27 results on '"Klaus Stahl"'
Search Results
2. The authors reply
- Author
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Benjamin Seeliger, Klaus Stahl, Pedro David Wendel-Garcia, Daniel Hofmaenner, Christian Bode, and Sascha David
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Critical Care and Intensive Care Medicine - Published
- 2022
3. Covid-19 associated ARDS in pregnant women and timing of delivery: a single center experience
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Markus Busch, Marius M. Hoeper, Constantin von Kaisenberg, Thomas Stueber, and Klaus Stahl
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Respiratory Distress Syndrome ,Pregnancy ,COVID-19 ,Humans ,Female ,Pregnant Women ,Pregnancy Complications, Infectious ,Critical Care and Intensive Care Medicine - Published
- 2022
4. Extrakorporale Behandlungsstrategien der Sepsis: die Rolle der Plasmapherese
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Christian Bode, Sascha David, Klaus Stahl, University of Zurich, and David, Sascha
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Gynecology ,medicine.medical_specialty ,business.industry ,610 Medicine & health ,030208 emergency & critical care medicine ,General Medicine ,Critical Care and Intensive Care Medicine ,03 medical and health sciences ,0302 clinical medicine ,Anesthesiology and Pain Medicine ,Emergency Medicine ,Medicine ,Therapeutic plasma exchange ,2703 Anesthesiology and Pain Medicine ,030212 general & internal medicine ,10023 Institute of Intensive Care Medicine ,2711 Emergency Medicine ,2706 Critical Care and Intensive Care Medicine ,business - Abstract
Zusammenfassung Hintergrund Die Mortalität bei Sepsis bleibt hoch. Verschiedene Techniken zur extrakorporalen Zytokinelimination wurden als zusätzliche therapeutische Maßnahmen bei Sepsis und septischem Schock untersucht. Ziele Zusammenfassung einer Auswahl extrakorporaler Blutreinigungstechniken und der aktuellen Erkenntnisse in der klinischen Anwendung mit besonderem Schwerpunkt auf dem therapeutischen Plasmaaustausch. Methoden Nicht systematische Literaturrecherche. Ergebnisse Verschiedene extrakorporale Blutreinigungstechniken mit unterschiedlichen Evidenzniveaus hinsichtlich Zytokinelimination, Verbesserung der Hämodynamik und Verringerung der Mortalität werden derzeit klinisch eingesetzt. Die am ausführlichsten untersuchten Modalitäten umfassen die hochvolumige Hämofiltration/Dialyse mit und ohne High-Cut-off-Filter sowie Hämoadsorptionstechniken (einschließlich CytoSorb- und Polymyxin-B-Filter). Trotz teilweise ermutigender Beobachtungen bezüglich der Entfernung proinflammatorischer Zytokine und verbesserten Hämodynamik zeigten randomisierte Studien bislang keinen positiven Einfluss auf das Überleben. Aufgrund der Verwendung von Spenderplasma als Substitutionsflüssigkeit stellt der therapeutische Plasmaaustausch das einzige Verfahren dar, das zusätzlich verbrauchte protektive Faktoren ersetzen kann. Schlussfolgerungen Die Anwendung extrakorporaler Blutreinigungsmethoden kann für Sepsispatienten außerhalb klinischer Studien bisher nicht empfohlen werden, da derzeit keine Beweise für ihre Wirksamkeit vorliegen. Zukünftige Untersuchungen sollten darauf abzielen, das untersuchte Patientenkollektiv hinsichtlich des klinischen Schweregrads, des Zeitpunkts der Intervention und verschiedener inflammatorischer (Sub-)Phänotypen zu homogenisieren.
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- 2021
5. It takes two to bleed: anticoagulation intensity and the host's vascular susceptibility
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Benjamin Seeliger, Pedro David Wendel-Garcia, Klaus Stahl, Christian Bode, Sascha David, University of Zurich, and David, Sascha
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Anticoagulants ,Humans ,610 Medicine & health ,Hemorrhage ,10023 Institute of Intensive Care Medicine ,2706 Critical Care and Intensive Care Medicine ,Critical Care and Intensive Care Medicine ,Blood Coagulation - Published
- 2022
6. Extracorporeal Membrane Oxygenation for Severe ARDS Due to Immune Diffuse Alveolar Hemorrhage
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Benjamin Seeliger, Christian Kuehn, Tobias Welte, Julius J. Schmidt, Heiko Schenk, Olaf Wiesner, Klaus Stahl, Johann Bauersachs, Marius M. Hoeper, and Sascha David
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Pulmonary and Respiratory Medicine ,ARDS ,business.industry ,medicine.medical_treatment ,Retrospective cohort study ,Diffuse alveolar hemorrhage ,Critical Care and Intensive Care Medicine ,medicine.disease ,Immune system ,Anesthesia ,Extracorporeal membrane oxygenation ,Medicine ,Cardiology and Cardiovascular Medicine ,business - Published
- 2020
7. Effect of therapeutic plasma exchange on endothelial activation and coagulation-related parameters in septic shock
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Klaus Stahl, Bernhard M W Schmidt, Hermann Haller, Ulrich Budde, Christian Bode, Sascha David, Tobias Welte, Marius M. Hoeper, Julius J. Schmidt, and Benjamin Seeliger
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Adult ,Male ,medicine.medical_specialty ,Hemangioblasts ,Antithrombin III ,ADAMTS13 Protein ,Extracorporeal treatment ,030204 cardiovascular system & hematology ,von Willebrand factor ,Critical Care and Intensive Care Medicine ,Gastroenterology ,Sepsis ,Endothelial activation ,03 medical and health sciences ,0302 clinical medicine ,Von Willebrand factor ,Internal medicine ,Septic shock ,medicine ,Humans ,Platelet ,Prospective Studies ,ADAMTS-13 ,Blood Coagulation ,biology ,Plasma Exchange ,business.industry ,Research ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,030208 emergency & critical care medicine ,Plasmapheresis ,lcsh:RC86-88.9 ,Middle Aged ,medicine.disease ,Shock, Septic ,ADAMTS13 ,biology.protein ,Female ,Fresh frozen plasma ,business ,Protein C ,medicine.drug - Abstract
Background A dysbalanced coagulation system is part of the pathological host response to infection in sepsis. Activation of pro-coagulant pathways and attenuation of anti-coagulant activity ultimately lead to microvascular stasis and consequent organ failure. No treatment approaches specifically targeting this axis are available. We explored the effects of therapeutic plasma exchange (TPE) on microvascular coagulation dysbalance in septic shock. Methods We conducted a prospective single-center study enrolling 31 patients with early septic shock (onset 0.4 μg/kg/min). Clinical and biochemical data, including measurement of protein C; a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13); and von Willebrand factor antigen (vWF:Ag), were obtained before and after TPE against fresh frozen plasma. Results Antithrombotic acting proteins such as antithrombin-III (ATIII) and protein C were markedly reduced in septic patients, but their activity increased after TPE (ATIII, 51% (41–61) vs. 63% (48–70), p = 0.029; protein C, 47% (38–60) vs. 62% (54–69), p = 0.029). Median ADAMTS13 activity was increased by TPE from 27 (21–42) % before to 47 (38–62) % after TPE (p p p = 0.001, R2 = 0.316). Conclusions Septic shock was associated with activation of pro-coagulant pathways and simultaneous depletion of anti-coagulant factors. TPE partially attenuated this dysbalance by removing pro- and by replacing anti-coagulant factors. Trial registration ClinicalTrials.gov, NCT03065751. Retrospectively registered on 28 February 2017.
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- 2020
8. Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry
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Pedro David, Wendel-Garcia, André, Moser, Marie-Madlen, Jeitziner, Hernán, Aguirre-Bermeo, Pedro, Arias-Sanchez, Janina, Apolo, Ferran, Roche-Campo, Diego, Franch-Llasat, Gian-Reto, Kleger, Claudia, Schrag, Urs, Pietsch, Miodrag, Filipovic, Sascha, David, Klaus, Stahl, Souad, Bouaoud, Amel, Ouyahia, Patricia, Fodor, Pascal, Locher, Martin, Siegemund, Nuria, Zellweger, Sara, Cereghetti, Peter, Schott, Gianfilippo, Gangitano, Maddalena Alessandra, Wu, Mario, Alfaro-Farias, Gerardo, Vizmanos-Lamotte, Hatem, Ksouri, Nadine, Gehring, Emanuele, Rezoagli, Fabrizio, Turrini, Herminia, Lozano-Gómez, Andrea, Carsetti, Raquel, Rodríguez-García, Bernd, Yuen, Anja Baltussen, Weber, Pedro, Castro, Jesus Oscar, Escos-Orta, Alexander, Dullenkopf, Maria C, Martín-Delgado, Theodoros, Aslanidis, Marie-Helene, Perez, Frank, Hillgaertner, Samuele, Ceruti, Marilene, Franchitti Laurent, Julien, Marrel, Riccardo, Colombo, Marcus, Laube, Alberto, Fogagnolo, Michael, Studhalter, Tobias, Wengenmayer, Emiliano, Gamberini, Christian, Buerkle, Philipp K, Buehler, Stefanie, Keiser, Muhammed, Elhadi, Jonathan, Montomoli, Philippe, Guerci, Thierry, Fumeaux, Reto A, Schuepbach, Stephan M, Jakob, Yok-Ai, Que, Matthias Peter, Hilty, Saba, Al-Ameri, Wendel-Garcia, P, Moser, A, Jeitziner, M, Aguirre-Bermeo, H, Arias-Sanchez, P, Apolo, J, Roche-Campo, F, Franch-Llasat, D, Kleger, G, Schrag, C, Pietsch, U, Filipovic, M, David, S, Stahl, K, Bouaoud, S, Ouyahia, A, Fodor, P, Locher, P, Siegemund, M, Zellweger, N, Cereghetti, S, Schott, P, Gangitano, G, Wu, M, Alfaro-Farias, M, Vizmanos-Lamotte, G, Ksouri, H, Gehring, N, Rezoagli, E, Turrini, F, Lozano-Gomez, H, Carsetti, A, Rodriguez-Garcia, R, Yuen, B, Weber, A, Castro, P, Escos-Orta, J, Dullenkopf, A, Martin-Delgado, M, Aslanidis, T, Perez, M, Hillgaertner, F, Ceruti, S, Franchitti Laurent, M, Marrel, J, Colombo, R, Laube, M, Fogagnolo, A, Studhalter, M, Wengenmayer, T, Gamberini, E, Buerkle, C, Buehler, P, Keiser, S, Elhadi, M, Montomoli, J, Guerci, P, Fumeaux, T, Schuepbach, R, Jakob, S, Que, Y, Hilty, M, Graduate School, Translational Physiology, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, and AII - Inflammatory diseases
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Disease dynamic ,Disease dynamics ,Pandemic ,Critical Illness ,COVID-19 ,610 Medicine & health ,Middle Aged ,Critical Care and Intensive Care Medicine ,Intensive Care Units ,Humans ,Female ,ARDS ,Intensive care unit ,Prospective Studies ,Registries ,Pandemics - Abstract
BackgroundIt remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic.MethodsProspective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic.ResultsFour thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60–63] years vs 64 [62–66] years,p p p p 2/FiO2at admission was lower (132 [123–141] mmHg vs 101 [91–113] mmHg,p p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4–7]% vs 20 [14–29],p p p p p ConclusionCharacteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.
- Published
- 2022
9. Modulation of The Permeability-Inducing Factor Angiopoietin-2 Through Bifonazole in Systemic Inflammation
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Hermann Haller, Valerie Etzrodt, Klaus Stahl, Benjamin Seeliger, Temitayo O Idowu, Sascha David, Thorben Pape, and University of Zurich
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Antifungal Agents ,Bifonazole ,Stimulation ,610 Medicine & health ,Pharmacology ,Critical Care and Intensive Care Medicine ,Systemic inflammation ,Angiopoietin-2 ,Capillary Permeability ,Sepsis ,In vivo ,medicine ,Humans ,MTT assay ,Cells, Cultured ,Barrier function ,Inflammation ,business.industry ,Imidazoles ,Endothelial Cells ,medicine.disease ,In vitro ,Emergency Medicine ,medicine.symptom ,10023 Institute of Intensive Care Medicine ,business ,medicine.drug - Abstract
BACKGROUND Vascular barrier breakdown in sepsis represents a key component of the maladaptive host response to infection and the release of endothelial Angiopoietin-2 (Angpt-2) is a mechanistic driver of endothelial hyperpermeability. Angpt-2 is associated with morbidity and mortality but a targeted therapeutic approach is not available. We screened for U.S. Food and Drug Administration (FDA) approved drugs that might have off-target effects decreasing Angpt-2 and therefore, ameliorating capillary leakage. METHODS Endothelial cells were isolated from human umbilical veins (HUVECs) and used for in vitro studies at baseline and after stimulation (FDA-library screening, RT-PCR, ELISA, immunocytochemistry, MTT assay). On the functional level, we assessed real-time transendothelial electrical resistance (TER) using an ECIS (electric cell-substrate impedance sensing) device. RESULTS We found that the anti-fungal Bifonazole (BIFO) reduces spontaneous Angpt-2 release in a time- and dose-dependent manner after 8, 12 and 24 h (24 h: veh: 15.6 ± 0.7 vs. BIFO: 8.6 ± 0.8 ng/mL, p
- Published
- 2021
10. Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock
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Hermann Haller, Julius J. Schmidt, Sascha David, Heiko Schenk, Marius M. Hoeper, Tobias Welte, Bernhard M W Schmidt, Uta Hillebrand, Christian Bode, Heiner Wedemeyer, Klaus Stahl, Malgorzata Wygrecka, Benjamin Seeliger, Thorben Pape, Agnes Sauer, Yulia Kiyan, and University of Zurich
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Stimulation ,Extracorporeal treatment ,Heparan sulfate ,610 Medicine & health ,Critical Care and Intensive Care Medicine ,Gastroenterology ,Internal medicine ,Medicine ,DAMP ,Heparanase ,Research Articles ,business.industry ,Septic shock ,RC86-88.9 ,Medical emergencies. Critical care. Intensive care. First aid ,Plasmapheresis ,medicine.disease ,Biomarker (medicine) ,Therapeutic plasma exchange ,Fresh frozen plasma ,10023 Institute of Intensive Care Medicine ,business ,Ex vivo - Abstract
Background Disruption of the endothelial glycocalyx (eGC) is observed in septic patients and its injury is associated with multiple-organ failure and inferior outcomes. Besides this biomarker function, increased blood concentrations of shedded eGC constituents might play a mechanistic role in septic organ failure. We hypothesized that therapeutic plasma exchange (TPE) using fresh frozen plasma might influence eGC-related pathology by removing injurious mediators of eGC breakdown while at the time replacing eGC protective factors. Methods We enrolled 20 norepinephrine-dependent (NE > 0.4 μg/kg/min) patients with early septic shock (onset Results SDF demonstrated a decrease in eGC thickness in septic patients compared to healthy individuals (p = 0.001). Circulating HS levels were increased more than sixfold compared to controls and decreased significantly following TPE [controls: 16.9 (8–18.6) vs. septic patients before TPE: 105.8 (30.8–143.4) μg/ml, p p p = 0.001; vs. septic patients after TPE: 13.2 (11.2–31.8), p Conclusions Septic shock results in profound degradation of the eGC and an acquired deficiency of the protective regulator Hpa-2. TPE removed potentially injurious eGC degradation products and partially attenuated Hpa-2 deficiency. Trial registration clinicaltrials.gov NCT04231994, retrospectively registered 18 January 2020
- Published
- 2021
11. The authors reply
- Author
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Benjamin Seeliger, Klaus Stahl, Pedro David Wendel-Garcia, Daniel Hofmaenner, Christian Bode, and Sascha David
- Subjects
Critical Care and Intensive Care Medicine - Published
- 2022
12. Unraveling the secret of re-balancing homeostasis in sepsis: a critical view on extracorporeal blood purification modalities
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Sascha David, Klaus Stahl, Christian Bode, Pedro David Wendel-Garcia, University of Zurich, and Stahl, Klaus
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medicine.medical_specialty ,Pain medicine ,MEDLINE ,610 Medicine & health ,Critical Care and Intensive Care Medicine ,Sepsis ,Extracorporeal blood purification ,Anesthesiology ,Correspondence ,Medicine ,Homeostasis ,Humans ,Intensive care medicine ,Modalities ,business.industry ,Shock ,medicine.disease ,Shock, Septic ,Hemoperfusion ,Cytokines ,Adsorption ,10023 Institute of Intensive Care Medicine ,Hemofiltration ,2706 Critical Care and Intensive Care Medicine ,business - Published
- 2021
13. The Janus Face of Coronavirus Disease 2019-Associated Coagulopathy
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Benjamin Seeliger, Klaus Stahl, Michael R.G. Doebler, Sascha David, Christian Bode, Daniel A. Hofmaenner, and University of Zurich
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Online Letters to the Editor ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Coagulopathy ,Medicine ,610 Medicine & health ,10023 Institute of Intensive Care Medicine ,Critical Care and Intensive Care Medicine ,business ,medicine.disease ,Virology - Published
- 2021
14. Flow-dependent regulation of endothelial Tie2 by GATA3 in vivo
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Joerg Heineke, Thorben Pape, Klaus Stahl, Valerie Etzrodt, Hermann Haller, Temitayo O Idowu, Sascha David, and University of Zurich
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0301 basic medicine ,610 Medicine & health ,Inflammation ,Vascular permeability ,Critical Care and Intensive Care Medicine ,Permeability ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Medicine ,Research Articles ,Barrier function ,Vascular leakage ,Gene knockdown ,RC86-88.9 ,business.industry ,GATA3 ,Shock ,Medical emergencies. Critical care. Intensive care. First aid ,Blood flow ,Capillary leakage ,030104 developmental biology ,Shock (circulatory) ,cardiovascular system ,Cancer research ,10023 Institute of Intensive Care Medicine ,Hypotension ,medicine.symptom ,Signal transduction ,business ,030217 neurology & neurosurgery - Abstract
Background Reduced endothelial Tie2 expression occurs in diverse experimental models of critical illness, and experimental Tie2 suppression is sufficient to increase spontaneous vascular permeability. Looking for a common denominator among different critical illnesses that could drive the same Tie2 suppressive (thereby leak inducing) phenotype, we identified “circulatory shock” as a shared feature and postulated a flow-dependency of Tie2 gene expression in a GATA3 dependent manner. Here, we analyzed if this mechanism of flow-regulation of gene expression exists in vivo in the absence of inflammation. Results To experimentally mimic a shock-like situation, we developed a murine model of clonidine-induced hypotension by targeting a reduced mean arterial pressure (MAP) of approximately 50% over 4 h. We found that hypotension-induced reduction of flow in the absence of confounding disease factors (i.e., inflammation, injury, among others) is sufficient to suppress GATA3 and Tie2 transcription. Conditional endothelial-specific GATA3 knockdown (B6-Gata3tm1-Jfz VE-Cadherin(PAC)-cerERT2) led to baseline Tie2 suppression inducing spontaneous vascular leak. On the contrary, the transient overexpression of GATA3 in the pulmonary endothelium (jet-PEI plasmid delivery platform) was sufficient to increase Tie2 at baseline and completely block its hypotension-induced acute drop. On the functional level, the Tie2 protection by GATA3 overexpression abrogated the development of pulmonary capillary leakage. Conclusions The data suggest that the GATA3–Tie2 signaling pathway might play a pivotal role in controlling vascular barrier function and that it is affected in diverse critical illnesses with shock as a consequence of a flow-regulated gene response. Targeting this novel mechanism might offer therapeutic opportunities to treat vascular leakage of diverse etiologies.
- Published
- 2021
15. A Retrospective Analysis of Nonocclusive Mesenteric Ischemia in Medical and Surgical ICU Patients: Clinical Data on Demography, Clinical Signs, and Survival
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Marius M. Hoeper, Sascha David, Bernhard C. Meyer, Olaf Wiesner, Jan Fuge, Michael P. Manns, Jan B. Hinrichs, Markus Busch, Sabine K Maschke, Klaus Stahl, and Andrea Schneider
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Icu patients ,Organ Dysfunction Scores ,shock ,030204 cardiovascular system & hematology ,Nonocclusive mesenteric ischemia ,Critical Care and Intensive Care Medicine ,Sepsis ,sepsis ,03 medical and health sciences ,0302 clinical medicine ,intestinal failure ,Intestinal failure ,Intensive care ,medicine ,Retrospective analysis ,Humans ,Aged ,Demography ,Retrospective Studies ,business.industry ,Original Articles ,nonocclusive mesenteric ischemia ,Middle Aged ,medicine.disease ,Intensive Care Units ,030220 oncology & carcinogenesis ,Shock (circulatory) ,Mesenteric Ischemia ,medicine.symptom ,business - Abstract
Background: To analyze demography, clinical signs, and survival of intensive care patients diagnosed with nonocclusive mesenteric ischemia (NOMI) and to evaluate the effect of a local intra-arterial prostaglandin therapy. Methods: Retrospective observational study screening 455 intensive care patients with acute arterial mesenteric perfusion disorder in a tertiary care hospital within the past 8 years. Lastly, 32 patients with NOMI were enrolled, of which 11 received local intra-arterial prostaglandin therapy. The diagnosis of NOMI was based on the clinical presentation and established biphasic computed tomography criteria. Clinical and biochemical data were obtained 24 hours before, at the time, and 24 hours after diagnosis. Results: Patients were 60.5 (49.3-73) years old and had multiple comorbidities. Most of them were diagnosed with septic shock requiring high doses of norepinephrine (NE: 0.382 [0.249-0.627] μg/kg/min). The Sequential Organ Failure Assessment (SOFA) score was 18 (16-20). A decrease in oxygenation (Pao 2/Fio 2), pH, and bicarbonate and an increase in international normalized ratio, lactate, bilirubin, leucocyte count, and NE dose were early indicators of NOMI. Median SOFA score significantly increased in the last 24 hours before diagnosis of NOMI (16 vs 18, P < .0001). Overall, 28-day mortality was 75% (81% nonintervention vs 64% intervention cohort; P = .579). Median SOFA scores 24 hours after intervention increased by +5% in the nonintervention group and decreased by 5.5% in the intervention group ( P = .0059). Conclusions: Our data suggest that NOMI is a detrimental disease associated with progressive organ failure and a high mortality. Local intra-arterial prostaglandin application might hold promise as a rescue treatment strategy. These data encourage future randomized controlled trials are desirable.
- Published
- 2019
16. Extracorporeal membrane oxygenation in non-intubated immunocompromised patients
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Marius M. Hoeper, Heiko Schenk, Sascha David, Klaus Stahl, Christian Kühn, Olaf Wiesner, and University of Zurich
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Adult ,Male ,Respiratory Distress Syndrome ,medicine.medical_specialty ,RC86-88.9 ,business.industry ,medicine.medical_treatment ,MEDLINE ,Medical emergencies. Critical care. Intensive care. First aid ,610 Medicine & health ,Middle Aged ,Critical Care and Intensive Care Medicine ,Immunocompromised Host ,Extracorporeal Membrane Oxygenation ,Research Letter ,medicine ,Extracorporeal membrane oxygenation ,Humans ,Female ,10023 Institute of Intensive Care Medicine ,Intensive care medicine ,business - Published
- 2021
17. Role of endothelial microRNA 155 on capillary leakage in systemic inflammation
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Matijs van Meurs, Valerie Etzrodt, Robert Geffers, Ankita Garg, Thorben Pape, Hermann Haller, Temitayo O Idowu, Antje Prasse, Janina Müller-Deile, Thomas Thum, Samir M. Parikh, Benjamin Seeliger, Heiko Schenk, Kristina Thamm, Klaus Stahl, Sascha David, Groningen Kidney Center (GKC), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany., University of Zurich, and David, Sascha
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Endothelium ,Respiratory distress syndrome ,610 Medicine & health ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,Systemic inflammation ,Umbilical vein ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Downregulation and upregulation ,In vivo ,Sepsis ,Medicine ,Animals ,Humans ,ddc:610 ,Tight junctions ,Zebrafish ,030304 developmental biology ,0303 health sciences ,Tight junction ,business.industry ,Research ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,Heterozygote advantage ,lcsh:RC86-88.9 ,Systemic Inflammatory Response Syndrome ,MicroRNAs ,medicine.anatomical_structure ,Knockout mouse ,Cancer research ,Endothelium, Vascular ,10023 Institute of Intensive Care Medicine ,medicine.symptom ,2706 Critical Care and Intensive Care Medicine ,business ,Capillary Leak Syndrome - Abstract
Background Capillary leakage is a key contributor to the pathological host response to infections. The underlying mechanisms remain incompletely understood, and the role of microRNAs (MIR) has not been investigated in detail. We hypothesized that specific MIRs might be regulated directly in the endothelium thereby contributing to vascular leakage. Methods SmallRNA sequencing of endotoxemic murine pulmonary endothelial cells (ECs) was done to detect regulated vascular MIRs. In vivo models: transgenic zebrafish (flk1:mCherry/l-fabp:eGFP-DPB), knockout/wildtype mouse (B6.Cg-Mir155tm1.1Rsky/J); disease models: LPS 17.5 mg/kgBW and cecal ligation and puncture (CLP); in vitro models: stimulated human umbilical vein EC (HUVECs), transendothelial electrical resistance. Results Endothelial MIR155 was identified as a promising candidate in endotoxemic murine pulmonary ECs (25 × upregulation). Experimental overexpression in a transgenic zebrafish line and in HUVECs was sufficient to induce spontaneous vascular leakage. To the contrary, genetic MIR155 reduction protects against permeability both in vitro and in endotoxemia in vivo in MIR155 heterozygote knockout mice thereby improving survival by 40%. A tight junction protein, Claudin-1, was down-regulated both in endotoxemia and by experimental MIR155 overexpression. Translationally, MIR155 was detectable at high levels in bronchoalveolar fluid of patients with ARDS compared to healthy human subjects. Conclusions We found that MIR155 is upregulated in the endothelium in mouse and men as part of a systemic inflammatory response and might contribute to the pathophysiology of vascular leakage in a Claudin-1-dependent manner. Future studies have to clarify whether MIR155 could be a potential therapeutic target.
- Published
- 2021
18. Comparison of anticoagulation strategies for veno-venous ECMO support in acute respiratory failure
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Marius M. Hoeper, Christian Kühn, Johann Bauersachs, Jens-Christian Schewe, Andreas Tiede, Benjamin Seeliger, Christian Bode, Klaus Stahl, Sascha David, Stefan F. Ehrentraut, Christian Putensen, Folkert Steinhagen, Robert Friedrich, Michael Döbler, Tobias Welte, University of Zurich, David, Sascha, and Bode, Christian
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Adult ,Male ,ARDS ,Letter ,Organ Dysfunction Scores ,medicine.medical_treatment ,Activated clotting time ,610 Medicine & health ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Extracorporeal Membrane Oxygenation ,Thromboembolism ,Germany ,Extracorporeal membrane oxygenation ,medicine ,Humans ,Oxygenator ,Blood Coagulation ,Retrospective Studies ,Simplified Acute Physiology Score ,medicine.diagnostic_test ,business.industry ,Bleeding ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,Anticoagulants ,030208 emergency & critical care medicine ,Retrospective cohort study ,lcsh:RC86-88.9 ,Middle Aged ,medicine.disease ,Heparinization ,Treatment Outcome ,SAPS II ,Anesthesia ,Female ,Blood Coagulation Tests ,ECMO ,10023 Institute of Intensive Care Medicine ,business ,Respiratory Insufficiency ,2706 Critical Care and Intensive Care Medicine ,Cohort study ,Partial thromboplastin time - Abstract
Background Extracorporeal membrane oxygenation (ECMO) support in acute respiratory failure may be lifesaving, but bleeding and thromboembolic complications are common. The optimal anticoagulation strategy balancing these factors remains to be determined. This retrospective study compared two institutional anticoagulation management strategies focussing on oxygenator changes and both bleeding and thromboembolic events. Methods We conducted a retrospective observational cohort study between 04/2015 and 02/2020 in two ECMO referral centres in Germany in patients receiving veno-venous (VV)-ECMO support for acute respiratory failure for > 24 h. One centre routinely applied low-dose heparinization aiming for a partial thromboplastin time (PTT) of 35–40 s and the other routinely used a high-dose therapeutic heparinization strategy aiming for an activated clotting time (ACT) of 140–180 s. We assessed number of and time to ECMO oxygenator changes, 15-day freedom from oxygenator change, major bleeding events, thromboembolic events, 30-day ICU mortality, activated clotting time and partial thromboplastin time and administration of blood products. Primary outcome was the occurrence of oxygenator changes depending on heparinization strategy; main secondary outcomes were the occurrence of severe bleeding events and occurrence of thromboembolic events. The transfusion strategy was more liberal in the low-dose centre. Results Of 375 screened patients receiving VV-ECMO support, 218 were included in the analysis (117 high-dose group; 101 low-dose group). Disease severity measured by SAPS II score was 46 (IQR 36–57) versus 47 (IQR 37–55) and ECMO runtime was 8 (IQR 5–12) versus 11 (IQR 7–17) days (P = 0.003). There were 14 oxygenator changes in the high-dose group versus 48 in the low-dose group. Freedom from oxygenator change at 15 days was 73% versus 55% (adjusted HR 3.34 [95% confidence interval 1.2–9.4]; P = 0.023). Severe bleeding events occurred in 23 (19.7%) versus 14 (13.9%) patients (P = 0.256) and thromboembolic events occurred in 8 (6.8%) versus 19 (19%) patients (P = 0.007). Mortality at 30 days was 33.3% versus 30.7% (P = 0.11). Conclusions In this retrospective study, ECMO management with high-dose heparinization was associated with lower rates of oxygenator changes and thromboembolic events when compared to a low-dose heparinization strategy. Prospective, randomized trials are needed to determine the optimal anticoagulation strategy in patients receiving ECMO support.
- Published
- 2021
19. Adjuvant therapeutic plasma exchange in septic shock
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Christian Bode, Tobias Welte, Klaus Stahl, Sascha David, and Christian Putensen
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2019-20 coronavirus outbreak ,Letter ,Coronavirus disease 2019 (COVID-19) ,Plasma Exchange ,Septic shock ,business.industry ,medicine.medical_treatment ,Plasmapheresis ,Pharmacology ,Critical Care and Intensive Care Medicine ,medicine.disease ,Shock, Septic ,Sepsis ,Shock (circulatory) ,medicine ,Humans ,Therapeutic plasma exchange ,medicine.symptom ,business ,Adjuvant - Published
- 2020
20. Injury to the endothelial glycocalyx in critically ill patients with COVID-19
- Author
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Hermann Haller, Marius M. Hoeper, Thorben Pape, Klaus Stahl, Anna Bertram, Sascha David, Phillip Alexander Gronski, Yulia Kiyan, Benjamin Seeliger, Tobias Welte, and University of Zurich
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Endothelium ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Critical Illness ,Pneumonia, Viral ,610 Medicine & health ,Comorbidity ,Glycocalyx ,Critical Care and Intensive Care Medicine ,Betacoronavirus ,Correspondence ,Medicine ,Humans ,Pandemics ,Aged ,business.industry ,Critically ill ,SARS-CoV-2 ,COVID-19 ,Middle Aged ,Endothelial glycocalyx ,Prognosis ,medicine.anatomical_structure ,Critical illness ,Female ,Endothelium, Vascular ,10023 Institute of Intensive Care Medicine ,business ,Coronavirus Infections ,Biomarkers - Published
- 2020
21. First do no harm—beware the risk of therapeutic plasma exchange in severe COVID-19
- Author
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Christian Bode, Klaus Stahl, and Sascha David
- Subjects
2019-20 coronavirus outbreak ,Do no harm ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,biology ,business.industry ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,lcsh:RC86-88.9 ,Critical Care and Intensive Care Medicine ,medicine.disease ,biology.organism_classification ,medicine.disease_cause ,Pneumonia ,Pandemic ,medicine ,Therapeutic plasma exchange ,Intensive care medicine ,business ,Betacoronavirus ,Coronavirus - Published
- 2020
22. Early therapeutic plasma exchange in septic shock: a prospective open-label nonrandomized pilot study focusing on safety, hemodynamics, vascular barrier function, and biologic markers
- Author
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Hermann Haller, Temitayo O Idowu, Hannah Knaup, Klaus Stahl, Bernhard M W Schmidt, Olaf Wiesner, Sascha David, Jan T. Kielstein, Marius M. Hoeper, Markus Busch, and Tobias Welte
- Subjects
Male ,Time Factors ,Organ Dysfunction Scores ,medicine.medical_treatment ,Hemodynamics ,Pilot Projects ,Extracorporeal treatment ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,Blood purification ,Norepinephrine ,0302 clinical medicine ,Fresh frozen plasma ,Germany ,Vasoconstrictor Agents ,Prospective Studies ,APACHE ,Plasma Exchange ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,Plasmapheresis ,Middle Aged ,Shock, Septic ,Renal Replacement Therapy ,Female ,Patient Safety ,Adult ,Mean arterial pressure ,medicine.medical_specialty ,Multiple Organ Failure ,Urology ,Proinflammatory cytokine ,03 medical and health sciences ,medicine ,Humans ,Endothelium ,Adverse effect ,Biologic marker ,Septic shock ,business.industry ,Research ,Endothelial Cells ,030208 emergency & critical care medicine ,lcsh:RC86-88.9 ,medicine.disease ,Respiration, Artificial ,business ,Biomarkers - Abstract
Background Given the pathophysiological key role of the host response to an infection rather than the infection per se, an ideal therapeutic strategy would also target this response. This study was designed to demonstrate safety and feasibility of early therapeutic plasma exchange (TPE) in severely ill individuals with septic shock. Methods This was a prospective single center, open-label, nonrandomized pilot study enrolling 20 patients with early septic shock (onset 0.4 μg/kg/min) out of 231 screened septic patients. Clinical and biochemical data were obtained before and after TPE. Plasma samples were taken for ex-vivo stimulation of human umbilical vein endothelial cells (HUVECs) to analyze barrier function (immunocytochemistry and transendothelial electrical resistance (TER)). Cytokines were measured by cytometric bead array (CBA) and enzyme-linked immunosorbent assays (ELISAs). An immediate response was defined as > 20% NE reduction from baseline to the end of TPE. Results TPE was well tolerated without the occurrence of any adverse events and was associated with a rapid reduction in NE (0.82 (0.61–1.17) vs. 0.56 (0.41–0.78) μg/kg/min, p = 0.002) to maintain mean arterial pressure (MAP) above 65 mmHg. The observed 28-day mortality was 65%. Key proinflammatory cytokines and permeability factors (e.g., interleukin (IL)-6, IL-1b, and angiopoietin-2) were significantly reduced after TPE, while the protective antipermeability factor angiopoietin-1 was not changed. Ex-vivo stimulation of HUVECs with plasma obtained before TPE induced substantial cellular hyperpermeability, which was completely abolished with plasma obtained after TPE. Conclusions Inclusion of early septic shock patients with high doses of vasopressors was feasible and TPE was safe. Rapid hemodynamic improvement and favorable changes in the cytokine profile in patients with septic shock were observed. It has yet to be determined whether early TPE also improves outcomes in this patient cohort. An appropriately powered multicenter randomized controlled trial is desirable. Trial registration Clinicaltrials.gov, NCT03065751. Retrospectively registered on 28 February 2017. Electronic supplementary material The online version of this article (10.1186/s13054-018-2220-9) contains supplementary material, which is available to authorized users.
- Published
- 2018
23. Extracorporeal cytokine removal in severe CAR-T cell associated cytokine release syndrome
- Author
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Christine S. Falk, Nora Möhn, Matthias Eder, Sascha David, Christian Koenecke, Bernhard M W Schmidt, Marius M. Hoeper, Gernot Beutel, Arnold Ganser, Tobias Welte, Thomas Skripuletz, and Klaus Stahl
- Subjects
Male ,Resuscitation ,Chemokine ,medicine.medical_treatment ,T-Lymphocytes ,Receptors, Antigen, T-Cell ,Pharmacology ,Critical Care and Intensive Care Medicine ,Immunotherapy, Adoptive ,Endothelial activation ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Longitudinal Studies ,Receptors, Chimeric Antigen ,biology ,business.industry ,Interleukin-6 ,Endothelial Cells ,030208 emergency & critical care medicine ,Middle Aged ,medicine.disease ,Hemoperfusion ,Immunohistochemistry ,Cytokine release syndrome ,Cytokine ,Treatment Outcome ,030228 respiratory system ,Methylprednisolone ,biology.protein ,Cytokines ,Adsorption ,business ,Cytokine Release Syndrome ,Ex vivo ,medicine.drug - Abstract
Purpose Life-threatening complications of CD-19 Chimeric antigen receptor - T (CAR-T) cells such as the cytokine release syndrome (CRS)) have been reported. Treatment is limited to IL-6 blockade and steroids although global removal of elevated soluble inflammatory factors might be more effective. Methods Clinical course of a CRS patient treated with extracorporeal cytokine adsorption (Cytosorb®). A panel of 48 cytokines, chemokines and endothelial markers has been analyzed longitudinally. Ex vivo stimulation of endothelial cells to visualize (immunocytochemistry) and quantify (ECIS, TER) endothelial barrier effects. Results Following CAR-T cell application a 65 years old male developed grade 4 CRS with refractory shock (3 vasopressors) and severe capillary leakage (+37 L/24 h resuscitation). Treatment included IL-6 blockade, methylprednisolone and additionally Cytosorb hemoperfusion. While multiple soluble inflammatory factors were elevated and most of them decreased by more than 50% following Cytosorb, markers of endothelial injury increased steadily (e.g. Angpt-2/Angpt-1) leading to profound endothelial activation and leakage in ex vivo assays. Conclusion This is the first reported use of cytokine adsorption for CRS showing efficacy in absorption of various cytokines but not endothelial growth factors. A randomized controlled trial to evaluate additional Cytosorb treatment in CRS is currently recruiting at our institution ( NCT04048434 ).
- Published
- 2019
24. To remove and replace—a role for plasma exchange in counterbalancing the host response in sepsis
- Author
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Sascha David and Klaus Stahl
- Subjects
Extracorporeal Circulation ,medicine.medical_specialty ,Letter ,Critical Illness ,Host response ,Review ,Critical Care and Intensive Care Medicine ,Sepsis ,Immune System Phenomena ,Extracorporeal technique ,High volume hemofiltration ,Medicine ,Humans ,Intensive care medicine ,Plasma Exchange ,business.industry ,Renal replacement therapy ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,lcsh:RC86-88.9 ,Coupled plasma filtration adsorption ,medicine.disease ,Acute kidney injury ,High cut-off membranes ,Adsorption ,Hemofiltration ,business - Abstract
Sepsis is one of the leading causes of morbidity and mortality worldwide. It is characterized by a dysregulated immune response to infections that results in life-threatening organ dysfunction and even death. Bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns (PAMPs), as well as damage-associated molecular patterns (DAMPs) released by host injured cells, are well-recognized triggers resulting in the elevation of both pro-inflammatory and anti-inflammatory cytokines. Understanding this complex pathophysiology has led to the development of therapeutic strategies aimed at restoring a balanced immune response by eliminating/deactivating these inflammatory mediators. Different extracorporeal techniques have been studied in recent years in the hope of maximizing the effect of renal replacement therapy in modulating the exaggerated host inflammatory response, including the use of high volume hemofiltration (HVHF), high cut-off (HCO) membranes, adsorption alone, and coupled plasma filtration adsorption (CPFA). These strategies are not widely utilized in practice, depending on resources and local expertise. The literature examining their use in septic patients is growing, but the evidence to support their use at this stage is considered of low level. Our aim is to provide a comprehensive overview of the technical aspects, clinical applications, and associated side effects of these techniques.
- Published
- 2019
25. Staying Awake in Severe Acute Respiratory Distress Syndrome: A Perspective on Immunocompromised Patients
- Author
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Marius M. Hoeper, Sascha David, Heiko Schenk, Benjamin Seeliger, Christian Kühn, Klaus Stahl, and Olaf Wiesner
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,ARDS ,business.industry ,medicine.medical_treatment ,Perspective (graphical) ,Immunosuppression ,Acute respiratory distress ,Critical Care and Intensive Care Medicine ,medicine.disease ,Correspondence ,Medicine ,business ,Intensive care medicine - Published
- 2021
26. Direct evidence of SARS-CoV-2 in gut endothelium
- Author
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Klaus Stahl, Sascha David, Jan Hinrich Bräsen, Marius M. Hoeper, University of Zurich, and David, Sascha
- Subjects
Adult ,Male ,2019-20 coronavirus outbreak ,medicine.medical_specialty ,Endothelium ,Coronavirus disease 2019 (COVID-19) ,Colon ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pain medicine ,Pneumonia, Viral ,MEDLINE ,610 Medicine & health ,Critical Care and Intensive Care Medicine ,Betacoronavirus ,Anesthesiology ,Pandemic ,Humans ,Medicine ,Pandemics ,SARS-CoV-2 ,business.industry ,COVID-19 ,Virology ,medicine.anatomical_structure ,10023 Institute of Intensive Care Medicine ,Coronavirus Infections ,2706 Critical Care and Intensive Care Medicine ,business ,Imaging in Intensive Care Medicine - Published
- 2020
27. Nonocclusive Mesenteric Ischemia and Interventional Local Vasodilatory Therapy: A Meta-Analysis and Systematic Review of the Literature
- Author
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Markus Busch, Jan B. Hinrichs, Bernhard C. Meyer, Andrea Schneider, Sascha David, Michael P. Manns, Nina Rittgerodt, Jan Fuge, Sabine K Maschke, Marius M. Hoeper, and Klaus Stahl
- Subjects
medicine.medical_specialty ,Critical Care ,Vasodilator Agents ,Vasodilation ,030204 cardiovascular system & hematology ,Nonocclusive mesenteric ischemia ,Critical Care and Intensive Care Medicine ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Emergency surgery ,Internal medicine ,Intensive care ,medicine ,Odds Ratio ,Humans ,Retrospective Studies ,business.industry ,Mortality rate ,Standard of Care ,medicine.disease ,Intensive Care Units ,Treatment Outcome ,030220 oncology & carcinogenesis ,Shock (circulatory) ,Meta-analysis ,Mesenteric Ischemia ,Cardiology ,medicine.symptom ,business - Abstract
Background:Intensive care patients with nonocclusive mesenteric ischemia (NOMI) show mortality rates of 70% to 90%. Besides emergency surgery, different interventional local vasodilatory treatment (LVT) attempts have been described. We performed a systematic review and a meta-analysis to evaluate feasibility, efficacy, and tolerability of LVT in patients with life-threatening NOMI.Methods:Searches of PubMed, EMBASE, Web of Science, and Cochrane Library databases were performed until February 2019. Measured outcomes included immediate technical success rates (as indicated by mesenteric vasodilation on angiography or clinical improvement) and adverse events (AEs). Therapeutic efficacy was measured by the assessment of overall mortality.Results:Twelve studies (335 patients, 245 received LVT) from 1977 to 2018 were included. All studies were retrospective (4 comparative and 8 noncomparative). Different intra-arterial vasodilators (4× papaverine, 6× prostaglandin E1, 1× tolazoline/heparin, 1× tolazoline + iloprost) were reported. Initial technical success rate was 75.9% (95% confidence interval [CI], 55.1%-89%, P = .017) with an AE rate of 2.9% (95% CI: 1.3%-6.6%; P = .983). Overall mortality in LVT patients was 40.3% (95% CI: 28.7%-53%, P = .134). In 4 studies, outcomes were compared between patients receiving LVT to those who received standard of care (odds ratio for death in LVT patients was 0.261 [95% CI: 0.095-0.712, P = .009]).Conclusions:Local vasodilatory treatment appears to be safe in patients with NOMI and might have the potential to at least partially reverse mesenteric vasoconstriction features in control angiographies. However, with no randomized and prospective studies available yet, the overall quality of published studies has to be considered as low; therefore, it is not possible to draw generalizable conclusions from the present data concerning clinical end points. Its application might hold promise as a rescue treatment strategy and deserves further evaluation in randomized controlled trials.
- Published
- 2019
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