Diss. (sammanfattning) Uppsala : Uppsala universitet, 2004. / Härtill 4 uppsatser.

ContextualizaÃÃo: A obtenÃÃo de uma boa sincronia paciente-ventilador consiste em um dos maiores desafios no manejo da ventilaÃÃo mecÃnica (VM). A ventilaÃÃo com pressÃo de suporte ou pressure support ventilation (PSV) à uma modalidade ventilatÃria amplamente utilizada no processo de desmame da VM. A ventilaÃÃo assistida proporcional ou proportional assist ventilation (PAV) à uma modalidade de suporte ventilatÃrio onde o ventilador gera assistÃncia proporcional e instantÃnea aos esforÃos do paciente. O Auto-Trak digital consiste em uma tecnologia capaz de ajustar automaticamente, ciclo a ciclo, os mecanismos de disparo e ciclagem durante o modo PSV. Objetivos: Determinar a influÃncia da mecÃnica respiratÃria sobre a assincronia paciente-ventilador durante os modos PSV, com e sem sistema de disparo e ciclagem automÃticos e na PAV, em modelo pulmonar mecÃnico e identificar padrÃes nas curvas de ventilaÃÃo apresentadas na tela do ventilador que sejam relacionadas aos tipos de assincronia investigados. MÃtodos: Trata-se de estudo experimental, de bancada utilizando o simulador pulmonar mecÃnico, ASL 5000Â. Estudaram-se trÃs perfis de mecÃnica respiratÃria: normal, obstrutivo e restritivo, com variaÃÃo do tempo inspiratÃrio neural 0,5, 1,0, 1,5 e 2,0 segundos, sendo a intensidade mÃxima do esforÃo muscular (Pmus) fixada em -7.5 cmH2O, durante a VM nos modos PSV e PAV, em cinco ventiladores de UTI, de circuito duplo, e um ventilador de circuito Ãnico. O Auto-Trak foi estudado quando disponÃvel no ventilador. Os desfechos primÃrios foram: tempo de retardo inspiratÃrio e tempo de assincronia de ciclagem identificando, neste segundo caso, dois tipos possÃveis, ciclagem tardia ou precoce. AlÃm disso, procedeu-se a uma anÃlise por inspeÃÃo visual comparativa entre as curvas de mecÃnica: fluxo, VC e Pmus do ASL 5000 e as curvas na tela grÃfica do ventilador mecÃnico de VC, fluxo e pressÃo x tempo, na tentativa de se identificar padrÃes associados à assincronia, que fossem passÃveis de identificaÃÃo pela simples observaÃÃo na tela do ventilador pulmonar. Resultados: Houve marcante influÃncia da mecÃnica respiratÃria sobre a assincronia paciente-ventilador. O tempo de retardo inspiratÃrio foi maior e clinicamente significativo (> 100 ms) no perfil obstrutivo de mecÃnica respiratÃria, e foi menor, muitas vezes zero, no ventilador de circuito Ãnico; a assincronia de ciclagem foi comum no perfil obstrutivo, sendo predominantemente do tipo ciclagem tardia, enquanto no perfil restritivo predominou o tipo ciclagem precoce. O emprego do Auto-trak eliminou a ocorrÃncia de assincronia do tipo auto-disparo no ventilador de circuito Ãnico. A anÃlise visual das curvas detectou padrÃes de traÃados da curva de fluxo x tempo que sÃo caracterÃsticos de assincronia do tipo ciclagem precoce e ciclagem tardia e passÃveis de identificaÃÃo por inspeÃÃo visual direta na tela do ventilador. ConclusÃo: as assincronias de disparo e ciclagem entre o paciente e o ventilador sÃo a regra e nÃo a exceÃÃo durante os modos PSV e PAV, sendo estas influenciadas pela mecÃnica respiratÃria. O emprego do sistema Auto-trakÂ, mostrou benefÃcio durante o uso do ventilador de circuito Ãnico com melhora substancial do disparo. A inspeÃÃo visual da curva de fluxo na tela do ventilador pode favorecer a identificaÃÃo destes tipos de assincronia. Palavras-chave: / Obtaining a good patient-ventilator synchrony is one of the biggest challenges in the management of mechanical ventilation (MV). Pressure support ventilation (PSV) is a ventilator mode widely used in the MV weaning process. Proportional assist ventilation (PAV) is a mode of ventilator support in which the ventilator generates assistance proportional and instant to the efforts of the patient. Digital Auto-TrakTM consists in a technology capable of automatically adjusting, cycle by cycle, the mechanisms of triggering and cycling in PSV mode. Objectives: To determine the influence of respiratory mechanics on patient-ventilator asynchrony during PSV mode, with and without automatic triggering and cycling system, and PAV, in a mechanic lung model and to identify patterns on ventilation curves presented on the ventilator screen, which are related to the types of asynchrony investigated. Methods: This is an experimental bench study using the mechanic lung model, ASL 5000TM. Three profiles of respiratory mechanics were studied: normal, obstructive and restrictive, with variation of neural inspiratory time of 0.5, 1.0, 1.5 and 2.0 seconds, with maximum intensity of muscle effort (Pmus) fixed in -7.5 cmH2O, during MV in PSV and PAV modes, in five ICU ventilators, with double limb, and in one single limb ventilator. Auto-TrakTM was studied when avaliable in the ventilator. Primary outcomes were: inspiratory delay time and cycling asynchrony time identifying, in the second case, two possible types, late or premature cycling. Furthermore, we proceeded to an analysis by visual inspection of the: flow, VT and Pmus curves of ASL 5000TM and the: VT, flow and pressure curves on the ventilator screen in an attempt to identify patterns associated to asynchrony that would be identified through simple observation. Results: There was a marked influence of respiratory mechanics on patient-ventilator asynchrony. The inspiratory delay time was higher and clinically significant in the obstructive profile of respiratory mechanics, and lower, many times âzeroâ, with the single limb ventilator. Cycling asynchrony was common in the obstructive profile, predominantly the late cycling type, while in the restrictive profile, the premature cycling type predominated. The use of Auto-TrakTM system eliminated the occurrence of auto triggering asynchrony type in the single limb ventilator. Visual analysis of the curves detected patterns of flow x time curves that are characteristic of premature and late cycling asynchrony types and which can be identified by direct visual inspection of the ventilator screen. Conclusion: Triggering and cycling asynchronies between the patient and the ventilator are the rule rather than the exception during PSV and PAV modes, which are influenced by respiratory mechanics. The use of Auto-TrakTM system showed benefit during the use of the single limb ventilator, with substantial improvement of the triggering. Visual inspection of the flow curve on the ventilator screen may favor the identification of these types of asynchrony.

High frequency oscillatory ventilation (HFOV) relies on low tidal volumes cycled at supraphysiologic rates, producing fundamentally different mechanisms for gas transport and exchange compared to conventional mechanical ventilation. Despite the appeal of using low tidal volumes to mitigate the risks of ventilator- induced lung injury (VILI), HFOV does not improve mortality in most clinical applications. One possible explanation for this is that HFOV distributes flows throughout the lung in a non-uniform and frequency-dependent manner, especially in the presence of mechanical heterogeneity. This thesis is a systematic investigation of the relationship between carbon dioxide elimination and frequency content during oscillatory ventilation, with emphasis on the frequency- dependent effects of mechanical heterogeneity and various gas transport mechanisms. A computational model consisting of an anatomically-structured airway network was used to simulate ventilation distribution and gas exchange in a canine lung. These simulations were validated against theoretical predictions and experimental data for eucapnic oscillatory ventilation. The model was also used to assess the impact of mechanical heterogeneity on ventilation distribution and gas transport. Simulations demonstrated a critical transition at the resonant frequency, above which the ventilation patterns became spatially clustered and frequency-dependent. Finally, the model demonstrated that pairs of oscillatory frequencies could yield eucapnic conditions with less potential for VILI compared to traditional single frequency HFOV. These results illustrate the importance of frequency selection in managing the distribution of ventilation and gas transport in the heterogeneous lung, and suggest that the frequency content in oscillatory waveforms may be optimized to achieve eucapnic gas exchange using less injurious ventilation. / 2017-10-27T00:00:00Z

Acute Respiratory Distress Syndrome (ARDS) is associated with lung inflammation and fluid filling, resulting in a stiffer lung with reduced intrapulmonary gas volume. ARDS patients are admitted to the Intensive Care Unit (ICU) and require Mechanical Ventilation (MV) for breathing support. Positive End Expiratory Pressure (PEEP) is applied to aid recovery by improving gas exchange and maintaining recruited lung volume. However, high PEEP risks further lung injury due to overstretching of healthy lung units, and low PEEP risks further lung injury due to the repetitive opening and closing of lung units. Thus, selecting PEEP is a balance between avoiding over-stretching and repetitive opening of alveoli. Furthermore, specific protocols to determine optimal PEEP do not currently exist, resulting in variable PEEP selection. Thus, ensuring an optimal PEEP would have significant impact on patient mortality, and the cost and duration of MV therapy. Two important metrics that can be used to aid MV therapy are the elastance of the lungs as a function of PEEP, and the quantity of recruited lung volume as a function of PEEP. This thesis describes several models and model-based methods that can be used to select optimal PEEP in the ICU. Firstly, a single compartment lung model is investigated for its ability to capture the respiratory mechanics of a mechanically ventilated ARDS patient. This model is then expanded upon, leading to a novel method of mapping and visualising dynamic respiratory system elastance. Considering how elastance changes, both within a breath and throughout the course of care, provides a new clinical perspective. Next, a model using only the expiratory portion of the breathing cycle is developed and presented, providing an alternative means to track changes in disease state throughout MV therapy. Finally, four model-based methods are compared based on their capability of estimating the quantity of recruited lung volume due to PEEP. The models and model-based methods described in this thesis enable rapid parameter identification from readily available clinical data, providing a means of tracking lung condition and selecting optimal patient-specific PEEP. Each model is validated using data from clinical ICU patients and/or experimental ARDS animal models.

Le principal objectif de ce travail est l’étude de l’influence de la pesanteur sur la mécanique respiratoire et le contrôle de la respiration, ainsi que sur les interactions cardio-respiratoires pendant les différents stades du sommeil. Le chapitre introductif présente le contexte général et les objectifs de la thèse. Des sections abordant le sommeil, la respiration, et l’interaction cardio-respiratoire y sont présentées, résumant l’état actuel des connaissances sur les effets de la pesanteur sur chacun de ces systèmes. Dans le deuxième chapitre, l’expérience “Sleep and Breathing in microgravity”, qui constitue la source des données à la base de ce travail, est présentée en détail. L’étude des signaux de longue durée requiert avant tout de disposer d’outils performants d’analyse des signaux. La première partie de la thèse présente en détail deux algorithmes : un algorithme de détection automatique d’événements respiratoires (inspiration / expiration) basé sur des réseaux neuronaux artificiels, et un algorithme de quantification de l’amplitude et de la phase de l’arythmie sinusale pendant le sommeil, utilisant la méthode des ondelettes. La validation de chaque algorithme est présentée, et leur performance évaluée. Cette partie inclut aussi des courtes introductions théoriques aux réseaux de neurones artificiels ainsi qu’aux méthodes d’analyse temps–fréquence (Fourier et ondelettes). Une approche similaire à celle utilisée pour la détection automatique d’événements respiratoires a été appliquée à la détection d’événements dans des signaux de vitesse du sang dans l’artère cérébrale moyenne, mesures obtenues par Doppler transcrânien. Ceci est le sujet de la thèse annexe. Ces deux algorithmes ont été appliqués aux données expérimentales pour extraire des informations physiologiques quant à l’impact de la pesanteur sur la mécanique respiratoire et l’interaction cardio-respiratoire. Ceci constitue la deuxième partie de la thèse. Un chapitre est consacré aux effets de l’apesanteur sur la mécanique respiratoire pendant le sommeil. Ce chapitre a mis en évidence, pour tous les stades de sommeil, une augmentation de la contribution abdominale en microgravité, suivi d’un retour progressif vers des valeurs observées avant le vol. L’augmentation initiale était attendue, mais l’adaptation progressive observée ne peut pas être expliquée par un effet purement mécanique, et nous suggère la présence d’un mécanisme d’adaptation central. Un deuxième chapitre présente les résultats comparant l’arythmie sinusale pendant le sommeil avant le vol, en apesanteur et après le retour sur terre. Le rythme cardiaque pendant le sommeil dans l’espace présente une moindre variabilité. Les différences NREM–REM observées sur terre pour les influences vagales et sympathiques sont accentuées dans l’espace. Aucun changement significatif n’est présent pour le gain et la différence de phase entre les les signaux cardiaque et respiratoire en comparant le sommeil sur terre et en apesanteur. La dissertation termine par une discussion générale du travail effectué, incluant les prin- cipales conclusions ainsi que les perspectives qui en découlent.

Inhalation of chemical substances can cause irritation to airways and in high doses acute airway injury. When mice are exposed to the alkylating nitrogen mustard analogue melphalan they develop an acute airway inflammation with a rapid influx of neutrophils to the lungs. The acute phase is followed by long-term respiratory complications characterized by bronchitis, lung fibrosis, and airway hyperreactivity.      In this thesis, a mouse model for chemical airway inflammation was established and the effects on the lungs in a time span from 6 hours up to 3 months were investigated in order to study both acute effects and possible chronic injury. We find that treatment with corticosteroids, e.g. dexamethasone, effectively blocks the inflammatory reaction in several ways: Neutrophil influx to the lungs is diminished, the expression of the proinflammatory cytokines interleukin (IL) -6 and IL-1b is decreased and edema formation as well as development of lung fibrosis is mitigated. In acute airway inflammation we show that the antioxidant vitamin E can be used as a possible complement to corticosteroids but not as a replacement since it causes insufficient downregulation of the inflammatory response. We show the importance of the T lymphocytes as they play a prominent role in the pathogenesis of long-term lung injuries caused by melphalan. Especially the minor gd T cell subset is of major importance orchestrating a number of responses including the acute cytokine and neutrophil response and late-phase lung fibrosis. In order to find the critical time for dexamethasone treatment, mice were exposed to melphalan, treated with dexamethasone at specific time points and lung physiology and airway reactivity was measured in anaesthetized, tracheostomized mice using a small animal ventilator. From these results we conclude that an early treatment, i.e. within one hour after exposure, with dexamethasone is needed to prevent chronic lung injury.  This thesis was undertaken with the main goal to better understand the pathogenesis of melphalan-induced airway inflammation. We believe that our findings have shed new light in this area of research and hope that this increased knowledge may be of future clinical use.

Diss. (sammanfattning) Linköping : Univ., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 4 uppsatser.

Thesis (Ph.D.) -- Virginia Commonwealth University, 2004. / Title from title-page of electronic thesis. Prepared for: Dept. of Physiology. Bibliography: p. 156-178.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 88-97).