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While non-invasive assessment of macro- and micro-circulation has the promise to optimize anesthesia management, evidence is lacking for the relationship between invasive and non-invasive measurements of cardiac output and microcirculatory indices.We aimed to compare the abilities of non-invasive techniques to detect changes in macro- and micro-circulation following deep anesthesia and subsequent restoration of the compromised hemodynamic by routinely used vasopressors in a randomized experimental study.A 20%-25% drop in mean arterial pressure was induced by sevoflurane in anesthetized mechanically ventilated just-weaned piglets (n = 12) prior to the administration of vasopressors in random order (dopamine, ephedrine, noradrenaline, and phenylephrine). Simultaneous transpulmonary thermodilution cardiac output assessment with the invasive pulse index continuous contour (PiCCO) method was compared with non-invasive estimates obtained with electrical conductivity (ICON) and echo Doppler (Cardio Q). Changes in microcirculation were characterized by sublingual red blood cell velocity, jugular cerebral venous oxygen saturation, and arterial lactate.Cardiac output indices obtained by invasive and non-invasive methods.Changes in cardiac output measured invasively and non-invasively correlated significantly after sevoflurane (r = .78, p = .003 and r = .76, p = .006 between PiCCO and ICON or Cardio Q, respectively). Following the administration of vasopressors, invasive and non-invasive cardiac output assessments were unrelated with significant correlations observed only between PiCCO and ICON after dopamine and ephedrine. Sevoflurane-induced hypotension decreased jugular cerebral venous oxygen saturation significantly and was recovered by all vasopressors. Sevoflurane and vasopressors had no effect on red blood cell velocity, which increased only after dopamine. No consistent changes in lactate were observed during the study period.The results of this study suggest that non-invasive cardiac output measurements may not accurately reflect changes in macrocirculation after hemodynamic optimization by vasopressors. Due to the incoherence between macro- and micro-circulation, monitoring microcirculation is essential to guide patient management.

BACKGROUND Capnoperitoneum during laparoscopy leads to cranial shift of the diaphragm, loss in lung volume, and risk of impaired gas exchange. Infants are susceptible to these changes and bedside assessment of lung volume during laparoscopy might assist with optimizing the ventilation. Thus, the primary aim was to investigate the monitoring value of a continuous end-expiratory lung volume (EELV) assessment method based on CO2 dynamics ( EELVCO2 ) in a pediatric capnoperitoneum model by evaluating the correlation and trending ability against helium washout (EELVHe ). METHODS Intra-abdominal pressure (IAP) was randomly varied between 0, 6, and 12 mm Hg with CO2 insufflation, while positive end-expiratory pressure (PEEP) levels of 3, 6, and 9 cm H2 O were randomly applied in eight anesthetized and mechanically ventilated chinchilla rabbits. Concomitant EELVCO2 and EELVHe and lung clearance index (LCI) were obtained under each experimental condition. RESULTS Significant correlations were found between EELVCO2 and EELVHe before capnoperitoneum (r = .85, P

Extraordinary progress has been made during the past few decades in the development of anesthesia machines and ventilation techniques. With unprecedented precision and performance, modern machines for pediatric anesthesia can deliver appropriate mechanical ventilation for children and infants of all sizes and with ongoing respiratory diseases, ensuring very small volume delivery and compensating for circuit compliance. Along with highly accurate monitoring of the delivered ventilation, modern ventilators for pediatric anesthesia also have a broad choice of ventilation modalities, including synchronized and assisted ventilation modes, which were initially conceived for ventilation weaning in the intensive care setting. Despite these technical advances, there is still room for improvement in pediatric mechanical ventilation. There is a growing effort to minimize the harm of intraoperative mechanical ventilation of children by adopting the protective ventilation strategies that were previously employed only for prolonged mechanical ventilation. More than ever, the pediatric anesthesiologist should now recognize that positive-pressure ventilation is potentially a harmful procedure, even in healthy children, as it can contribute to both ventilator-induced lung injury and ventilator-induced diaphragmatic dysfunction. Therefore, careful choice of the ventilation modality and its parameters is of paramount importance to optimize gas exchange and to protect the lungs from injury during general anesthesia. The present report reviews the novel ventilation techniques used for children, discussing the advantages and pitfalls of the ventilation modalities available in modern anesthesia machines, as well as innovative ventilation modes currently under development or research. Several innovative strategies and devices are discussed. These novel modalities are likely to become part of the armamentarium of the pediatric anesthesiologist in the near future and are particularly relevant for challenging ventilation scenarios.

Changes in lung mechanics are frequently inferred from intact-chest measures of total respiratory system mechanics without consideration of the chest wall contribution. The participation of lungs and chest wall in respiratory mechanics has not been evaluated systematically in small animals commonly used in respiratory research. Thus, we compared these contributions in intact-chest mice, rats, and rabbits and further characterized the influence of positive end-expiratory pressure (PEEP). Forced oscillation technique was applied to anesthetized mechanically ventilated healthy animals to obtain total respiratory system impedance (Zrs) at 0, 3, and 6 cmH2O PEEP levels. Esophageal pressure was measured by a catheter-tip micromanometer to separate Zrs into pulmonary (ZL) and chest wall (Zcw) components. A model containing a frequency-independent Newtonian resistance (RN), inertance, and a constant-phase tissue damping (G) and elastance (H) was fitted to Zrs, ZL, and Zcw spectra. The contribution of Zcw to RN was negligible in all species and PEEP levels studied. However, the participation of Zcw in G and H was significant in all species and increased significantly with increasing PEEP and animal size (rabbit > rat > mice). Even in mice, the chest wall contribution to G and H was still considerable, reaching 47.0 ± 4.0(SE)% and 32.9 ± 5.9% for G and H, respectively. These findings demonstrate that airway parameters can be assessed from respiratory system mechanical measurements. However, the contribution from the chest wall should be considered when intact-chest measurements are used to estimate lung parenchymal mechanics in small laboratory models (even in mice), particularly at elevated PEEP levels. NEW & NOTEWORTHY In species commonly used in respiratory research (rabbits, rats, mice), esophageal pressure-based estimates revealed negligible contribution from the chest wall to the Newtonian resistance. Conversely, chest wall participation in the viscoelastic tissue mechanical parameters increased with body size (rabbit > rat > mice) and positive end-expiratory pressure, with contribution varying between 30 and 50%, even in mice. These findings demonstrate the potential biasing effects of the chest wall when lung tissue mechanics are inferred from intact-chest measurements in small laboratory animals.

Background MD-PhD programs confer degrees that empower medical doctors with in-depth scientific skills to contribute to biomedical research and academic medicine, alongside clinical practice. Whilst the career options and research opportunities related to graduates following these programs in the US are well documented, little is known about their European counterparts. In this article, we studied graduates who had completed the MD-PhD program at the University of Geneva between 2010 and 2019. Methods A cross-sectional survey was performed in April 2019, targeting all medical doctors who had obtained the MD-PhD degree from the University of Geneva since 2010. Demographics, opinions, and career outcomes of the MD-PhD graduates were assessed through an online anonymous questionnaire. Results Twenty-one questionnaires were collected from 31 MD-PhD graduates (response rate 65.5%). Most respondents (57.1%) had performed an MD-PhD training in basic sciences; however, only 14.3% had pursued this type of research thereafter. Most of the respondents held a position at a University hospital (90.5%), although a significant number of them were no longer involved in research in their current position (28.6%). 85.7% mentioned obstacles and challenges in combining clinical duties with research. Despite this, the majority (85.7%) declared that the MD-PhD degree had given them advantages in their career path, granting access to clinical and academic positions, as well as funding. Conclusions Graduates from the MD-PhD program in Geneva were for the most part, satisfied with their training. However, because of the challenges and obstacles in combining clinical duties with research, the implementation of research activities in their current position proved difficult.

BACKGROUND MD-PhD programmes throughout the world provide a platform for medical trainees to commit to a physician-scientist career, qualifying with both a medical degree (MD or equivalent) and Doctor of Philosophy (PhD). However, there are limited studies assessing the characteristics of MD-PhD programmes in Europe and the outcomes of MD-PhD students and graduates. PURPOSE This study aims at a first country-wise exploration of characteristics, opinions, and academic outcomes of MD-PhD students and graduates in Europe. METHODS Two questionnaires were developed to assess the demographics, MD-PhD programme characteristics, opinions, future career paths and academic outcomes of European MD-PhD students and graduates. An online survey of 278 MD-PhD students and 121 MD-PhD graduates from nine and six European countries, respectively, was completed between April 2016 and December 2017. The country-wise categorical responses were then compared through chi-square analysis followed by multiple logistic regression. RESULTS Responses from 266 MD-PhD students and 117 MD-PhD graduates were considered valid. Significant country-wise differences (p

Background: MD-PhD programs are research-oriented degrees that empower medical doctors with in-depth scientific skills. ‘Physician-scientists’ graduating from these programs are expected to highly contribute to biomedical research and academic medicine, alongside clinical practice. In that respect, however, there is limited knowledge about the outcomes and careers of the MD-PhD workforce, particularly in Europe. In the present study, we surveyed the MD-PhD graduates from the University of Geneva between 2010 and 2019.Methods: A cross-sectional survey was performed in April 2019, targeting all medical doctors who had obtained the MD-PhD degree from the University of Geneva since 2010. Features, career outcomes and opinions of MD-PhD graduates were assessed through an online anonymous questionnaire.Results: Twenty-one questionnaires were collected from 31 MD-PhD graduates (response rate 65.5 %). Most respondents (57.1%) had performed an MD-PhD training in basic sciences; however, only 14.3% had pursued this type of research thereafter. Most of the respondents were holding a position at a University hospital (90.5%), although a significant number of them were no longer doing research in their current position (28.6%) and 85.7% were facing obstacles and challenges to combine clinical duties and research. Despite this, the majority declared that the MD-PhD degree had given them an edge during the career (85.7%). Conclusions: The physician-scientists who graduated from the MD-PhD program in Geneva were globally satisfied with their training. However, many challenges and obstacles to combine clinical duties and research were reported by MD-PhD graduates, precluding the implementation of research activities in their current position.

BACKGROUND Capnoperitoneum provides a ventilatory challenge due to reduction in end-expiratory lung volume and peritoneal carbon dioxide absorption in both children and adults. The primary aim of this controlled interventional trial was to determine the positive end-expiratory pressure (PEEP) level needed to ensure for adequate carbon dioxide clearance and preservation of carbon dioxide homeostasis in an experimental model of infant laparoscopy. The secondary aim was to evaluate potential effects on cardiac output of PEEP and abdominal pressure level variations in the same setting. METHODS Eight chinchilla bastard rabbits were anesthetized and mechanically ventilated. Intra-abdominal pressures were randomly set to 0, 6, and 12 mm Hg by carbon dioxide insufflation. Carbon dioxide clearance using volumetric capnography, arterial blood gas data, and cardiac output was recorded, while PEEP 3, 6, and 9 cmH2 O were applied in a random order. RESULTS A PEEP of 9 cmH2 O showed restoration of carbon dioxide clearance without causing changes in arterial partial pressure of carbon dioxide and bicarbonate and with no associated deterioration in cardiac output. CONCLUSION The results promote a PEEP level of 9 cmH2 O in this model of infant capnoperitoneum to allow for adequate carbon dioxide removal with subsequent preservation of carbon dioxide homeostasis. The use of high PEEP was not associated with any decrease in cardiac output.

IntroductionThe advantages of physiologically variable ventilation (PVV) based on a spontaneous breathing pattern have been demonstrated in several respiratory conditions. However, its potential benefits in chronic obstructive pulmonary disease (COPD) have not yet been characterized. We used an experimental model of COPD to compare respiratory function outcomes after 6 h of PVV versus conventional pressure-controlled ventilation (PCV).Materials and MethodsRabbits received nebulized elastase and lipopolysaccharide throughout 4 weeks. After 30 days, animals were anesthetized, tracheotomized, and randomized to receive 6 h of physiologically variable (n = 8) or conventional PCV (n = 7). Blood gases, respiratory mechanics, and chest fluoroscopy were assessed hourly.ResultsAfter 6 h of ventilation, animals receiving variable ventilation demonstrated significantly higher oxygenation index (PaO2/FiO2 441 ± 37 (mean ± standard deviation) versus 354 ± 61 mmHg, p < 0.001) and lower respiratory elastance (359 ± 36 versus 463 ± 81 cmH2O/L, p < 0.01) than animals receiving PCV. Animals ventilated with the variable mode also presented less lung derecruitment (decrease in lung aerated area, –3.4 ± 9.9 versus –17.9 ± 6.7%, p < 0.01) and intrapulmonary shunt fraction (9.6 ± 4.1 versus 17.0 ± 5.8%, p < 0.01).ConclusionPVV applied to a model of COPD improved oxygenation, respiratory mechanics, lung aeration, and intrapulmonary shunt fraction compared to conventional ventilation. A reduction in alveolar derecruitment and lung tissue stress leading to better aeration and gas exchange may explain the benefits of PVV.

Background Mechanical ventilation during status asthmaticus is challenging and increases the risk of severe complications. We recently reported the value of physiologically variable ventilation (PVV) in healthy and acutely injured lungs. We investigated whether PVV provides benefits compared with pressure-controlled ventilation (PCV) in an experimental model of severe acute asthma. Methods Allergen-sensitised rabbits were anaesthetised and randomised to either PCV (n=10) or PVV (n=12) during sustained bronchoconstriction induced by allergen and cholinergic stimuli for 6 h. The PVV pattern was generated from pre-recorded spontaneous breathing. Ventilation parameters, oxygenation index (PaO2/FiO2), and respiratory mechanics were measured hourly. Histological injury and inflammation were quantified after 6 h of ventilation. Results PVV resulted in lower driving pressures (13.7 cm H2O [12.5–14.9], mean [95% confidence interval]), compared with pressure-controlled ventilation (17.6 cm H2O [15.4–19.8]; P=0.002). PVV improved PaO2/FiO2 (PVV: 55.1 kPa [52–58.2]; PCV: 45.6 kPa [39.3–51.9]; P=0.018) and maintained tissue elastance (PVV: +8.7% [–0.6 to 18]; PCV: –11.2% [–17.3 to –5.1]; P=0.03). PVV resulted in less lung injury as assessed by lower histological injury score (PVV: 0.65 [0.62–0.65]; PCV: 0.71 [0.69–0.73]; P=0.003), cell count (PVV: 247 104 ml−1 [189–305]; PCV: 447 104 ml−1 [324–570]; P=0.005), and protein concentration in bronchoalveolar lavage fluid (PVV: 0.14 μg ml−1 [0.10–0.18]; PCV: 0.21 μg ml−1 [0.15–0.27]; P=0.035). Conclusions Applying physiological variable ventilation in a model of asthma exacerbation led to improvements in gas exchange, ventilatory pressures, and respiratory tissue mechanics, and reduced lung injury. A global reduction in lung shear stress and recruitment effects may explain the benefits of PVV in status asthmaticus.

Background Benefits of variable mechanical ventilation based on the physiological breathing pattern have been observed both in healthy and injured lungs. These benefits have not been characterized in pediatric models and the effect of this ventilation mode on regional distribution of lung inflammation also remains controversial. Here, we compare structural, molecular and functional outcomes reflecting regional inflammation between PVV and conventional pressure-controlled ventilation (PCV) in a pediatric model of healthy lungs and acute respiratory distress syndrome (ARDS). Methods New-Zealand White rabbit pups (n = 36, 670 ± 20 g [half-width 95% confidence interval]), with healthy lungs or after induction of ARDS, were randomized to five hours of mechanical ventilation with PCV or PVV. Regional lung aeration, inflammation and perfusion were assessed using x-ray computed tomography, positron-emission tomography and single-photon emission computed tomography, respectively. Ventilation parameters, blood gases and respiratory tissue elastance were recorded hourly. Results Mechanical ventilation worsened respiratory elastance in healthy and ARDS animals ventilated with PCV (11 ± 8%, 6 ± 3%, p 18F]fluorodeoxyglucose uptake in healthy (1.49 ± 0.62 standardized uptake value, SUV) and ARDS animals (1.86 ± 0.47 SUV) compared to PCV (2.33 ± 0.775 and 2.28 ± 0.3 SUV, respectively, p Conclusions Variable ventilation based on a physiological respiratory pattern, compared to conventional pressure-controlled ventilation, reduced global and regional inflammation in both healthy and injured lungs of juvenile rabbits.

The ablation threshold for ultrashort pulses of common optical materials (BK7 glass, Sapphire and Fused Silica), was measured using the D-Scan technique, for positive and negative dispersions covering pulse durations from 30 fs to 100 fs. We observed that the ablation threshold for a single shot and at saturation increase with the pulse duration and the material bandgap, and also that defects which decrease the threshold values accumulate faster as the material bandgap increases.

Mechanical ventilation (MV) can worsen lung injury, particularly in ARDS, both through atelectrauma and volutrauma. It is not clear how these mechanisms contribute to lung inflammation and worsening injury with prolonged MV. ARDS was induced in juvenile rabbits (4-5 weeks, n=9), by combining iv endotoxin (20µg/kg) and injurious MV, followed by 5 hours of protective MV (pressure-control, PEEP 6 cmH2O; Pplateau 20-22 cmH2O). CT and PET imaging were performed thereafter. Lung regions (ROI) were segmented and partitioned based on normalized CT density into Aerated, Poorly-aerated and Collapsed regions. Standardised uptake values (SUV) were calculated. Moderate ARDS was triggered (PaO2/FiO2 = 226 ± 91 [SD]). Representative images are shown in Figure 1. ROI volumes were 16.6±3.4; 6.8±1.7; 5.4±1.2 mL in Aerated, Poorly-aerated and Collapsed lung regions, respectively. SUV was significantly higher within collapsed (0.84±0.29, p Significantly higher SUV in Poorly-aerated and Collapsed lung regions suggest that atelectrauma may contribute to lung inflammation, despite a protective ventilation strategy. Further study is underway to compare this outcome with normal lung and alternative ventilation strategies in ARDS. Grant: FNRS32003B_169334

OBJECTIVES The forced oscillation technique (FOT) is the method of choice for assessment of respiratory tissue mechanics. A laryngeal mask airway (LMA) is increasingly used to secure the airways in subjects under sedation or general anesthesia. While FOT is routinely performed using an endotracheal tube (ETT), the accuracy of information about airway and tissue mechanics obtained with FOT using a LMA has not been characterized. Therefore, we compared the mechanical parameters obtained with FOT using LMA and ETT in rabbits. APPROACH FOT was performed through a LMA at normal and reduced oscillatory amplitudes in anesthetized and mechanically ventilated rabbits (n = 9) at positive end-expiratory pressures (PEEP) of 3 and 6 cmH2O. These measurements were repeated at normal amplitude for the same animal using an ETT. Airway resistance, inertance, respiratory tissue damping (G) and elastance (H) were measured under each condition by FOT. The potential bias of the distensible upper airways when FOT was applied using LMA was assessed with a simulation study. MAIN RESULTS Values of parameters reflecting airway mechanics were significantly higher when measured using LMA at both PEEPs and oscillatory amplitudes than with ETT. Conversely, regardless of the condition, there was a correlation (r = 0.89 both at normal and reduced amplitudes; p

Whereas time capnography (Tcap) is routinely displayed during mechanical ventilation, the volumetric representation (Vcap) is seldom used. We compared the diagnostic value of indices derived from Tcap and Vcap following ventilation to perfusion ratio () mismatch subsequent to experimentally induced acute respiratory distress syndrome (ARDS), and alveolar recruitment by elevating the positive end-expiratory pressure (PEEP). Lung injury was induced by iv lipopolysaccharide, whole lung lavage and injurious ventilation in anesthetized, mechanically ventilated rabbits (n = 26). Mainstream Tcap and Vcap were performed to assess normalized phase 2 (Sn2T, Sn2V) and phase 3 slopes (Sn3T, Sn3V) in the time and volumetric domains. Vcap was also used to estimate Enghoff’s physiological dead space (VDE). Lung oxygenation index (PaO2/FiO2) and intrapulmonary shunt (Qs/Qt) were derived from arterial and central venous blood gas samples. All measurements were made under baseline conditions, and, following lung injury, under moderate (6 cmH2O) and high PEEP levels (9 cmH2O). Lung injury deteriorated the PaO2/FiO2 (baseline vs. injured 466 ± 10.2 [95% confidence interval] vs. 77.3 ± 17.1 mmHg, p < 0.05) and compromised all mechanical parameters significantly, whereas Tcap parameters exhibited contradictory or inconsistent changes. Conversely, Vcap indices exhibited consistent changes and provided excellent diagnostic value in detecting lung-function deterioration subsequent to lung injury [area under the receiver operating characteristic (ROC) curve of 1.0 ± 0.0, 0.87 ± 0.22 and 0.86 ± 0.22 for VDE, Sn3V and Sn3V/Sn2V, respectively]. Elevated PEEP increased PaO2/FiO2 and decreased Qs/Qt, which was reflected only in the Vcap slope ratio (Sn3V/Sn2V, p < 0.05). Our findings demonstrate the limited value of Tcap to detect ventilation to perfusion ratio () mismatch, following severe lung injury. Conversely, indices derived from Vcap proved to be sensitive for detecting lung volume loss and alveolar recruitment. Therefore, promotion of Vcap is of paramount importance as a real-time, non-invasive, bedside monitoring modality to detect the development of and to follow-up the progression of lung injury in a model of ARDS.