Einfluss einer antiinfektiven Therapie mit Meropenem auf flüchtige organische Verbindun-gen in der Ausatemluft während polymikrobieller Sepsis bei der Ratte

Das Krankheitsbild der Sepsis stellt derzeit die häufigste Todesursache auf nicht kardiologi-schen Intensivstationen dar. Ursachen sind neben Viren und Pilzen vor allem bakterielle In-fektionen. Diese führen zu einer körpereigenen generalisierten Entzündungsreaktion mit der Folge einer Veränderung der Makrozirkulation, wie auch der Mikrozirkulation, welche nicht selten zu einem Multiorganversagen führen können. Steigende Erkrankungszahlen bei gleichbleibend hoher Letalität lassen das Krankheitsbild unter gesundheitsökonomischen Gesichtspunkten zunehmend bedeutungsvoll erscheinen. Von hoher Relevanz für das Über-leben der Patienten ist eine frühzeitige Diagnose und antiinfektive Therapie. Diese erfolgt, trotz modernster Labor- und mikrobiologischer Nachweisverfahren, aufgrund unspezifischer allgemeiner Symptome häufig sehr spät. Neue zusätzliche Diagnoseverfahren könnten die-sem Missstand entgegenwirken. Mithilfe der Ionenmobilitätsspektrometrie ist es zwischenzeitlich möglich flüchtige organi-sche Verbindungen in der Atemluft verschiedener Individuen nachzuweisen. Eine veränderte Zusammensetzung dieser flüchtigen organischen Verbindungen in der Ausa-temluft, auch Exhalom genannt, kann wichtige Informationen über den Zustand des Orga-nismus geben und sogar auf verschiedenste Krankheiten hinweisen. Dies konnte in der Ver-gangenheit z.B. für die Tuberkulose, das Bronchialkarzinom und für verschiedene Infektionen mit Bakterien und Pilzen gezeigt werden. Die vorliegende Arbeit konnte zeigen, dass die Applikation des Antibiotikums Meropenem zu einer Veränderung des Exhaloms bei der Ratte führt. Wurde eine polymikrobielle Sepsis mit-tels Coecum Ligatur und Inzision induziert, konnte anhand der veränderten Atemluftsignale von 1-Propanol, 3-Pentanon, Aceton, Butanal, Acetophenon, Cyclohexanon und 1,2-Butandiol zwischen septischen und ,,gesunden“ Tieren unterschieden werden. Diese Ergebnisse zeigen, dass mittels der Ionenmobilitätsspektrometrie eine Unterscheidung zwischen septischen und scheinoperierten Tieren nach einer Antibiotikagabe mit Merope-nem möglich ist. Obwohl der Ursprung der meisten Analyten noch unbekannt ist, könnte die Atemluftanalyse mittels Ionenmobilitätsspektrometrie einen wertvollen Baustein zwischen Diagnose und Therapie der Sepsis darstellen.Sepsis is currently the most frequent cause of death in non-cardiac intensive care units. Causes are, in addition to viruses and fungi, mainly bacterial infections which lead to a systemic inflammatory response, consequently changing the macrocirculation as well as the microcirculation, which also often leads to multi-organ failure. Rising disease numbers with a consistently high lethality make the disease sepsis also important from a health-economic point of view. Early diagnosis and anti-infective therapy is of crucial importance for the sur-vival of the patients. Yet, despite the latest laboratory and microbiological detection meth-ods, this is often greatly delayed due to non-specific general symptoms. New supportive di-agnostic procedures could counteract this maladministration. By using Ion-Mobility Spectrometry, a non-invasive and affordable method for breath analysis, it is now possible to detect volatile organic compounds in the respiratory air of dif-ferent individuals in many research areas. A modified composition of these volatile organic compounds in the exhaled air, also called exhalome, can give important information about the condition of the organism and even point out various diseases. This has been shown in the past, for example for tuberculosis, bronchial carcinoma, and various infections caused by bacteria and fungi. This study has shown that the application of the anti-infective substance Meropenem influ-enced the composition of the exhalome in rats. When a polymicrobial sepsis was induced by coecum ligation and incision, a differentiation was made between septic and "healthy" ani-mals by means of the altered respiratory air signals of 1-propanol, 3-pentanone, acetone, butanal, acetophenone, cyclohexanone, and 1,2-butanediol. The results obtained verify that by using the Ion-Mobility Spectrometry, a distinction between septic and “healthy” animals after the administration of the antibiotic Meropenem is possible. Even if the origin of most breath-derived signals is still unknown, using Ion-Mobility Spectrometry for exhaled air anal-yses in the future could be an innovative possibility that could support the physician in find-ing an early diagnosis

Levosimendan Ameliorates Cardiopulmonary Function but Not Inflammatory Response in a Dual Model of Experimental ARDS

The calcium sensitiser levosimendan, which is used as an inodilator to treat decompensated heart failure, may also exhibit anti-inflammatory properties. We examined whether treatment with levosimendan improves cardiopulmonary function and is substantially beneficial to the inflammatory response in acute respiratory response syndrome (ARDS). Levosimendan was administered intravenously in a new experimental porcine model of ARDS. For comparison, we used milrinone, another well-known inotropic agent. Our results demonstrated that levosimendan intravenously improved hemodynamics and lung function in a porcine ARDS model. Significant beneficial alterations in the inflammatory response and lung injury were not detected

Levosimendan Ameliorates Cardiopulmonary Function but Not Inflammatory Response in a Dual Model of Experimental ARDS

The calcium sensitiser levosimendan, which is used as an inodilator to treat decompensated heart failure, may also exhibit anti-inflammatory properties. We examined whether treatment with levosimendan improves cardiopulmonary function and is substantially beneficial to the inflammatory response in acute respiratory response syndrome (ARDS). Levosimendan was administered intravenously in a new experimental porcine model of ARDS. For comparison, we used milrinone, another well-known inotropic agent. Our results demonstrated that levosimendan intravenously improved hemodynamics and lung function in a porcine ARDS model. Significant beneficial alterations in the inflammatory response and lung injury were not detected

Clinical dosage of lidocaine does not impact the biomedical outcome of sepsis-induced acute respiratory distress syndrome in a porcine model

Background Sepsis is a common disease in intensive care units worldwide, which is associated with high morbidity and mortality. This process is often associated with multiple organ failure including acute lung injury. Although massive research efforts have been made for decades, there is no specific therapy for sepsis to date. Early and best treatment is crucial. Lidocaine is a common local anesthetic and used worldwide. It blocks the fast voltage-gated sodium (Na+) channels in the neuronal cell membrane responsible for signal propagation. Recent studies show that lidocaine administered intravenously improves pulmonary function and protects pulmonary tissue in pigs under hemorrhagic shock, sepsis and under pulmonary surgery. The aim of this study is to show that lidocaine inhalative induces equivalent effects as lidocaine intravenously in pigs in a lipopolysaccharide (LPS)-induced sepsis with acute lung injury. Methods After approval of the local State and Institutional Animal Care Committee, to induce the septic inflammatory response a continuous infusion of lipopolysaccharide (LPS) was administered to the pigs in deep anesthesia. Following induction and stabilisation of sepsis, the study medication was randomly assigned to one of three groups: (1) lidocaine intravenously, (2) lidocaine per inhalation and (3) sham group. All animals were monitored for 8 h using advanced and extended cardiorespiratory monitoring. Postmortem assessment included pulmonary mRNA expression of mediators of early inflammatory response (IL-6 & TNF-alpha), wet-to-dry ratio and lung histology. Results Acute respiratory distress syndrome (ARDS) was successfully induced after sepsis-induction with LPS in all three groups measured by a significant decrease in the PaO2/FiO2 ratio. Further, septic hemodynamic alterations were seen in all three groups. Leucocytes and platelets dropped statistically over time due to septic alterations in all groups. The wet-to-dry ratio and the lung histology showed no differences between the groups. Additionally, the pulmonary mRNA expression of the inflammatory mediators IL-6 and TNF-alpha showed no significant changes between the groups. The proposed anti-inflammatory and lung protective effects of lidocaine in sepsis-induced acute lung injury could not be proven in this study

High PEEP Levels during CPR Improve Ventilation without Deleterious Haemodynamic Effects in Pigs

Background: Invasive ventilation during cardiopulmonary resuscitation (CPR) is very complex due to unique thoracic pressure conditions. Current guidelines do not provide specific recommendations for ventilation during ongoing chest compressions regarding positive end-expiratory pressure (PEEP). This trial examines the cardiopulmonary effects of PEEP application during CPR. Methods: Forty-two German landrace pigs were anaesthetised, instrumented, and randomised into six intervention groups. Three PEEP levels (0, 8, and 16 mbar) were compared in high standard and ultralow tidal volume ventilation. After the induction of ventricular fibrillation, mechanical chest compressions and ventilation were initiated and maintained for thirty minutes. Blood gases, ventilation/perfusion ratio, and electrical impedance tomography loops were taken repeatedly. Ventilation pressures and haemodynamic parameters were measured continuously. Postmortem lung tissue damage was assessed using the diffuse alveolar damage (DAD) score. Statistical analyses were performed using SPSS, and p values <0.05 were considered significant. Results: The driving pressure (Pdrive) showed significantly lower values when using PEEP 16 mbar than when using PEEP 8 mbar (p = 0.045) or PEEP 0 mbar (p < 0.001) when adjusted for the ventilation mode. Substantially increased overall lung damage was detected in the PEEP 0 mbar group (vs. PEEP 8 mbar, p = 0.038; vs. PEEP 16 mbar, p = 0.009). No significant differences in mean arterial pressure could be detected. Conclusion: The use of PEEP during CPR seems beneficial because it optimises ventilation pressures and reduces lung damage without significantly compromising blood pressure. Further studies are needed to examine long-term effects in resuscitated animals

Ultra-low tidal volume ventilation during cardiopulmonary resuscitation shows no mitigating effect on pulmonary end-organ damage compared to standard ventilation: insights from a porcine model

Abstract Objective This study aimed to determine whether ultra-low tidal volume ventilation (ULTVV) applied during cardiopulmonary resuscitation (CPR) compared with standard ventilation (intermittent positive pressure ventilation, IPPV) can reduce pulmonary end-organ damage in the post-resuscitation period. Methods A prospective, randomized trial was conducted using a porcine model (n = 45). The animals were divided into three groups: IPPV, ULTVV, and a sham control group. Juvenile male pigs underwent CPR after inducing ventricular fibrillation and received the designated ventilation intervention [IPPV: tidal volume 6–8 ml per kilogram body weight (ml/kg BW), respiratory rate 10/min, FiO2 1.0; ULTVV: tidal volume 2–3 ml/kg BW, respiratory rate 50/min, FiO2 1.0]. A 20-h observation period followed if return of spontaneous circulation was achieved. Histopathological examination using the diffuse alveolar damage scoring system was performed on postmortem lung tissue samples. Arterial and venous blood gas analyses and ventilation/perfusion measurements via multiple inert gas elimination technique (MIGET) were repeatedly recorded during the experiment. Results Out of the 45 experiments conducted, 28 animals were excluded based on predefined criteria. Histopathological analysis showed no significant differences in lung damage between the ULTVV and IPPV groups. ULTVV demonstrated adequate oxygenation and decarboxylation. MIGET measurements during and after resuscitation revealed no significant differences between the intervention groups. Conclusion In the short-term follow-up phase, ULTVV demonstrated similar histopathological changes and functional pulmonary parameters compared to standard ventilation. Further research is needed to investigate the long-term effects and clinical implications of ULTVV in resuscitation settings