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 (P_drive) 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.

The use of extracorporeal life support (ECLS) as part of cardio-circulatory support has increased rapidly in recent years. Severe hyperlactatemia is not uncommon in this group of patients. Lactate peak concentrations and lactate clearance have already been identified as independent marker for mortality in critical ill patients without mechanical device support. The aim of this study was to determine a supposed correlation between the variables lactate peak concentration and clearance in the blood and mortality in the ECLS context. Therefore, a total of 51 cardiac surgery ICU patients with ECLS therapy were included in this retrospective, clinical observational study (survivors n = 23; non-survivors n = 28). Lactate measurement was performed before, during and after ECLS therapy. Further, common ICU scores (SAPSII, SOFA, TISS28), the rates of transfusion and the different vasopressor therapies will be compared. Significant elevated peak lactate levels and poor lactate clearance were associated with higher mortality during ECLS therapy (p < 0.001). Deceased patients had higher SAPSII scores (p < 0.001), received more transfusions (p < 0.001) and presented with higher rates of epinephrine (p < 0.001). In conclusion, hyperlactatemia during ECLS therapy is a time sensitive emergency. Lactate cannot be cleared in all patients. Reversible causes should be explored and treated. In cases where the cause is irreversible, the prognosis of elevated lactate concentrations and reduced clearance is very poor.

The treatment of ARDS continues to pose major challenges for intensive care physicians in the 21st century with mortality rates still reaching up to 50% in severe cases. Further research efforts are needed to better understand the complex pathophysiology of this disease. There are different well-established animal models to induce acute lung injury but none has been able to adequately mimic the complex pathomechanisms of ARDS. The most crucial factor for the development of this condition is the damage to the alveolar capillary unit. The combination of two well-established lung injury models allow us to mimic in more detail the underlying pathomechanism. Bronchoalveolar lavage (BAL) leads to surfactant depletion as well as alveolar collapse. The repeated instillation of fluid volumes causes subsequent hypoxemia. Surfactant depletion is a key factor of ARDS in humans. BAL is often combined with other lung injury approaches, but not with a second hit followed by oleic acid injection (OAI) yet. Oleic acid injection leads to severely impaired gas exchange, a deterioration of lung mechanics and disruption of the alveolo-capillary barrier. The OAI mimics most of the expected effects of ARDS consisting of extended inflammation of lung tissue with an increase of alveolar leakage and gas exchange impairment. A disadvantage of the combination of different models is the difficulty to determine the influence to the lung injury caused by BAL alone, OAI alone or both together. The model presented in this report represents the combination of BAL and OAI as a new double-hit lung injury model. This new model is easy to implement and an alternative to study different therapeutic approaches in ARDS in the future.

Influencing the inflammatory response represents an important branch in ARDS research. The naturally occurring polyphenol derivative resveratrol has already been confirmed to have strong anti-inflammatory effects on the cardiac and metabolic system. In the present study, we investigated the propagated anti-inflammatory effects of intravenous resveratrol in a porcine ARDS model. 20 domestic pigs (30 ± 2 kg; approval G20-1-135), divided into three groups: 1. resveratrol high dose (HD; n = 8), single bolus of 20 mg/kg over 15 min. 2. resveratrol low dose (LD; n = 8), single bolus of 10 mg/kg over 15 min. 3. Vehicle (n = 4), with the carrier solution DMSO over 15 min administered after ARDS induction. ARDS induction: using BAL/oleic acid and a subsequent test period of 8 h. Measurement parameters: Hemodynamics/spirometry data were collected continuously, BGA/laboratory parameters repetitively. Post-mortem: analysis of pulmonary inflammatory markers. Two-way analysis of variance (repeated measurement) and Student-Newman-Keuls method. Resveratrol HD significantly reduced the expression of TNF-alpha in lung tissue compared to the LD group (p < 0.05). A significantly increased functional residual capacity (FRC) could be demonstrated for the HD group at the end of the test (p < 0.05 for HD vs. LD/vehicle). Further, resveratrol HD reduced statistically the EVLWI compared to LD/vehicle (p < 0.05 at T4/T8). In this study, resveratrol HD ameliorated pulmonary mechanics as reported for the FRC and EVLWI. Further, the proposed anti-inflammatory effects of resveratrol, a significant reduction in the expression of TNF-alpha was observed in the HD group.

Background: Acute respiratory distress syndrome (ARDS) is a common disease in intensive care medicine. Despite intensive research, mortality rates are high, not even in COVID-19 ARDS. Thereby, pigs offer some advantages to study the characteristics of ARDS. Many different ARDS models exist. Most of the articles published focused on histopathological and microscopic lung alterations to identify the most suitable animal ARDS model. “Macroscopic” observations and descriptions are often missing. Therefore, we performed a post-hoc comparison of two common ARDS models for pigs: lipopolysaccharide (LPS) vs. a double-hit model (bronchoalveolar lavage + oleic acid infusion). We investigated hemodynamic, spirometric and laboratory changes as another main clinical part of ARDS. Results: The groups were compared by two-way analysis of variance (ANOVA) with a post-hoc Student–Newman–Keuls test. A p value lower than 0.05 was accepted as significant. All animals (n = 8 double-hit ARDS; n = 8 LPS ARDS) survived the observation period of 8 h. ARDS induction with reduced oxygen indices was successful performed in both models (76 ± 35/225 ± 54/212 ± 79 vs. 367 ± 64; T0/T4/T8 vs. BLH for double-hit; 238 ± 57/144 ± 59 vs. 509 ± 41; T4/T8 vs. BLH for LPS; p < 0.05). ARDS induced with LPS leads to more hemodynamic (mean arterial pulmonary pressure 35 ± 3/30 ± 3 vs. 28 ± 4/23 ± 4; T4/T8 LPS vs. double-hit; p < 0.05; doses of norepinephrine 1.18 ± 1.05 vs. 0.11 ± 0.16; LPS vs. double-hit for T8; p < 0.05) and inflammatory (pulmonary IL-6 expression: 2.41e−04 ± 1.08e−04 vs. 1.45e−05 ± 7.26e−06; LPS vs. double-hit; p < 0.05) alterations. ARDS induced by double-hit requires a more invasive ventilator strategy to maintain a sufficient oxygenation (PEEP at T4: 8 ± 3 vs. 6 ± 2; double-hit vs. LPS; p < 0.05). Conclusions: Both animal ARDS models are feasible and are similar to human presentation of ARDS. If your respiratory research focus on hemodynamic/inflammation variables, the LPS-induced ARDS is a feasible model. Studying different ventilator strategies, the double-hit ARDS model offers a suitable approach.

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.