Intégration, évaluation et modélisation de signaux physiologiques permettant d’optimiser la ventilation d’urgence et la réanimation cardio pulmonaire

La ventilation mécanique en situation d'urgence est complexe. Une compréhension approfondie des dispositifs de ventilation utilisés dans ce contexte, ainsi que les interactions entre la physiologie respiratoire et cardiovasculaire sont nécessaires pour délivrer une ventilation adéquate. Lors de la crise COVID, en raison de l'afflux massif de patients à l'hôpital, différents ventilateurs de transport ont été déployés pour étendre les murs des réanimations. Nous avons évalué les performances de ces ventilateurs utilisant une seule alimentation en oxygène pressurisé, et démontré qu'ils peuvent être utilisés avec une précision acceptable en terme de volumes délivrés et de seuils de déclenchements. Les limites des technologies Venturi pneumatiques par rapport aux systèmes de turbine plus récents ont également pu être identifiées. Ces différences suggèrent que la technologie à turbine est plus adaptée à la ventilation d’urgence, notamment au cours de la réanimation cardio-pulmonaire (RCP). L'autre partie de la thèse se concentre sur la ventilation pendant la RCP, et l'analyse du signal CO2 qui pourrait permettre de guider la ventilation.Trois patterns de CO2 ont été identifiés à partir de données cliniques et reproduits sur des modèles animaux, sur cadavres et sur bancs. Ces patterns reflètent le volume pulmonaire pendant la RCP en regard de la capacité résiduelle fonctionnelle, et semblent être associés à certains effets adverses de la ventilation sur la circulation : « fermeture des voies aériennes » caractérisée par de faibles volumes pulmonaires, « distension thoracique » associée à des volumes insufflés potentiellement trop élevés ou « pattern régulier ». Sur la base de ces observations, une stratégie de ventilation guidée par l’aspect des capnogrammes pourrait permettre d'optimiser la ventilation pendant la RCP, avec une reconnaissance en temps réel des capnogrammes. L'augmentation de la pression expiratoire positive pourrait être envisagée en cas de fermeture des voies aériennes, tandis que la réduction du volume courant pourrait être proposée en cas de « distension thoracique ». Des travaux supplémentaires sont nécessaires avant de développer une telle approche ventilatoire sur un ventilateur, mais ces résultats pourraient permettre de mieux comprendre la ventilation pendant la RCP.Mechanical ventilation in emergency situations may be challenging. A deep understanding of the ventilation devices used in this context, as well as the complex interactions between respiratory and cardiovascular physiology are necessary to deliver adequate ventilation. During the COVID crisis, due to the massive influx of patients in the hospital, different transport ventilators have been deployed to extend the walls of the intensive care units. We evaluated the performances of those ventilators using only oxygen pressure supply, and demonstrated that they may be used with an acceptable accuracy in terms of delivered volumes and triggering capacities. The limitations of Venturi pneumatic technologies compared to more recent turbine systems have also been emphasized. Those differences suggest that turbine technology may be more adapted to emergency ventilation, particularly during cardiopulmonary resuscitation (CPR).The other part of the thesis focuses on ventilation during cardiopulmonary resuscitation (CPR), and the analysis of CO2 signal that could guide ventilation. Three CO2 patterns have been identified on clinical data and reproduced on animal, cadaver and bench models. Those CO2 patterns reflect thoracic lung volume during CPR in light of the functional residual capacity, and appear to be related to some adverse effects of ventilation on circulation : “intrathoracic airway closure” characterized by low lung volumes, “thoracic distension” associated with potentially too high insufflated volumes or “regular pattern”. Based on these observations, a capnogram-based ventilation strategy may permit to optimize ventilation during CPR, with a real-time identification of capnograms. Positive end expiratory pressure increase could be considered in case of in trathoracic airway closure, while tidal volume reduction could be proposed in case of “thoracic distension”. Further evidence is needed before developing such ventilatory approach on a ventilator, but these findings may be of potential additional value to better understand ventilation during CPR

Intégration, évaluation et modélisation de signaux physiologiques permettant d’optimiser la ventilation d’urgence et la réanimation cardio pulmonaire

Mechanical ventilation in emergency situations may be challenging. A deep understanding of the ventilation devices used in this context, as well as the complex interactions between respiratory and cardiovascular physiology are necessary to deliver adequate ventilation. During the COVID crisis, due to the massive influx of patients in the hospital, different transport ventilators have been deployed to extend the walls of the intensive care units. We evaluated the performances of those ventilators using only oxygen pressure supply, and demonstrated that they may be used with an acceptable accuracy in terms of delivered volumes and triggering capacities. The limitations of Venturi pneumatic technologies compared to more recent turbine systems have also been emphasized. Those differences suggest that turbine technology may be more adapted to emergency ventilation, particularly during cardiopulmonary resuscitation (CPR).The other part of the thesis focuses on ventilation during cardiopulmonary resuscitation (CPR), and the analysis of CO2 signal that could guide ventilation. Three CO2 patterns have been identified on clinical data and reproduced on animal, cadaver and bench models. Those CO2 patterns reflect thoracic lung volume during CPR in light of the functional residual capacity, and appear to be related to some adverse effects of ventilation on circulation : “intrathoracic airway closure” characterized by low lung volumes, “thoracic distension” associated with potentially too high insufflated volumes or “regular pattern”. Based on these observations, a capnogram-based ventilation strategy may permit to optimize ventilation during CPR, with a real-time identification of capnograms. Positive end expiratory pressure increase could be considered in case of in trathoracic airway closure, while tidal volume reduction could be proposed in case of “thoracic distension”. Further evidence is needed before developing such ventilatory approach on a ventilator, but these findings may be of potential additional value to better understand ventilation during CPR.La ventilation mécanique en situation d'urgence est complexe. Une compréhension approfondie des dispositifs de ventilation utilisés dans ce contexte, ainsi que les interactions entre la physiologie respiratoire et cardiovasculaire sont nécessaires pour délivrer une ventilation adéquate. Lors de la crise COVID, en raison de l'afflux massif de patients à l'hôpital, différents ventilateurs de transport ont été déployés pour étendre les murs des réanimations. Nous avons évalué les performances de ces ventilateurs utilisant une seule alimentation en oxygène pressurisé, et démontré qu'ils peuvent être utilisés avec une précision acceptable en terme de volumes délivrés et de seuils de déclenchements. Les limites des technologies Venturi pneumatiques par rapport aux systèmes de turbine plus récents ont également pu être identifiées. Ces différences suggèrent que la technologie à turbine est plus adaptée à la ventilation d’urgence, notamment au cours de la réanimation cardio-pulmonaire (RCP). L'autre partie de la thèse se concentre sur la ventilation pendant la RCP, et l'analyse du signal CO2 qui pourrait permettre de guider la ventilation.Trois patterns de CO2 ont été identifiés à partir de données cliniques et reproduits sur des modèles animaux, sur cadavres et sur bancs. Ces patterns reflètent le volume pulmonaire pendant la RCP en regard de la capacité résiduelle fonctionnelle, et semblent être associés à certains effets adverses de la ventilation sur la circulation : « fermeture des voies aériennes » caractérisée par de faibles volumes pulmonaires, « distension thoracique » associée à des volumes insufflés potentiellement trop élevés ou « pattern régulier ». Sur la base de ces observations, une stratégie de ventilation guidée par l’aspect des capnogrammes pourrait permettre d'optimiser la ventilation pendant la RCP, avec une reconnaissance en temps réel des capnogrammes. L'augmentation de la pression expiratoire positive pourrait être envisagée en cas de fermeture des voies aériennes, tandis que la réduction du volume courant pourrait être proposée en cas de « distension thoracique ». Des travaux supplémentaires sont nécessaires avant de développer une telle approche ventilatoire sur un ventilateur, mais ces résultats pourraient permettre de mieux comprendre la ventilation pendant la RCP

Quaternary low-temperature serpentinization and carbonation in the New Caledonia ophiolite

Abstract The low-temperature alteration (< 150 °C) of ophiolites by infiltrated meteoric waters removes atmospheric CO 2 through mineral carbonation and is assumed to generate H 2 and possibly CH 4 according to so-called serpentinization reactions. This overall alteration pattern is primarily constrained by the chemical composition of alkaline springs that are issued in several ophiolites worldwide. Here we report on the fingerprint, as veinlet mineralization, of the reactive percolation of such meteoric waters in the New Caledonia ophiolite (Massif du Sud). The mineralization which resulted from carbonation and serpentinization reactions, is young (< 2 Ma) and formed at a temperature of ca. 95 °C. It is mainly composed of lizardite, dolomite, magnetite ± pyroaurite. Thermochemical simulation of mineral–water equilibria shows that the percolating aqueous fluid was alkaline and H 2 bearing. The δ 13 C of dolomite is exceptionally high, between 7.1 and up to 17.3‰, and is interpreted as evidence of low-temperature methanogenesis. Overall, the percolating fluid had a chemical composition similar to that of the waters issued today in the (hyper)alkaline springs of the Massif du Sud. The studied veinlets are thus interpreted as a sample of the plumbing system that fed an ancient Quaternary alkaline spring in the area

Gas Exchange and Respiratory Mechanics After a Cardiac Arrest: A Clinical Description of Cardiopulmonary Resuscitation-Associated Lung Edema

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Reliability and limits of transport-ventilators to safely ventilate severe patients in special surge situations

International audienceBackground Intensive Care Units (ICU) have sometimes been overwhelmed by the surge of COVID-19 patients. Extending ICU capacity can be limited by the lack of air and oxygen pressure sources available. Transport ventilators requiring only one O-2 source may be used in such places. Objective To evaluate the performances of four transport ventilators and an ICU ventilator in simulated severe respiratory conditions. Materials and methods Two pneumatic transport ventilators, (Oxylog 3000, Draeger; Osiris 3, Air Liquide Medical Systems), two turbine transport ventilators (Elisee 350, ResMed; Monnal T60, Air Liquide Medical Systems) and an ICU ventilator (Engstrom Carestation-GE Healthcare) were evaluated on a Michigan test lung. We tested each ventilator with different set volumes (Vt(set) = 350, 450, 550 ml) and compliances (20 or 50 ml/cmH(2)O) and a resistance of 15 cmH(2)O/l/s based on values described in COVID-19 Acute Respiratory Distress Syndrome. Volume error (percentage of Vt(set)) with P-0.1 of 4 cmH(2)O and trigger delay during assist-control ventilation simulating spontaneous breathing activity with P-0.1 of 4 cmH(2)O and 8 cmH(2)O were measured. Results Grouping all conditions, the volume error was 2.9 +/- 2.2% for Engstrom Carestation; 3.6 +/- 3.9% for Osiris 3; 2.5 +/- 2.1% for Oxylog 3000; 5.4 +/- 2.7% for Monnal T60 and 8.8 +/- 4.8% for Elisee 350. Grouping all conditions (P-0.1 of 4 cmH(2)O and 8 cmH(2)O), trigger delay was 50 +/- 11 ms, 71 +/- 8 ms, 132 +/- 22 ms, 60 +/- 12 and 67 +/- 6 ms for Engstrom Carestation, Osiris 3, Oxylog 3000, Monnal T60 and Elisee 350, respectively. Conclusions In surge situations such as COVID-19 pandemic, transport ventilators may be used to accurately control delivered volumes in locations, where only oxygen pressure supply is available. Performances regarding triggering function are acceptable for three out of the four transport ventilators tested

A novel method for assessment of airway opening pressure without the need for low-flow insufflation

Abstract Background Airway opening pressure (AOP) detection and measurement are essential for assessing respiratory mechanics and adapting ventilation. We propose a novel approach for AOP assessment during volume assist control ventilation at a usual constant-flow rate of 60 L/min. Objectives To validate the conductive pressure (P cond) method, which compare the P cond—defined on the airway pressure waveform as the difference between the airway pressure level at which an abrupt change in slope occurs at the beginning of insufflation and PEEP—to resistive pressure for AOP detection and measurement, and to compare its respiratory and hemodynamic tolerance to the standard low-flow insufflation method. Methods The proof-of-concept of the P cond method was assessed on mechanical (lung simulator) and physiological (cadavers) bench models. Its diagnostic performance was evaluated in 213 patients, using the standard low-flow insufflation method as a reference. In 45 patients, the respiratory and hemodynamic tolerance of the P cond method was compared with the standard low-flow method. Measurements and main results Bench assessments validated the P cond method proof-of-concept. Sensitivity and specificity of the P cond method for AOP detection were 93% and 91%, respectively. AOP obtained by P cond and standard low-flow methods strongly correlated (r = 0.84, p < 0.001). Changes in SpO2 were significantly lower during P cond than during standard method (p < 0.001). Conclusion Determination of P cond during constant-flow assist control ventilation may permit to easily and safely detect and measure AOP

Melanomas Associated With Blue Nevi or Mimicking Cellular Blue Nevi: Clinical, Pathologic, and Molecular Study of 11 Cases Displaying a High Frequency of GNA11 Mutations, BAP1 Expression Loss, and a Predilection for the Scalp

International audienceMelanomas associated with blue nevi (MABN) or mimicking cellular blue nevi (MMCBN) represent exceptional variants of malignant cutaneous melanocytic tumors. Uveal and leptomeningeal melanomas frequently have somatic mutations of GNAQ or GNA11, which are believed to be early driver mutations. In uveal melanomas, monosomy 3, linked to the BAP1 gene, is an adverse prognostic factor. We have studied the clinical, histologic, BAP1 expression profile, and molecular data of 11 cases of MABN/MMCBN and 24 cellular blue nevi. Most of the cases of MABN/MMCBN occurred on the scalps of adult patients and presented as rapidly growing nodules, typically \textgreater1 cm, often arising at the site of a preexisting melanocytic lesion. The MABN/MMCBN were composed of dense nests of large dermal atypical melanocytes, in some cases lying adjacent to a blue nevus. Four patients developed metastatic disease, and 2 died from their disease. A GNA11 mutation was found in 8/11 cases and a GNAQ mutation in 1 case. Seven of 11 cases showed loss of nuclear BAP1 immunohistochemical (IHC) expression in the malignant component, sparing the adjacent nevus. Array comparative genomic hybridization revealed recurrent deletions of chromosomes 1p, 3p, 4q, 6q, 8p, 16q, and 17q and recurrent gains of chromosomes 6p, 8q, and 21q. The 24 cases of cellular blue nevi frequently occurred on the sacrum, had GNAQ mutations, and showed normal positive IHC staining for BAP1. These results underscore overlapping features in all blue-like malignant melanocytic tumors. Loss of BAP1 IHC expression was restricted to melanomas, including all metastatic case

A new reservoir-based CPAP with low oxygen consumption: the Bag-CPAP

Abstract Background Several noninvasive ventilatory supports rely in their design on high oxygen consumption which may precipitate oxygen shortage, as experienced during the COVID-19 pandemic. In this bench-to-bedside study, we assessed the performance of a new continuous positive airway pressure (CPAP) device integrating a large reservoir (“Bag-CPAP”) designed to minimize oxygen consumption, and compared it with other CPAP devices. Methods First, a bench study compared the performances of Bag-CPAP and four CPAP devices with an intensive care unit ventilator. Two FiO2 targets (40–60% and 80–100%) at a predefined positive end expiratory pressure (PEEP) level between 5 and 10 cm H2O were tested and fraction of inspired oxygen (FiO2) and oxygen consumption were measured. Device-imposed work of breathing (WOB) was also evaluated. Second, an observational clinical study evaluated the new CPAP in 20 adult patients with acute respiratory failure in two hospitals in France. Actual FiO2, PEEP, peripheral oxygen saturation, respiratory rate, and dyspnea score were assessed. Results All six systems tested in the bench study reached the minimal FiO2 target of 40% and four reached at least 80% FiO2 while maintaining PEEP in the predefined range. Device-delivered FiO2/consumed oxygen ratio was the highest with the new reservoir-based CPAP irrespective of FiO2 target. WOB induced by the device was higher with Bag-CPAP. In the clinical study, Bag-CPAP was well tolerated and could reach high (> 90%) and moderate (> 50%) FiO2 with an oxygen flow rate of 15 [15–16] and 8 [7–9] L/min, respectively. Dyspnea score improved significantly after introduction of Bag-CPAP, and SpO2 increased. Conclusions In vitro, Bag-CPAP exhibited the highest oxygen saving properties albeit had increased WOB. It was well accepted clinically and reduced dyspnea. Bag-CPAP may be useful to treat patients with acute respiratory failure in the field, especially when facing constraints in oxygen delivery

A novel capnogram analysis to guide ventilation during cardiopulmonary resuscitation: clinical and experimental observations

International audienceBackground Cardiopulmonary resuscitation (CPR) decreases lung volume below the functional residual capacity and can generate intrathoracic airway closure. Conversely, large insufflations can induce thoracic distension and jeopardize circulation. The capnogram (CO2 signal) obtained during continuous chest compressions can reflect intrathoracic airway closure, and we hypothesized here that it can also indicate thoracic distension. Objectives To test whether a specific capnogram may identify thoracic distension during CPR and to assess the impact of thoracic distension on gas exchange and hemodynamics. Methods (1) In out-of-hospital cardiac arrest patients, we identified on capnograms three patterns: intrathoracic airway closure, thoracic distension or regular pattern. An algorithm was designed to identify them automatically. (2) To link CO2 patterns with ventilation, we conducted three experiments: (i) reproducing the CO2 patterns in human cadavers, (ii) assessing the influence of tidal volume and respiratory mechanics on thoracic distension using a mechanical lung model and (iii) exploring the impact of thoracic distension patterns on different circulation parameters during CPR on a pig model. Measurements and main results (1) Clinical data: 202 capnograms were collected. Intrathoracic airway closure was present in 35%, thoracic distension in 22% and regular pattern in 43%. (2) Experiments: (i) Higher insufflated volumes reproduced thoracic distension CO2 patterns in 5 cadavers. (ii) In the mechanical lung model, thoracic distension patterns were associated with higher volumes and longer time constants. (iii) In six pigs during CPR with various tidal volumes, a CO2 pattern of thoracic distension, but not tidal volume per se, was associated with a significant decrease in blood pressure and cerebral perfusion. Conclusions During CPR, capnograms reflecting intrathoracic airway closure, thoracic distension or regular pattern can be identified. In the animal experiment, a thoracic distension pattern on the capnogram is associated with a negative impact of ventilation on blood pressure and cerebral perfusion during CPR, not predicted by tidal volume per se

Advanced respiratory mechanics assessment in mechanically ventilated obese and non-obese patients with or without acute respiratory distress syndrome

Abstract Background Respiratory mechanics is a key element to monitor mechanically ventilated patients and guide ventilator settings. Besides the usual basic assessments, some more complex explorations may allow to better characterize patients’ respiratory mechanics and individualize ventilation strategies. These advanced respiratory mechanics assessments including esophageal pressure measurements and complete airway closure detection may be particularly relevant in critically ill obese patients. This study aimed to comprehensively assess respiratory mechanics in obese and non-obese ICU patients with or without ARDS and evaluate the contribution of advanced respiratory mechanics assessments compared to basic assessments in these patients. Methods All intubated patients admitted in two ICUs for any cause were prospectively included. Gas exchange and respiratory mechanics including esophageal pressure and end-expiratory lung volume (EELV) measurements and low-flow insufflation to detect complete airway closure were assessed in standardized conditions (tidal volume of 6 mL kg−1 predicted body weight (PBW), positive end-expiratory pressure (PEEP) of 5 cmH2O) within 24 h after intubation. Results Among the 149 analyzed patients, 52 (34.9%) were obese and 90 (60.4%) had ARDS (65.4% and 57.8% of obese and non-obese patients, respectively, p = 0.385). A complete airway closure was found in 23.5% of the patients. It was more frequent in obese than in non-obese patients (40.4% vs 14.4%, p < 0.001) and in ARDS than in non-ARDS patients (30% vs. 13.6%, p = 0.029). Respiratory system and lung compliances and EELV/PBW were similarly decreased in obese patients without ARDS and obese or non-obese patients with ARDS. Chest wall compliance was not impacted by obesity or ARDS, but end-expiratory esophageal pressure was higher in obese than in non-obese patients. Chest wall contribution to respiratory system compliance differed widely between patients but was not predictable by their general characteristics. Conclusions Most respiratory mechanics features are similar in obese non-ARDS and non-obese ARDS patients, but end-expiratory esophageal pressure is higher in obese patients. A complete airway closure can be found in around 25% of critically ill patients ventilated with a PEEP of 5 cmH2O. Advanced explorations may allow to better characterize individual respiratory mechanics and adjust ventilation strategies in some patients. Trial registration NCT03420417 ClinicalTrials.gov (February 5, 2018)