Refine
Has Fulltext
- yes (346)
Is part of the Bibliography
- yes (346)
Year of publication
Document Type
- Journal article (190)
- Doctoral Thesis (155)
- Book article / Book chapter (1)
Keywords
- COVID-19 (15)
- Blut-Hirn-Schranke (13)
- blood-brain barrier (12)
- ARDS (11)
- inflammation (11)
- Maligne Hyperthermie (9)
- Myokardprotektion (9)
- Schmerz (9)
- endothelial cells (8)
- malignant hyperthermia (8)
- molecular docking (8)
- Schlaganfall (7)
- blood–brain barrier (7)
- pain (7)
- stroke (7)
- Anästhesie (6)
- Desfluran (6)
- Entzündung (6)
- Erbrechen (6)
- Herzinfarkt (6)
- PONV (6)
- Präkonditionierung (6)
- SARS-CoV-2 (6)
- Schmerzforschung (6)
- cytokines (6)
- preconditioning (6)
- sepsis (6)
- volatile anesthetics (6)
- CRPS (5)
- Medizin (5)
- Schmerztherapie (5)
- Tight junction (5)
- in vitro (5)
- microRNA (5)
- tight junctions (5)
- Ischämische Präkonditionierung (4)
- Neuropathischer Schmerz (4)
- Polytrauma (4)
- Sevofluran (4)
- acute respiratory distress syndrome (4)
- blood brain barrier (4)
- breast cancer (4)
- cardioprotection (4)
- chronic pain (4)
- critical illness (4)
- desflurane (4)
- expression (4)
- halothane (4)
- microdialysis (4)
- neuropathic pain (4)
- sevoflurane (4)
- traumatic brain injury (4)
- Amisulprid (3)
- Anästhetikum (3)
- Chronischer Schmerz (3)
- First Responder (3)
- Gibbs free energy of binding (3)
- HFOV (3)
- Halothan (3)
- Intensivtransport (3)
- Kardioprotektion (3)
- Komplexes regionales Schmerzsyndrom (3)
- Meerschweinchen (3)
- Mikrodialyse (3)
- Narkose (3)
- Nausea (3)
- Neuralgie (3)
- Notfallmedizin (3)
- Propofol (3)
- Regionalanästhesie (3)
- Schädel-Hirn-Trauma (3)
- Succinylcholine (3)
- Systematische Übersichtsarbeit (3)
- Therapie (3)
- Tiermodell (3)
- Ultraschall (3)
- Ventilation (3)
- Videolaryngoskopie (3)
- Volatile Anästhetika (3)
- acute kidney injury (3)
- airway management (3)
- analgesia (3)
- astrocytes (3)
- atrial fibrillation (3)
- caffeine (3)
- central nervous system (3)
- claudin-1 (3)
- critical care (3)
- electrical impedance tomography (3)
- gene expression (3)
- intensive care (3)
- ischemia (3)
- macrophages (3)
- metabolic test (3)
- metabolischer Test (3)
- minimal invasiv (3)
- molecular dynamics (3)
- myocardial infarction (3)
- oxygen/glucose deprivation (3)
- patient blood management (3)
- postoperative nausea and vomiting (3)
- pregnancy (3)
- skeletal muscle (3)
- systematic review (3)
- ventilation (3)
- Übelkeit (3)
- Alzheimer’s disease (2)
- Analgesie (2)
- Anästhesiologie (2)
- Anästhetika-induzierte Postkonditionierung (2)
- Anästhetika-induzierte Präkonditionierung (2)
- BK-Kanal (2)
- Beatmung (2)
- Blut-Nerven-Barriere (2)
- Blut-Nerven-Schranke (2)
- Blutverlust (2)
- Bupivacain (2)
- CNS disorders (2)
- Claudin (2)
- Claudin-1 (2)
- Claudine <Biologie> (2)
- Coronavirus (2)
- Covid-19 (2)
- Dünndarm (2)
- Dünndarmmotilität (2)
- ECMO-Therapie (2)
- Elektroimpedanztomographie (2)
- Endothel (2)
- Endotracheale Intubation (2)
- Erste Hilfe (2)
- Extracorporeal Membrane Oxygenation (2)
- Extrakorporale Membranoxygenierung (2)
- Geburtshilfe (2)
- Germany (2)
- HES (2)
- Hochfrequenz-Oszillations-Ventilation (2)
- Hydroxyethylstärke (2)
- Inflammation (2)
- Injury Severity Score (2)
- Intensivkapazitäten (2)
- Intubation (2)
- Ionenkanal (2)
- Ischämie (2)
- Ischämie/Reperfusionsschaden (2)
- Lactate (2)
- Laryngoskop (2)
- Laryngoskopie (2)
- Lungenfunktion (2)
- MK801 (2)
- Malignant hyperthermia (2)
- Metaanalyse (2)
- Metoprolol (2)
- Monitoring (2)
- NMDA-Antagonist (2)
- NMDA-Rezeptor (2)
- Narkoseeinleitung (2)
- Narkosezwischenfall (2)
- Nervenblockade (2)
- Nervenstimulation (2)
- Notfall (2)
- Operation (2)
- Opioide (2)
- Pandemie (2)
- Paracetamol (2)
- Patientengesteuerte Analgesie (2)
- Peristaltik (2)
- Phospholipide (2)
- Plexus brachialis (2)
- Proteasom (2)
- Pädiatrie (2)
- QST (2)
- Qualitätsmanagement (2)
- Reanimation (2)
- Remifentanil (2)
- Resuscitation (2)
- Rettungskette (2)
- Ropivacain (2)
- Schwangerschaft (2)
- Sectio caesarea (2)
- Sepsis (2)
- Spinalanästhesie (2)
- TRPA1 (2)
- Toll like receptors (2)
- Volumensubstitution (2)
- Volumentherapie (2)
- Wiederbelebung (2)
- ZO-1 (2)
- acetaminophen (2)
- acute lung injury (2)
- age-related hearing loss (2)
- aging (2)
- anaemia (2)
- anaesthesiology (2)
- analysis of variance (2)
- anesthetics (2)
- animal model (2)
- anticoagulation (2)
- antimicrobial stewardship (2)
- av-ECLA (2)
- barrier (2)
- blood (2)
- blood gas analysis (2)
- blood loss (2)
- blood nerve barrier (2)
- blood-nerve barrier (2)
- blood–labyrinth barrier (2)
- brain (2)
- bridging (2)
- cEND (2)
- capsaicin (2)
- cerebEND (2)
- chemokines (2)
- clinical trial (2)
- comparison (2)
- complex regional pain syndrome (2)
- critically ill (2)
- cytotoxicity (2)
- difficult airway (2)
- endotoxemia (2)
- etomidate (2)
- evaluation (2)
- exosomes (2)
- glioma (2)
- glucocorticoid receptor (2)
- glucocorticoids (2)
- heart failure (2)
- hyperalgesia (2)
- in vitro contracture test (2)
- inflammatory pain (2)
- iron deficiency (2)
- ischemia-reperfusion injury (2)
- ischemia/reperfusion injury (2)
- lactate (2)
- lessons learned (2)
- lungenprotektive Beatmung (2)
- mRNA (2)
- mass casualties (2)
- medical nutrition therapy (2)
- meta-analysis (2)
- miRNS (2)
- mice (2)
- minimally invasive (2)
- mitochondrial permeability transition pore (2)
- monocytes (2)
- multidrug resistance (2)
- neuropathy (2)
- neurotrophins (2)
- oxidative stress (2)
- pain therapy (2)
- perineurium (2)
- perioperative care (2)
- peristalsis (2)
- postoperative (2)
- postoperative bleeding (2)
- propofol (2)
- randomized controlled trial (2)
- rat (2)
- resuscitation (2)
- rolipram (2)
- rtPA (2)
- safety (2)
- simulation (2)
- small intestine (2)
- spiral ganglion neuron (2)
- terror attack (2)
- therapy (2)
- thromboembolism (2)
- thrombosis (2)
- tight junction (2)
- ultrasound (2)
- video laryngoscopy (2)
- vitamin C (2)
- vitamin D (2)
- volatile Anästhetika (2)
- vomiting (2)
- zinc (2)
- (cardiac) surgery (1)
- 3D in vitro model (1)
- 4-HNE (1)
- 4D (1)
- 6-percent hydroxyethyl starch (1)
- ABC-Transporter (1)
- AD pathogenesis (1)
- AED (1)
- ANIMAX (1)
- APC (1)
- APD421 (1)
- ARDS (acute respiratory distress syndrome) (1)
- ATP-binding cassette transporter (1)
- Accelerometry (1)
- Acetylsalicylsäure (1)
- Acute Kidney Injury (1)
- Acute Respiratory Distress Syndrome (1)
- Adherens-Junction (1)
- Afferent nerve stimulation (1)
- Airtraq (1)
- Akutes Lungenversagen (1)
- Akutes Nierenversagen (1)
- Alarmierungsalgorithmus (1)
- Algorithmus (1)
- Allgemeinanästhesie (1)
- Alternative (1)
- Alzheimer's disease (1)
- Amisulprid Kombinationsprophylaxe (1)
- Amisulprid PONV (1)
- Analgesia (1)
- Analgetika (1)
- Animax (1)
- Anthocyane (1)
- Anthocyanidine (1)
- Antidepressiva (1)
- Antiinflammatory agents (1)
- Antikoagulation (1)
- Antikonvulsiva (1)
- Antineuropathika (1)
- Antinozizeption (1)
- Anwenderschulung (1)
- ApoA-I D-4F (1)
- Apoptosis (1)
- Apple Watch 7 (1)
- Articular afferent (1)
- Arztbegleiteter Patiententransport (1)
- Aspartate Aminotransferases (1)
- Assistierte Beatmung (1)
- Atemwegsmanagement (1)
- Audiovisuelle Medien (1)
- Augenbewegungen (1)
- Augenfolgebewegung (1)
- Ausstattung (1)
- AutoPulse (1)
- Autoantikörper (1)
- Automated External Defibrillators (1)
- Automatischer Externer Defibrillator (1)
- Autophagie (1)
- Autophagie <Physiologie> (1)
- Autophagy (1)
- Außerklinischer Herz-Kreislauf-Stillstand (1)
- Axl tyrosine kinase (1)
- Axonschaden (1)
- BDNF (1)
- BIRC7 (1)
- BIS (1)
- BK channel (1)
- BV-2 (1)
- Barriereeigenschaften (1)
- Bauchlage (1)
- Befindlichkeit (1)
- Behinderung (1)
- Berichterstattung (1)
- Beta-Rezeptor (1)
- Betaadrenerge Rezeptoren (1)
- Bias (1)
- Bland–Altman (1)
- Blood-Brain-Barrier (1)
- Blood–brain barrier (1)
- Blut-Luft-Schranke (1)
- Blut-Nerve-Schranke (1)
- Blut-Rückenmarkschranke (1)
- Blutgerinnung (1)
- Blutgerinnungshemmung (1)
- Blutvolumen (1)
- Bowel (1)
- Bradykinin (1)
- Breastcancer (1)
- Brustkrebs (1)
- C-MAC (1)
- C6 (1)
- CASP (1)
- CCL2 (1)
- CLP-Verfahren (1)
- CLP-procedure (1)
- CNS diseases (1)
- CNS injury (1)
- COVID 19 (1)
- COVID-19 pandemic (1)
- COVID-19-ARDS (1)
- COVID-19-Pademie (1)
- COVID‐19 (1)
- CPIP (1)
- CSM (1)
- CT (1)
- CX3CL1 (1)
- CXCL13 (1)
- CXCR4-targeting (1)
- Ca2+ homeostasis (1)
- Ca2+ ion analysis (1)
- Ca2+ leak (1)
- Ca2+ oscillation (1)
- CaM-Kinase II (1)
- Cadherine (1)
- Calcium Imaging (1)
- Calcium-Calmodulinkinase II (1)
- Capsaicin (1)
- Carrier-Proteine (1)
- Catecholamine (1)
- Catheter duration (1)
- Central venous-pressure (1)
- Cerebral Oxygen Saturation (1)
- Cerebral edema (1)
- Charmi-Index (1)
- Chemokin CXCL10 (1)
- Chest-Compression rate (1)
- Chirurgie (1)
- Cholesterintransporter (1)
- Chronische Schmerzen (1)
- Chronische Wunden (1)
- Claudin-12 (1)
- Claudin-5 (1)
- Claudine (1)
- ClearSight\(^®\) (1)
- Clusterkopfschmerz (1)
- Co-Analgetika (1)
- Cocamidopropylbetain (1)
- Cochrane Review (1)
- Coffein (1)
- Colloids (1)
- Complex regional pain syndrome (1)
- Complication (1)
- Computertomografie (1)
- Computertomographie (1)
- Conductance Katheter (1)
- Controlled cortical impact (1)
- Corona virus (1)
- Coronavirus Disease 2019 (1)
- Corticotropin-Releasing-Factor (1)
- Creatine Kinase (1)
- Critical Care (1)
- Critically-ill patients (1)
- Crystalloids (1)
- Cutaneous hyperemia (1)
- Cyclodextrine (1)
- D-4F (1)
- DAMGO (1)
- DRG (1)
- Darm (1)
- Darmmotilität (1)
- Darmmotilitätsstörung (1)
- Detergentien (1)
- Deutscher Schmerzfragebogen (1)
- Dexamethason (1)
- Diabetische Polyneuropathie (1)
- Diagnose (1)
- Dimethylsulfoxid (1)
- Disaster response (1)
- Dissertation (1)
- Dokumentationsqualität (1)
- Doppel-Ganzkörper-CT-Schockraum (1)
- Doppellumentubus (1)
- Dorsal Root Ganglion (1)
- Drug Targeting (1)
- Dünndarmfunktion (1)
- Dünndarmperistaltik (1)
- E06 mAb (1)
- ECLA (1)
- ECMO (1)
- ECMO indication (1)
- ECMO therapy (1)
- ELISA (1)
- ER Ca2+ imaging (1)
- ER Ca2+ store (1)
- Einfluss (1)
- Elastomere Schmerzpumpe (1)
- Elective cesarean-section (1)
- Electrical impedance tomography (1)
- Elektroakupunktur (1)
- Elektroencephalogramm (1)
- Emery-Dreifuss muscular dystrophy (1)
- Endogenous opioids (1)
- Endorphin (1)
- Endothelzelle (1)
- Endothelzelllinie (1)
- Enoxaparin (1)
- Entzündungsmodell (1)
- Epidural Analgesia (1)
- Epiduralanästhesie (1)
- Erk (1)
- Ernährungstherapie (1)
- Erwachsene (1)
- Ethanol (1)
- Etomidat (1)
- Evaluation (1)
- Everolimus (1)
- Exercise testing (1)
- Exosom <Vesikel> (1)
- Expertise (1)
- Expression (1)
- Extracorporeal life support (1)
- Extrakorporale kardiopulmonale Reanimation (1)
- Eye-Tracking (1)
- FIFA World Cup 2006 (1)
- Faktor V-Leiden (1)
- Fentanyl (1)
- Fibromyalgie (1)
- Fibromyalgiesyndrom (1)
- Fisher Z-score transformation (1)
- Fitbit Sense (1)
- Fluorchinolone (1)
- Fluorescence (1)
- Fluoreszenz (1)
- Fluoreszenzspektrometer (1)
- Formulierung (1)
- Fresh Freeze Plasma (1)
- GABA\(_A\) (1)
- GBM (1)
- GDNF (1)
- GRO alpha (1)
- Garmin Fenix 6 Pro (1)
- Geburt (1)
- Geburtshilfliche Intensivmedizin (1)
- Geburtsschmerz (1)
- Gene expression vectors (1)
- General anaesthesia (1)
- Geriatrie (1)
- German Pain Questionnaire (1)
- GlideScope-Videolaryngoskop (1)
- GlideScope-videolaryngoscope (1)
- Glucocorticosteroidrezeptor (1)
- Glucosetransport (1)
- Glucosetransportproteine (1)
- Glukokortikoide (1)
- Glutamin (1)
- Graphen (1)
- Gutmotility (1)
- H2O2 (1)
- HCW (1)
- HER2 conversion (1)
- HER2 targeted therapy (1)
- HER2-low (1)
- HIV (1)
- HK-2 Zellen (1)
- HPβCD (1)
- HUVEC (1)
- Halothane (1)
- Haltung (1)
- Hamman's syndrome (1)
- Healthcare Cost (1)
- Healthcare Economics (1)
- Helfer vor Ort (1)
- Hernie (1)
- Herzinfarktforschung (1)
- High-Frequency Ventilation (1)
- High-frequency oscillatory ventilation (1)
- High-volume-low-concentration-Technik (1)
- Hirnendothelzellen (1)
- Hirnkreislauf (1)
- Hirnmetastasen (1)
- Hirnschädigung (1)
- Hirnödem (1)
- Hochwasser (1)
- Horowitz Quotient (1)
- Hospital emergency plan (1)
- Humanalbumin (1)
- Hyberbaric oxygen therapy (1)
- Hydroxyethyl starch (1)
- Hydroxyäthylstärke (1)
- Hyperalgesie (1)
- Hypermetabolismus (1)
- Hypertonic saline 7.5-percent (1)
- Hypertonie (1)
- Hypovolämischer Schock (1)
- Hypoxie (1)
- HÄS (1)
- Hämatogene Oxidationstherapie (1)
- H�modynamik (1)
- ICU capacities (1)
- ICU staff (1)
- ICU treatment (1)
- IENFD (1)
- IL-6 (1)
- IL6 (1)
- ILA (1)
- IMA2.1 (1)
- INR rebound (1)
- ISS (1)
- ITW (1)
- IgG (1)
- IgY (1)
- Ileuseinleitung (1)
- Immunonutrition (1)
- Impedanztomografie (1)
- In Situ Nick-End Labeling (1)
- In Vitro Kontrakturtest (1)
- In vitro contracture test (1)
- In vitro models (1)
- In-hospital cardiac arrest (1)
- Induction of general anaesthesia (1)
- Infektionswellen (1)
- Inferior Vena Cava (1)
- Inflammatory Pain (1)
- Inflammatory pain (1)
- Inhalationsanaesthesien (1)
- Inhalationsnarkotikum (1)
- Intensivmedizin (1)
- Intensivpersonal (1)
- Intensivstation (1)
- Interactive Ventilatory Support (1)
- Interaktionsanalyse (1)
- Interdisziplinäre Schmerztherapie (1)
- Interhospitaltransfer (1)
- Interhospitaltransport (1)
- Interskalenäre Blockade (1)
- Intubationsschwierigkeiten (1)
- Intubationszeit (1)
- Inzidenz <Medizin> (1)
- Ischämische Postkonditionierung (1)
- Isosteviol-Natrium (1)
- Joint pain (1)
- Kaninchen (1)
- Karbonylierung (1)
- Katastrophe (1)
- Katastrophenschutz (1)
- Katecholamine (1)
- Katheterliegedauer (1)
- Knockout (1)
- Koffein (1)
- Kohlendioxidpartialdruckmessung (1)
- Kohlenstoffmonoxid (1)
- Kolloidale Volumenersatztherapie (1)
- Kombinationsprophylaxe PONV (1)
- Komplikation (1)
- Kontroll-Computertomografie (1)
- Krankenhausatlas (1)
- Kritische Infrastruktur (1)
- Künstliche Beatmung (1)
- Künstliche Lunge (1)
- L-Cystein (1)
- L-Lactate Dehydrogenase (1)
- L-cysteine (1)
- LPS (1)
- LRP1 (1)
- Labour Analgesia (1)
- Labour Pain (1)
- Lactated ringers solution (1)
- Laktat (1)
- Lamarckian genetic algorithms (1)
- Langerhans cells (1)
- Langzeitbeatmung (1)
- Lasermikrodissektion (1)
- Latrophilin (1)
- Leber (1)
- Lessons Learnt (1)
- Linksventrikuläre Funktionsparameter (1)
- Lokalanästhesie (1)
- Lokalanästhetikaintoxikation (1)
- Longitudinal analysis (1)
- Lucas CPR (1)
- Luftembolie (1)
- Lung Injury (1)
- Lunge (1)
- Lungenalveole (1)
- Lungenschädigung (1)
- Lungenultraschall (1)
- Lungprotective Ventilation (1)
- Luzindol Ileus (1)
- Lösungsmittel (1)
- MMP9 (1)
- Macintosh (1)
- Macintosh-Laryngoskop (1)
- Macintosh-laryngoscope (1)
- Macrophage Migration Inhibitory Factor (MIF) (1)
- Major abdominal surgery (1)
- Malignant Hyperthermia (1)
- Mammakarzinom (1)
- Mangansuperoxiddismutase (1)
- Mass critical care (1)
- Massenanfall (1)
- Medical Managment (1)
- Medizinische Fakultät (1)
- Medizinische Task Force (1)
- Melatonin (1)
- Memantin (1)
- Membranproteine (1)
- Metamizol (1)
- Metastatic breast cancer (1)
- Methohexital (1)
- Microcirculation (1)
- Microdialyse (1)
- Migräne (1)
- Minimal-invasive Chirurgie (1)
- Mitochondrien (1)
- Mobile intensive care unit (1)
- Mobilität (1)
- Monozyt (1)
- Monozyten (1)
- Motilitydysfunction (1)
- Myelin-Barriere (1)
- NCI H441 Zellen (1)
- NF-kappa-B (1)
- NMDAR (1)
- NRS-Skala (1)
- NS1608 (1)
- NSAIDs (1)
- NaV1.8 (1)
- Nahinfrarot-Spektroskopie (1)
- Nahinfrarotspektroskopie (1)
- Nanopartikel (1)
- Narkoseinduktion (1)
- Narkosetechnik (1)
- Narkosetiefe (1)
- Natrium/Glucose-Cotransporter (1)
- Natriumlaurylsulfat (1)
- Near-Infrared Spectroscopy (1)
- Neogenin-1 (1)
- Nephrotoxizität (1)
- Nerven (1)
- Netrin-1 (1)
- Neurogenie inflammation (1)
- Neurological complications (1)
- Neurologische Komplikationen (1)
- Neuromuscular disorders (1)
- Neuromuskuläre Erkrankungen (1)
- Neuropathic Pain (1)
- Neuropathic pain (1)
- Neuropathy (1)
- Neurotoxizität (1)
- Neutrophils (1)
- New Zealand (1)
- Nicardipine (1)
- Nicht-invasive Beatmung (1)
- Nierenversagen (1)
- Nitric oxide (NO) (1)
- Nociceptor (1)
- North American (1)
- Notarzt (1)
- OAA/S (1)
- OSC (1)
- Oberkörperhochlage (1)
- Obstetrics (1)
- Occludin (1)
- Omega-3-Fettsäure (1)
- Open-Lung-Beatmung (1)
- Open-lung-ventilation (1)
- Opioidsparender Effekt (1)
- Oxidized Phospholipids (1)
- Oxygen uptake (1)
- Oxygen-glucose deprivation (1)
- P-Welle (1)
- P-glycoprotein (1)
- P-gp inhibitors (1)
- PARs (1)
- PBM (1)
- PCA (1)
- PCDHGC3 (1)
- PCEA (1)
- PCIA (1)
- PCR (1)
- PDE4-inhibitor roflumilast (1)
- PEEP (1)
- PIK3R1 (1)
- POLO-chart (1)
- POLSCORE (1)
- Pain (1)
- Pain therapy (1)
- Patient (1)
- Patient Blood Management (PBM) (1)
- Patient Controlled Analgesia (1)
- Patient Satisfaction (1)
- Patientenaufnahme (1)
- Patiententransport (1)
- PcdhgC3 (1)
- Pearson correlation coefficient (1)
- Perineurium (1)
- Peroxisomen-Proliferator-aktivierter Rezeptor (1)
- Phase II trials (1)
- Phthalsäureester (1)
- Pim-1 Kinase (1)
- Polymerase chain reaction (1)
- Positive-Pressure Respiration (1)
- Post dural puncture headache (1)
- Postaggressorisches Syndrom (1)
- Postagressionsstoffwechsel (1)
- Postkonditionierung (1)
- Postkonditonierung (1)
- Postoperative Phase (1)
- Postoperative complications (1)
- Postoperatives Erbrechen (1)
- Postpunktionskopfschmerz (1)
- Predict fluid responsiveness (1)
- Pregnancy (1)
- Prilocain (1)
- Prognose (1)
- Prostacyclin (1)
- Prostaglandine (1)
- Proteinkinase A (1)
- Protocadherin gamma C3 (1)
- Protocadherine (1)
- Prozessqualität (1)
- Prädiktor (1)
- Präklinik (1)
- Pr�konditionierung (1)
- Psychologische Profile (1)
- Psychosoziale Belastung (1)
- Publikationsbias (1)
- Pulmonary Embolism (1)
- Pulmonary function tests (1)
- Puls-pressure variation (1)
- Quantitativ sensorische Testung (1)
- Quantitative sensory testing (1)
- Questionnaire (1)
- RECK (1)
- RSI (1)
- Randomized controlled-trial (1)
- Rapid Entire Body Assessment (1)
- Rapid Sequence Induction (1)
- Rapid sequence induction (1)
- Regional anesthesia (1)
- Regressionsanalyse (1)
- Reperfusion (1)
- Reperfusions-induzierter Schaden (1)
- Retrospektive Datenanalyse (1)
- Rettungshubschrauber (1)
- Risikofaktor (1)
- Risikoscore (1)
- RyR1 mutations (1)
- SARS-CoV2 (1)
- SARS-CoV‑2 (1)
- SERCA (1)
- SGLT (1)
- SIRS (1)
- SOFA Score (1)
- SOR (1)
- SWCNT CNTs (1)
- Sanger sequencing (1)
- Sauerstoff (1)
- Sauerstoffkonzentration (1)
- Schmerztagesklinik (1)
- Schnittstelle (1)
- Schockraum (1)
- Schockraumbehandlung (1)
- Schockraummanagement (1)
- Schockraumteam (1)
- Schwefelwasserstoff (1)
- Selektive Endpunktberichterstattung (1)
- Serotonin (5-HT) (1)
- Severe Acute Respiratory Syndrome Coronavirus 2 (1)
- Shotgun method (1)
- Signaltransduktion (1)
- Siliciumdioxid (1)
- Simulation (1)
- Skelettmuskel (1)
- Sodium/glucose cotransporter (1)
- Sonografie (1)
- Spirometrie (1)
- Spumaviren (1)
- Starch volumetherapy nephrotoxicity HK-2 cells (1)
- Statine (1)
- Steroide (1)
- Stevia rebaudiana (1)
- Strain (1)
- Strainrate (1)
- Stress (1)
- Stress-Kardiomyopathie (1)
- Sturzflut (1)
- Succinylcholin (1)
- Sudeck (1)
- Sudeck-Syndrom (1)
- Sufentanil (1)
- Surgery (1)
- Swine (1)
- Synthetic biology (1)
- TNF-α (1)
- TRP channel (1)
- TRPA1 channel (1)
- TTFields (1)
- TTS (1)
- Takotsubo cardiomyopathy (1)
- Takotsubo syndrome (1)
- Takotsubo-Syndrom (1)
- Targeted drug delivery (1)
- Temperaturreiz (1)
- Terror (1)
- Thermodilution (1)
- Thorax (1)
- Thoraxkompressionsfrequenz (1)
- Thoraxröntgenbild (1)
- Thrombose (1)
- Tight Junction (1)
- Tight Junction Proteine (1)
- Tight Junction Proteins (1)
- Tight-Junction-Protein (1)
- Tjap1 (1)
- Toll-like Rezeptoren (1)
- Toxizität (1)
- Tramadol (1)
- Transfektion (1)
- Transwell® system (1)
- Transösophageale Ultraschallkardiographie (1)
- Traumatologie (1)
- Tumor-Treating Fields (TTFields) (1)
- Tyrian purple (1)
- UNC5B (1)
- USRA (1)
- Ultraschalldiagnostik (1)
- Ultraschallphantom (1)
- Ultraschallsichtbarkeit von Regionalanästhesienadeln (1)
- University Hospital (1)
- User Training (1)
- VACV (1)
- VILI (1)
- Vena jugularis interna (1)
- Venous Thrombosis (1)
- Vergleich (1)
- Verlegungsarzt (1)
- Verletzte (1)
- Verzerrung (1)
- Virtual sequencing (1)
- Visuelle Aufmerksamkeit (1)
- Volatile anesthetics (1)
- Volumenmanagement (1)
- Volumenregulation (1)
- Vomiting (1)
- WNT signaling (1)
- Wachheit (1)
- Weaning (1)
- Wehenschmerz (1)
- Wellenplan (1)
- Wirkspiegel (1)
- Withings ScanWatch (1)
- Wnt signaling (1)
- ZVK (1)
- ZVK-Lage (1)
- Zeitvorteil (1)
- Zell-Zell-Kontakte (1)
- Zellkontakt (1)
- Zellkultur (1)
- Zellkulturmodell (1)
- Zellskelett (1)
- Zerebrale Gewebeoxygenierung (1)
- Zika virus (1)
- Zufriedenheit (1)
- \(^1\)H-NMR spectroscopy (1)
- acetylsalicylic acid (1)
- activated-receptor gamma (1)
- activity-dependent slowing (1)
- acupuncture (1)
- acute Respiratory Distress Syndrome (1)
- acute liver failure (1)
- acute respiratory distress syndrome (ARDS) (1)
- adherens junction (1)
- adhesion molecules (1)
- admission capacity (1)
- adrenal tumor (1)
- adrenocortical cancer (1)
- adsorption (1)
- adultsPostoperatives Erbrechen ist ein häufiges und den Patienten belastendes Problem (1)
- aged 80 and over (1)
- aggregation (1)
- agnoists (1)
- air embolism (1)
- akutes Nierenversagen (1)
- alveolar epithelium in vitro model, claudin-1, claudin-3, claudin-4, claudin-5 (1)
- alzheimer's disease (1)
- amyloid cardiomyopathy (1)
- anaemia walk‐in clinic (1)
- anaesthesia (1)
- anaesthetics (1)
- analgesics (1)
- anesthesia (1)
- anesthesiologists (1)
- anesthesiology (1)
- anesthetic preconditioning (1)
- anesthetic-induced preconditioning (1)
- aneurysm repair (1)
- aneurysmal subarachnoid haemorrhage (1)
- angiogenesis (1)
- angioplasty (1)
- animals (1)
- anthocyanin derivatives (1)
- anti-cancer drug-like molecules (1)
- anti-hormonal therapy (1)
- antibacterial activity (1)
- antibiotic prescribing quality (1)
- anticoagulant therapy (1)
- antiemetic strategies (1)
- antiemetics (1)
- antiemetische Strategien (1)
- antioxidant (1)
- antioxidative Vitamine (1)
- antioxidative vitamins (1)
- antithrombotic therapy (1)
- anxiety (1)
- anästhetikainduzierte Präkonditionierung (1)
- apolipoprotein J (1)
- apoptosis (1)
- approved drugs (1)
- arteriovenous extracorporeal hemadsorption technique (1)
- artificial intelligence (1)
- astrocytoma (1)
- autoantibodies (1)
- autoimmun (1)
- autoimmune (1)
- automated external defibrillators (1)
- autonomic nervous system (1)
- avoidable blood loss (1)
- awake prone positioning (1)
- awareness (1)
- axillary plexus (1)
- axillary plexus block (1)
- axilläre Plexusanästhesie (1)
- axonal damage (1)
- barrier properties (1)
- betaadrenergic receptors (1)
- bibliometrics (1)
- bioactive peptide (1)
- bioelectronics (1)
- biopsychosocial model of pain (1)
- biopsychosoziales Schmerzmodell (1)
- bleeding (1)
- blockchain anchoring (1)
- blockchain in healthcare (1)
- blockchain in the pharmaceutical industry (1)
- blockchain interoperability (1)
- blood purification (1)
- blood transfusion (1)
- blood volume (1)
- blood–brain barrier choline transporter (1)
- bradykinin (1)
- brain endothelial cell line (1)
- brain pathology (1)
- brain-metastasis (1)
- breast cancer metastases (1)
- bupivacaine (1)
- c-fos (1)
- cEND-Zellen (1)
- calcitonin gene-related peptide (1)
- calcium level (1)
- calcium-activated potassium channel (1)
- calorimetry (1)
- cancer (1)
- carbon dioxide (1)
- carbon nanoparticles (1)
- carcinogen activation (1)
- cardiac arrest documentation (1)
- cardiac protection (1)
- cardiac surgery (1)
- cardio-pulmonary resuscitation (1)
- cardiopulmonary resuscitation (1)
- carrier proteins (1)
- caspase-3 (1)
- ceasarean section (1)
- cell stretch (1)
- cell-adhesion (1)
- central autonomic network (1)
- central core disease (1)
- cerebEND cells (1)
- cerebral ischemia (1)
- cerebral tissue oxygenation (1)
- cerebrovascular disorders (1)
- chain-of-survival (1)
- chemical similarity (1)
- chest-compression rate (1)
- children (1)
- chronic constriction injury (1)
- chronic constriction nerve injury (1)
- chronic musculoskeletal pain (1)
- chronic wounds (1)
- chronisches Schmerzsyndrom (1)
- civil protection (1)
- claudin 1 (1)
- claudin-12 (1)
- claudin-5 (1)
- clinical decision support (1)
- clinical measurement in health technology (1)
- clinical studies (1)
- clinical trials (1)
- cluster headache (1)
- clusterin transporter (1)
- coagulation (1)
- cocamidopropylbetaine (1)
- colloids (1)
- colorectal carcinoma (1)
- comparative molecular field analysis (1)
- comparative molecular similarity index analysis (1)
- complex regional pain syndrom (1)
- complications (1)
- conductance catheter (1)
- conference abstracts (1)
- connective tissue (1)
- contracture test (1)
- coronary artery bypass (1)
- coronavirus disease 2019 (1)
- corticoid (1)
- corticosteroids (1)
- corticotropin-releasing-factor gut motility guinea pig (1)
- costs (1)
- creatinine (1)
- critical infrastructure (1)
- cut and sew technique (1)
- cvc (1)
- cyclodextrin (1)
- cyclodextrin formulations (1)
- cytochrome P450 3A4 (1)
- cytokine expression (1)
- data display (1)
- death (1)
- defibrillation (1)
- delivery (1)
- demography (1)
- density functional theory (1)
- depression (1)
- depth of anaesthesia (1)
- dermal B cells (1)
- dexamethasone (1)
- diabetes mellitus (1)
- diabetic nephropathy (1)
- diabetic retinopathy (1)
- diagnose (1)
- diagnostic blood loss (1)
- diagnostic correctness (1)
- diazepam (1)
- differentially expressed genes (1)
- diffusion (1)
- digital phenotyping (1)
- dimethylsulfoxide (1)
- dipyrone (1)
- disability (1)
- disease (1)
- diskontinuierlich (1)
- doctor in own practice (1)
- documentation quality (1)
- dorsal root ganglion (1)
- dose-dependency (1)
- driving pressure (1)
- drug delivery (1)
- drug delivery vector (1)
- drug repurposing (1)
- drug transporter (1)
- drug-drug interactions (1)
- dual-room trauma suite (1)
- dual-room whole-body CT (1)
- dysfunction (1)
- eCPR (1)
- ecological momentary assessment (1)
- electrical excitability (1)
- emergency (1)
- emergency first aid (1)
- emergency information (1)
- emergency medical aid (1)
- emergency preparedness (1)
- emesis (1)
- encephalitis dementia (1)
- endocarditis (1)
- endogenous opioids (1)
- endothelial injury (1)
- endothelium (1)
- endotoxin (1)
- endsystolic elastance (1)
- endsystolische Elastanz (1)
- enhanced recovery after surgery (1)
- enoxaparin (1)
- enzyme-linkes immunoassays (1)
- epidural anaesthesia (1)
- epidural analgesia (1)
- epidural anesthesia (1)
- epitheliae Barriere (1)
- equipment (1)
- erste Welle (1)
- estrogens (1)
- ethanol (1)
- ether (1)
- eudaimonia (1)
- evidence synthesis (1)
- exercise (1)
- exposure (1)
- extracellular vesicles (1)
- extracorporeal hemadsorption (1)
- extracorporeal membrane oxygenation (1)
- extracorporeal membrane oxygenation (ECMO) (1)
- extracorporeal techniques in hemadsorption therapy (1)
- extravascular lung water (1)
- factor v-Leiden (1)
- factorial design (1)
- failure (1)
- faktorielles Studiendesign (1)
- fascia (1)
- fears (1)
- femoral (1)
- fentanyl (1)
- fermentation (1)
- fetal lung (1)
- fibromyalgia (1)
- fibrosis (1)
- first responder (1)
- first responders (1)
- fish oil (1)
- fitness trackers (1)
- flooding (1)
- fluid therapy (1)
- fluorescein isothiocyanate (1)
- fluorescence microscopy (1)
- fluoroquinolones (1)
- formulations (1)
- frailty (1)
- free energy (1)
- free energy of solvation (1)
- free flap surgery (1)
- fullerenes (1)
- funktionell offenes Foramen ovale (1)
- gastrointestinal tract (1)
- gene ontology (1)
- general anaesthesia (1)
- general anesthesia (1)
- genetic polymorphisms (1)
- genotoxicity (1)
- giant ventral hernia (1)
- glioblastoma multiforme (1)
- glut1 (1)
- glutamine (1)
- good clinical practice (1)
- gradient optimisation (1)
- graft surgery (1)
- growth differentiation factor 15 (1)
- guanylyl cyclase (1)
- guideline adherence (1)
- guideline usage (1)
- guinea pig (1)
- gut motilty (1)
- gynäkologische Eingriffe (1)
- hCMEC/D3 (1)
- haemoglobin concentration (1)
- haemostasis (1)
- health care (1)
- health care payers (1)
- health care workers (1)
- health sciences (1)
- health tracker (1)
- health-care workers (1)
- healthcare (1)
- heart (1)
- hedonia (1)
- hemadsorption (1)
- high-flow nasal cannula (1)
- high-volume-low-concentration-technique (1)
- histopathology (1)
- hospital atlas (1)
- human (1)
- human brain microvascular endothelial cells (HBMVEC) (1)
- human cells (1)
- human factors (1)
- human immunodeficiency virus (1)
- humans (1)
- hydrochloride (1)
- hydrogen sulfide (1)
- hypertonic solution (1)
- hypovolemia (1)
- hypoxia (1)
- höheres Lebensalter (1)
- iatrogenic anemia (1)
- ileum (1)
- immortalization (1)
- immune response (1)
- immunology (1)
- immunonutrition (1)
- immunosorbents (1)
- immunostaining (1)
- impedance aggregometry; WHOLE-BLOOD THROMBOELASTOMETRY; DEFINITION; DISEASE (1)
- implementation (1)
- in vitro cell culture models (1)
- in vitro model (1)
- in vivo (1)
- in-bed cycling (1)
- in-hospital cardiac arrest (1)
- in-vitro Modellsystem (1)
- indigo (1)
- induced impairment (1)
- infiltration (1)
- inflammatory bowel disease (1)
- inflammatory cytokines (1)
- inflammatory response (1)
- infodemic (1)
- information strategies (1)
- inguinal (1)
- inhalation anesthetics (1)
- inhalational anaesthesias (1)
- inhibition (1)
- injury severity score (1)
- inner ear (1)
- innerklinischer Herz-Kreislaufstillstand (1)
- innovative surgical methods (1)
- inos (1)
- insbesondere (1)
- insular cortex (1)
- intensive care medicine (1)
- intensive care transport (1)
- intensive care unit (1)
- interaction analysis (1)
- interhospital transfer (1)
- internalization (1)
- internet of things (1)
- interscalene block (1)
- intestinal absorption (1)
- intestinal microvascular perfusion (1)
- intestinal motility (1)
- intestine (1)
- intracerebral haemorrhage (1)
- intraoperativ (1)
- intubation (1)
- intubation time (1)
- involvement (1)
- ion channel (1)
- ion channels in the nervous system (1)
- ischemic preconditioning (1)
- isosteviol sodium (1)
- isosteviol sodium (STVNA) (1)
- kidney (1)
- kidney ischemia/reperfusion injury (1)
- kidneys (1)
- kontinuierlich und patientenkontrolliert (1)
- kritisch-kranke Patienten (1)
- laparoscopic surgery (1)
- laparostomy (1)
- laryngoscopy (1)
- laterality (1)
- left atrial appendage occlusion (1)
- left-ventricular assist device (1)
- leftventricular funktionparameters (1)
- levosimendan (1)
- lidocaine (1)
- lipids (1)
- livin (1)
- lnterleukin-lβ (1)
- logistic regression analysis (1)
- logistische Regressionsanalyse (1)
- long-term ventilation (1)
- longitudinal studies (1)
- low molecular heparin (1)
- low molecular heparine (1)
- low-molecular heparin (1)
- low-risk intra-abdominal infections (1)
- lps (1)
- lung function (1)
- lung injury (1)
- lung protective ventilation (1)
- lung ultrasound (1)
- machine learning (1)
- macrophage migration inhibitory factor (MIF) (1)
- major bleeding (1)
- malignant hyperthemia (1)
- management (1)
- mass casualty incident (1)
- mast cells (1)
- maternal critical care (1)
- mean force potential (1)
- meaning (1)
- mechanical power (1)
- mechanical ventilation (1)
- mechanical ventilator weaning (1)
- mechanisms (1)
- medical devices (1)
- medical task force (1)
- medicine (1)
- memantine (1)
- metablic test (1)
- metabolizing rate (1)
- metastasis (1)
- methohexital (1)
- methylprednisolone (1)
- metoprolol (1)
- miRNA (1)
- mices (1)
- microRNA-132 (1)
- microRNA-212 (1)
- microanastomosis (1)
- microarray (1)
- microglia (1)
- micronutrients (1)
- microparticles (1)
- microvascular complications (1)
- microvascular endothelial cells (1)
- midazolam (1)
- migraine (1)
- mikrodialysis (1)
- milk proteins (1)
- mimetic peptide (1)
- minimal invasive (1)
- minimal-invasiv (1)
- minimal-invasive (1)
- minimally invasive surgery (1)
- mission strategies (1)
- mitochondria (1)
- mobile crowdsensing (1)
- mobile health (1)
- moderate sedation (1)
- molecular imaging (1)
- molecular liphophilicity potential (1)
- molecular medicine (1)
- molecular modeling (1)
- molecular modelling (1)
- mortality (1)
- mouse models (1)
- movable sliding gantry (1)
- multidisciplinary (1)
- multimodal treatments (1)
- multiple sclerosis (1)
- multiwalled carbon nanotube (1)
- muscle (1)
- muscle disease (1)
- myelin barrier (1)
- myeloperoxidase (1)
- myocardial-infarction (1)
- myofibroblasts (1)
- myotonia congenita (1)
- nanomedicine (1)
- necrosis factor alpha (1)
- need satisfaction (1)
- nerve (1)
- nerve injury (1)
- nerve stimulation (1)
- nervestimulation (1)
- nervous system (1)
- netrin-1 (1)
- network meta-analysis (1)
- neurochirurgische Operation (1)
- neurological complications (1)
- neurology (1)
- neuronal tracing (1)
- neuroprotection (1)
- neuropsychiatric disorders (1)
- neuroscience (1)
- neurosurgical operations (1)
- neurotrophic factor (1)
- neurovascular disorders (1)
- neurovasculature (1)
- neutrophil (1)
- niedergelassener Arzt (1)
- niedermolekulares Heparin (1)
- nitric oxide (1)
- no-flow fraction (1)
- nociception (1)
- nociceptive Schwann cells (1)
- non-invasive ventilation (1)
- nutrient supplementation (1)
- nutrition (1)
- nutrition therapy (1)
- obstetrics (1)
- off-chain data (1)
- older adults (1)
- omega-3 fatty acid (1)
- omega-3-fatty acids (1)
- omega-6 fatty acid (1)
- one‐lung ventilation (1)
- open abdomen (1)
- opendsu (1)
- opioid peptides (1)
- opioid receptors (1)
- opioids (1)
- opioidsparing effect (1)
- optical laryngoscopes (1)
- optische Laryngoskope (1)
- oral anticoagulants (1)
- oral nutrition supplements (1)
- orthopaedic patients (1)
- out-of-hospital cardiac arrest (1)
- oxidativer Stress (1)
- oxidised lipids (1)
- oxidized phospholipids (1)
- oxygen-glucose deprivation (1)
- p-wave (1)
- pCO2 (1)
- pain behavior (1)
- pain research (1)
- pain-related disability (1)
- pandemia (1)
- pandemic (1)
- parenteral analgesia (1)
- parenteral nutrition (1)
- patent foramen ovale (1)
- pathophysiology (1)
- patient (1)
- patient controlled analgesia (1)
- patient safety (1)
- patient serum (1)
- patient-controlled (1)
- patientenkontrollierte Analgesie (1)
- patients (1)
- paxilline (1)
- pediatric (1)
- peptide synthesis (1)
- performance (1)
- pericytes (1)
- perioperative Myokardischämien (1)
- perioperative antibiotic prophylaxis (1)
- perioperative myocardial ischemia (1)
- peripartal (1)
- peripheral nerve (1)
- peripheral nerve injury (1)
- peripherer Nerv (1)
- permeability (1)
- peroxisome-proliferator-activated receptor (1)
- personalized antimicrobial therapy (1)
- personalized medicine (1)
- pharmaceutical applications (1)
- pharmacokinetic delivery (1)
- pharmacokinetics (1)
- pharmacology (1)
- pharmacotherapy (1)
- pharmaledger (1)
- phenprocoumon (1)
- phosphatidylinositol (1)
- phosphodiesterase (1)
- photoplethysmography (1)
- phthalates (1)
- physical activity (1)
- pi-pi stacking (1)
- pigs (1)
- pioglitazone (1)
- piperacillin/tazobactam (1)
- point of care testing (1)
- point-of-care (1)
- point-of-care-testing (1)
- polarization (1)
- polymers (1)
- polytrauma (1)
- population characteristics (1)
- position (1)
- positive pressure respiration (1)
- post-traumatic stress disorder (1)
- postconditioning (1)
- postoperativ (1)
- postoperative Nausea (1)
- postoperative complications (1)
- postoperative Übelkeit (1)
- postoperative Übelkeit und Erbrechen (1)
- postoperatives Befinden (1)
- predictor (1)
- prehabilitation (1)
- prehospital (1)
- preoperative anaemia management (1)
- presynaptic inhibition (1)
- preterm birth (1)
- prevalence (1)
- prilocaine (1)
- primary endpoint (1)
- primary microvascular endothelial cells (1)
- primary outcome (1)
- prognostic marker (1)
- proliferation (1)
- propranolol (1)
- prospective studies (1)
- prostacyclin (1)
- prostaglandins (1)
- proteasome (1)
- protein (1)
- protein corona (1)
- protein expression (1)
- protein hydrolysis (1)
- protein-protein interaction network (1)
- proteins (1)
- protocadherin gamma C3 (1)
- public health (1)
- public health preparedness (1)
- publication bias (1)
- pulmonary edema (1)
- pulmonary function tests (1)
- pulmonary surgical procedures (1)
- pulse therapy (1)
- punctate mechanical allodynia (1)
- qualitative research (1)
- quality assurance (1)
- quality indicators (1)
- quality of life (1)
- quantum mechanics (1)
- questionnaire (1)
- rabbits (1)
- rapid sequence induction (1)
- rational drug design (1)
- reactive oxygen species (1)
- receptor antagonist (1)
- receptors (1)
- recombinant DNA (1)
- recurrence (1)
- red blood cell transfusion (1)
- red blood cells (1)
- regional anesthesia (1)
- relapse (1)
- reperfusion injury (1)
- repetitive firing (1)
- rescue mission (1)
- research integrity (1)
- resolvin (1)
- respiratory distress syndrome (1)
- respiratory failure (1)
- resuscitation time (1)
- reticulocyte haemoglobin (1)
- risk factor (1)
- risk prediction (1)
- risk score (1)
- robotic surgery (1)
- ropivacaine (1)
- ryanodine receptor gene (1)
- salvage therapy (1)
- sarcoplasmic reticulum (1)
- satisfaction (1)
- scaffold search (1)
- scanning electron microscopy (1)
- sceletal muscle (1)
- schmerzbedingte Beeinträchtigung (1)
- schwieriger Atemweg (1)
- sciatic nerve (1)
- scurvy (1)
- selective outcome reporting (1)
- selen (1)
- selenium (1)
- self-sovereign identities (1)
- senescence (1)
- sensory neurons (1)
- septic shock (1)
- serielle Computertomografie (1)
- severe multiple trauma (1)
- sex hormone (1)
- sglt1 (1)
- shape-based approach (1)
- sheep (1)
- side-effects (1)
- single-electron transistor (1)
- single-walled carbon nanotubes (1)
- sitting position (1)
- situation awareness (1)
- situational awareness (1)
- sitzende Lagerung (1)
- skin punch biopsy (1)
- smartwatch (1)
- smooth muscle cells (1)
- sodiumlaurylsulfate (1)
- solnatide (1)
- solvents (1)
- spinal anaesthesia (1)
- spinal dorsal horn (1)
- spontaneous pneumomediastinum (1)
- spontaneous pneumopericardium (1)
- sport medicine (1)
- statins (1)
- stent (1)
- store-operated Ca2+ entry (1)
- strain (1)
- strainrate (1)
- stress (1)
- stress resilience (1)
- structure-activity relationship (1)
- subarachnoid hemorrhage (1)
- succinylcholine (1)
- sudden flood (1)
- supine hypotensive syndrome (1)
- surgery (1)
- survey (1)
- susceptibility (1)
- suxamethonium (1)
- syndrome (1)
- synthetic mesh (1)
- systematic review, (1)
- systemic inflammatory response syndrome (1)
- systemic reviews (1)
- targeting (1)
- team-training (1)
- technology (1)
- terror attacks (1)
- theranostics (1)
- therapeutic antibody (1)
- therapeutic drug monitoring (1)
- therapiefreies Intervall (1)
- thermal threshold (1)
- thermodilution (1)
- three-dimensional quantitative structure–activity relationship (1)
- thromboelastometry (1)
- tight junction protein (1)
- tight junction proteins (1)
- time varying elastance (1)
- tissue resident T cells (1)
- torsional energy (1)
- trace elements (1)
- tramadol (1)
- transesophageal echocardiography (1)
- transfusion (1)
- transgenic mouse (1)
- transient receptor potential channels (1)
- transition state (1)
- transnasal TEE (1)
- transnasale TEE (1)
- transport inhibition assay (1)
- transporter (1)
- trastuzumab (1)
- trastuzumab deruxtecan (1)
- trauma centre (1)
- trauma management (1)
- trial protocol (1)
- trial registration (1)
- trimethyl-β-cyclodextrin (1)
- tumor (1)
- tumor microenvironment (1)
- tumor necrosis factor-α (1)
- ulfobutylether-\(\beta\)-cyclodextrin (1)
- ultrasound strain elastography (1)
- ultrastructure (1)
- urgent surgery (1)
- urine (1)
- urämische Enzephalopathie (1)
- user experience (1)
- user-centred design (1)
- vaccination (1)
- vaccination campaign (1)
- vaccination hesitancy (1)
- vaccine (1)
- vaccine hesitancy (1)
- vaccine refusal (1)
- vacuum conditioning (1)
- video-assisted laryngoscopy (1)
- viral load (1)
- virtual reality (1)
- virtual screening (1)
- viruses (1)
- vitamins (1)
- vitro contracture test (1)
- volume clamp (1)
- volunteer locally (1)
- warfarin interruption (1)
- water (1)
- weaning (1)
- wearable (1)
- white blood cells (1)
- wistar rats (1)
- x (1)
- x-ray (1)
- zentralvenöser Katheter (1)
- µ-Opioid receptor (1)
Institute
- Klinik und Poliklinik für Anästhesiologie (ab 2004) (346) (remove)
Sonstige beteiligte Institutionen
- Zentrallabor, Universitätsklinikum Würzburg (2)
- Apotheke, Universitätsklinikum Würzburg (1)
- Department of Medicinal Chemistry, University of Vienna, Althanstraße 14, 1090 Vienna, Austria (1)
- Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, 1090 Vienna, Austria (1)
- EMBL Mouse Biology Unit, Monterotondo, Italien (1)
- Interdisziplinäres Zentrum für Klinische Forschung (ZIKF), Würzburg (1)
- Klinik für Anästhesiologie, Universität Mainz (1)
- Klinik und Poliklinik für Anästhesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie des Universitätsklinikums Würzburg (1)
- Klinikum Fulda gAG (1)
- Krankenhaushygiene und Antimicrobial Stewardship (1)
Mit dem Auftreten des SARS-CoV-2 Virus im Jahr 2020 war der Informationsgewinn für vulnerable Patientengruppen essentiell. Ziel dieser Arbeit war es maternale Charakteristika und das klinische Bild SARS-CoV-2 positiver Frauen mit Notwendigkeit einer intensivmedizinischen Behandlung während der Schwangerschaft und postpartal darzustellen, und diese Kohorte mit den SARS-CoV-2 positiven Schwangeren ohne intensivmedizinischen Handlungsbedarf zu vergleichen. Die Daten stammten aus dem deutschen CRONOS-Register, einem prospektiven, multizentrischen Register für SARS-CoV-2 positive schwangere Frauen. Eingeschlossen wurden alle schwangeren und postpartalen Frauen, die während ihrer SARS-CoV-2 Infektion auf eine ITS aufgenommen wurden. Diese wurden hinsichtlich maternaler Charakteristika, Krankheitsverlauf, sowie Outcomes verglichen.
In 101 von 2650 Fällen (4%) der Patientinnen des CRONOS-Registers, kam es zu einer Aufnahme auf die ITS. Als invasivste Form der COVID-19 Behandlung war bei 6 Patientinnen nur eine Überwachung notwendig, 30 Patientinnen benötigten eine Sauerstoffinsufflation, 22 wurden nicht-invasiv beatmet, 28 erhielten eine invasive Beatmung und bei 15 Frauen wurde die Behandlung zur ECMO-Therapie eskaliert. Es wurden keine klinisch signifikanten Unterschiede zwischen Patientinnen gefunden, die unterschiedliche Behandlungsformen benötigten. Die Gruppe der ITS und Non-ITS Patientinnen unterschied sich statistisch signifikant beim Einfluss von Alter, BMI bei Einschluss und der Herkunft. Die Prävalenz der Frühgeburtlichkeit war unter den invasiv behandelten Patientinnen signifikant höher und auch im Vergleich der ITS mit den Non-ITS Patientinnen zeigte sich ein signifikanter Unterschied. Vier Frauen verstarben an COVID-19 und sechs Feten der ITS-Gruppe waren Totgeburten.
Diese Kohorte zeigt, dass schwere COVID-19 Erkrankung bei schwangeren Frauen und Wöchnerinnen selten sind. Die Frühgeburtenrate ist hoch und COVID-19 mit Notwendigkeit einer Atemunterstützung erhöht das Risiko für ein schlechtes maternales und neonatales Outcome. Unter anderem ein höheres Alter und BMI sind mit einem höheren Risiko für eine ITS-Aufnahme verbunden.
No abstract available.
Die Hochfrequenzoszillation (HFOV; Frequenz 12-15 Hz) reduziert in Kombination mit einer ECLA die beatmungsinduzierte Lungenschädigung und das Lungenbiotrauma im Vergleich zur konventionellen lungenprotektiven Beatmung (PCV) mit niedrigen Tidalvolumina (6 ml/kg KG) Die HFOV hat in Kombination mit ECLA keine negativen Auswirkungen auf den Gasaustausch und die Hämodynamik
We investigated the ionization profiles for open-ring (OR) and closed-ring (CR) forms of midazolam and drug-binding modes with heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (trimethyl-β-cyclodextrin; TRIMEB) using molecular modeling techniques and quantum mechanics methods. The results indicated that the total net charges for different molecular forms of midazolam tend to be cationic for OR and neutral for CR at physiological pH levels. The thermodynamic calculations demonstrated that CR is less water-soluble than OR, mainly due to the maximal solvation energy (ΔG(CR)(solv = -9.98 kcal·mol ⁻¹), which has a minimal ΔG(OR)(solv) of -67.01 kcal·mol⁻¹. A cell viability assay did not detect any signs of TRIMEB and OR/CR-TRIMEB complex toxicity on the cEND cells after 24 h of incubation in either Dulbecco's Modified Eagles Medium or in heat-inactivated human serum. The molecular docking studies identified the more flexible OR form of midazolam as being a better binder to TRIMEB with the fluorophenyl ring introduced inside the amphiphilic cavity of the host molecule. The OR binding affinity was confirmed by a minimal Gibbs free energy of binding (ΔG(bind)) value of -5.57 ± 0.02 kcal·mol⁻¹, an equilibrium binding constant (K(b)) of 79.89 ± 2.706 μM, and a ligand efficiency index (LE(lig)) of -0.21 ± 0.001. Our current data suggest that in order to improve the clinical applications of midazolam via its complexation with trimethyl-β-cyclodextrin to increase drug's overall aqueous solubility, it is important to concern the different forms and ionization states of this anesthetic. All mean values are indicated with their standard deviations.
Clinical trials of novel therapeutics for Alzheimer’s Disease (AD) have consumed a significant amount of time and resources with largely negative results. Repurposing drugs already approved by the Food and Drug Administration (FDA), European Medicines Agency (EMA), or Worldwide for another indication is a more rapid and less expensive option. Therefore, we apply the scaffold searching approach based on known amyloid-beta (Aβ) inhibitor tramiprosate to screen the DrugCentral database (n = 4,642) of clinically tested drugs. As a result, menadione bisulfite and camphotamide substances with protrombogenic and neurostimulation/cardioprotection effects were identified as promising Aβ inhibitors with an improved binding affinity (ΔGbind) and blood-brain barrier permeation (logBB). Finally, the data was also confirmed by molecular dynamics simulations using implicit solvation, in particular as Molecular Mechanics Generalized Born Surface Area (MM-GBSA) model. Overall, the proposed in silico pipeline can be implemented through the early stage rational drug design to nominate some lead candidates for AD, which will be further validated in vitro and in vivo, and, finally, in a clinical trial.
In this study, the ability of a multiwalled carbon nanotube functionalized with fluorescein isothiocyanate (MWCNT-FITC) was assessed as a prospective central nervous system-targeting drug delivery system to permeate the blood-brain barrier. The results indicated that the MWCNT-FITC conjugate is able to penetrate microvascular cerebral endothelial monolayers; its concentrations in the Transwell® system were fully equilibrated after 48 hours. Cell viability test, together with phase-contrast and fluorescence microscopies, did not detect any signs of MWCNT-FITC toxicity on the cerebral endothelial cells. These microscopic techniques also revealed presumably the intracellular localization of fluorescent MWCNT-FITCs apart from their massive nonfluorescent accumulation on the cellular surface due to nanotube lipophilic properties. In addition, the 1,000 ps molecular dynamics simulation in vacuo discovered the phenomenon of carbon nanotube aggregation driven by van der Waals forces via MWCN-TFITC rapid dissociation as an intermediate phase.
The purpose of this study was to develop and implement an in silico model of indigoid-based single-electron transistor (SET) nanodevices, which consist of indigoid molecules from natural dye weakly coupled to gold electrodes that function in a Coulomb blockade regime. The electronic properties of the indigoid molecules were investigated using the optimized density-functional theory (DFT) with a continuum model. Higher electron transport characteristics were determined for Tyrian purple, consistent with experimentally derived data. Overall, these results can be used to correctly predict and emphasize the electron transport functions of organic SETs, demonstrating their potential for sustainable nanoelectronics comprising the biodegradable and biocompatible materials.
The cytochrome P450 (CYP)3A4 enzyme affects the metabolism of most drug-like substances, and its inhibition may influence drug safety. Modulation of CYP3A4 by flavonoids, such as anthocyanins, has been shown to inhibit the mutagenic activity of mammalian cells. Considering the previous investigations addressing CYP3A4 inhibition by these substances, we studied the three-dimensional quantitative structure-activity relationship (3D-QSAR) in a series of anthocyanin derivatives as CYP3A4 inhibitors. For the training dataset (n=12), comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) yielded crossvalidated and non-crossvalidated models with a q (2) of 0.795 (0.687) and r (2) of 0.962 (0.948), respectively. The models were also validated by an external test set of four compounds with r (2) of 0.821 (CoMFA) and r (2) of 0.812 (CoMSIA). The binding affinity modes associated with experimentally derived IC50 (half maximal inhibitory concentration) values were confirmed by molecular docking into the CYP3A4 active site with r (2) of 0.66. The results obtained from this study are useful for a better understanding of the effects of anthocyanin derivatives on inhibition of carcinogen activation and cellular DNA damage.
The objective of the present investigation was to study the ability of sulfobutylether-\(\beta\)-cyclodextrin (SBECD) to form an inclusion complex with sevoflurane (SEV), a volatile anesthetic with poor water solubility. The inclusion complex was prepared, characterized and its cellular toxicity and blood-brain barrier (BBB) permeation potential of the formulated SEV have also been examined for the purpose of controlled drug delivery. The SEV-SBE\(\beta\)CD complex was nontoxic to the primary brain microvascular endothelial (pEND) cells at a clinically relevant concentration of sevoflurane. The inclusion complex exhibited significantly higher BBB permeation profiles as compared with the reference substance (propranolol) concerning calculated apparent permeability values (P\(_{app}\)). In addition, SEV binding affinity to SBE\(\beta\)CD was confirmed by a minimal Gibbs free energy of binding (ΔG\(_{bind}\)) value of -1.727 ± 0.042 kcal・mol\(^{-1}\) and an average binding constant (K\(_{b}\)) of 53.66 ± 9.24 mM indicating rapid drug liberation from the cyclodextrin amphiphilic cavity.
Diabetes mellitus is a common disease affecting more than 537 million adults worldwide. The microvascular complications that occur during the course of the disease are widespread and affect a variety of organ systems in the body. Diabetic retinopathy is one of the most common long-term complications, which include, amongst others, endothelial dysfunction, and thus, alterations in the blood-retinal barrier (BRB). This particularly restrictive physiological barrier is important for maintaining the neuroretina as a privileged site in the body by controlling the inflow and outflow of fluid, nutrients, metabolic end products, ions, and proteins. In addition, people with diabetic retinopathy (DR) have been shown to be at increased risk for systemic vascular complications, including subclinical and clinical stroke, coronary heart disease, heart failure, and nephropathy. DR is, therefore, considered an independent predictor of heart failure. In the present review, the effects of diabetes on the retina, heart, and kidneys are described. In addition, a putative common microRNA signature in diabetic retinopathy, nephropathy, and heart failure is discussed, which may be used in the future as a biomarker to better monitor disease progression. Finally, the use of miRNA, targeted neurotrophin delivery, and nanoparticles as novel therapeutic strategies is highlighted.
Alzheimer's disease (AD), the most common cause of dementia in the elderly, is a neurodegenerative disorder associated with neurovascular dysfunction and cognitive decline. While the deposition of amyloid β peptide (Aβ) and the formation of neurofibrillary tangles (NFTs) are the pathological hallmarks of AD-affected brains, the majority of cases exhibits a combination of comorbidities that ultimately lead to multi-organ failure. Of particular interest, it can be demonstrated that Aβ pathology is present in the hearts of patients with AD, while the formation of NFT in the auditory system can be detected much earlier than the onset of symptoms. Progressive hearing impairment may beget social isolation and accelerate cognitive decline and increase the risk of developing dementia. The current review discusses the concept of a brain–ear–heart axis by which Aβ and NFT inhibition could be achieved through targeted supplementation of neurotrophic factors to the cochlea and the brain. Such amyloid inhibition might also indirectly affect amyloid accumulation in the heart, thus reducing the risk of developing AD-associated amyloid cardiomyopathy and cardiovascular disease.
Retroviral vectors are potent tools for gene delivery and various biomedical applications. To accomplish a gene transfer task successfully, retroviral vectors must effectively transduce diverse cell cultures at different phases of a cell cycle. However, very promising retroviral vectors based on the foamy viral (FV) backbone lack the capacity to efficiently transduce quiescent cells. It is hypothesized that this phenomenon might be explained as the inability of foamy viruses to form a pre-integration complex (PIC) with nuclear import activity in growth-arrested cells, which is the characteristic for lentiviruses (HIV-1). In this process, the HIV-1 central polypurine tract (cPPT) serves as a primer for plus-strand synthesis to produce a “flap” element and is believed to be crucial for the subsequent double-stranded cDNA formation of all retroviral RNA genomes. In this study, the effects of the lentiviral cPPT element on the FV transduction potential in dividing and growth-arrested (G1/S phase) adenocarcinomic human alveolar basal epithelial (A549) cells are investigated by experimental and theoretical methods. The results indicated that the HIV-1 cPPT element in a foamy viral vector background will lead to a significant reduction of the FV transduction and viral titre in growth-arrested cells due to the absence of PICs with nuclear import activity.
The blood–brain barrier choline transporter (BBB-ChT) may have utility as a drug delivery vector to the central nervous system (CNS). We therefore initiated molecular docking studies with the AutoDock and AutoDock Vina (ADVina) algorithms to develop predictive models for compound screening and to identify structural features important for binding to this transporter. The binding energy predictions were highly correlated with r2=0.88, F=692.4, standard error of estimate =0.775, and P-value<0.0001 for selected BBB-ChT-active/inactive compounds (n=93). Both programs were able to cluster active (Gibbs free energy of binding <−6.0 kcal*mol-1) and inactive (Gibbs free energy of binding >−6.0 kcal*mol-1) molecules and dock them significantly better than at random with an area under the curve value of 0.86 and 0.84, respectively. In ranking smaller molecules with few torsional bonds, a size-related bias in scoring producing false-negative outcomes was detected. Finally, important blood–brain barrier parameters, such as the logBBpassive and logBBactive values, were assessed to predict compound transport to the CNS accurately. Knowledge gained from this study is useful to better understand the binding requirements in BBB-ChT, and until such time as its crystal structure becomes available, it may have significant utility in developing a highly predictive model for the rational design of drug-like compounds targeted to the brain.
P-glycoprotein (P-gp) is an ATP (adenosine triphosphate)-binding cassette transporter that causes multidrug resistance of various chemotherapeutic substances by active efflux from mammalian cells. P-gp plays a pivotal role in limiting drug absorption and distribution in different organs, including the intestines and brain. Thus, the prediction of P-gp–drug interactions is of vital importance in assessing drug pharmacokinetic and pharmacodynamic properties. To find the strongest P-gp blockers, we performed an in silico structure-based screening of P-gp inhibitor library (1,300 molecules) by the gradient optimization method, using polynomial empirical scoring (POLSCORE) functions. We report a strong correlation (r2=0.80, F=16.27, n=6, P<0.0157) of inhibition constants (Kiexp or pKiexp; experimental Ki or negative decimal logarithm of Kiexp) converted from experimental IC50 (half maximal inhibitory concentration) values with POLSCORE-predicted constants (KiPOLSCORE or pKiPOLSCORE), using a linear regression fitting technique. The hydrophobic interactions between P-gp and selected drug substances were detected as the main forces responsible for the inhibition effect. The results showed that this scoring technique might be useful in the virtual screening and filtering of databases of drug-like compounds at the early stage of drug development processes.
The dispersion routes of cyclodextrin complexes with nicardipine (NC), such as hydrophilic hydroxypropyl-\(\beta\)-cyclodextrin (NC/HP\(\beta\)CD) and hydrophobic triacetyl-\(\beta\)-cyclodextrin (NC/TA\(\beta\)CD), through the body for controlled drug delivery and sustained release have been examined. The two-compartment pharmacokinetic model described the mechanisms of how the human body handles with ingestion of NC-cyclodextrin complexes in gastrointestinal tract (GI), distribution in plasma, and their metabolism in the liver. The model showed that drug bioavailability was significantly improved after oral administration of cyclodextrin complexes. The mathematical significance of this study to predict nicardipine delivery using pharmacokinetic two-compartment mathematical model with linear ordinary differential equations (ODE) approach represents a valuable tool to emphasize its effectiveness and metabolizing rate and diminish the side effects.
Central nervous system dysfunction is an important cause of morbidity and mortality in patients with human immunodeficiency virus type 1 (HIV-1) infection and acquired immunodeficiency virus syndrome (AIDS). Patients with AIDS are usually affected by HIV-associated encephalitis (HIVE) with viral replication limited to cells of monocyte origin. To examine the molecular mechanisms underlying HIVE-induced dementia, the GSE4755 Affymetrix data were obtained from the Gene Expression Omnibus database and the differentially expressed genes (DEGs) between the samples from AIDS patients with and without apparent features of HIVE-induced dementia were identified. In addition, protein–protein interaction networks were constructed by mapping DEGs into protein–protein interaction data to identify the pathways that these DEGs are involved in. The results revealed that the expression of 1,528 DEGs is mainly involved in the immune response, regulation of cell proliferation, cellular response to inflammation, signal transduction, and viral replication cycle. Heat-shock protein alpha, class A member 1 (HSP90AA1), and fibronectin 1 were detected as hub nodes with degree values >130. In conclusion, the results indicate that HSP90A and fibronectin 1 play important roles in HIVE pathogenesis.
P-glycoprotein (P-gp)-mediated efflux system plays an important role to maintain chemical balance in mammalian cells for endogenous and exogenous chemical compounds. However, despite the extensive characterisation of P-gp potential interaction with drug-like molecules, the interaction of carbon nanoparticles with this type of protein molecule is poorly understood. Thus, carbon nanoparticles were analysed, such as buckminsterfullerenes (C20, C60, C70), capped armchair single-walled carbon nanotube (SWCNT or C168), and P-gp interactions using different molecular docking techniques, such as gradient optimisation algorithm (ADVina), Lamarckian genetic algorithm (FastDock), and shape-based approach (PatchDock) to estimate the binding affinities between these structures. The theoretical results represented in this work show that fullerenes might be P-gp binders because of low levels of Gibbs free energy of binding (ΔG) and potential of mean force (PMF) values. Furthermore, the SWCNT binding is energetically unfavourable, leading to a total decrease in binding affinity by elevation of the residual area (Ares), which also affects the π-π stacking mechanisms. Further, the obtained data could potentially call experimental studies using carbon nanostructures, such as SWCNT for development of drug delivery vehicles, to administer and assess drug-like chemical compounds to the target cells since organisms probably did not develop molecular sensing elements to detect these types of carbon molecules.
Background
Processing and analysis of DNA sequences obtained from next-generation sequencing (NGS) face some difficulties in terms of the correct prediction of DNA sequencing outcomes without the implementation of bioinformatics approaches. However, algorithms based on NGS perform inefficiently due to the generation of long DNA fragments, the difficulty of assembling them and the complexity of the used genomes. On the other hand, the Sanger DNA sequencing method is still considered to be the most reliable; it is a reliable choice for virtual modeling to build all possible consensus sequences from smaller DNA fragments.
Results
In silico and in vitro experiments were conducted: (1) to implement and test our novel sequencing algorithm, using the standard cloning vectors of different length and (2) to validate experimentally virtual shotgun sequencing using the PCR technique with the number of cycles from 1 to 9 for each reaction.
Conclusions
We applied a novel algorithm based on Sanger methodology to correctly predict and emphasize the performance of DNA sequencing techniques as well as in de novo DNA sequencing and its further application in synthetic biology. We demonstrate the statistical significance of our results.
Der Zusammenhang von neuropathischem Schmerz mit einer gestörten Blut-Nerven-
Schranke (BNS) ist bekannt. Die BNS wird durch Tight Junction Proteine (TJP) gebildet.
Netrin-1 (Ntn1) hat je nach Rezeptorbindung verschiedene Effekte auf TJP und somit auf
die Barriereeigenschaften.
In dieser Arbeit wurde im Tiermodell (Chronic Constriction Injury-CCI) untersucht, ob
Netrin-1 einen Einfluss auf die BNS hat und die Wirkung der Rezeptoren Unc5b und
Neogenin-1 beleuchtet. Es wurde untersucht, ob der barrierestabilisierende Netrin-1-
Spiegel auch von neuropathischen Schmerzen, im Speziellen durch „Chronic Regional
Pain Syndrom“ (CRPS), beeinflusst wird.
Männl. Wistar-Ratten wurde lokal Unc5b Antikörper injeziert oder nach Netrin-1 Gabe
der Neogeninrezeptor durch lokale Neogenin-1-siRNA Injektion geblockt. Die mRNA
Expression von Ntn1, seine Rezeptoren sowie der TJP (Claudine-Cldn) wurde mittels q-
PCR untersucht. Netrin-1 wurde im Rattennerven mittels Western Blot bestimmt. Die
Netrin-1-Spiegel im Plasma von CRPS Patient*innen und Kontrollen wurde mittels ELISA
bestimmt. Im Rattenmodell war die Ntn1 vermehrt exprimiert, die Proteinexpression
mittels Western Blot tendenziell vermindert. Die Claudinexpression war nach CCI
herabreguliert. Netrin-1-Injektion steigerte die Expression von Cldn5 und 19. Der
Netrin-1-Rezeptor UNC5B wird bei Neuropathie verstärkt und Neogenin-1 vermindert
exprimiert. Die Expression von Cldn 12 und Cldn19 war bei Blockade des Unc5b
Rezeptors gesteigert und bei Blockade des Neogenin-1 Rezeptors tendenziell
vermindert. Im Plasma von CRPS Patient*innen zeigte sich ein verminderter Netrin-1-
Spiegel.
Die Ergebnisse der vorliegenden Experimente legen nahe, dass Netrin-1 über die
Stabilisierung der Blut-Nerven-Schranke einen lindernden Effekt auf neuropathische
Schmerzen hat und sich auch die Expression dieses Proteins durch CRPS verändert.
Wir nahmen an, dass nach intramuskulärer Injektion von Koffein und Halothan in Schweinen mit Veranlagung (MHS) und ohne Verlangung (MHN) für eine maligne Hyperthermie, es zu einem dosisabhängigen intramuskulären Laktatanstieg kommt. Des weiteren ist die Ausdehnung des dadurch ausgelösten Hypermetabolismus nur auf ein kleines Areral um die Injektionsstelle begrenzt. Eine systemische MH-Krise wird nicht ausgelöst. Mikrodialysesonden wurden in die Hinterläufe von 7 MHN und 7 MHS Schweinen platziert und mit Ringerlösung perfundiert. Nach Einstellen eines Gleichgewichtes wurden Boli von Halothan und Koffein in aufsteigenden Konzentrationen in den Muskel appliziert. Für den zweiten Versuchsansatz, die regionale Ausbreitung betreffend, wurden wiederum Mikrodialysesonden im Abstand von 10 mm und 25 mm zum Injektionsort platziert. Das Laktat wurde photospektrometrisch im Dialysat gemessen. Durch intramuskuläre Halothan- und Koffeinapplikation kommt es zu einer dosisabhänigen Erhöhung der intramuskulären Laktatkonzentration mehr beim MHS als MHN-Tieren mit signifikantem Unterschied. Laktaterhöhungen fanden sich darüber hinaus nur an der Injektionsstelle der Trigger- substanzen, nicht jedoch in 10 und 25 mm Entfernung davon. Somit ist der Anstieg der lokalen Laktatkonzentration im Muskel nur auf ein kleines Areal um die Injektionsstelle begrenzt.
Visual Blood, a 3D animated computer model to optimize the interpretation of blood gas analysis
(2023)
Acid–base homeostasis is crucial for all physiological processes in the body and is evaluated using arterial blood gas (ABG) analysis. Screens or printouts of ABG results require the interpretation of many textual elements and numbers, which may delay intuitive comprehension. To optimise the presentation of the results for the specific strengths of human perception, we developed Visual Blood, an animated virtual model of ABG results. In this study, we compared its performance with a conventional result printout. Seventy physicians from three European university hospitals participated in a computer-based simulation study. Initially, after an educational video, we tested the participants’ ability to assign individual Visual Blood visualisations to their corresponding ABG parameters. As the primary outcome, we tested caregivers’ ability to correctly diagnose simulated clinical ABG scenarios with Visual Blood or conventional ABG printouts. For user feedback, participants rated their agreement with statements at the end of the study. Physicians correctly assigned 90% of the individual Visual Blood visualisations. Regarding the primary outcome, the participants made the correct diagnosis 86% of the time when using Visual Blood, compared to 68% when using the conventional ABG printout. A mixed logistic regression model showed an odds ratio for correct diagnosis of 3.4 (95%CI 2.00–5.79, p < 0.001) and an odds ratio for perceived diagnostic confidence of 1.88 (95%CI 1.67–2.11, p < 0.001) in favour of Visual Blood. A linear mixed model showed a coefficient for perceived workload of −3.2 (95%CI −3.77 to −2.64) in favour of Visual Blood. Fifty-one of seventy (73%) participants agreed or strongly agreed that Visual Blood was easy to use, and fifty-five of seventy (79%) agreed that it was fun to use. In conclusion, Visual Blood improved physicians’ ability to diagnose ABG results. It also increased perceived diagnostic confidence and reduced perceived workload. This study adds to the growing body of research showing that decision-support tools developed around human cognitive abilities can streamline caregivers’ decision-making and may improve patient care.
Die Öffnung der Blut-Nerven-Schranke ist ein wichtiger Baustein in der Pathogenese neuropathischer Schmerzen. Die Blut-Nerven-Schranke schützt das periphere Nervensystem vor externen Einflüssen, wahrt die endoneurale Homöostase und trägt zur Aufrechterhaltung der neuronalen Signalweiterleitung bei. Sie wird durch die Pars epitheloidea des Perineuriums und endoneurale Gefäßzellen gebildet. Essentieller Bestandteil der Blut-Nerven-Schranke sind zwischen Perineural- und Gefäßzellen exprimierte Tight Junctions. Im Rahmen dieser Dissertation wurden die Tight Junction Proteine ZO-1, Claudin-1, -5, -19 und Occludin sowohl in einem Tiermodell neuropathischer Schmerzen, der Chronic Constriction Injury, als auch in Nervenbiopsien (N. suralis) von an Polyneuropathien erkrankten Patienten mittels Immunfluoreszenzfärbungen qualitativ und quantitativ untersucht.
Genetische und erworbene thrombophile Gerinnungsstörungen als Quelle chronischer Schmerzsyndrome
(2012)
Anhand einer umfassenden Falldarstellung einer jungen Patientin mit einem lebensbedrohlichen Gesichtsschmerzsyndrom, das nach septischer Thrombose der periorbitalen venösen und arteriellen Gefäße aufgetreten war, wurde die Bedeutung einer medikamentösen Antikoagulation für die erfolgreiche Schmerztherapie herausgearbeitet. An diesem Fallbeispiel konnte aber auch gezeigt werden, dass keine sicheren Parameter für die Indikation einer solchen Gerinnungstherapie vorlagen. Die Bedeutung dieses Falls lag unzweifelhaft in der Erkenntnis, dass in einer anhaltenden Aktivierung des Kontaktsystems der Gerinnung ein bislang unterschätztes Potential für die Entstehung und Unterhaltung ungeklärter Schmerzen liegen könnte und nicht zuletzt auch daran, dass sich diese ätiologische Komponente in der Komplexität der Erkrankung diagnostisch nicht eindeutig sichern ließ. Mit der Translokation von LPS aus der intestinalen Mukosa in endothelial vorgeschädigte Gefäßabschnitte wurde eine Hypothese vorgetragen, die neben einer schwer detektierbaren inflammatorischen Komponente auch das prokoagulatorische Potential der Schmerzentstehung erklären könnte. Die prokoagulatorische Komponente dieses hypothetischen Entstehungs-mechanismus chronischer Schmerzen müsste, so die Arbeitshypothese, umso dominanter sein, wenn prokoagulatorisch wirksame genetische Faktoren bei den Patienten hinzukommen. Unter der Annahme, dass eine solche zusätzliche Diathese nicht nur eine Schrittmacherfunktion haben, sondern auch einen diagnostischen Beitrag liefern könnte, wurde dieses diagnostische Pilotprojekt mit der empirisch begründeten Heparintherapie von 97 Schmerzpatienten verbunden. Alle Pa-tienten wurden mit dem niedermolekularen Heparin Enoxaparin behandelt und nach zehn Behandlungstagen in vier verschiedene Respondergruppen (Gruppe 1 bis 4) eingeteilt. Diese Gruppen wurden auf fünf prothrombotische Parameter untersucht. Dazu wurden die Allelprävalenzen des Plasminogen Aktivator Inhibitor-(PAI-1 4G/5G) Polymorphismus, der Faktor V-Leiden-Mutation, der Prothrombin (G20210A) Genmutation sowie die Prävalenzen der Hyperfibrinogenämie und des Protein S-Mangels ermittelt. Mit Hilfe des exakten Fisher Tests wurden jeweils die Allelprävalenzen und Parameter sowohl der Respondergruppen 1 bis 3 mit einem Kollektiv der Allgemeinbevölkerung als auch mit dem Kollektiv der Non-Responder (Gruppe 4) verglichen. Die Prävalenz des Allels A der Faktor V-Leiden-Mutation G1691A war im Enoxaparin-Kollektiv bei den Respondern der Gruppen 1 bis 3 im Vergleich zur Allgemeinbevölkerung und zur Non-Respondergruppe (Gruppe 4) signifikant erhöht. Die Allelprävalenzen und Parameter der übrigen prokoagulatorischen Faktoren unterschieden sich von denen der Kontrollgruppen nicht. Anhand des Kallikrein-Kinin-Systems als möglichem Effektor des Hämosta-sesystems konnten Hinweise auf die kausale Wirksamkeit des nieder-molekularen Heparins Enoxaparin bei der Behandlung chronischer Schmerzen gegeben werden.
Emery-Dreifuss muscular dystrophy (EDMD) is a hereditary neuromuscular disorder characterized by slowly progressive muscle weakness, early contractures, and dilated cardiomyopathy. We reported an uneventful general anaesthesia using total intravenous anaesthesia (TIVA) for cardiac transplantation in a 19-year-old woman suffering from EDMD. In vitro contracture test results of two pectoralis major muscle bundles of the patient suggest that exposition to triggering agents does not induce a pathological sarcoplasmic calcium release in the lamin A/C phenotype. However, due to the lack of evidence in the literature, we would recommend TIVA for patients with EDMD if general anaesthesia is required.
Background
Malignant hyperthermia (MH), a metabolic myopathy triggered by volatile anesthetics and depolarizing muscle relaxants, is a potentially lethal complication of general anesthesia in susceptible patients. The implementation of modern inhalation anesthetics that research indicates as less potent trigger substances and the recommended limitations of succinylcholine use, suggests there may be considerable decline of fulminant MH cases. In the presented study, the authors analyzed suspected MH episodes during general anesthesia of patients that were referred to the Wuerzburg MH unit between 2007 and 2011, assuming that MH is still a relevant anesthetic problem in our days.
Methods
With approval of the local ethics committee data of patients that underwent muscle biopsy and in vitro contracture test (IVCT) between 2007 and 2011 were analyzed. Only patients with a history of suspected MH crisis were included in the study. The incidents were evaluated retrospectively using anesthetic documentation and medical records.
Results
Between 2007 and 2011 a total of 124 patients were tested. 19 of them were referred because of suspected MH events; 7 patients were diagnosed MH-susceptible, 4 MH-equivocal and 8 MH-non-susceptible by IVCT. In a majority of cases masseter spasm after succinylcholine had been the primary symptom. Cardiac arrhythmias and hypercapnia frequently occurred early in the course of events. Interestingly, dantrolene treatment was initiated in a few cases only.
Conclusions
MH is still an important anesthetic complication. Every anesthetist must be aware of this life-threatening syndrome at any time. The rapid onset of adequate therapy is crucial to avoid major harm and possibly lethal outcome. Dantrolene must be readily available wherever MH triggering agents are used for anesthesia.
Malignant hyperthermia is a rare but life-threatening complication of general anesthesia in predisposed patients usually triggered by potent inhalation anesthetics and/or the depolarizing muscle relaxant succinylcholine. The authors present a case of delayed sevoflurane-induced malignant hyperthermia in a 21-year-old male patient that was sufficiently treated by discontinuation of trigger agent application and dantrolene infusion. After surviving an MH episode diagnostic procedures are indicated to increase patient safety. In the presented case, the use of a novel minimal-invasive metabolic test with intramuscular injection of halothane and caffeine successfully confirmed MH susceptibility and hence might be an alternative for invasive in vitro contracture testing in selected cases.
Background
While the impact of volatile anaesthetics to induce malignant hyperthermia (MH) is abundantly clear, the role of succinylcholine still remains controversial. To evaluate the influence of succinylcholine on porcine MH events, the authors investigated the hemodynamic and metabolic responses in MH susceptible (MHS) and non-susceptible (MHN) swine following either succinylcholine or halothane application alone or a combination of both substances.
Methods
With approval of the local animal care committee 27 MHS and 30 MHN pigs were anaesthetized and mechanically ventilated. Fiberoptic probes for continuous PCO2 measurement were inserted into the femoral vein and the triceps muscle. Group A received succinylcholine 4 mg/kg, group B incremental doses of halothane (0.5, 1.0 vol%) and group C succinylcholine and halothane simultaneously. Vital signs were recorded continuously.
Results
Prior to drug application measured values did not differ between MHS and MHN. While MHN pigs did not show relevant alterations, succinylcholine, halothane and the combination of both lead to significant hemodynamic and metabolic changes in MHS swine.
Conclusions
Hemodynamic and metabolic alterations following succinylcholine were similar to halothane in MHS pigs. The combination of both pharmacological agents potentiated the observed effects. According to these results succinylcholine acted as an independent and supportive factor during onset of an MH episode.
Background:
The calcium sensitizer levosimendan is increasingly used to improve hemodynamics in patients with acutely decompensated heart failure. By binding to cardiac troponin C the conformation of the calcium-troponin C complex is stabilized, which leads to acceleration of actin-myosin crossbrigde formation and increased force generating capacity of muscle fibers. Besides indications in cardiac failure, beneficial effects of levosimendan in skeletal muscle disorders are currently evaluated. The aim of this study was to investigate differential effects of levosimendan on skeletal muscle of pigs with and without susceptibility to malignant hyperthermia (MH) in order to identify possible risks of this emerging drug for patients with predisposition to MH.
Methods:
Muscle bundles of 17 pigs (9 MH susceptible (MHS); 8 MH non-susceptible (MHN)) were excised under general anesthesia and examined in the tissue bath with increasing concentrations of levosimendan (0.065; 0.125; 0.5; 1.0; 10 and 50 μg/ml). Baseline tension and twitch force were monitored continuously. Data are presented as median and interquartile range. Statistical evaluation was performed using D’Agostino & Pearson test for normal distribution and student’s t test and 2-way ANOVA for differences between the groups. P < 0.05 was considered significant.
Results:
There were no differences between the groups concerning length, weight, initial twitch force and pre-drug resting tension of the investigated muscle strips. After an initial decrease in both groups, twitch amplitude was significantly higher in MHN (− 3.0 [− 5.2–0.2] mN) compared to MHS (− 7.5 [− 10.8- -4.5] mN) (p = 0.0034) muscle at an applied levosimendan concentration of 50 μg/ml. A marked increase in resting tension was detected following levosimendan incubation with 50 μg/ml in MHS muscle bundles (3.3 [0.9–6.1] mN) compared to MHN (− 0.7 [− 1.3–0.0] mN) (p < 0.0001).
Conclusions:
This in vitro investigation revealed the development of significant contractures in muscle bundles of MHS pigs after incubation with levosimendan. However, the effect appeared only at supra-therapeutic concentrations and further research is needed to determine the impact of levosimendan on MHS individuals in vivo.
Es wurden die Einsätze des ITW Würzburg des Jahres 2005 anhand der vorhandenen Intensivtransportprotokolle ausgewertet. Ziel der Arbeit war eine quantitative und qualitative Bestandsaufnahme des Interhospitalverkehrs unter besonderer Beachtung des Beatmungsmanagements. Insgesamt wurden 249 reine ITW-Einsätze im Jahr 2005 gefahren, von denen 243 durch ein vorhandenes Intensivtransportprotokoll dokumentiert waren. Die Dokumentation des Intensivtransportprotokolls war recht different. Zum einen hing die Qualität der Dokumentation vom transportbegleiteten Arzt ab und zum anderen wiesen einzelne Bereiche des Protokolls eine schlechtere Dokumentation auf als andere. Insgesamt waren Scores oder Angaben, die verschlüsselt einzutragen waren durchweg schlechter dokumentiert. Außerdem wurden viele Angaben im Übernahmestatus nicht dokumentiert, da diese oft schon im Verlaufsprotokoll protokolliert waren, was allerdings die digitale Erfassung erschwerte. Aufgrund dieser Beobachtungen entstand der Eindruck, dass hier ein Bedarf zur Vereinfachung des Protokolls besteht. Die Einsatzfrequenz war mit 0,68 Einsätzen pro Tag relativ gering, was mit dem großen Einsatzbereich und der geringen Einwohner-, und Krankenhausdichte zusammenhängt. Der ITW Würzburg wurde vorwiegend während der regulären Vorbehaltszeiten genutzt. Nur ein geringer Anteil (<10%) der Einsätze fanden außerhalb dieser Zeiten statt. Die Gesamteinsatzdauer im Median betrug 3 Std. 30 Min. pro ITW-Einsatz. Der längste Einsatzabschnitt war dabei die Nachbereitungszeit mit 1 Std. 15 Min. im Median. Sie beinhaltete sowohl die Wiederherstellung der Einsatzbereitschaft des Fahrzeugs, sowie die Rückfahrt zum Standort und Pausen. Der kürzeste Einsatzabschnitt war die Behandlungszeit vor Ort mit 30 Minuten im Median. Dabei fiel auf, dass zentripetale Transporte signifikant längere Behandlungszeiten vor Ort erforderten als zentrifugale Transporte. Nur 67,5% der Einsätze erreichten den Patienten innerhalb einer Stunde. Um eine Eintreffzeit von einer Stunde zu realisieren, wären mindestens zwei weitere ITW-Standorte in Schweinfurt und Aschaffenburg nötig. Dies erscheint aber vor dem Hintergrund der Auslastung des ITW Würzburgs, der geringen Zahl an Sofort-transporten und der Kosten nicht adäquat. Drei Viertel aller Transporte waren Ferntransporte, mit einer durchschnittlichen Entfernung der Zielklinik von 72 Km. Hier erscheint der Standort Würzburg hinsichtlich der guten Verkehrsanbindung als zentraler Standort des ITWs sinnvoll. Zentripetale und zentrifugale Transporte waren annähernd gleich vertreten. Das Patientenkollektiv des ITW Würzburg entsprach dem auf Intensivstationen. Knapp dreiviertel der Patienten war über 50 Jahre alt. Insgesamt überwog der Anteil der männlichen Patienten. Am häufigsten wurden Patienten mit intrakraniellen Blutungen, zerebralen Ischämien und Schädelhirntraumen transportiert. Dieser Gruppe folgten Patienten mit akutem Koronarsyndrom und Patienten mit Sepsis. Über die Hälfte, der mit dem ITW Würzburg transportierten Patienten, waren beatmungspflichtig. Dabei fiel auf, dass unabhängig von der Transportart, die Zahl der BIPAP beatmeten Patienten zunahm. Am stärksten war dieser Anstieg bei den zentrifugalen Transporten. Der PEEP wurde bei zentripetalen Transporten signifikant öfters erhöht als bei zentrifugalen oder zentri-zentralen Transporten, was wie schon die Behandlungszeit vor Ort, auf eine intensivere Therapie schließen lässt. Die Strukturqualität des ITW Würzburgs in Form von Ausstattung und Personal wird den geforderten Standards gerecht. Gerade vor dem Hintergrund des Patientenkollektivs kommt der Ausstattung des ITWs und der Qualifikation des Personals eine entscheidende Bedeutung zu. Bestehende Standards dürfen im Hinblick auf eine adäquate Versorgung der Patienten nicht unterschritten werden. Verbesserungsbedarf besteht lediglich hinsichtlich der Prozessqualität. Dies gilt insbesondere für die Dokumentation, die entsprechenden Dokumentationswerkzeuge und die Auslastung des ITW Würzburgs. Hinsichtlich der Dokumentation ist eine möglichst zeitnahe elektronische Doku-mentation wünschenswert mit Ausbau der im Rahmen dieser Arbeit erstellten Datenbank. Was die Auslastung des ITW betrifft, so ist sicherlich noch Potential vorhanden, das es auszuschöpfen gilt. Hier ist eine bessere Informationspolitik über die Vorteile und Einsatzmöglichkeiten des ITWs von Nöten. Das Beatmungsmanagement zeigte eine Intensivierung der Beatmung vor allem bei zentripetalen Transporten, was die Bedeutung des ITWs als Teil der Intensiv-medizinischen Versorgung unterstreicht.
At any moment in time, cells coordinate and balance their calcium ion (Ca\(^{2+}\)) fluxes. The term ‘Ca\(^{2+}\) homeostasis’ suggests that balancing resting Ca2+ levels is a rather static process. However, direct ER Ca\(^{2+}\) imaging shows that resting Ca\(^{2+}\) levels are maintained by surprisingly dynamic Ca\(^{2+}\) fluxes between the ER Ca\(^{2+}\) store, the cytosol, and the extracellular space. The data show that the ER Ca\(^{2+}\) leak, continuously fed by the high-energy consuming SERCA, is a fundamental driver of resting Ca\(^{2+}\) dynamics. Based on simplistic Ca\(^{2+}\) toolkit models, we discuss how the ER Ca\(^{2+}\) leak could contribute to evolutionarily conserved Ca\(^{2+}\) phenomena such as Ca\(^{2+}\) entry, ER Ca\(^{2+}\) release, and Ca\(^{2+}\) oscillations.
Therapeutic drug monitoring (TDM) is increasingly relevant for an individualized antibiotic therapy and subsequently a necessary tool to reduce multidrug-resistant pathogens, especially in light of diminishing antimicrobial capabilities. Critical illness is associated with profound pharmacokinetic and pharmacodynamic alterations, which challenge dose finding and the application of particularly hydrophilic drugs such as β-lactam antibiotics. Methods: Implementation strategy, potential benefit, and practicability of the developed standard operating procedures were retrospectively analyzed from January to December 2020. Furthermore, the efficacy of the proposed dosing target of piperacillin in critically ill patients was evaluated. Results: In total, 160 patients received piperacillin/tazobactam therapy and were subsequently included in the study. Of them, 114 patients received piperacillin/tazobactam by continuous infusion and had at least one measurement of piperacillin serum level according to the standard operating procedure. In total, 271 measurements were performed with an average level of 79.0 ± 46.0 mg/L. Seventy-one piperacillin levels exceeded 100 mg/L and six levels were lower than 22.5 mg/L. The high-level and the low-level group differed significantly in infection laboratory parameters (CRP (mg/dL) 20.18 ± 11.71 vs. 5.75 ± 5.33) and renal function [glomerular filtration rate (mL/min/1.75 m2) 40.85 ± 26.74 vs. 120.50 ± 70.48]. Conclusions: Piperacillin levels are unpredictable in critically ill patients. TDM during piperacillin/tazobactam therapy is highly recommended for all patients. Although our implementation strategy was effective, further strategies implemented into the daily clinical workflow might support the health care staff and increase the clinicians' alertness.
PURPOSE
The threat of national and international terrorism remains high. Preparation is the key requirement for the resilience of hospitals and out-of-hospital rescue forces. The scientific evidence for defining medical and tactical strategies often feeds on the analysis of real incidents and the lessons learned derived from them. This systematic review of the literature aims to identify and systematically report lessons learned from terrorist attacks since 2001.
METHODS
PubMed was used as a database using predefined search strategies and eligibility criteria. All countries that are part of the Organization for Economic Cooperation and Development (OECD) were included. The time frame was set between 2001 and 2018.
RESULTS
Finally 68 articles were included in the review. From these, 616 lessons learned were extracted and summarized into 15 categories. The data shows that despite the difference in attacks, countries, and casualties involved, many of the lessons learned are similar. We also found that the pattern of lessons learned is repeated continuously over the time period studied.
CONCLUSIONS
The lessons from terrorist attacks since 2001 follow a certain pattern and remained constant over time. Therefore, it seems to be more accurate to talk about lessons identified rather than lessons learned. To save as many victims as possible, protect rescue forces from harm, and to prepare hospitals at the best possible level it is important to implement the lessons identified in training and preparation.
Purpose: The threat of national and international terrorism remains high. Preparation is the key requirement for the resilience of hospitals and out-of-hospital rescue forces. The scientific evidence for defining medical and tactical strategies often feeds on the analysis of real incidents and the lessons learned derived from them. This systematic review of the literature aims to identify and systematically report lessons learned from terrorist attacks since 2001.
Methods: PubMed was used as a database using predefined search strategies and eligibility criteria. All countries that are part of the Organization for Economic Cooperation and Development (OECD) were included. The time frame was set between 2001 and 2018.
Results: 68 articles were included in the review. From these, 616 lessons learned were extracted and summarized into 15 categories. The data shows that despite the difference in attacks, countries, and casualties involved, many of the lessons learned are similar. We also found that the pattern of lessons learned is repeated continuously over the time period studied.
Conclusions: The lessons from terrorist attacks since 2001 follow a certain pattern and remained constant over time. Therefore, it seems to be more accurate to talk about lessons identified rather than lessons learned. To save as many victims as possible, protect rescue forces from harm, and to prepare hospitals at the best possible level it is important to implement the lessons identified in training and preparation.
Die Präkonditionierung ist ein endogener Schutzmechanismus, bei dem die Toleranz einer Zelle gegen die Auswirkungen eines späteren ischämischen Schadens erhöht wird. Volatile Anästhetika sind in der Lage den durch die Ischämie verursachten Gewebsschaden zu vermindern, indem sie diesen Schutzmechanismus aktivieren. Ziel der vorliegenden Arbeit war die Untersuchung der CaMK II in der Anästhetika-induzierten Präkonditionierung und in der durch Metoprolol vermittelten Kardioprotektion, sowie der dosisabhängige Effekt von Metoprolol auf die Kardioprotektion und die Desfluran-induzierte Präkonditionierung. Dazu wurde der spezifische Inhibitor der CaMK II, KN-93, sowie der kardioselektive Betablocker Metoprolol in verschiedenen Dosierungen, jeweils vor der Koronarokklusion alleine oder zusammen mit Desfluran, verabreicht. Die Versuche wurden in einem in vivo Herzinfarktmodell an weißen Neuseelandkaninchen durchgeführt. Die Resultate dieser Untersuchungen ergaben, dass KN-93 die Infarktgröße nicht reduzierte und die Desfluran-induzierte Präkonditionierung aufgehoben wurde. Die effektive Hemmung der CaMK II wurde durch Western blot Analysen bestätigt. Die weiteren Ergebnisse ergaben, dass erst eine Metoprolol-Dosis von 1,75 mg/kg und 2,5 mg/kg die Myokardinfarktgröße signifikant verminderte. Die Western blot Analyse zeigte eine effektive Blockade beider Phosphorylierungsstellen des PLB. Außerdem wurde die Desfluran-induzierte Präkonditionierung durch 0,2 mg/kg Metoprolol abgeschwächt, durch 1,0 mg/kg, 1,75 mg/kg oder 2,5 mg/kg Metoprolol wurde sie vollständig aufgehoben. Aus diesen Ergebnissen resultiert, dass die Desfluran-induzierte Präkonditionierung über die Calcium/Calmodulin Kinase II abhängige Phosphorylierung des Phospholamban vermittelt wird. Dagegen wird die Metoprolol-induzierte Kardioprotektion während der Reperfusion durch die Blockade der PKA- und CaMK II-abhängigen Phosphorylierung des PLB vermittelt. Außerdem deuten die Ergebnisse auf eine negative Interaktion zwischen der Desfluran-induzierten Präkonditionierung und der beta-adrenergen Blockade hin.
Ziel dieser Arbeit ist es, anhand dreier quantitativer, systematischer Übersichtsarbeiten (Cochrane Reviews) die Möglichkeiten und Grenzen der EBM zu beleuchten. Dabei wird exemplarisch die Verwendung von hyperbarem Sauerstoff zur Therapie von chronischen Wunden, eines akuten ischämischen Schlaganfalls, sowie von Migräne- und Clusterkopfschmerzen untersucht.
Bei 155 Ärzten und Arzthelferinnen wurde ein Notfalltraining durchgeführt. Davor und danach wurde ein multiple-choice-Test mit acht Fragen zur Reanimation durchgeführt. Es zeigte sich ein signifikanter Anstieg der richtigen Antworten von 69,7 % auf 94,7%. Teilnehmer, deren letztes Training bis zu zwei Jahre zurücklag, erreichten signifikant bessere Ergebnisse. Ebenso wurde durch Fragebögen die Ausstattung von 118 Arztpraxen untersucht. Hier zeigten sich erhebliche Unterschiede je nach Fachrichtung des Arztes. Nur ca. 20 % der Ärzte sind mit modernen AED-Geräten zur Defibrillation ausgestattet. Gerätschaften zur Intubation halten ca. 90 % vor, Sauerstoff dagegen nur ca. 80%, Sauerstoff-Reservoire weniger als die Hälfte. Opiate sind nur bei 72% bevorratet, Cordarex nur bei einem Drittel. Folgende Forderung lassen sich ableiten: -verpflichtende Fortbildungsmaßnahmen zur Reanimation -dies mindestens alle zwei Jahre (im Rahmen des Qualitätsmanagements) -Verbesserung der notfallmedizinischen Geräte- und Medikamentenausstattung
Purpose
Anaemia is common in patients presenting with aneurysmal subarachnoid (aSAH) and intracerebral haemorrhage (ICH). In surgical patients, anaemia was identified as an idenpendent risk factor for postoperative mortality, prolonged hospital length of stay (LOS) and increased risk of red blood cell (RBC) transfusion. This multicentre cohort observation study describes the incidence and effects of preoperative anaemia in this critical patient collective for a 10-year period.
Methods
This multicentre observational study included adult in-hospital surgical patients diagnosed with aSAH or ICH of 21 German hospitals (discharged from 1 January 2010 to 30 September 2020). Descriptive, univariate and multivariate analyses were performed to investigate the incidence and association of preoperative anaemia with RBC transfusion, in-hospital mortality and postoperative complications in patients with aSAH and ICH.
Results
A total of n = 9081 patients were analysed (aSAH n = 5008; ICH n = 4073). Preoperative anaemia was present at 28.3% in aSAH and 40.9% in ICH. RBC transfusion rates were 29.9% in aSAH and 29.3% in ICH. Multivariate analysis revealed that preoperative anaemia is associated with a higher risk for RBC transfusion (OR = 3.25 in aSAH, OR = 4.16 in ICH, p < 0.001), for in-hospital mortality (OR = 1.48 in aSAH, OR = 1.53 in ICH, p < 0.001) and for several postoperative complications.
Conclusions
Preoperative anaemia is associated with increased RBC transfusion rates, in-hospital mortality and postoperative complications in patients with aSAH and ICH.
Der unbehandelte Herz-Kreislauf-Stillstand führt zwangsläufig zum Tod des Patienten. Die anfängliche Überlebensrate von 90% fällt mit jeder weiteren Minute um 10%. Von neurologischen Schäden ist ab der 4. Minute eines Herz-Kreislauf-Stillstands auszugehen. Nach 10 Minuten kann man schon nicht mehr von einer erfolgreichen Reanimation ausgehen. Die vorliegende Untersuchung beschäftigt sich mit dem Problem, das sich dem First-Responder bei Eintreffen am Einsatzort stellt. Um die Chancen auf eine langfristig erfolgreiche Reanimation des Patienten zu optimieren, ist es wichtig, dass der einzelne First-Responder in der Lage ist, den Zeitvorteil von 5 Minuten vor Eintreffen weiterer professioneller Hilfe mit einer hochwertigen und vor allem gleichmäßigen Reanimation zu überbrücken. In der vorliegenden Arbeit wurde untersucht, inwieweit der First-Responder hierbei durch den Einsatz eines halbautomatischen Hilfsgeräts unterstützt wird.
Der perioperative Myokardinfarkt ist eine der Hauptursachen perioperativer Morbidität und Mortalität, wobei bis zu 40% der Patienten an einem akuten Ereignis versterben. Eine der Hauptaufgaben der anästhesiologischen Forschung besteht daher in der Entwicklung neuer, verbesserter Strategien sowohl in der Erkennung und Prophylaxe als auch in der Therapie perioperativer Myokardischämien. In einer wegweisenden Studie zeigten Kersten et al. 1997 erstmals einen kardioprotektiven Effekt für volatile Anästhetika: Die Verabreichung von Isofluran vor der Induktion eines Ischämie-Reperfusions-Schadens (I/R-Schaden) führte zu einer signifikanten Reduktion der resultierenden Infarktgröße. Diese kardioprotektiven Eigenschaften wurden in der Folge auch für andere volatile Anästhetika aufgezeigt, ebenso wie die Induktion eines zweiten Fensters der Präkonditionierung (SWOP) beginnend 24h post-donum. Essentielle molekulare Mechanismen der protektiven Signalkaskade sind hierbei u.a. eine gesteigerte Synthese von Prostaglandinen sowie die erhöhte Produktion von Stickstoffmonoxid (NO). Vergleichbare NO-abhängige, kardioprotektive Wirkungen zeigen sich ebenso für Agonisten der Peroxysomen-Proliferator-aktivierten Rezeptoren (PPAR) α und γ. Die PPAR sind Transkriptionsfaktoren, die nach Liganden-vermittelter Aktivierung (u.a. 15d-Prostaglandin J2, 15d-PGJ2) ihre Wirkungen entfalten. Daher testeten wir die Hypothese, dass das zweite Fenster der Desfluran-induzierten Präkonditionierung durch eine erhöhte Produktion von 15d-PGJ2 mit der nachfolgenden Aktivierung von PPAR α und γ vermittelt wird. Die Experimente wurden in einem etablierten in-vivo Herzinfarktmodell des Kaninchens durchgeführt. Männliche weiße Neuseeland-Kaninchen wurden randomisiert 6 Gruppen zugeteilt. Alle Tiere erhielten eine 30-minütige Okklusion der linken Koronararterie (KAO) gefolgt von einer 3-stündigen Reperfusion. Zwei Gruppen erhielten entweder Desfluran (1.0 MAC, DES) oder Raumluft (Kontrolle, KON) 24h vor KAO. In weiteren Gruppen erhielten die Tiere den PPARα-Antagonisten GW6471 oder den PPARγ-Antagonisten GW9662, jeweils alleine (GW6471 bzw. GW9662) oder in Kombination mit vorheriger Desfluranapplikation (DES+GW6471 bzw. DES+GW9662). Die Infarktgröße (IS/AAR) wurde nach Bestimmung des Ischämieareals (AAR) und des Infarktareals (IS) gravimetrisch nach TTC-Färbung ermittelt. Sechs identische Gruppen wurden instrumentiert zur Entnahme des Herzens und anschließender Analyse der PPAR-DNA-Bindungsaktivität sowie der Gewebekonzentrationen von 15d-PGJ2 und NO mittels spezifischer Assays. Als Ergebnis zeigte sich eine signifikant reduzierte Herzinfarktgröße (DES 42,2±3,1%* vs. KON 61,8±2,8%; *p<0,05) 24h nach der Applikation des volatilen Anästhetikums. Dieser kardioprotektive Phänotyp war begleitet von einer erhöhten PPAR-DNA-Bindungsaktivität (DES 289,9±33RLU* vs. KON 102,9±18RLU, *p<0,05), als auch erhöhten Gewebskonzentrationen von 15d-PGJ2 (DES 224,4±10,2pg/ml* vs. KON 116,9±14,2pg/ml) und NO (DES 14,9±0,7μM* vs. KON 5,4±0,7μM). Unter spezifischer pharmakologischer Blockade von PPARα oder PPARγ kam es zum Verlust dieser protektiven Effekte, wobei sowohl die Infarktgrößenreduktion (DES+GW6471 60,0±2,8% bzw. DES+GW9662 56,5±2,9%), als auch die Elevation der PPAR-DNA-Bindungsaktivität (DES+GW6471 128,1±20,9RLU bzw. DES+GW9662 91,2±31RLU) und der myokardialen NO Konzentrationen (DES+GW6471 5,7±0,3μM bzw. DES+GW9662 5,9±0,9μM) aufgehoben wurde. Unbeeinflusst von der Blockade der PPAR blieb der durch Desfluran erhöhte 15d-PGJ2-Spiegel (DES+GW6471 199,5±8,1pg/ml* und DES+GW9662 179,0±11,7pg/ml*; p<0,05 vs. KON). Insgesamt zeigen die Ergebnisse dieser Arbeit, dass das zweite Fenster der Desfluran-induzierten Präkonditionierung durch die Aktivierung der PPARα und γ vermittelt wird. Die Applikation von Desfluran scheint hierbei durch die erhöhte Produktion von 15d-PGJ2 eine Signalkaskade in Gang zu setzen, welche nicht nur in der Aktivierung von PPARα und PPARγ resultiert, sondern ebenso durch die konsekutiv erhöhte myokardiale Verfügbarkeit von NO die Kardioprotektion vermittelt.
Background
Acute respiratory distress syndrome (ARDS) is a complex clinical diagnosis with various possible etiologies. One common feature, however, is pulmonary permeability edema, which leads to an increased alveolar diffusion pathway and, subsequently, impaired oxygenation and decarboxylation. A novel inhaled peptide agent (AP301, solnatide) was shown to markedly reduce pulmonary edema in animal models of ARDS and to be safe to administer to healthy humans in a Phase I clinical trial. Here, we present the protocol for a Phase IIB clinical trial investigating the safety and possible future efficacy endpoints in ARDS patients.
Methods
This is a randomized, placebo-controlled, double-blind intervention study. Patients with moderate to severe ARDS in need of mechanical ventilation will be randomized to parallel groups receiving escalating doses of solnatide or placebo, respectively. Before advancing to a higher dose, a data safety monitoring board will investigate the data from previous patients for any indication of patient safety violations. The intervention (application of the investigational drug) takes places twice daily over the course of 7 days, ensued by a follow-up period of another 21 days.
Discussion
The patients to be included in this trial will be severely sick and in need of mechanical ventilation. The amount of data to be collected upon screening and during the course of the intervention phase is substantial and the potential timeframe for inclusion of any given patient is short. However, when prepared properly, adherence to this protocol will make for the acquisition of reliable data. Particular diligence needs to be exercised with respect to informed consent, because eligible patients will most likely be comatose and/or deeply sedated at the time of inclusion.
Trial registration
This trial was prospectively registered with the EU Clinical trials register (clinicaltrialsregister.eu). EudraCT Number: 2017-003855-47.
Background: Acute respiratory failure is the most important organ dysfunction of COVID-19 patients. While non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) oxygen are frequently used, efficacy and safety remain uncertain. Benefits and harms of awake prone positioning (APP) in COVID-19 patients are unknown. Methods: We searched for randomized controlled trials (RCTs) comparing HFNC vs. NIV and APP vs. standard care. We meta-analyzed data for mortality, intubation rate, and safety. Results: Five RCTs (2182 patients) were identified. While it remains uncertain whether HFNC compared to NIV alters mortality (RR: 0.92, 95% CI 0.65–1.33), HFNC may increase rate of intubation or death (composite endpoint; RR 1.22, 1.03–1.45). We do not know if HFNC alters risk for harm. APP compared to standard care probably decreases intubation rate (RR 0.83, 0.71–0.96) but may have little or no effect on mortality (RR: 1.08, 0.51–2.31). Conclusions: Certainty of evidence is moderate to very low. There is no compelling evidence for either HFNC or NIV, but both carry substantial risk for harm. The use of APP probably has benefits although mortality appears unaffected.
Background
Data on the routine use of video-assisted laryngoscopy in peri-operative intubations are rather inconsistent and ambiguous, in part due to small populations and non-uniform outcome measures in past trials. Failed or prolonged intubation procedures are a reason for relevant morbidity and mortality. This study aims to determine whether video-assisted laryngoscopy (with both Macintosh-shaped and hyperangulated blades) is at least equal to the standard method of direct laryngoscopy with respect to the first-pass success rate. Furthermore, validated tools from the field of human factors will be applied to examine within-team communication and task load during this critical medical procedure.
Methods
In this randomized, controlled, three-armed parallel group design, multi-centre trial, a total of more than 2500 adult patients scheduled for perioperative endotracheal intubation will be randomized. In equally large arms, video-assisted laryngoscopy with a Macintosh-shaped or a hyperangulated blade will be compared to the standard of care (direct laryngoscopy with Macintosh blade). In a pre-defined hierarchical analysis, we will test the primary outcome for non-inferiority first. If this goal should be met, the design and projected statistical power also allow for subsequent testing for superiority of one of the interventions.
Various secondary outcomes will account for patient safety considerations as well as human factors interactions within the provider team and will allow for further exploratory data analysis and hypothesis generation.
Discussion
This randomized controlled trial will provide a solid base of data in a field where reliable evidence is of major clinical importance. With thousands of endotracheal intubations performed every day in operating rooms around the world, every bit of performance improvement translates into increased patient safety and comfort and may eventually prevent significant burden of disease. Therefore, we feel confident that a large trial has the potential to considerably benefit patients and anaesthetists alike.
Trial registration
ClincalTrials.gov NCT05228288.
Protocol version
1.1, November 15, 2021.
Background
The viral load and tissue distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain important questions. The current study investigated SARS-CoV-2 viral load, biodistribution and anti-SARS-CoV-2 antibody formation in patients suffering from severe corona virus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS).
Methods
This is a retrospective single-center study in 23 patients with COVID-19-induced ARDS. Data were collected within routine intensive care. SARS-CoV-2 viral load was assessed via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Overall, 478 virology samples were taken. Anti-SARS-CoV-2-Spike-receptor binding domain (RBD) antibody detection of blood samples was performed with an enzyme-linked immunosorbent assay.
Results
Most patients (91%) suffered from severe ARDS during ICU treatment with a 30-day mortality of 30%. None of the patients received antiviral treatment. Tracheal aspirates tested positive for SARS-CoV-2 in 100% of the cases, oropharyngeal swabs only in 77%. Blood samples were positive in 26% of the patients. No difference of viral load was found in tracheal or blood samples with regard to 30-day survival or disease severity. SARS-CoV-2 was never found in dialysate. Serologic testing revealed significantly lower concentrations of SARS-CoV-2 neutralizing IgM and IgA antibodies in survivors compared to non-survivors (p = 0.009).
Conclusions
COVID-19 induced ARDS is accompanied by a high viral load of SARS-CoV-2 in tracheal aspirates, which remained detectable in the majority throughout intensive care treatment. Remarkably, SARS-CoV-2 RNA was never detected in dialysate even in patients with RNAemia. Viral load or the buildup of neutralizing antibodies was not associated with 30-day survival or disease severity.
Background
Evidence concerning combined general anesthesia (GA) and thoracic epidural analgesia (EA) is controversial and the procedure appears heterogeneous in clinical implementation. We aimed to gain an overview of different approaches and to unveil a suspected heterogeneity concerning the intraoperative management of combined GA and EA.
Methods
This was an anonymous survey among Members of the Scientific working group for regional anesthesia within the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) conducted from February 2020 to August 2020.
Results
The response rate was 38%. The majority of participants were experienced anesthetists with high expertise for the specific regimen of combined GA and EA. Most participants establish EA in the sitting position (94%), prefer early epidural initiation (prior to skin incision: 80%; intraoperative: 14%) and administer ropivacaine (89%) in rather low concentrations (0.2%: 45%; 0.375%: 30%; 0.75%: 15%) mostly with an opioid (84%) in a bolus-based mode (95%). The majority reduce systemic opioid doses intraoperatively if EA works sufficiently (minimal systemic opioids: 58%; analgesia exclusively via EA: 34%). About 85% manage intraoperative EA insufficiency with systemic opioids, 52% try to escalate EA, and only 25% use non-opioids, e.g. intravenous ketamine or lidocaine.
Conclusions
Although, consensus seems to be present for several aspects (patient's position during epidural puncture, main epidural substance, application mode), there is considerable heterogeneity regarding systemic opioids, rescue strategies for insufficient EA, and hemodynamic management, which might explain inconsistent results of previous trials and meta-analyses.
Häufig stellt die frühe Phase der innerklinischen Traumaversorgung bei Polytraumapatienten besonders die Schädel-Hirn-Verletzungen betreffend einen sehr dynamischen Zeitraum dar, weshalb zeitlich getriggerte Kontrolluntersuchungen weit verbreitet sind. Andererseits bedeutet der Transport zur Untersuchung für beatmete Patienten eine zusätzliche Gefahr. Untersucht wurde, wie häufig sich in einer frühen Kontroll-Computertomografie des Schädels neue oder verschlechterte Befunde finden und, wie diese neuen Informationen die Intensivtherapie beeinflussen. Methode: Retrospektive Analyse aus Befunddaten und Krankenakten. Eingeschlossen wurden 150 beatmete Patienten mit SHT oder Verdacht auf ein SHT, die eine frühe CCT-Kontrolle bekamen. Ergebnisse: Eine Verschlechterung der Befunde wurde bei 63 Patienten (42%) und neue Befunde bei 18 Patienten (12%) gefunden. Bei 47 Pateinten (31%) wurde die Intensivtherapie aufgrund der frühen Kontroll-CCT geändert. Schlussfolgerung: Bei beatmeten Polytraumapatienten treten in mehr als der Hälfte der Fälle Verschlechterungen oder neue intracranielle Befunde auf. Eine frühe CCT-Kontrolle kann diese erkennen und zu einer rechtzeitigen Therapieoptimierung führen.
Hintergrund: Bei der Einleitung einer Narkose eines nicht-nüchternen Patienten wird das Relaxanz in unmittelbarer Folge zum Induktionsmittel appliziert. Welches der Hypnotika Propofol, Etomidat oder Methohexital führt am schnellsten zur ausreichend tiefen Narkose?
Material/Methoden: Standardisierte Narkoseinduktion, je 20 ASA1/2 Patienten pro Medikament. Bestimmung Schlaftiefe mittels CSI: 1. vor Beginn , nach Midazolamgabe, 2. zwei Min. nach Fentanylgabe, 3. direkt nach Gabe des Hypnotikum (Dauer Injektion 1Min.), 4. nach 1 Min.
Propofol 3 mg/kg KG, Etomidat 0,3 mg/kg KG, Methohexital 1 mg/kg KG. Fentanyl 3 µg/kg KG, Midazolam 7,5mg
Ergebnisse: CSI direkt nach Injektion bei Methohexital mit 70,80 (+/-13,93) niedriger (p=0,024) als bei Propofol mit 81,05 (+/-10,82) und als bei Etomidat (p=0,026) mit 81,45 (+/-12,04). Abnahme des CSI während der Injektion bei Methohexital mit -9,6 (+/-12,14) größer (p=0,006) als bei Propofol mit –0,1 (+/-8,31). CSI <60 direkt nach Injektion bei Propofol 2x, Etomidat 3x, Methohexital 4x , nach einer Minute Propofol 17x, Etomidat 10x, Methohexital 16x.
Schlussfolgerung: Methohexital ermöglicht eine schnellere Narkoseinduktion als Etomidat und Propofol.
Background: Septic acute liver and intestinal failure is associated with a high mortality. We therefore investigated the influence of volume resuscitation with different crystalloid or colloid solutions on liver and intestine injury and microcirculation in septic rodents. Methods: Sepsis was induced by cecal ligation and puncture (CLP) in 77 male rats. Animals were treated with different crystalloids (NaCl 0.9% (NaCl), Ringer’s acetate (RA)) or colloids (Gelafundin 4% (Gel), 6% HES 130/0.4 (HES)). After 24 h animals were re-anesthetized and intestinal (n = 6/group) and liver microcirculation (n = 6/group) were obtained using intravital microscopy, as well as macrohemodynamic parameters were measured. Blood assays and organs were harvested to determine organ function and injury. Results: HES improved liver microcirculation, cardiac index and DO2-I, but significantly increased IL-1β, IL-6 and TNF-α levels and resulted in a mortality rate of 33%. Gel infused animals revealed significant reduction of liver and intestine microcirculation with severe side effects on coagulation (significantly increased PTT and INR, decreased haemoglobin and platelet count). Furthermore Gel showed severe hypoglycemia, acidosis and significantly increased ALT and IL-6 with a lethality of 29%. RA exhibited no derangements in liver microcirculation when compared to sham and HES. RA showed no intestinal microcirculation disturbance compared to sham, but significantly improved the number of intestinal capillaries with flow compared to HES. All RA treated animals survided and showed no severe side effects on coagulation, liver, macrohemodynamic or metabolic state. Conclusions: Gelatine 4% revealed devastated hepatic and intestinal microcirculation and severe side effects in CLP induced septic rats, whereas the balanced crystalloid solution showed stabilization of macro- and microhemodynamics with improved survival. HES improved liver microcirculation, but exhibited significantly increased pro-inflammatory cytokine levels. Crystalloid infusion revealed best results in mortality and microcirculation, when compared with colloid infusion.
Balanced hydroxyethylstarch (HES 130/0.4) impairs kidney function in-vivo without inflammation
(2015)
Volume therapy is a standard procedure in daily perioperative care, and there is an ongoing discussion about the benefits of colloid resuscitation with hydroxyethylstarch (HES). In sepsis HES should be avoided due to a higher risk for acute kidney injury (AKI). Results of the usage of HES in patients without sepsis are controversial. Therefore we conducted an animal study to evaluate the impact of 6% HES 130/0.4 on kidney integrity with sepsis or under healthy conditions Sepsis was induced by standardized Colon Ascendens Stent Peritonitis (sCASP). sCASP-group as well as control group (C) remained untreated for 24 h. After 18 h sCASP+HES group (sCASP+VOL) and control+HES (C+VOL) received 50 ml/KG balanced 6% HES (VOL) 130/0.4 over 6h. After 24h kidney function was measured via Inulin- and PAH-Clearance in re-anesthetized rats, and serum urea, creatinine (crea), cystatin C and Neutrophil gelatinase-associated lipocalin (NGAL) as well as histopathology were analysed. In vitro human proximal tubule cells (PTC) were cultured +/- lipopolysaccharid (LPS) and with 0.1–4.0% VOL. Cell viability was measured with XTT-, cell toxicity with LDH-test. sCASP induced severe septic AKI demonstrated divergent results regarding renal function by clearance or creatinine measure focusing on VOL. Soleley HES (C+VOL) deteriorated renal function without sCASP. Histopathology revealed significantly derangements in all HES groups compared to control. In vitro LPS did not worsen the HES induced reduction of cell viability in PTC cells. For the first time, we demonstrated, that application of 50 ml/KG 6% HES 130/0.4 over 6 hours induced AKI without inflammation in vivo. Severity of sCASP induced septic AKI might be no longer susceptible to the way of volume expansion
Background
Up to 50% of septic patients develop acute kidney injury (AKI). The pathomechanism of septic AKI is poorly understood. Therefore, we established an innovative rodent model to characterize sepsis-induced AKI by standardized colon ascendens stent peritonitis (sCASP). The model has a standardized focus of infection, an intensive care set up with monitoring of haemodynamics and oxygenation resulting in predictable impairment of renal function, AKI parameters as well as histopathology scoring.
Methods
Anaesthetized rats underwent the sCASP procedure, whereas sham animals were sham operated and control animals were just monitored invasively. Haemodynamic variables and blood gases were continuously measured. After 24 h, animals were reanesthetized; cardiac output (CO), inulin and PAH clearances were measured and later on kidneys were harvested; and creatinine, urea, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) were analysed. Additional sCASP-treated animals were investigated after 3 and 9 days.
Results
All sCASP-treated animals survived, whilst ubiquitous peritonitis and significantly deteriorated clinical and macrohaemodynamic sepsis signs after 24 h (MAP, CO, heart rate) were obvious. Blood analyses showed increased lactate and IL-6 levels as well as leucopenia. Urine output, inulin and PAH clearance were significantly decreased in sCASP compared to sham and control. Additionally, significant increase in cystatin C and NGAL was detected. Standard parameters like serum creatinine and urea were elevated and sCASP-induced sepsis increased significantly in a time-dependent manner. The renal histopathological score of sCASP-treated animals deteriorated after 3 and 9 days.
Conclusions
The presented sCASP method is a standardized, reliable and reproducible method to induce septic AKI. The intensive care set up, continuous macrohaemodynamic and gas exchange monitoring, low mortality rate as well as the opportunity of detailed analyses of kidney function and impairments are advantages of this setup. Thus, our described method may serve as a new standard for experimental investigations of septic AKI.
Das Schädel-Hirn-Trauma (SHT) ist ein großes medizinisches Problem. Das Hirnödem mit konsekutiv erhöhten intrakraniellen Drücken ist eine häufige und schwerwiegende Komplikation des schweren SHT. Es ist der signifikanteste Prädiktor für ein schlechtes Outcome. Obwohl Glukokortikoide (GK) die Ausbildung eines Hirnödems bei neuroinflammatorischen Erkrankungen und manchen Hirntumoren reduzieren können, ist diese Substanzklasse im SHT ineffektiv oder sogar schädlich.
Nach controlled cortical impact (CCI) in Mäusen, einem etablierten SHT-Modell in-vivo, zeigte sich ein Zusammenbruch der Blut-Hirn-Schranke (BHS). Des Weiteren wurde der BHS-stabilisierende Effekt der GK nach CCI durch proteasomalen Abbau des Glukokortikoidrezeptors (GR) behindert. Eine Inhibierung des Proteasoms durch den Proteasomeninhibitor Bortezomib zusammen mit einer GK-Therapie mit Dexamethason reduzierte den Abbau des GR und sorgte für eine Restitution der BHS-Integrität.
Unglücklicherweise ließen sich diese Ergebnisse in-vitro nicht auf in Sauerstoff-/Glukosemangel-Modell in der humanen Hirnendothelzelllinie hCMEC/D3 übertragen. Daher konnte für die Kombinationstherapie aus dem Proteasomeninhibitor Bortezomib und Dexamethason kein positiver Effekt gezeigt werden.