Does an instructional video as a stand-alone tool promote the acquisition of practical clinical skills? A randomised simulation research trial of skills acquisition and short-term retention.

BACKGROUND: The effectiveness of instructional videos as a stand-alone tool for the acquisition of practical skills is yet unknown because instructional videos are usually didactically embedded. Therefore, we evaluated the acquisition of the skill of a humeral intraosseous access via video in comparison to that of a self-study with an additional retention test. METHODS: After ethical approval, we conducted two consecutive studies. Both were designed as randomised controlled two-armed trials with last-year medical students as independent samples at our institutional simulation centre of a tertiary university hospital centre. In Study 1, we randomly assigned 78 participants to two groups: Vid-Self participants watched an instructional video as an intervention, followed by a test, and after seven days did a self-study as a control, followed by a test. Self-Vid ran through the trial in reverse order. In Study 2, we investigated the influence of the sequence of the two teaching methods on learning success in a new sample of 60 participants: Vid-Self watched an instructional video and directly afterward did the self-study followed by a test, whereas Self-Vid ran through that trial in reverse order. In Studies 1 and 2, the primary outcome was the score (worst score = 0, best score = 20) of the test after intervention and control. The secondary outcome in Study 1 was the change in score after seven days. RESULTS: Study 1: The Vid-Self (Participants n = 42) was superior to the Self-Vid (n = 36) (mean score 14.8 vs. 7.7, p < 0.001). After seven days, Self-vid outperformed Vid-Self (mean score 15.9 vs. 12.5, p < 0.001). Study 2: The Vid-Self (n = 30) and Self-Vid (n = 30) scores did not significantly differ (mean 16.5 vs. mean 16.5, p = 0.97). CONCLUSION: An instructional video as a stand-alone tool effectively promotes the acquisition of practical skills. The best results are yielded by a combination of an instructional video and self-study right after each other, irrespective of sequence. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT05066204 (13/04/2021) (Study 1) and NCT04842357 (04/10/2021) (Study 2).

Influence of rosuvastatin treatment on cerebral inflammation and nitro-oxidative stress in experimental lung injury in pigs.

BACKGROUND: Many patients with acute respiratory distress syndrome (ARDS) suffer from cognitive impairment after hospital discharge. Different mechanisms have been implicated as potential causes for this impairment, inter alia cerebral inflammation. A class of drugs with antioxidant and anti-inflammatory properties are ß-HMG-CoA-reductase inhibitors ("statins"). We hypothesized that treatment with rosuvastatin attenuates cerebral cytokine mRNA expression and nitro-oxidative stress in an animal model of acute lung injury. METHODS: After approval of the institutional and state animal care committee, we performed this prospective randomized controlled animal study in accordance with the international guidelines for the care and use of laboratory animals. Thirty-two healthy male pigs were randomized to one of four groups: lung injury by central venous injection of oleic acid (n = 8), statin treatment before and directly after lung injury (n = 8), statin treatment after lung injury (n = 8), or ventilation-only controls (n = 8). About 18 h after lung injury and standardized treatment, the animals were euthanised, and the brains and lungs were collected for further examinations. We determined histologic lung injury and cerebral and pulmonal cytokine and 3-nitrotyrosine production. RESULTS: We found a significant increase in hippocampal IL-6 mRNA after lung injury (p < 0.05). Treatment with rosuvastatin before and after induction of lung injury led to a significant reduction of hippocampal IL-6 mRNA (p < 0.05). Cerebral 3-nitrotyrosine was significantly higher in lung-injured animals compared with all other groups (p < 0.05 vs. animals treated with rosuvastatin after lung injury induction; p < 0.001 vs. all other groups). 3-Nitrotyrosine was also increased in the lungs of the lung-injured pigs compared to all other groups (p < 0.05 each). CONCLUSIONS: Our findings highlight cerebral cytokine production and nitro-oxidative stress within the first day after induction of lung injury. The treatment with rosuvastatin reduced IL-6 mRNA and 3-nitrotyrosine concentration in the brains of the animals. In earlier trials, statin treatment did not reduce mortality in ARDS patients but seemed to improve quality of life in ARDS survivors. Whether this is attributable to better cognitive function because of reduced nitro-oxidative stress and inflammation remains to be elucidated.

Effect of fluid resuscitation on cerebral integrity: A prospective randomised porcine study of haemorrhagic shock.

BACKGROUND: The treatment of haemorrhagic shock is a challenging task. Colloids have been regarded as standard treatment, but their safety and benefit have been the subject of controversial debates. Negative effects, including renal failure and increased mortality, have resulted in restrictions on their administration. The cerebral effects of different infusion regimens are largely unknown. OBJECTIVES: The current study investigated the impact of gelatine-polysuccinate, hydroxyethyl starch (HES) and balanced electrolyte solution (BES) on cerebral integrity, focusing on cerebral inflammation, apoptosis and blood flow in pigs. DESIGN: Randomised experimental study. SETTING: University-affiliated large animal research unit. ANIMALS: Twenty-four juvenile pigs aged 8 to 12 weeks. INTERVENTION: Haemorrhagic shock was induced by controlled arterial blood withdrawal to achieve a combination of relevant blood loss (30 to 40 ml kg-1) and haemodynamic deterioration. After 30 min of shock, fluid resuscitation was started with either gelatine-polysuccinate, HES or BES. The animals were then monitored for 4 h. MAIN OUTCOME MEASURES: Cerebral perfusion and diffusion were measured via arterial-spin-labelling MRI. Peripheral tissue perfusion was evaluated via white light spectroscopy. Cortical and hippocampal samples were collected at the end of the experiment. The numbers of cerebral cell nuclei were counted and mRNA expression of markers for cerebral apoptosis [glucose transporter protein type 1 (SLC2A), lipocalin 2 (LCN-2), aquaporin-4 (AQP4)] and inflammation [IL-6, TNF-α, glial fibrillary acidic protein (GFAP)] were determined. RESULTS: The three fluid protocols all stabilised the macrocirculation. Fluid resuscitation significantly increased the cerebral perfusion. Gelatine-polysuccinate and HES initially led to a higher cardiac output but caused haemodilution. Cerebral cell counts (as cells µm-2) were lower after colloid administration in the cortex (gelatine-polysuccinate, 1.8 ±â€Š0.3; HES, 1.9 ±â€Š0.4; each P < 0.05 vs. BES, 2.3 ±â€Š0.2) and the hippocampus (gelatine-polysuccinate, 0.8 ±â€Š0.2; HES, 0.9 ±â€Š0.2; each P < 0.05 vs. BES, 1.1 ±â€Š0.1). After gelatine-polysuccinate, the hippocampal SLC2A and GFAP were lower. After gelatine-polysuccinate, the cortical LCN-2 and TNF-α expression levels were increased (each P < 0.05 vs. BES). CONCLUSION: In a porcine model, fluid resuscitation by colloids, particularly gelatine-polysuccinate, was associated with the occurrence of cerebral injury. ETHICAL APPROVAL NUMBER: 23 177-07/G 15-1-092; 01/2016.

Targeted fibre-optical intrabronchial lipopolysaccharide administration in pigs - a methodical refinement for improved accuracy in respiratory research.

OBJECTIVE: To establish and evaluate a standardized method of targeted, intrabronchial drug delivery in pigs. STUDY DESIGN: Randomized controlled trial. ANIMALS: A total of 16 German Landrace pigs (Sus scrofa), age range 12‒16 weeks, and weighing 28‒35 kg. METHODS: The animals were anaesthetized, intubated, and instrumented with extended cardiovascular monitoring. Lung injury was induced by administering via a flexible fibre-optic endoscope using 100 mL saline solution containing either 20 mg of Escherichia coli lipopolysaccharide (E. coli LPS) (n = 8) or no additive (sham, n = 8) into the two distal mainstem bronchi. The animals were monitored for 8 hours and arterial oxygenation, inspiratory pressure and arterial blood pressure were measured repeatedly. Post-mortem, lung tissue was prepared for histologic damage scoring and determination of proinflammatory cytokines Interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα). Statistical analyses were performed using inter-group analysis of variance and Student's t tests. Data are presented as mean ± standard deviation. A p value <0.05 was considered significant. RESULTS: The targeted application of LPS led to significant deterioration of oxygenation consistent with mild-to-moderate acute respiratory distress syndrome (ARDS) and hypotension (Horowitz ratio: sham 2 hour, 300 ± 39; LPS 2 hour, 193.7 ± 52; p < 0.001). Histologic analyses identified increased inflammation and oedema in the tissues of the animals in the LPS group IL-6 sham: 6.4 ± 4.4 × 10-5 pg mL-1; IL-6 LPS: 2.8 ± 2.4 × 10-4 pg mL-1, p = 0.015. CONCLUSIONS: The targeted application of agents via flexible fibre-optic endoscopy is a valid, reliable method of causing controlled lung damage in a porcine model. The data presented suggest the feasibility and possible advantages of controlled application and could expand the array of techniques used to help understand the critical condition of ARDS. In addition, a targeted approach could help reduce animal numbers used for this purpose.

Flexible fibreoptic intubation in swine - improvement for resident training and animal safety alike.

BACKGROUND: Efficient airway management to facilitate tracheal intubation encompasses essential skills in anaesthesiologic and intensive care. The application of flexible fibreoptic intubation in patients with difficult airways has been identified as the recommended method in various international guidelines. However, providing the opportunity to adequately train residents can be challenging. Using large animals for practice during ongoing studies could help to improve this situation, but there is no recent data on fibreoptic intubation in swine available. METHODS: Thirty male German landrace pigs were anesthetized, instrumented and randomized into two groups. The animals were either intubated conventionally using direct laryngoscopy or a single-use flexible video-endoscope. The intervention was carried out by providers with 3 months experience in conventional intubation of pigs and a brief introduction into endoscopy. Intubation attempts were supervised and aborted, when SpO2 dropped below 93%. After three failed attempts, an experienced supervisor intervened and performed the intubation. Intubation times and attempts were recorded and analysed. RESULTS: Flexible fibreoptic intubation showed a significantly higher success rate in first attempt endotracheal tube placement (75% vs. 47%) with less attempts overall (1.3 ± 0.6 vs. 2.1 ± 1.3, P = 0.043). Conventional intubation was faster (42 s ± 6 s vs. 67 s ± 10s, P < 0.001), but showed a higher complication rate and more desaturation episodes during the trial. CONCLUSIONS: Flexible fibreoptic intubation in swine is feasible and appears to be a safer and more accessible method for inexperienced users to learn. This could not only improve resident training options in hospitals with animal research facilities but might also prevent airway complications and needless animal suffering.

Responses of retinal arterioles and ciliary arteries in pigs with acute respiratory distress syndrome (ARDS).

Acute respiratory distress syndrome (ARDS) is a clinical syndrome of acute lung failure in critically sick patients, which severely compromises the function of multiple organs, including the brain. Although, the optic nerve and the retina are a part of the central nervous system, the effects of ARDS on these ocular structures are completely unknown. Thus, the major goal of this study was to test the hypothesis that ARDS affects vascular function in the eye. ARDS was induced in anesthetized pigs by intratracheal injection of lipopolysaccharide (LPS). Sham-treated animals served as controls. Pigs were monitored for 8 h and then sacrificed. Subsequently, retinal arterioles and short posterior ciliary arteries were isolated and cannulated with micropipettes to measure vascular responses by videomicroscopy. Levels of reactive oxygen species (ROS) were quantified in isolated vessels using dihydroethidium (DHE). Messenger RNA expression of hypoxic, inflammatory, prooxidative, and antioxidative genes was assessed by real-time PCR. When group-dependent differences in mRNA expression levels were found for a particular gene, immunostainings were conducted. Strikingly, responses to the endothelium-dependent vasodilator, bradykinin, were markedly impaired in retinal arterioles of LPS-treated pigs, but no differences were seen between ciliary arteries of LPS- and sham-treated animals. ROS levels were increased in retinal arterioles but not in ciliary arteries of LPS-treated pigs. Messenger RNA levels for HIF-1α, VEGF-A and NOX2 were markedly increased in retinal arterioles of LPS-treated pigs, whereas ciliary arteries had only negligible mRNA level changes. Pronounced immunoreactivity for HIF-1α, VEGF-A and NOX2 was seen in the endothelium of retinal arterioles from LPS-treated pigs. Histologically, massive edema was seen especially in the retinal nerve fiber layer of pigs treated with LPS. Our study provides the first evidence that ARDS induced by intratracheal LPS application evokes endothelial dysfunction in porcine retinal arterioles together with retinal edema, indicative of vascular leakage. In contrast, ciliary arteries appear to be resistant to intratracheal LPS application.

Cyclic PaO2 oscillations assessed in the renal microcirculation: correlation with tidal volume in a porcine model of lung lavage.

BACKGROUND: Oscillations of the arterial partial pressure of oxygen induced by varying shunt fractions occur during cyclic alveolar recruitment within the injured lung. Recently, these were proposed as a pathomechanism that may be relevant for remote organ injury following acute respiratory distress syndrome. This study examines the transmission of oxygen oscillations to the renal tissue and their tidal volume dependency. METHODS: Lung injury was induced by repetitive bronchoalveolar lavage in eight anaesthetized pigs. Cyclic alveolar recruitment was provoked by high tidal volume ventilation. Oscillations of the arterial partial pressure of oxygen were measured in real-time in the macrocirculation by multi-frequency phase fluorimetry and in the renal microcirculation by combined white-light spectrometry and laser-Doppler flowmetry during tidal volume down-titration. RESULTS: Significant respiratory-dependent oxygen oscillations were detected in the macrocirculation and transmitted to the renal microcirculation in a substantial extent. The amplitudes of these oscillations significantly correlate to the applied tidal volume and are minimized during down-titration. CONCLUSIONS: In a porcine model oscillations of the arterial partial pressure of oxygen are induced by cyclic alveolar recruitment and transmitted to the renal microcirculation in a tidal volume-dependent fashion. They might play a role in organ crosstalk and remote organ damage following lung injury.

Inhalation therapy with the synthetic TIP-like peptide AP318 attenuates pulmonary inflammation in a porcine sepsis model.

BACKGROUND: The lectin-like domain of TNF-α can be mimicked by synthetic TIP peptides and represents an innovative pharmacologic option to treat edematous respiratory failure. TIP inhalation was shown to reduce pulmonary edema and improve gas exchange. In addition to its edema resolution effect, TIP peptides may exert some anti-inflammatory properties. The present study therefore investigates the influence of the inhaled TIP peptide AP318 on intrapulmonary inflammatory response in a porcine model of systemic sepsis. METHODS: In a randomized-blinded setting lung injury was induced in 18 pigs by lipopolysaccharide-infusion and a second hit with a short period of ventilator-induced lung stress, followed by a six-hour observation period. The animals received either two inhalations with the peptide (AP318, 2×1 mg kg(-1)) or vehicle. Post-mortem pulmonary expression of inflammatory and mechanotransduction markers were determined by real-time polymerase chain reaction (IL-1ß, IL-6, TNF-α, COX-2, iNOS, amphiregulin, and tenascin-c). Furthermore, regional histopathological lung injury, edema formation and systemic inflammation were quantified. RESULTS: Despite similar systemic response to lipopolysaccharide infusion in both groups, pulmonary inflammation (IL-6, TNF-α, COX-2, tenascin-c) was significantly mitigated by AP318. Furthermore, a Western blot analysis shows a significantly lower of COX-2 protein level. The present sepsis model caused minor lung edema formation and moderate gas exchange impairment. Six hours after onset pathologic scoring showed no improvement, while gas exchange parameters and pulmonary edema formation were similar in the two groups. CONCLUSION: In summary, AP318 significantly attenuated intrapulmonary inflammatory response even without the presence or resolution of severe pulmonary edema in a porcine model of systemic sepsis-associated lung injury. These findings suggest an anti-inflammatory mechanism of the lectin-like domain beyond mere edema reabsorption in endotoxemic lung injury in vivo.

Low tidal volume pressure support versus controlled ventilation in early experimental sepsis in pigs.

BACKGROUND: In moderate acute respiratory distress syndrome (ARDS) several studies support the usage of assisted spontaneous breathing modes. Only limited data, however, focus on the application in systemic sepsis and developing lung injury. The present study examines the effects of immediate initiation of pressure support ventilation (PSV) in a model of sepsis-induced ARDS. METHODS: 18 anesthetized pigs received a two-staged continuous lipopolysaccharide infusion to induce lung injury. The animals were randomly assigned to PSV or volume controlled (VCV) lung protective ventilation (tidal volume each 6 ml kg-1, n = 2x9) over six hours. Gas exchange parameters, hemodynamics, systemic inflammation, and ventilation distribution by multiple inert gas elimination and electrical impedance tomography were assessed. The post mortem analysis included histopathological scoring, wet to dry ratio, and alveolar protein content. RESULTS: Within six hours both groups developed a mild to moderate ARDS with comparable systemic inflammatory response and without signs of improving gas exchange parameters during PSV. The PSV group showed signs of more homogenous ventilation distribution by electrical impedance tomography, but only slightly less hyperinflated lung compartments by multiple inert gas elimination. Post mortem and histopathological assessment yielded no significant intergroup differences. CONCLUSIONS: In a porcine model of sepsis-induced mild ARDS immediate PSV was not superior to VCV. This contrasts with several experimental studies from non-septic mild to moderate ARDS. The present study therefore assumes that not only severity, but also etiology of lung injury considerably influences the response to early initiation of PSV.

TIP peptide inhalation in experimental acute lung injury: effect of repetitive dosage and different synthetic variants.

BACKGROUND: Inhalation of TIP peptides that mimic the lectin-like domain of TNF-α is a novel approach to attenuate pulmonary oedema on the threshold to clinical application. A placebo-controlled porcine model of acute respiratory distress syndrome (ARDS) demonstrated a reduced thermodilution-derived extravascular lung water index (EVLWI) and improved gas exchange through TIP peptide inhalation within three hours. Based on these findings, the present study compares a single versus a repetitive inhalation of a TIP peptide (TIP-A) and two alternate peptide versions (TIP-A, TIP-B). METHODS: Following animal care committee approval ARDS was induced by bronchoalveolar lavage followed by injurious ventilation in 21 anaesthetized pigs. A randomised-blinded three-group setting compared the single-dosed peptide variants TIP-A and TIP-B as well as single versus repetitive inhalation of TIP-A (n = 7 per group). Over two three-hour intervals parameters of gas exchange, transpulmonary thermodilution, calculated alveolar fluid clearance, and ventilation/perfusion-distribution were assessed. Post-mortem measurements included pulmonary wet/dry ratio and haemorrhage/congestion scoring. RESULTS: The repetitive TIP-A inhalation led to a significantly lower wet/dry ratio than a single dose and a small but significantly lower EVLWI. However, EVLWI changes over time and the derived alveolar fluid clearance did not differ significantly. The comparison of TIP-A and B showed no relevant differences. Gas exchange and ventilation/perfusion-distribution significantly improved in all groups without intergroup differences. No differences were found in haemorrhage/congestion scoring. CONCLUSIONS: In comparison to a single application the repetitive inhalation of a TIP peptide in three-hour intervals may lead to a small additional reduction the lung water content. Two alternate TIP peptide versions showed interchangeable characteristics.

A novel non-invasive nociceptive monitoring approach fit for intracerebral surgery: a retrospective analysis.

Background: Measuring depth of anesthesia during intracerebral surgery is an important task to guarantee patient safety, especially while the patient is fixated in a Mayfield-clamp. Processed electro-encephalography measurements have been established to monitor deep sedation. However, visualizing nociception has not been possible until recently and has not been evaluated for the neurosurgical setting. In this single-center, retrospective observational analysis, we routinely collected the nociceptive data via a nociception level monitor (NOL®) of 40 patients undergoing intracerebral tumor resection and aimed to determine if this monitoring technique is feasible and delivers relevant values to potentially base therapeutic decisions on. Methods: Forty patients (age 56 ± 18 years) received total intravenous anesthesia and were non-invasively connected to the NOL® via a finger clip as well as a bispectral-index monitoring (BIS®) to confirm deep sedation. The measured nociception levels were retrospectively evaluated at specific time points of nociceptive stress (intubation, Mayfield-positioning, incision, extubation) and compared to standard vital signs. Results: Nociceptive measurements were successfully performed in 35 patients. The largest increase in nociceptive stimulation occurred during intubation (NOL® 40 ± 16) followed by Mayfield positioning (NOL® 39 ± 16) and incision (NOL® 26 ± 12). Correlation with BIS measurements confirmed a sufficiently deep sedation during all analyzed time points (BIS 45 ± 13). Overall, patients showed an intraoperative NOL® score of 10 or less in 56% of total intervention time. Conclusions: Nociceptive monitoring using the NOL® system during intracerebral surgery is feasible and might yield helpful information to support therapeutic decisions. This could help to reduce hyperanalgesia, facilitating shorter emergence periods and less postoperative complications. Prospective clinical studies are needed to further examine the potential benefits of this monitoring approach in a neurosurgical context. Trial registration: German trial registry, registration number DRKS00029120.

Analysis of the Effects of Epidural Anesthesia on the Nociception Level Index (NOL®) during Abdominal Surgery.

Background: The NOL® system (PMD-200™ Nociception Level Monitor; Medasense Ltd., Ramat Gan, Israel) is used for the real-time detection of physiological nociception in anesthetized patients by assessing the parameters indicative of sympathetic activity, such as photoplethysmography, skin conductance, peripheral temperature, and accelerometry, which are quantified into the NOL®-Index. This index is more sensitive than traditional clinical parameters in estimating pain and stress responses. While its effectiveness in general anesthesia is well documented, its efficacy in epidural anesthesia needs further investigation. Methods: This retrospective study analyzed NOL®-Index dynamics compared to conventional parameters after epidural administration of bupivacaine. Following ethics committee approval, 119 NOL® measurements were retrospectively analyzed after thoracic epidural catheter administration in 40 patients undergoing abdominal and urological surgery. The NOL-Index® was assessed at 0, 1, 3, and 5 min post application and compared to heart rate, blood pressure, and bispectral index dynamics. Results: This study showed a significant decrease in the NOL®-Index post-local-anesthetic administration with better sensitivity than classical clinical parameters (0 min = 38 ± 11; 1 min = 22 ± 13*; 3 min = 17 ± 11*; 5 min = 12 ± 10*). Higher doses of local anesthetics led to a significant, dose-dependent decrease in NOL®-Index (low dose, 5 min = 15 ± 10*; high dose, 5 min = 8 ± 8*). Conclusions: This study is the first to demonstrate the effectiveness of the NOL®-Index in measuring nociceptive effects following epidural administration, highlighting its potential superiority over conventional parameters and its sensitivity to dose variations.

Effects of volume management on free flap perfusion and metabolism in a large animal model study.

Free flap failure represents a substantial clinical burden. The role of intraoperative volume management remains controversial, with valid studies lacking. Here, using a large animal model, we investigated the influence of volume management on free flap perfusion and metabolism. Autotransfer of a musculocutaneous gracilis flap was performed on 31 German domestic pigs, with arterial anastomosis and catheterization of the pedicle vein for sequential blood sampling. Flap reperfusion was followed by induction of a hemorrhagic shock with maintenance for 30 min and subsequent circulation stabilization with crystalloid solution, crystalloid solution and catecholamine, autotransfusion or colloidal solution. Flap perfusion and oxygenation were periodically assessed using hyperspectral imaging. Flap metabolism was assessed via periodic blood gas analyses. Hyperspectral imaging revealed no difference in either superficial or deep tissue oxygen saturation, tissue hemoglobin or tissue water content between the test groups at any time point. Blood gas analyses showed that lactate levels were significantly increased in the group that received crystalloid solution and catecholamine, after circulatory stabilization and up to 2 h after. We conclude that, in hemorrhagic shock, volume management impacts acid-base balance in free flaps. Crystalloid solutions with norepinephrine increase lactate levels, yet short-term effects on flap perfusion seem minimal, suggesting that vasopressors are not detrimental.

Analysis of cerebral Interleukin-6 and tumor necrosis factor alpha patterns following different ventilation strategies during cardiac arrest in pigs.

Hypoxia-induced neuroinflammation after cardiac arrest has been shown to be mitigated by different ventilation methods. In this prospective randomized animal trial, 35 landrace pigs were randomly divided into four groups: intermittent positive pressure ventilation (IPPV), synchronized ventilation 20 mbar (SV 20 mbar), chest compression synchronized ventilation 40 mbar (CCSV 40 mbar) and a control group (Sham). After inducing ventricular fibrillation, basic life support (BLS) and advanced life support (ALS) were performed, followed by post-resuscitation monitoring. After 6 hours, the animals were euthanized, and direct postmortem brain tissue samples were taken from the hippocampus (HC) and cortex (Cor) for molecular biological investigation of cytokine mRNA levels of Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα). The data analysis showed that CCSV 40 mbar displayed low TNFα mRNA-levels, especially in the HC, while the highest TNFα mRNA-levels were detected in SV 20 mbar. The results indicate that chest compression synchronized ventilation may have a potential positive impact on the cytokine expression levels post-resuscitation. Further studies are needed to derive potential therapeutic algorithms from these findings.

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.

The Impact of Transfer-Related Ischemia on Free Flap Metabolism and Electrolyte Homeostasis-A New In Vivo Experimental Approach in Pigs.

Free flap tissue transfer represents the gold standard for extensive defect reconstruction, although malperfusion due to thrombosis remains the leading risk factor for flap failure. Recent studies indicate an increased immune response and platelet activation in connection with pathologic coagulation. The underlying cellular and molecular mechanisms remain poorly understood, however. The presented study, therefore, aims to investigate if transfer-related ischemia alters intra-flap metabolism and electrolyte concentrations compared to central venous blood after free flap transfer in pigs to establish a novel experimental model. Free transfer of a myocutaneous gracilis flap to the axillary region was conducted in five juvenile male pigs. The flap artery was anastomosed to the axillary artery, and intra-flap venous blood was drained and transfused using a rubber-elastic fixed intravenous catheter. Blood gas analysis was performed to assess the effect of transfer time-induced ischemia on intra-flap electrolyte levels, acid-base balance, and hemoglobin concentrations compared to central venous blood. Time to flap reperfusion was 52 ± 10 min on average, resulting in a continuous pH drop (acidosis) in the flaps' venous blood compared to the central venous system (p = 0.037). Potassium (p = 0.016), sodium (p = 0.003), and chloride (p = 0.007) concentrations were significantly increased, whereas bicarbonate (p = 0.016) and calcium (p = 0.008) significantly decreased within the flap. These observations demonstrate the induction of anaerobic glycolysis and electrolyte displacement resulting in acidosis and hence significant tissue damage already after a short ischemic period, thereby validating the novel animal model for investigating intra-flap metabolism and offering opportunities for exploring various (immuno-) thrombo-hemostatic issues in transplantation surgery.

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.

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.

Resveratrol influences pulmonary mechanics and inflammatory response in a porcine ARDS model.

AIMS: 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. MAIN METHODS: 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. STATISTICS: Two-way analysis of variance (repeated measurement) and Student-Newman-Keuls method. KEY FINDINGS: 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). SIGNIFICANCE: 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.

The Influence of Ultra-Low Tidal Volume Ventilation during Cardiopulmonary Resuscitation on Renal and Hepatic End-Organ Damage in a Porcine Model.

The optimal ventilation strategy during cardiopulmonary resuscitation (CPR) has eluded scientists for years. This porcine study aims to validate the hypothesis that ultra-low tidal volume ventilation (tidal volume 2-3 mL kg-1; ULTVV) minimizes renal and hepatic end-organ damage when compared to standard intermittent positive pressure ventilation (tidal volume 8-10 mL kg-1; IPPV) during CPR. After induced ventricular fibrillation, the animals were ventilated using an established CPR protocol. Upon return of spontaneous circulation (ROSC), the follow-up was 20 h. After sacrifice, kidney and liver samples were harvested and analyzed histopathologically using an Endothelial, Glomerular, Tubular, and Interstitial (EGTI) scoring system for the kidney and a newly developed scoring system for the liver. Of 69 animals, 5 in the IPPV group and 6 in the ULTVV group achieved sustained ROSC and were enlisted, while 4 served as the sham group. Creatinine clearance was significantly lower in the IPPV-group than in the sham group (p < 0.001). The total EGTI score was significantly higher for ULTVV than for the sham group (p = 0.038). Aminotransferase levels and liver score showed no significant difference between the intervention groups. ULTVV may be advantageous when compared to standard ventilation during CPR in the short-term ROSC follow-up period.

Lipopolysaccharide Infusion as a Porcine Endotoxemic Shock Model.

Sepsis and septic shock are frequently encountered in patients treated in intensive care units (ICUs) and are among the leading causes of death in these patients. It is caused by a dysregulated immune response to an infection. Even with optimized treatment, mortality rates remain high, which makes further insights into the pathophysiology and new treatment options necessary. Lipopolysaccharide (LPS) is a component of the cell membrane of gram-negative bacteria, which are often responsible for infections causing sepsis and septic shock. The severity and high mortality of sepsis and septic shock make standardized experimental studies in humans impossible. Thus, an animal model is needed for further studies. The pig is especially well suited for this purpose as it closely resembles humans in anatomy, physiology, and size. This protocol provides an experimental model for endotoxemic shock in pigs by LPS infusion. We were able to reliably induce changes frequently observed in septic shock patients, including hemodynamic instability, respiratory failure, and acidosis. This will allow researchers to gain valuable insight into this highly relevant condition and evaluate new therapeutic approaches in an experimental setting.