Charakteristika und Outcome von 70 beatmeten COVID-19-Patienten : Bilanz nach der ersten Welle an einem universitären Zentrum

BACKGROUND In a pandemic situation the overall mortality rate is of considerable interest; however, these data must always be seen in relation to the given healthcare system and the availability of local level of care. A recently published German data evaluation of more than 10,000 COVID-19 patients treated in 920 hospitals showed a high mortality rate of 22% in hospitalized patients and of more than 50% in patients requiring invasive ventilation. Because of the high infection rates in Bavaria, a large number of COVID-19 patients with considerable severity of disease were treated at the intensive care units of the LMU hospital. The LMU hospital is a university hospital and a specialized referral center for the treatment of patients with acute respiratory distress syndrome (ARDS). OBJECTIVE Data of LMU intensive care unit (ICU) patients were systematically evaluated and compared with the recently published German data. METHODS Data of all COVID-19 patients with invasive and noninvasive ventilation and with completed admission at the ICU of the LMU hospital until 31 July 2020 were collected. Data were processed using descriptive statistics. RESULTS In total 70 critically ill patients were included in the data evaluation. The median SAPS II on admission to the ICU was 62~points. The median age was 66 years and 81% of the patients were male. More than 90% were diagnosed with ARDS and received invasive ventilation. Treatment with extracorporeal membrane oxygenation (ECMO) was necessary in 10% of the patients. The median duration of ventilation was 16 days, whereby 34.3% of patients required a tracheostomy. Of the patients 27.1% were transferred to the LMU hospital from external hospitals with reference to our ARDS/ECMO program. Patients from external hospitals had ARDS of higher severity than the total study population. In total, nine different substances were used for virus-specific treatment of COVID-19. The most frequently used substances were hydroxychloroquine and azithromycin. Immunomodulatory treatment, such as Cytosorb® (18.6%) and methylprednisolone (25.7%) were also frequently used. The overall in-hospital mortality rate of ICU patients requiring ventilation was 28.6%. The mortality rates of patients from external hospitals, patients with renal replacement therapy and patients with ECMO therapy were 47.4%, 56.7% and 85.7%, respectively. CONCLUSION The mortality rate in the ventilated COVID-19 intensive care patients was considerably different from the general rate in Germany. The data showed that treatment in an ARDS referral center could result in a lower mortality rate. Low-dose administration of steroids may be another factor to improve patient outcome in a preselected patient population. In the authors' opinion, critically ill COVID-19 patients should be treated in an ARDS center provided that sufficient resources are available.ZUSAMMENFASSUNG HINTERGRUND: Eine aktuelle, deutschlandweite Datenerhebung zeigte bei beatmeten Patienten mit COVID-19 eine Letalität von über 50 %. Auch am LMU Klinikum wurde eine große Anzahl an Patienten mit COVID-19 mit teils erheblicher Erkrankungsschwere intensivmedizinisch behandelt. FRAGESTELLUNG Die Daten der am LMU-Klinikum behandelten COVID-19-Patienten wurden systematisch ausgewertet und mit den deutschlandweiten Daten verglichen. METHODIK Für die vorliegende Studie wurden die Daten aller Patienten, die bis zum 31.07.2020 am LMU-Klinikum aufgrund von COVID-19 invasiv und nichtinvasiv beatmet wurden und deren Krankenhausaufenthalt zum Zeitpunkt der Auswertung bereits abgeschlossen war, analysiert und mittels deskriptiver Statistik aufgearbeitet. ERGEBNISSE Insgesamt wurden 70 kritisch kranke, beatmete Patienten (SAPS-II-Median: 62 Punkte) analysiert (Altersmedian: 66 Jahre, 81 % männlich). Über 90 % wurden wegen eines akuten Lungenversagens (ARDS) unterschiedlicher Schweregrade behandelt. Eine Therapie mittels extrakorporaler Membranoxygenierung (ECMO) war bei 10 % erforderlich. Die Übernahme von externen Kliniken im Rahmen einer ARDS/ECMO-Anfrage erfolgte bei 27,1 % der Patienten. Häufig eingesetzte immunmodulatorische Therapien waren die Behandlung mit Cytosorb® (18,6 %) und die prolongierte Gabe von Methylprednisolon (25,7 %). Die krankenhausinterne Letalität betrug 28,6 %. FAZIT Trotz erheblicher Erkrankungsschwere lag die Letalität bei beatmeten COVID-19-Intensivpatienten im LMU-Kollektiv deutlich unter der deutschlandweit erhobenen Letalität. Ein möglicher Faktor ist die Behandlung in einem Zentrum für ARDS

Workshop: Anforderungen und Lösungen für ein schlankes Auftragsmanagement

Die Erfahrungen des Fraunhofer IPA zeigen, dass die Auswahl geeigneter Auftragsmanagementmethoden und Produktionsprinzipien wesentlich von den Anforderungen an das Unternehmen abhängen. Somit ist das Erreichen einer hohen Termintreue, geringer Lieferzeiten oder niedriger Bestände weniger eine Frage der "Philosophie", als vielmehr durch die systematische Ableitung von Lösungsprinzipien aus den Unternehmensanforderungen zu erreichen. Das Fraunhofer IPA hat hierfür Methoden und Werkzeuge entwickelt, die sich im Rahmen zahlreicher Industrieprojekte bewährt haben. Im Rahmen des Workshops werden Methoden und Werkzeuge vorgestellt, Anforderungen anhand von Fallbeispielen aufgenommen und strukturiert sowie Lösungen für ein schlankes Auftragsmanagement abgeleitet

Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability edema in patients with moderate-to-severe ARDS - a randomized, placebo-controlled, double-blind trial

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