheotomised and on mechanical ventilation due to neurological disorders (Stroke (10), Critical Illness Polyneuropathy (CIP) (4), other (3)) were screened for severe dysphagia (minimum scores: dysphagia severity ratings scale = 6 (a 13-point scale where 0 = normal, 12 = severe; Jayasekeran et al. 2010), penetration-aspiration scale = 4) and their suitability for PES treatment. Patients meeting the inclusion/exclusion were subsequently recruited into a multicentre registry (PHADER, ISRCTN87110165). All patients provided consent as per the local ethics committee approval rules (ref. A16/14). Patients were assessed at baseline and after finishing PES treatment (between day 1-3 (FU1); between day 7-21 (FU2); between day 50-120 (FU3)). Data are shown as Mean ± Standard Deviation (SD). Results: Group (n=17) mean improvement from baseline to FU3 was observed in all swallowing measures: PAS = 5.2 ± 1.8 points (range 7.6-2.4), DSRS = 7.8 ± 4.1 points (range 12-4.2) (Figure 1). In a subgroup of patients (n=4) that received PES treatment whilst intubated, further exploratory analyses were performed. In these patients, Fiberoptic Endoscopic Evaluation of Swallowing assessments prior to PES treatment revealed that it was not possible to trigger swallowing reflexes and massive pooling of saliva in the entire pharynx (PAS = 7.8 ± 0.5) was observed. Therefore extubation was not possible and tracheotomy was the recommended airway management plan. Following PES treatment, all 4 patients showed significant improvement in swallowing (Figure 2), were extubated and tracheotomy prevented. Analysis revealed mean time from disorder onset to PES treatment was on average 6 days shorter in the subgroup (23.8 ± 14.5 days) when compared to the remaining patients (29.6 ± 17.5 days). Conclusion:In this uncontrolled open label study, PES was associated with improved swallowing and may benefit those on ventilation by accelerating extubation and potentially preventing tracheotomy and should be explored further in future randomised controlled studies like the PHAST-TRAC study (ISRCTN18137204). Figure 1: Swallowing improvement after PES (n=17) Figure 2: Swallowing improvement: Subgroup Analyses in subgroups (Group 1 - PES during intubation (n=4), Group 2 - PES without intubation (n=13)) References: Ajemian et al., Arch Surg. 2001 Apr;136(4):434-7 Jayasekeran et al., Gastroent. 2010 May;138:1737-46 Macht et al., Crit Care. 2013 Jun 20;17(3):R119. Skoretz et al., Chest. 2010 Mar;137(3):665-73. Suntrup et al., Int Care Med. 2015 Sep;41(9):1629-37
  • Song I-K, Kim E-H, Lee J-H, Kim J-T, Kim H-S
    Pharmacodynamic model of intravenous dexmedetomidine in mechanically ventilated children
    Seoul National University Hospital Objective: Dexmedetomidine is a selective alpha-2 adrenerginc agonist with significant sedative and analgesic effects. We investigated the pharmacodynamics (PDs), efficacy, and safety of dexmedetomidine in mechanically ventilated children. Methods: Children aged between 2 and 12, who were mechanically ventilated in the intensive care unit (ICU), were randomized into two groups according to the intravenous dexmedetomidine dosing regimen. Low dose group (n = 15) received a loading dose of 0.25 μg/kg for 10 min followed by a maintenance dose of 0.25 μg/kg/h for 50 min and high dose group (n = 14) received a loading dose of 0.5 μg/kg followed by a maintenance dose of 0.5 μg/kg/h for same time. The sedative effect of dexmedetomidine was assessed by Bispectral Index and University of Michigan Sedation Scale. Electrocardiograms, and vital signs including blood pressure, heart rate, and pulse oximetry were also monitored. Results: PD of dexmedetomidine was best described using a linear-rebound model. The estimates of parameters were: ke0 (min-1) = 0.038 and koff (min-1) = 0.88. There were no serious adverse events or hemodynamic changes requiring dexmedetomidine discontinuation. Conclusions: High dose of dexmedetomidine was suitable for postoperative sedation in mechanically ventilated children in the ICU. An integrated linear-rebound model was developed for explaining pharmacodynamic effects of dexmedetomidine.
  • Ganzhorn A, Milder L, Fuchs G, Wegscheider T
    Critical Care Transfer: Der Transport kritisch kranker Patientinnen und Patienten im innerklinischen Bereich - Effekte eines simulationsbasierten Ausbildungsprogrammes für Medizinstudierende
    Universitätsklinik für Anästhesiologie und Intensivmedizin, Klinische Abteilung für Spezielle Anästhesiologie, Schmerz-und Intensivmedizin, Medizinische Universität Graz Zielsetzung Bei innerklinischen Transporten kritisch Kranker kommt es trotz Begleitung durch ärztliches Personal regelmäßig zu vermeidbaren, teils lebensbedrohlichen Zwischenfällen1. Obwohl durch strukturierte Ausbildung Zwischenfälle reduziert werden können und Fachleitlinien dies empfehlen, fehlt es im österreichischen Hochschulraum bis heute an einem strukturierten Ausbildungsprogramm, um medizinisches Fachpersonal auf die Herausforderungen innerklinischer Transporte vorzubereiten2,3. Mit dem Ziel diese Lücke zu schließen, wurde an der Medizinischen Universität Graz ein simulationsbasiertes, leitlinienorientiertes Ausbildungsprogramm für Medizinstudierende entwickelt, implementiert und hinsichtlich seiner Effektivität evaluiert. Methode Die "Grazer SIMLine: Critical Care Transfer" vermittelt als Teil der Lehrveranstaltungsreihe "Die Grazer SIMLine" in 30 Unterrichtseinheiten die leitlinienkonforme Planung und Durchführung innerklinischer Transporte kritisch Kranker. Die theoretischen und praktischen Ausbildungsinhalte orientieren sich an aktuellen Empfehlungen internationaler Fachgesellschaften und berücksichtigen die häufigsten kritischen Transportzwischenfälle. In kurzen, einführenden Seminaren erwerben die Studierenden zentrale theoretische Grundlagen der Intensivmedizin. Workshops, Algorithmus- und High-Fidelity-Simulationstrainings vermitteln in Kleingruppen technische und kommunikative Kompetenzen aus den Bereichen PatientInnenassessment und Übergabe, hämodynamisches Monitoring, invasive und nicht-invasive Beatmung, Umgang mit zentralen Invasivitäten und Drainagen sowie das Management der häufigsten Transportkomplikationen. Praktische Procedure-Proficiency-Checks (PPCs) sowie theoretische Formativ-Integrative Tests (FITs) bilden den Lernfortschritt der Studenten und Studentinnen multidimensional ab. Zum Abschluss der Lehrveranstaltung absolvieren die TeilnehmerInnen in kleinen Teams einen vollständig simulierten PatientInnentransport mit anschließendem Debriefing nach "Anesthesia Crisis Resource Management" (ACRM)-Standard. Ergebnisse und Diskussion In den audiovisuell aufgezeichneten Abschlussszenarien erreichten die 19 TeilnehmerInnen eine durchschnittliche Übereinstimmung mit den Kriterien der Leitlinien von 91%. Die theoretischen Überprüfungen der AbsolventInnen zeigten eine signifikante Steigerung der theoretischen Testergebnisse um 25% (p<0,001) gegenüber einer Kontrollgruppe, bestehend aus 24 Humanmedizinstudierenden gleichen Studienfortschrittes (siehe Abbildung 1). In den praktischen Checks wurden 85% der gestellten Aufgaben korrekt ausgeführt. Abbildung 1: Lernerfolg in den verschiedenen Themenbereichen Schlussfolgerung Durch die Kombination aus theoretischer Wissensvermittlung in Seminaren und praktischer Anwendung des Erlernten im realitätsnahen, simulierten Umfeld versetzt die Lehrveranstaltung "Die Grazer SIMLine - Critical Care Transfer" ihre AbsolventInnen in die Lage, innerklinische Intensivtransporte im simulierten Umfeld leitliniengerecht durchzuführen. Zukünftige Lehrveranstaltungen dieses Formats werden zeigen, ob dieses Lehrveranstaltungskonzept auch für den postgraduellen Bereich geeignet ist. Literatur: Parmentier-Decrucq E, Poissy J, Favory R, et al. Adverse events during intrahospital transport of critically ill patients: incidence and risk factors. Ann. Intensive Care 2013;3(1):10. doi:10.1186/2110-5820-3-10. Choi HK, Shin S Do, Ro YS, Kim DK, Shin SH, Kwak YH. A before- and after-intervention trial for reducing unexpected events during the intrahospital transport of emergency patients. Am. J. Emerg. Med. 2012;30(8):1433-40. doi:10.1016/j.ajem.2011.10.027. Frank O. Empfehlungen - Innerklinische Transporte Kritisch Kranker Patienten. Zürich: Stiftung für Patientensicherheit; 2014. Available at: http://www.patientensicherheit.ch/de/publikationen/Infomaterial-Schriften-B-cher.htm?prodId=d_aa2380b3-ee45-4d5b-996f-0dff2c8743e6l. Acknowledgement Unser Dank gilt der Firma Drägerwerk AG & Co KGaA für die unentgeltliche, apparative Unterstützung dieses innovativen Ausbildungskonzeptes. Korrespondenzadresse: Dr. Thomas Wegscheider Universitätsklinik für Anästhesiologie und Intensivmedizin, Klinische Abteilung für Spezielle Anästhesiologie, Schmerz-und Intensivmedizin Medizinische Universität Graz Auenbruggerplatz 29 8036 Graz Email: thomas.wegscheider@medunigraz.at