Experimental blunt chest trauma--cardiorespiratory effects of different mechanical ventilation strategies with high positive end-expiratory pressure: a randomized controlled study.

BACKGROUND: Uncertainty persists regarding the optimal ventilatory strategy in trauma patients developing acute respiratory distress syndrome (ARDS). This work aims to assess the effects of two mechanical ventilation strategies with high positive end-expiratory pressure (PEEP) in experimental ARDS following blunt chest trauma. METHODS: Twenty-six juvenile pigs were anesthetized, tracheotomized and mechanically ventilated. A contusion was applied to the right chest using a bolt-shot device. Ninety minutes after contusion, animals were randomized to two different ventilation modes, applied for 24 h: Twelve pigs received conventional pressure-controlled ventilation with moderately low tidal volumes (VT, 8 ml/kg) and empirically chosen high external PEEP (16 cmH2O) and are referred to as the HP-CMV-group. The other group (n = 14) underwent high-frequency inverse-ratio pressure-controlled ventilation (HFPPV) involving respiratory rate of 65 breaths · min(-1), inspiratory-to-expiratory-ratio 2:1, development of intrinsic PEEP and recruitment maneuvers, compatible with the rationale of the Open Lung Concept. Hemodynamics, gas exchange and respiratory mechanics were monitored during 24 h. Computed tomography and histology were analyzed in subgroups. RESULTS: Comparing changes which occurred from randomization (90 min after chest trauma) over the 24-h treatment period, groups differed statistically significantly (all P values for group effect <0.001, General Linear Model analysis) for the following parameters (values are mean ± SD for randomization vs. 24-h): PaO2 (100% O2) (HFPPV 186 ± 82 vs. 450 ± 59 mmHg; HP-CMV 249 ± 73 vs. 243 ± 81 mmHg), venous admixture (HFPPV 34 ± 9.8 vs. 11.2 ± 3.7%; HP-CMV 33.9 ± 10.5 vs. 21.8 ± 7.2%), PaCO2 (HFPPV 46.9 ± 6.8 vs. 33.1 ± 2.4 mmHg; HP-CMV 46.3 ± 11.9 vs. 59.7 ± 18.3 mmHg) and normally aerated lung mass (HFPPV 42.8 ± 11.8 vs. 74.6 ± 10.0 %; HP-CMV 40.7 ± 8.6 vs. 53.4 ± 11.6%). Improvements occurring after recruitment in the HFPPV-group persisted throughout the study. Peak airway pressure and VT did not differ significantly. HFPPV animals had lower atelectasis and inflammation scores in gravity-dependent lung areas. CONCLUSIONS: In this model of ARDS following unilateral blunt chest trauma, HFPPV ventilation improved respiratory function and fulfilled relevant ventilation endpoints for trauma patients, i.e. restoration of oxygenation and lung aeration while avoiding hypercapnia and respiratory acidosis.

Learning robust autonomous navigation and locomotion for wheeled-legged robots.

Autonomous wheeled-legged robots have the potential to transform logistics systems, improving operational efficiency and adaptability in urban environments. Navigating urban environments, however, poses unique challenges for robots, necessitating innovative solutions for locomotion and navigation. These challenges include the need for adaptive locomotion across varied terrains and the ability to navigate efficiently around complex dynamic obstacles. This work introduces a fully integrated system comprising adaptive locomotion control, mobility-aware local navigation planning, and large-scale path planning within the city. Using model-free reinforcement learning (RL) techniques and privileged learning, we developed a versatile locomotion controller. This controller achieves efficient and robust locomotion over various rough terrains, facilitated by smooth transitions between walking and driving modes. It is tightly integrated with a learned navigation controller through a hierarchical RL framework, enabling effective navigation through challenging terrain and various obstacles at high speed. Our controllers are integrated into a large-scale urban navigation system and validated by autonomous, kilometer-scale navigation missions conducted in Zurich, Switzerland, and Seville, Spain. These missions demonstrate the system's robustness and adaptability, underscoring the importance of integrated control systems in achieving seamless navigation in complex environments. Our findings support the feasibility of wheeled-legged robots and hierarchical RL for autonomous navigation, with implications for last-mile delivery and beyond.

Bedside estimation of nonaerated lung tissue using blood gas analysis.

OBJECTIVES: Studies correlating the arterial partial pressure of oxygen to the fraction of nonaerated lung assessed by CT shunt yielded inconsistent results. We systematically analyzed this relationship and scrutinized key methodological factors that may compromise it. We hypothesized that both physiological shunt and the ratio between PaO2 and the fraction of inspired oxygen enable estimation of CT shunt at the bedside. DESIGN: : Prospective observational clinical and laboratory animal investigations. SETTING: ICUs (University Hospital Leipzig, Germany) and Experimental Pulmonology Laboratory (University of São Paulo, Brazil). PATIENTS, SUBJECTS AND INTERVENTIONS: Whole-lung CT and arterial blood gases were acquired simultaneously in 77 patients mechanically ventilated with pure oxygen. A subgroup of 28 patients was submitted to different Fio2. We also studied 19 patients who underwent repeat CT. Furthermore we studied ten pigs with acute lung injury at multiple airway pressures, as well as a theoretical model relating PaO2 and physiological shunt. We logarithmically transformed the PaO2/Fio2 to change this nonlinear relationship into a linear regression problem. MEASUREMENTS AND MAIN RESULTS: We observed strong linear correlations between Riley's approximation of physiological shunt and CT shunt (R = 0.84) and between logarithmically transformed PaO2/Fio2 and CT shunt (R = 0.86), allowing us to construct a look-up table with prediction intervals. Strong linear correlations were also demonstrated within-patients (R = 0.95). Correlations were significantly improved by the following methodological issues: measurement of PaO2/Fio2 during pure oxygen ventilation, use of logarithmically transformed PaO2/Fio2 instead of the "raw" PaO2/Fio2, quantification of nonaerated lung as percentage of total lung mass and definition of nonaerated lung by the [-200 to +100] Hounsfield Units interval, which includes shunting units within less opacified lung regions. CONCLUSION: During pure oxygen ventilation, logarithmically transformed PaO2/Fio2 allows estimation of CT shunt and its changes in patients during systemic inflammation. Relevant intrapulmonary shunting seems to occur in lung regions with CT numbers between [-200 and +100] Hounsfield Units.

Computed tomographic assessment of lung weights in trauma patients with early posttraumatic lung dysfunction.

INTRODUCTION: Quantitative computed tomography (qCT)-based assessment of total lung weight (Mlung) has the potential to differentiate atelectasis from consolidation and could thus provide valuable information for managing trauma patients fulfilling commonly used criteria for acute lung injury (ALI). We hypothesized that qCT would identify atelectasis as a frequent mimic of early posttraumatic ALI. METHODS: In this prospective observational study, Mlung was calculated by qCT in 78 mechanically ventilated trauma patients fulfilling the ALI criteria at admission. A reference interval for Mlung was derived from 74 trauma patients with morphologically and functionally normal lungs (reference). Results are given as medians with interquartile ranges. RESULTS: The ratio of arterial partial pressure of oxygen to the fraction of inspired oxygen was 560 (506 to 616) mmHg in reference patients and 169 (95 to 240) mmHg in ALI patients. The median reference Mlung value was 885 (771 to 973) g, and the reference interval for Mlung was 584 to 1164 g, which matched that of previous reports. Despite the significantly greater median Mlung value (1088 (862 to 1,342) g) in the ALI group, 46 (59%) ALI patients had Mlung values within the reference interval and thus most likely had atelectasis. In only 17 patients (22%), Mlung was increased to the range previously reported for ALI patients and compatible with lung consolidation. Statistically significant differences between atelectasis and consolidation patients were found for age, Lung Injury Score, Glasgow Coma Scale score, total lung volume, mass of the nonaerated lung compartment, ventilator-free days and intensive care unit-free days. CONCLUSIONS: Atelectasis is a frequent cause of early posttraumatic lung dysfunction. Differentiation between atelectasis and consolidation from other causes of lung damage by using qCT may help to identify patients who could benefit from management strategies such as damage control surgery and lung-protective mechanical ventilation that focus on the prevention of pulmonary complications.

Extrapolation in the analysis of lung aeration by computed tomography: a validation study.

INTRODUCTION: Computed tomography (CT) is considered the gold standard for quantification of global or regional lung aeration and lung mass. Quantitative CT, however, involves the exposure to ionizing radiation and requires manual image processing. We recently evaluated an extrapolation method which calculates quantitative CT parameters characterizing the entire lung from only 10 reference CT-slices thereby reducing radiation exposure and analysis time. We hypothesized that this extrapolation method could be further validated using CT-data from pigs and sheep, which have a different thoracic anatomy. METHODS: We quantified volume and mass of the total lung and differently aerated lung compartments in 168 ovine and 55 porcine whole-lung CTs covering lung conditions from normal to gross deaeration. Extrapolated volume and mass parameters were compared to the respective values obtained by whole-lung analysis. We also tested the accuracy of extrapolation for all possible numbers of CT slices between 15 and 5. Bias and limits of agreement (LOA) were analyzed by the Bland-Altman method. RESULTS: For extrapolation from 10 reference slices, bias (LOA) for the total lung volume and mass of sheep were 18.4 (-57.2 to 94.0) ml and 4.2 (-21.8 to 30.2) grams, respectively. The corresponding bias (LOA) values for pigs were 5.1 (-55.2 to 65.3) ml and 1.6 (-32.9 to 36.2) grams, respectively. All bias values for differently aerated lung compartments were below 1% of the total lung volume or mass and the LOA never exceeded ± 2.5%. Bias values diverged from zero and the LOA became considerably wider when less than 10 reference slices were used. CONCLUSIONS: The extrapolation method appears robust against variations in thoracic anatomy, which further supports its accuracy and potential usefulness for clinical and experimental application of quantitative CT.

[Case report: sepsis and multi organ dysfunction syndrome in a patient returning from holiday on the Canary Islands: a difficult diagnosis]. / Kasuistik interaktiv: Lanzarote-Urlauber mit Sepsis und Multiorganversagen - Ein langer Weg bis zur richtigen Diagnose.

UNLABELLED: A forty-five year old male tourist suffers a febrile illness, delirium and severe abdominal pain on the fifth day of his holiday trip to the Canary Islands (Spain). After hospitalization he presents a surgical abdomen which requires emergency laparotomy however without detectable pathology. Progressing critical illness and septic shock leads to multiple organ failure, but focus identification is not possible. Well after return to Germany diagnostic uncertainty persists due to recurrent fever and possible travel-associated infections. Finally, besides a simple pararectal abscess, manifestation of acute intermittent porphyria is diagnosed. CONCLUSION: Clinicians should consider acute intermittent porphyria as a rare cause of a surgical abdomen. Its clinical presentation include abdominal pain, life-threatening neurovisceral, neurological and psychiatric symptoms, hypertension, tachycardia, hyponatriemia and reddish urine.

[Intra-abdominal hypertension and abdominal compartment syndrome--basic knowledge and anesthesiological aspects]. / Intraabdominelle Hypertonie und abdominelles Kompartmentsyndrom--Basiswissen und anästhesiologische Aspekte.

The increase in intra-abdominal pressure may be followed by a renal, gut, respiratory and cardial dysfunction and an increase in intra-cranial pressure. The review focuses risk factors and pathophysiological consequences of intra-abdominal hypertension and of abdominal compartment syndrome. Patients with intra-abdominal hypertension and abdominal compartment syndrome are critical ill and need special anesthesiological care due to risk of pulmonary aspiration, hemodynamic disturbances and difficult mechanical ventilation.

Early recovery from post-traumatic acute respiratory distress syndrome.

BACKGROUND: To present and discuss the rationale and possible benefits of timely alveolar recruitment in early post-traumatic acute respiratory distress syndrome. METHODS: A 17-year-old patient who had sustained blunt thoracic trauma presented with severe hypoxaemia on admission and whole body computed tomography showed pulmonary contusion and substantial bilateral atelectasis. Oxygenation and lung mechanics did not improve with low tidal volume ventilation using high positive end-expiratory pressures (PEEPs). Therefore we applied an alveolar recruitment manoeuvre 7 h after admission. After alveolar recruitment, PEEP was titrated to the lowest level which prevented alveolar derecruitment. RESULTS: Oxygenation and lung compliance improved rapidly and aeration of the entire lung was confirmed by computed tomography 27 h after the recruitment manoeuvre. The patient recovered completely and was discharged after 17 days. CONCLUSION: Although robust evidence is still lacking, several lines of evidence suggest potential benefits of timely alveolar recruitment. Patients with early post-traumatic respiratory failure seem to most readily respond to alveolar recruitment manoeuvres and could thus benefit from the gain in functional lung volume and oxygenation. Moreover the probability of ventilator associated complications may be reduced.

Circulatory Arrest due to Retrograde Embolization of a Transapically Implanted Aortic Valve Prosthesis with Subsequent Inversion and Left Ventricular Outflow Occlusion.

An 82-year-old man required aortic valve replacement because of aortic stenosis. A transapical approach was chosen to reduce surgical mortality. Initially, echocardiography and fluoroscopy confirmed correct valve positioning. Shortly thereafter, progressive paravalvular leakage, embolization of the valve prosthesis into the ventricle, and subsequent inversion of the prosthesis with complete left ventricular outflow occlusion were observed by echocardiography. Left ventricular outflow occlusion resulted in immediate circulatory arrest. We immediately converted to on-pump surgical aortic valve replacement. Cardiac output was restored once the valve was replaced. The patient fully recovered. This case report highlights the importance of periprocedural transesophageal echocardiography, which instantly detected the malpositioned valve and guided emergency management of this severe complication.

Correlation of lung collapse and gas exchange - a computer tomographic study in sheep and pigs with atelectasis in otherwise normal lungs.

BACKGROUND: Atelectasis can provoke pulmonary and non-pulmonary complications after general anaesthesia. Unfortunately, there is no instrument to estimate atelectasis and prompt changes of mechanical ventilation during general anaesthesia. Although arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt have both been suggested to correlate with atelectasis, studies yielded inconsistent results. Therefore, we investigated these correlations. METHODS: Shunt, PaO2 and atelectasis were measured in 11 sheep and 23 pigs with otherwise normal lungs. In pigs, contrasting measurements were available 12 hours after induction of acute respiratory distress syndrome (ARDS). Atelectasis was calculated by computed tomography relative to total lung mass (Mtotal). We logarithmically transformed PaO2 (lnPaO2) to linearize its relationships with shunt and atelectasis. Data are given as median (interquartile range). RESULTS: Mtotal was 768 (715-884) g in sheep and 543 (503-583) g in pigs. Atelectasis was 26 (16-47) % in sheep and 18 (13-23) % in pigs. PaO2 (FiO2 = 1.0) was 242 (106-414) mmHg in sheep and 480 (437-514) mmHg in pigs. Shunt was 39 (29-51) % in sheep and 15 (11-20) % in pigs. Atelectasis correlated closely with lnPaO2 (R2 = 0.78) and shunt (R2 = 0.79) in sheep (P-values<0.0001). The correlation of atelectasis with lnPaO2 (R2 = 0.63) and shunt (R2 = 0.34) was weaker in pigs, but R2 increased to 0.71 for lnPaO2 and 0.72 for shunt 12 hours after induction of ARDS. In both, sheep and pigs, changes in atelectasis correlated strongly with corresponding changes in lnPaO2 and shunt. DISCUSSION AND CONCLUSION: In lung-healthy sheep, atelectasis correlates closely with lnPaO2 and shunt, when blood gases are measured during ventilation with pure oxygen. In lung-healthy pigs, these correlations were significantly weaker, likely because pigs have stronger hypoxic pulmonary vasoconstriction (HPV) than sheep and humans. Nevertheless, correlations improved also in pigs after blunting of HPV during ARDS. In humans, the observed relationships may aid in assessing anaesthesia-related atelectasis.

Lack of correlation for sodium iodide symporter mRNA and protein expression and analysis of sodium iodide symporter promoter methylation in benign cold thyroid nodules.

Cold thyroid nodules (CTNs) are characterized by a reduced iodide uptake in comparison to normal thyroid tissue. The sodium iodide symporter (NIS) is the first step in thyroid hormone synthesis and mediates the active iodide transport in the thyroid cells suggesting that decreased iodide uptake could be a result of changes in NIS expression or molecular defects in the NIS gene. In contrast to previous studies, an intraindividual comparison of NIS mRNA expression in CTNs and their corresponding surrounding tissue was performed using direct detection of NIS mRNA. A significant reduction in NIS mRNA expression was detected in 86% of the 14 investigated CTNs. We hypothesized that human sodium iodide symporter (hNIS) transcriptional failure could be caused by primary molecular NIS gene defects and/or methylation of DNA in the NIS promoter. However, no mutation in the NIS cDNA nor in the NIS promoter region upstream up to-443 bp from the ATG start codon was detected. Therefore, primary molecular NIS gene defects were excluded. However, in 50% of CTNs with reduced NIS mRNA expression, the promoter region was hypermethylated. NIS mRNA expression in these hypermethylated CTNs only reached a maximum of 30% of the corresponding surrounding tissue. Hence, methylation of CpG islands in the NIS promotor could be a regulatory mechanism of NIS transcription in CTNs. Immunoblot revealed absent hNIS protein expression in the total cell membrane fraction in 45% of investigated nodules. In the majority of the remaining CTNs NIS protein expression was decreased in the nodule tissue compared to the corresponding surrounding tissue. For investigating protein expression immunhistochemistry has two advantages. First, the whole nodule area can be investigated, and second, NIS expression can be detected in areas where an immunoblot of a cell membrane fraction is negative. Interestingly, immunhistochemistry revealed higher NIS expression in 50% of CTNs compared to their corresponding surrounding tissues and NIS staining was predominantly intracellular. These data demonstrate that NIS protein expression does not reflect NIS mRNA expression. Therefore, factors that affect targeting of NIS to the plasma membrane are likely to be affected.

Evidence and consensus-based German guidelines for the management of analgesia, sedation and delirium in intensive care--short version.

Targeted monitoring of analgesia, sedation and delirium, as well as their appropriate management in critically ill patients is a standard of care in intensive care medicine. With the undisputed advantages of goal-oriented therapy established, there was a need to develop our own guidelines on analgesia and sedation in intensive care in Germany and these were published as 2(nd) Generation Guidelines in 2005. Through the dissemination of these guidelines in 2006, use of monitoring was shown to have improved from 8 to 51% and the use of protocol-based approaches increased to 46% (from 21%). Between 2006-2009, the existing guidelines from the DGAI (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin) and DIVI (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin) were developed into 3(rd) Generation Guidelines for the securing and optimization of quality of analgesia, sedation and delirium management in the intensive care unit (ICU). In collaboration with another 10 professional societies, the literature has been reviewed using the criteria of the Oxford Center of Evidence Based Medicine. Using data from 671 reference works, text, diagrams and recommendations were drawn up. In the recommendations, Grade "A" (very strong recommendation), Grade "B" (strong recommendation) and Grade "0" (open recommendation) were agreed. As a result of this process we now have an interdisciplinary and consensus-based set of 3(rd) Generation Guidelines that take into account all critically illness patient populations. The use of protocols for analgesia, sedation and treatment of delirium are repeatedly demonstrated. These guidelines offer treatment recommendations for the ICU team. The implementation of scores and protocols into routine ICU practice is necessary for their success.