Les pathologies respiratoires obstructives de l’enfant (asthme et broncho-alvéolites) sont l’une des principales causes d’admission en réanimation pédiatrique. Depuis plusieurs années, des progrès ont été faits pour réduire l’invasivité des soins se traduisant par une réduction de la morbidité. L’objectif de ce travail de thèse est de s’appuyer sur des mécanismes physiopathologiques pour proposer des stratégies d’optimisation ventilatoire et non ventilatoire chez ces enfants. Nous avons évalué l’impact du décubitus ventral couplé à la ventilation non invasive chez les nourrissons atteints de bronchiolite grave. Le décubitus ventral permet de réduire significativement l’effort inspiratoire et d’améliorer le couplage électromécanique du diaphragme. Ensuite nous avons évalué la « neurally adjusted ventilatory assist » (NAVA) qui est un mode ventilatoire proportionnel basé sur l’activité électrique du diaphragme. Nous avons démontré que la NAVA améliorait la synchronisation patient-respirateur et réduisait le travail respiratoire en comparaison à la « nasal continuous positive airway pressure » (nCPAP). Enfin, dans la pathologie asthmatique nous avons également décrit la faisabilité du haut débit nasal dans cette population. Ces stratégies nécessitent maintenant d’être validées sur des critères cliniques et feront l’objet de deux études multicentriques randomisées / Obstructive lung disease in children (asthma and bronchiolitis) are one of the main causes of admission to pediatric intensive care units. For several years, progress has been made to reduce the invasiveness of care resulting in a decrease in associated morbidity. The main objective of the thesis was to propose new ventilatory and non-ventilatory strategies based on physiopathology to optimize the care of such children.In children with severe bronchiolitis we evaluated the impact of prone position associated with non-invasive ventilation. The prone position decreases significantly the inspiratory work of breathing and improves the neuromechanical efficiency of the diaphragm. We also evaluated the effect of neurally adjusted ventilatory assist (NAVA) that is a proportional ventilatory mode based on the electrical activity of the diaphragm. We demonstrated that NAVA improved the patient-ventilator interactions and decrease the work of breathing in comparison with nasal continuous positive airway pressure (nCPAP). We also evaluated the feasibility of high flow nasal cannula as a respiratory support in children with severe asthma attack. These strategies need now to be validated on clinical outcomes and are the subject of two ongoing multicenter randomized trials

Background and aims: Lung recruitment maneuvers (brief episodes of high airway pressure) are a modern treatment alternative to achieve open lung conditions under mechanical ventilation of patients with acute lung injury. It is well known that positive pressure ventilation with high airway pressures cause negative circulatory effects, and that the effects on regional vascular beds can be even more pronounced than the systemic effects. Hypoperfusion of the mesenteric vascular bed can lead to tissue ischemia and local inflammation. This intestinal inflammation has been associated with subsequent development of multiple organ dysfunction syndrome, a syndrome that still carries a high mortality and is a leading cause of death for intensive care patients. The aim of this thesis was therefore to investigate whether lung recruitment maneuvers would cause negative effects on mesenteric circulation, oxygenation or metabolism. Methods and results: In an initial study on ten patients with acute lung injury, we could demonstrate a trend towards a decreased gastric mucosal perfusion during three repeated lung recruitment maneuvers. To more closely examine this finding, we set up an oleic acid lung injury model in pigs, and in our second study we established that this model was devoid of inherent intestinal effects and was adequate for subsequent studies of intestinal effects of lung recrutiment maneuvers. In the acute lung injury model, we also tested the effect of an infusion of a vasodilating agent concurrent with the recruitment maneuvers, the hypothesis being that a vasodilating agent would prevent intestinal vasoconstriction and hypoperfusion. We could show that three repeated lung recruitment maneuvers induced short term negative effects on mesenteric oxygenation and metabolism, but that these findings were transient and short lasting. Further, the effects of prostacyclin were minor and opposing. These findings of relative little impact on the intestines of lung recruitment maneuvers, lead us to investigate the hypothesis that repeated recruitment maneuvers maybe could elicite a protective intestinal preconditioning response, a phenomenon previously described both in the rat and in the dog. However, in our fourth study, using both classical ischemic preconditioning with brief periods of intestinal ischemia or repeated lung recrutiment maneuvers, we could not demonstrate the phenomenon of intestinal preconditioning in the pig. Conclusions: We conclude, that from a mesenteric point of view, lung recruitment maneuvers are safe, and only induce transient and short lasting negative effects. We also conclude that the cause of the minor effects of lung recruitment maneuvers is not dependent on intestinal preconditioning.

Einleitung: Bei PSV beendet der Respirator die Druckunterstützung, wenn der Inspirationsfluss auf einen prozentualen Anteil des Spitzenflusses, welcher als Umschaltkriterium be-zeichnet wird, absinkt. Bei obstruktiver Lungenerkrankung ist der Abfall des Inspirationsflusses verlangsamt, wodurch verspätetes Umschalten in die Exspiration begünstigt wird. Der verwendete Beatmungszugang, das etwaige Vorliegen von Leckage bei nicht-invasiver Beatmung, die Höhe der Druckunterstützung und die Atemfrequenz sind potentielle Faktoren, welche das Umschalten in die Exspiration beeinflussen können. Die synchrone Unterstützung der Patienteninspirationsbemühung ist entscheidend für den Erfolg der assistierten Beatmungstherapie. Methode: In einer Lungenmodellstudie wurde obstruktive Lungenmechanik simuliert und der Einfluss der Variation des Umschaltkriteriums auf die Patient-Respirator-Interaktion untersucht. Die Beatmungszugänge Endotrachealtubus, Nasen-Mund-Maske und Beatmungshelm wurden nacheinander in den Versuchsaufbau eingebracht. Bei nicht-invasiver Beatmung wurde mit und ohne Leckage gemessen. Bei Vorliegen von Leckage wurde zusätzlich in einem nicht-invasiven Beatmungsmodus beatmet. Die Höhe der Druckunterstützung (5 cmH2O, 15 cmH2O) und die Atemfrequenz (15/min, 30/min) wurden verändert. Die Patient-Respirator-Interaktion wurde bei Verwendung der Umschaltkriterien 10 %, 20 %, 30 %, 40 %, 50 %, 60 % und 70 % des Spitzenflusses analysiert. Aus aufgezeichneten Flusskurven wurden Parameter, welche die Synchronisation zwischen Patient und Respirator beschreiben (nicht-unterstützte Atemzüge, Doppeltrigger, inspiratorische und exspiratorische Triggerlatenz) sowie das Tidalvolumen bestimmt. Aus aufgezeichneten Druckkurven wurden der intrinsische PEEP und Druck-Zeit-Produkte bestimmt, welche in den verschiedenen Phasen des Atemzyklus die durch den Respirator geleistete Entlastung (PTPPEEP, PTPINSP) oder Belastung (PTPEXSP) der Atemmuskulatur beschreiben. Ergebnisse: Bei konventionell eingestelltem Umschaltkriterium (20 % - 30 %) wurde stets verspätetes Umschalten beobachtet. Die Erhöhung des Umschaltkriteriums resultierte in einer Reduktion der exspiratorischen Triggerlatenz, PTPEXSP und des intrinsischen PEEP. In der Folge wurden nicht-unterstützte Inspirationsbemühungen, die inspiratorischen Triggerlatenz sowie der zur Auslösung der Druckunterstützung erforderliche Kraftaufwand (PTPPEEP) reduziert. Bei übermäßiger Erhöhung des Umschaltkriteriums beendete der Respirator die Druckunterstützung vor dem Ende der simulierten Inspirationsbemühung. Vorzeitiges Umschalten ging mit einer Abnahme des Tidalvolumens und der effektive Druckunter-stützung (PTPINSP), sowie der Auslösung von Doppeltrigger, einher. Vorzeitiges Umschalten trat bei niedriger Atemfrequenz bei Verwendung der Umschaltkriterien 50 % bzw. 60 % bis 70 % auf. Bei Beatmung via Endotrachealtubus und Nasen-Mund-Maske wurden vergleichbare Ergebnisse beobachtet. Bei Beatmung via Beatmungshelm war die Interaktion zwischen Patient und Respirator wesentlich beeinträchtigt, wodurch vorzeitiges Umschalten begünstigt wurde. Bei Messungen mit Leckage war die exspiratorische Triggerlatenz verlängert. Bei Verwendung des NIV-Beatmungsmodus konnte die exspiratorische Triggerlatenz teilweise minimiert werden. Bei hoher Druckunterstützung war die exspiratorische Triggerlatenz, bei Beatmung via Endotrachealtubus und Nasen-Mund-Maske, verlängert. Konklusion: Die Variation des Umschaltkriteriums stellt eine effektive Möglichkeit dar, die Patient-Respirator-Interaktion zu optimieren. Bei obstruktiver Lungenerkrankung sollte das Umschaltkriterium, über das konventionell eingestellte Umschaltkriterium hinaus, erhöht werden. Das Umschaltkriterium ist maßvoll zu erhöhen, um eine vorzeitige Unterbrechung der Druckunterstützung zu verhindern. Das Risiko verfrühten Umschaltens ist bei Beatmung via Beatmungshelm, sowie bei niedriger Atemfrequenz, erhöht. Des Weiteren müssen das etwaige Vorliegen von Leckage, der bei nicht-invasiver Beatmung verwendete Beatmungsmodus, die Höhe der Druckunterstützung sowie die Atemfrequenz bei der Wahl des Umschaltkriteriums berücksichtigt werden.

Des études adultes sur l’œdème pulmonaire lésionnel et le Syndrome de Détresse Respiratoire Aiguë ont mené à l’établissement de recommandations sur les stratégies de ventilation mécanique à employer chez ces patients. Cependant, il n’est pas clair si les recommandations adultes sont également bénéfiques pour l’enfant. Objectif Décrire les stratégies de ventilation mécanique employées chez les enfants atteints d’un œdème pulmonaire lésionnel. Méthodes Étude épidémiologique transversale tenue dans 59 unités de Soins Intensifs Pédiatriques de 12 pays en Amérique du Nord et en Europe. Six jours d’étude ont eu lieu entre juin et novembre 2007. Les enfants atteints d’un œdème pulmonaire lésionnel étaient inclus et des données sur la sévérité de leur maladie, les paramètres de ventilation mécanique et les thérapies adjuvantes employées ont été recueillies. Résultats Des 3823 enfants dépistés, 414 (10.8%) avaient un œdème pulmonaire lésionnel et 165 (40%) ont été inclus dans l’étude (124 étaient sous ventilation mécanique conventionnelle, 27 sous ventilation à haute fréquence par oscillation et 14 sous ventilation non invasive). Dans le groupe sous ventilation conventionnelle, 43.5% étaient ventilés avec un mode contrôlé à pression, le volume courant moyen était de 8.3±3.3 ml/kg et l’utilisation de la PEP et FiO2 était hétérogène. Conclusions Cette étude démontre une hétérogénéité dans les stratégies de ventilation mécanique employées chez les enfants souffrant d’un œdème pulmonaire lésionnel. Celle-ci pourrait être en partie reliée à la robustesse des critères diagnostiques actuellement utilisés pour définir l’ALI/SDRA. Une évaluation rigoureuse de ces stratégies est nécessaire pour guider la standardisation des soins et optimiser l’issue de ces patients. / Acute Lung Injury and Acute Respiratory Distress Syndrome are life-threatening conditions frequently leading to respiratory support with mechanical ventilation. Studies on mechanical ventilation strategies in adult patients have led to lung protective ventilation recommendations. However, there are few pediatric clinical trials on optimal mechanical ventilation management in Acute Lung Injury and it is still unclear if strategies studied in adults are equally beneficial to children. Objective Describe mechanical ventilation strategies in Acute Lung Injury in children. Methods Cross-sectional study for six 24-hour periods from June to November 2007 across 59 Pediatric Intensive Care Units in 12 countries in North America and Europe. We identified children meeting Acute Lung Injury criteria and collected detailed information on illness severity, mechanical ventilation support and use of adjunctive therapies. Results Of 3823 patients screened, 414 (10.8%) were diagnosed with Acute Lung Injury and 165 were included in the study (124 received conventional mechanical ventilation, 27 high frequency oscillatory ventilation, 14 non-invasive mechanical ventilation). In the conventional mechanical ventilation group, 43.5% were ventilated in a pressure control mode, the mean tidal volume was 8.3±3.3 ml/kg and there was no clear relationship between PEEP and FiO2 delivery. Conclusions Our study reveals inconsistent mechanical ventilation practice and use of adjunctive therapies in children with Acute Lung Injury. Rigorous evaluation of ventilator management strategies in children with an Acute Lung Injury are urgently needed to guide standardization of care and optimize clinical outcomes.

Une morbidité et une mortalité néonatales élevées limitent l’efficacité du clonage somatique chez les bovins. Des malformations myoarthrosquelettiques, des anomalies ombilicales, des problèmes respiratoires et de la faiblesse ont été fréquemment observés chez les veaux clonés nouveaux-nés. Cette étude rétrospective porte sur 31 veaux clonés. Ses objectifs étaient de décrire les problèmes respiratoires rencontrés, leur évolution au cours du temps, les traitements instaurés pour soutenir la fonction respiratoire et la réponse aux traitements. Vingt-deux veaux ont souffert de problèmes respiratoires. La tachypnée, l’hypoxémie et l’hypercapnie sont les signes cliniques les plus fréquemment observés. L’analyse des gaz sanguins a été un outil essentiel dans le diagnostic et le suivi de la fonction respiratoire. La radiographie a permis une évaluation globale du poumon. L’oxygénothérapie intranasale et la ventilation mécanique ont permis de limiter la mortalité due à une insuffisance respiratoire à 18% (4/22). Cette étude a permis d’émettre des hypothèses quant à l’origine des problèmes respiratoires chez les veaux clonés. Plus d’une maladie semblent affecter les veaux clonés. La déficience en surfactant, l’hypertension pulmonaire persistante et le retard de résorption du fluide pulmonaire figurent parmi les entités pathologiques les plus probables. / High morbidity and mortality decrease the efficiency of somatic cell nuclear transfer. The main abnormalities observed in neonatal cloned calves are skeletal malformations, enlarged umbilical vessels, respiratory problems and weakness. This retrospective study involved 31 cloned calves. The objectives of this study were to describe the respiratory problems suffered by cloned calves during neonatal period, to assess their evolution, and to determine the possible causes. Secondary objectives were to describe the techniques used to assess and support respiratory function and the calves’ response. Respiratory problems affected 22 calves. Tachypnea, hypoxemia and hypercapnia were the most frequently observed signs. Arterial blood gas analyses and chest radiographs were precious to identify and assess respiratory problems. Intranasal oxygen and mechanical ventilation were efficient to limit mortality due to respiratory failure to 18% (4/22). It is plausible that more than one disease affect cloned calves. Delayed resorption of pulmonary fluid, persistent pulmonary hypertension and surfactant deficiency, or a combination of these factors, are among the most probable pathological entities.

This study explored the perspectives of children whose complex health needs included respiratory technology dependence, and that of their parents, regarding community life and helpful patterns of coping and relationship. In-depth interviews were conducted with 7 children (3-18 yrs. old) and 8 parents. Survey data collected from 31 parents contributed to a convergent mixed methods design. Findings showed that children viewed themselves as normal, but experienced "a constricted life". Parents' active engagement in their child's life, as system navigators and advocates, was necessary to ensure their child's wellbeing. Key relational components included "authentic engaged presence", caring, competence, communication and collaboration. Effective coping patterns included reliable social support and both emotion-focused and problem-focused strategies. Contextual factors significantly affecting parental coping and relationships included family structure and child’s dependence on invasive respiratory technology (tracheostomy). Respite reported inadequate. Findings have practice and policy implications for health, respite and education systems, professionals and parents.

Background: General anesthesia usually requires mechanical ventilation, which is traditionally accomplished with constant tidal volumes in volume- or pressure-controlled modes. Experimental studies suggest that the use of variable tidal volumes (variable ventilation) recruits lung tissue, improves pulmonary function and reduces systemic inflammatory response. However, it is currently not known whether patients undergoing open abdominal surgery might benefit from intraoperative variable ventilation. Methods/Design: The PROtective VARiable ventilation trial ('PROVAR') is a single center, randomized controlled trial enrolling 50 patients who are planning for open abdominal surgery expected to last longer than 3 hours. PROVAR compares conventional (non-variable) lung protective ventilation (CV) with variable lung protective ventilation (VV) regarding pulmonary function and inflammatory response. The primary endpoint of the study is the forced vital capacity on the first postoperative day. Secondary endpoints include further lung function tests, plasma cytokine levels, spatial distribution of ventilation assessed by means of electrical impedance tomography and postoperative pulmonary complications. Discussion: We hypothesize that VV improves lung function and reduces systemic inflammatory response compared to CV in patients receiving mechanical ventilation during general anesthesia for open abdominal surgery longer than 3 hours. PROVAR is the first randomized controlled trial aiming at intra- and postoperative effects of VV on lung function. This study may help to define the role of VV during general anesthesia requiring mechanical ventilation.

This study explored the perspectives of children whose complex health needs included respiratory technology dependence, and that of their parents, regarding community life and helpful patterns of coping and relationship. In-depth interviews were conducted with 7 children (3-18 yrs. old) and 8 parents. Survey data collected from 31 parents contributed to a convergent mixed methods design. Findings showed that children viewed themselves as normal, but experienced "a constricted life". Parents' active engagement in their child's life, as system navigators and advocates, was necessary to ensure their child's wellbeing. Key relational components included "authentic engaged presence", caring, competence, communication and collaboration. Effective coping patterns included reliable social support and both emotion-focused and problem-focused strategies. Contextual factors significantly affecting parental coping and relationships included family structure and child’s dependence on invasive respiratory technology (tracheostomy). Respite reported inadequate. Findings have practice and policy implications for health, respite and education systems, professionals and parents.

Mechanical ventilation can be a life saving treatment. However, due to the inhomogeneous and anisotropic behavior of the lung tissue, ventilation can also lead to overdistensions of lung regions whereas other areas remain even collapsed. A first step is a more comprehensive understanding of the flow mechanics under normal breathing conditions in a healthy lung as well as for a diseased, collapsed lung. This is the aim of this work. Therefore, a realistic model of the upper human airways has been generated at which experimental and numerical investigations could be carried out. Experimentally, the flow was analyzed by means of Particle Image Velocimetry (PIV) measurements which revealed new details about the flow patterns occurring during different ventilation frequencies. Numerical results were in good agreement with the experimental results and could provide new details about the three-dimensional flow structure and emerging secondary flow within the upper airways. The study of reopening of collapsed airways has shown that larger frequencies lead to airway reopening without overdistension of already open parts. Higher frequencies also lead to homogenization of mass flow distribution within the human lung. / Künstliche Beatmung ist meist eine lebensrettende Maßnahme. Aufgrund der räumlich anisotropen und inhomogenen Eigenschaften der Lunge kann die Beatmung jedoch auch zu einer Schädigung der Lunge führen. Daraus ergibt sich die Forderung einer „Protektiven Beatmung“. Ein erster Schritt dahingehend ist ein verbessertes Verständnis der Atmung und Beatmung am Beispiel der gesunden sowie kranken, teilweise kollabierten Lunge. Dies ist das Ziel der Arbeit. Hierfür wurde ein realistisches Modell der oberen Atemwege (Tracheobronchialbaum) angefertigt. An diesem Modell können sowohl experimentelle als auch numerische Untersuchungen durchgeführt werden. Experimentell wurde die Strömung mittels Particle Image Velocimetry (PIV) untersucht, wobei neue Details bezüglich der auftretenden Strömungsmuster für unterschiedliche Frequenzen gefunden wurden. Numerische Strömungsberechnungen stimmen gut mit den experimentellen Ergebnissen überein. Dreidimensionale Strömungsstrukturen sowie die Entwicklung von Sekundärwirbeln in der Lunge konnten erklärt werden. Eine Studie am kranken, teilweise kollabierten Lungenmodell zeigte, dass mit steigender Frequenz kollabierte Bereiche wiedereröffnet werden können. Höhere Frequenzen führen weiterhin zu einer Homogenisierung der Massenstromverteilung in der Lunge.

Orientador: José Roberto Fioretto / Resumo: A Síndrome do Desconforto Respiratório Agudo (SDRA) caracteriza-se por processo inflamatório que leva à quebra da barreira alvéolo-capilar com desenvolvimento de edema intersticial e alveolar, diminuição da complacência pulmonar, hipertensão pulmonar, desequilíbrio da relação ventilação/perfusão e hipoxemia refratária à administração de oxigênio. Apesar do progresso no entendimento de sua fisiopatologia e consequente avanço em estratégias terapêuticas de pacientes com SDRA, a mortalidade permanece elevada. Entre os mecanismos que levam a síndrome, várias evidências sugerem que pacientes portadores de SDRA estão expostos a elevado grau de estresse oxidativo (EO) induzido por ampla variedade de eventos. Por essa razão é fundamental a compreensão do papel do EO tanto na instalação como na perpetuação do processo infamatório que ocorre na doença. No entanto, apesar do uso de antioxidantes ter mostrado algum benefício na evolução da doença, ainda não há evidência clínica para sua utilização rotineira na prática. O licopeno é um carotenoide sem atividade provitamina A encontrado principalmente no tomate e nas frutas vermelhas. Em decorrência de seu grande número de duplas ligações conjugadas, o licopeno é considerado um dos melhores antioxidantes entre os carotenoides. Além disso, é um dos mais potentes antioxidantes encontrados no organismo humano, apresentando potência antioxidante 100 vezes maior do que a vitamina E e a vitamina C. A ventilação mecânica convencional protetora (V... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor