Chest pain is one of the most common symptoms responsible for emergency department and primary care office visits in the United States. Chest pain can be noncardiac and may be attributed to multiple causes. Esophageal disorders including reflux, motility and functional conditions, affect a large proportion of patients with NCCP and lead to significant morbidity. The use of HRM has changed the diagnostic approach to esophageal motility disorders. It is the most specific and sensitive test for diagnosing motor disorders and a promising procedure in detecting dysmotility disorders in patients with NCCP. Despite the increased sensitivity of HRM, the main indications for esophageal manometry exclude NCCP. This study assessed the percentage of undiagnosed esophageal motility disorders in patients with NCCP referred for high resolution manometry. Differences in HRM findings in patients with NCCP versus patients meeting AGA recommendations for the clinical use of esophageal manometry were also compared. A retrospective descriptive design was utilized. Two hundred-nineteen patient charts were reviewed. One hundred sixty-eight (77%) patients underwent HRM and met AGA recommendations for esophageal manometry; 51 (23%) patients underwent the procedure after receiving a NCCP diagnosis. Findings showed that 116 (69%) patients in the AGA group had abnormal findings while 52 (31%) did not. In the NCCP group 34 (67%) had abnormal findings compared to 17 (33%) who did not. To compare normal and abnormal HRM findings in patients with NCCP versus those meeting AGA criteria, Chi-Square analysis was performed between the groups. The results were not statistically significant (p = 0.10). iv There were no significant differences in the results of HRM in both groups indicating the findings on HRM are the same despite the indication for the procedure. The findings support the use of HRM as a diagnostic tool in patients with chest pain after cardiac workup and endoscopic evaluation. This indicates a possible need to update the AGA indications for esophageal manometry and increase the awareness among healthcare providers regarding the use of HRM in patients with chest pain. Implication for future research is also discussed.

Aspiration of gastric content and delayed or failed intubation are the leading causes of anesthesia-related mortality and morbidity. In the recovery period, airway obstruction with subsequent hypoxia is a relatively common cause of morbidity, and is highly associated to the amount of opioids administered, especially in obese patients. The overall aim of this thesis was to study these risk factors for airway complications and postoperative hypoxia in obese patients, and to evaluate possible strategies for their prevention. In Study I, intubation times and incidence of failed intubation in obese patients were compared between direct laryngoscopy and videolaryngoscopy with the Stortz® C-MAC™. In Studies II and III, the effect of esmolol vs. remifentanil on the esophageal junction, and the possible analgesic properties of low-dose esmolol vs. placebo were evaluated using high-resolution manometry and the cold pressor test, respectively. Finally, in Study IV, the possible opioid-sparing effect of esmolol after laparoscopic gastric bypass surgery was evaluated. The use of videlaryngoscopy did not shorten intubation times, however appeared to reduce the incidence of failed intubation. Our results also show that esmolol has a favorable profile, compared to remifentanil, with regard to the protection against passive regurgitation and aspiration of gastric content. No analgesic effect of low-dose esmolol was however demonstrated. The intraoperative administration of esmolol instead of remifentanil also did not reduce the requirement of morphine for treatment of post-operative pain. The use of Stortz® C-MAC™ may be recommended for intubation of obese patients. Further studies are however required to clarify the possible role of esmolol in anesthesia.

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Contexte & Objectifs : La manométrie perfusée conventionnelle et la manométrie haute résolution (HRM) ont permis le développement d’une variété de paramètres pour mieux comprendre la motilité de l'œsophage et quantifier les caractéristiques de la jonction œsophago-gastrique (JOG). Cependant, l'anatomie de la JOG est complexe et les enregistrements de manométrie détectent à la fois la pression des structures intrinsèques et des structures extrinsèques à l'œsophage. Ces différents composants ont des rôles distincts au niveau de la JOG. Les pressions dominantes ainsi détectées au niveau de la JOG sont attribuables au sphincter œsophagien inférieur (SOI) et aux piliers du diaphragme (CD), mais aucune des technologies manométriques actuelles n’est capable de distinguer ces différents composants de la JOG. Lorsqu’on analyse les caractéristiques de la JOG au repos, celle ci se comporte avant tout comme une barrière antireflux. Les paramètres manométriques les plus couramment utilisés dans ce but sont la longueur de la JOG et le point d’inversion respiratoire (RIP), défini comme le lieu où le pic de la courbe de pression inspiratoire change de positif (dans l’abdomen) à négatif (dans le thorax), lors de la classique manœuvre de « pull-through ». Cependant, l'importance de ces mesures reste marginale comme en témoigne une récente prise de position de l’American Gastroenterology Association Institute (AGAI) (1) qui concluait que « le rôle actuel de la manométrie dans le reflux gastro-œsophagien (RGO) est d'exclure les troubles moteurs comme cause des symptômes présentés par la patient ». Lors de la déglutition, la mesure objective de la relaxation de la JOG est la pression de relaxation intégrée (IRP), qui permet de faire la distinction entre une relaxation normale et une relaxation anormale de la JOG. Toutefois, puisque la HRM utilise des pressions moyennes à chaque niveau de capteurs, certaines études de manométrie laissent suggérer qu’il existe une zone de haute pression persistante au niveau de la JOG même si un transit est mis en évidence en vidéofluoroscopie. Récemment, la manométrie haute résolution « 3D » (3D-HRM) a été développée (Given Imaging, Duluth, GA) avec le potentiel de simplifier l'évaluation de la morphologie et de la physiologie de la JOG. Le segment « 3D » de ce cathéter de HRM permet l'enregistrement de la pression à la fois de façon axiale et radiale tout en maintenant une position fixe de la sonde, et évitant ainsi la manœuvre de « pull-through ». Par conséquent, la 3D-HRM devrait permettre la mesure de paramètres importants de la JOG tels que sa longueur et le RIP. Les données extraites de l'enregistrement fait par 3D-HRM permettraient également de différencier les signaux de pression attribuables au SOI des éléments qui l’entourent. De plus, l’enregistrement des pressions de façon radiaire permettrait d’enregistrer la pression minimale de chaque niveau de capteurs et devrait corriger cette zone de haute pression parfois persistante lors la déglutition. Ainsi, les objectifs de ce travail étaient: 1) de décrire la morphologie de la JOG au repos en tant que barrière antireflux, en comparant les mesures effectuées avec la 3D-HRM en temps réel, par rapport à celle simulées lors d’une manœuvre de « pull-through » et de déterminer quelles sont les signatures des pressions attribuables au SOI et au diaphragme; 2) d’évaluer la relaxation de la JOG pendant la déglutition en testant l'hypothèse selon laquelle la 3D-HRM permet le développement d’un nouveau paradigme (appelé « 3D eSleeve ») pour le calcul de l’IRP, fondé sur l’utilisation de la pression radiale minimale à chaque niveau de capteur de pression le long de la JOG. Ce nouveau paradigme sera comparé à une étude de transit en vidéofluoroscopie pour évaluer le gradient de pression à travers la JOG. Méthodes : Nous avons utilisé un cathéter 3D-HRM, qui incorpore un segment dit « 3D » de 9 cm au sein d’un cathéter HRM par ailleurs standard. Le segment 3D est composé de 12 niveaux (espacés de 7.5mm) de 8 capteurs de pression disposés radialement, soit un total de 96 capteurs. Neuf volontaires ont été étudiés au repos, où des enregistrements ont été effectués en temps réel et pendant une manœuvre de « pull-through » du segment 3D (mobilisation successive du cathéter de 5 mm, pour que le segment 3D se déplace le long de la JOG). Les mesures de la longueur du SOI et la détermination du RIP ont été réalisées. La longueur de la JOG a été mesurée lors du « pull-through » en utilisant 4 capteurs du segment 3D dispersés radialement et les marges de la JOG ont été définies par une augmentation de la pression de 2 mmHg par rapport à la pression gastrique ou de l’œsophage. Pour le calcul en temps réel, les limites distale et proximale de la JOG ont été définies par une augmentation de pression circonférentielle de 2 mmHg par rapport à la pression de l'estomac. Le RIP a été déterminée, A) dans le mode de tracé conventionnel avec la méthode du « pull-through » [le RIP est la valeur moyenne de 4 mesures] et B) en position fixe, dans le mode de représentation topographique de la pression de l’œsophage, en utilisant l’outil logiciel pour déterminer le point d'inversion de la pression (PIP). Pour l'étude de la relaxation de la JOG lors de la déglutition, 25 volontaires ont été étudiés et ont subi 3 études de manométrie (10 déglutitions de 5ml d’eau) en position couchée avec un cathéter HRM standard et un cathéter 3D-HRM. Avec la 3D-HRM, l’analyse a été effectuée une fois avec le segment 3D et une fois avec une partie non 3D du cathéter (capteurs standard de HRM). Ainsi, pour chaque individu, l'IRP a été calculée de quatre façons: 1) avec la méthode conventionnelle en utilisant le cathéter HRM standard, 2) avec la méthode conventionnelle en utilisant le segment standard du cathéter 3D-HRM, 3) avec la méthode conventionnelle en utilisant le segment « 3D » du cathéter 3D-HRM, et 4) avec le nouveau paradigme (3D eSleeve) qui recueille la pression minimale de chaque niveau de capteurs (segment 3D). Quatorze autres sujets ont subi une vidéofluoroscopie simultanée à l’étude de manométrie avec le cathéter 3D-HRM. Les données de pression ont été exportés vers MATLAB ™ et quatre pressions ont été mesurées simultanément : 1) la pression du corps de l’œsophage, 2cm au-dessus de la JOG, 2) la pression intragastrique, 3) la pression radiale moyenne de la JOG (pression du eSleeve) et 4) la pression de la JOG en utilisant la pression minimale de chaque niveau de capteurs (pression du 3D eSleeve). Ces données ont permis de déterminer le temps permissif d'écoulement du bolus (FPT), caractérisé par la période au cours de laquelle un gradient de pression existe à travers la JOG (pression œsophagienne > pression de relaxation de la JOG > pression gastrique). La présence ou l'absence du bolus en vidéofluoroscopie et le FPT ont été codés avec des valeurs dichotomiques pour chaque période de 0,1 s. Nous avons alors calculé la sensibilité et la spécificité correspondant à la valeur du FPT pour la pression du eSleeve et pour la pression du 3D eSleeve, avec la vidéofluoroscopie pour référence. Résultats : Les enregistrements avec la 3D-HRM laissent suggérer que la longueur du sphincter évaluée avec la méthode du « pull-through » était grandement exagéré en incorporant dans la mesure du SOI les signaux de pression extrinsèques à l’œsophage, asymétriques et attribuables aux piliers du diaphragme et aux structures vasculaires. L’enregistrement en temps réel a permis de constater que les principaux constituants de la pression de la JOG au repos étaient attribuables au diaphragme. L’IRP calculé avec le nouveau paradigme 3D eSleeve était significativement inférieur à tous les autres calculs d'IRP avec une limite supérieure de la normale de 12 mmHg contre 17 mmHg pour l’IRP calculé avec la HRM standard. La sensibilité (0,78) et la spécificité (0,88) du 3D eSleeve étaient meilleurs que le eSleeve standard (0,55 et 0,85 respectivement) pour prédire le FPT par rapport à la vidéofluoroscopie. Discussion et conclusion : Nos observations suggèrent que la 3D-HRM permet l'enregistrement en temps réel des attributs de la JOG, facilitant l'analyse des constituants responsables de sa fonction au repos en tant que barrière antireflux. La résolution spatiale axiale et radiale du segment « 3D » pourrait permettre de poursuivre cette étude pour quantifier les signaux de pression de la JOG attribuable au SOI et aux structures extrinsèques (diaphragme et artéfacts vasculaires). Ces attributs du cathéter 3D-HRM suggèrent qu'il s'agit d'un nouvel outil prometteur pour l'étude de la physiopathologie du RGO. Au cours de la déglutition, nous avons évalué la faisabilité d’améliorer la mesure de l’IRP en utilisant ce nouveau cathéter de manométrie 3D avec un nouveau paradigme (3D eSleeve) basé sur l’utilisation de la pression radiale minimale à chaque niveau de capteurs de pression. Nos résultats suggèrent que cette approche est plus précise que celle de la manométrie haute résolution standard. La 3D-HRM devrait certainement améliorer la précision des mesures de relaxation de la JOG et cela devrait avoir un impact sur la recherche pour modéliser la JOG au cours de la déglutition et dans le RGO. / Background & Aims: Conventional water-perfused manometry and high resolution manometry permitted the development of a variety of manometric methodologies and metrics to understand the motility of the esophagus and to quantify esophagogastric junction (EGJ) characteristics. However, the anatomy in the area of the EGJ is complex and intraluminal manometry recordings detect pressure signals referable both to intrinsic esophageal structures and to adjacent extrinsic structures impinging on the esophagus. Both have distinct sphincteric mechanisms within the EGJ. The dominant pressure signals detected near the EGJ are attributable to the lower esophageal sphincter (LES) and the crural diaphragm (CD). However, neither of these technologies were able to distinguish between the different components of the EGJ. When analyzing EGJ characteristics as a reflection of its competence against reflux, the more widely used manometric parameters are the EGJ length and the respiratory inversion point (RIP), defined as the location at which inspiratory pressure deflections change from positive (abdomen) to negative (chest). However, the significance of these metrics has not gained wide acceptance in the gastroenterology community as evident in a recent American Gastroenterology Association Institute (AGAI) Position Statement (1) concluding that ‘The current role of manometry in gastroesophageal reflux disease (GERD) is to exclude motor disorders as a cause of the continued symptoms’. During deglutition, the objective quantitative measurement of EGJ relaxation, the integrative relaxation pressure (IRP), permits one to distinguish between normal and abnormal EGJ relaxation. However, comparison between spatial pressure variation plots and relaxation pressures derived from circumferentially averaged pressures suggest a persistent high pressure at the hiatal center during a period that flow is known to be occurring whereas this was not seen using nadir radial pressure data. Recently, a 3D-high resolution manometry (3D-HRM) assembly (Given Imaging, Duluth, GA) has been developed with the potential to simplify the assessment of EGJ pressure morphology and physiology. The 3D segment of the array permits high resolution recording both axially and radially while maintaining a stationary sensor position. Consequently, 3D-HRM should allow for the measurement of important EGJ parameters such as length and RIP. Data extracted from the 3D-HRM recording may also allow differentiating pressure signals within the EGJ attributable to the intrinsic sphincter and to the surrounding elements. Moreover, 3D-HRM preserves the individual pressure values of each radially dispersed sensor within the array, permitting one to overcome the apparent persistent high pressure during the deglutitive relaxation. Thus, the aims of this work were 1) to describe the EGJ pressure morphology at rest, comparing measures made with real time 3D-HRM to simulations of a conventional pull-through protocol and to define the pressure signatures attributable to the diaphragmatic and LES pressure components within the 3D-HRM recording; 2) to assess deglutitive EGJ relaxation by testing the hypothesis that the 3D-HRM array using an analysis paradigm based on finding the minimal radial pressure at each axial level (3D-eSleeve) should provide a representation of the luminal pressure gradient across the EGJ that is more relevant to predicting periods of trans-sphincteric flow using barium transit on fluoroscopy as the comparator. We also sought to adapt the IRP metric to the 3D-HRM array using the 3D-eSleeve principle (3D-IRP) and compare normative values obtained with this new paradigm to standard IRP calculations. Methods: Patients were studied with a 3D-HRM assembly. The 3D-HRM assembly incorporated a 9 cm 3D-HRM segment into an otherwise standard HRM assembly; the 3D segment was comprised of 12 rings of 8 radially dispersed independent pressure sensors, spaced 7.5mm apart. At rest, 9 volunteers were studied and recordings were done during a station pull-through of the 3D-HRM segment withdrawing it across the EGJ at 5 mm increments with each position held for 30s (sufficient to capture several respiratory cycles). Conventional measures of ‘LES length’ were made using 4 radially dispersed sensors within the 3D-HRM array, defining the margins of the sphincter by a 2 mmHg pressure increase relative to gastric or esophageal pressure. In the 3D-HRM, the proximal and distal limits of the EGJ were defined as the axial locations first detecting a 360° circumferential pressure increase of 2 mmHg relative to the stomach. RIP was determined, A) in the tracing mode: using the pull-through of 4 single sensors spaced 7.5 mm apart [RIP is the average value of 4 radially dispersed sensors] and B) in a stationary position using the software pressure inversion point (PIP) tool. In the esophageal pressure topography (EPT) mode, the tracing changed progressively from a thoracic pattern to an abdominal pattern, and the RIP was localized within the inversion zone with the PIP tool tracing. For the study of the EGJ deglutitive relaxation, 25 volunteers underwent 3 consecutive 10-swallows protocols of 5 ml of water in the supine position with both the standard (once) and 3D-HRM (twice) devices in random sequence. During the 3D-HRM studies, the EGJ was measured once with the 3D-sleeve segment and once with a proximal (non-3D sleeve portion) of the device incorporating standard HRM sensors. For each subject, the IRP was calculated in four ways: 1) conventional method with the standard HRM device, 2) conventional method with a standard HRM segment of the 3D-HRM device, 3) conventional method using the 3D-HRM sleeve segment, and 4) a novel 3D-HRM eSleeve paradigm (3D-IRP) localizing the radial pressure minimum at each locus along the eSleeve. Fourteen additional subjects then underwent synchronized simultaneous videofluoroscopy and 3D-HRM (including two 5-ml barium swallows). Pressure data were exported to MATLAB™ and four pressures were measured simultaneously: 1) esophageal body pressure 2cm above EGJ, 2) intragastric pressure, 3) radially average eSleeve pressure and 4) 3D-eSleeve pressure. Data were plotted to determine the flow permissive time (FPT) characterized as periods during which a pressure gradient through the EGJ is present (esophageal pressure > EGJ relaxation pressure (radial average or 3D-eSleeve paradigm) > gastric pressure). FPT was calculated during a 10s time window after upper sphincter relaxation. The presence or absence of bolus transit or FPT was coded with dichotomous values for each 0.1 s. We calculated the corresponding sensitivity and specificity for both radial average and 3D-eSleeve analyses of FPT with bolus transit evident on fluoroscopy being the reference. Results: 3D-HRM recordings suggested that sphincter length assessed by a pull-through method greatly exaggerated the estimate of LES length by failing to discriminate among circumferential contractile pressure and asymmetric extrinsic pressure signals attributable to diaphragmatic and vascular structures. Real-time 3D EGJ recordings found that the dominant constituents of EGJ pressure at rest were attributable to the diaphragm. The 3D-IRP was significantly less than all other calculations of IRP with the upper limit of normal being 12 mmHg vs. 17 mmHg for the standard IRP. The sensitivity (0.78) and the specificity (0.88) of the 3D-eSleeve were also better than the standard eSleeve (0.55 and 0.85, respectively) for predicting flow permissive time verified fluoroscopically. Discussion & Conclusion: Our observations suggest that the 3D-HRM permits real-time recording of EGJ pressure morphology facilitating analysis of the EGJ constituents responsible for its function as a reflux barrier at rest. The axial and radial spatial resolution of the 9 cm 3D-HRM segment may permit further studies to differentiate pressure signals within the EGJ attributable to the LES and to extrinsic structures (diaphragm and vascular artifacts). These attributes of the 3D-HRM device suggest it to be a promising new tool in the study of GERD pathophysiology. During deglutition, we evaluated the feasibility of improving the measurement of IRP utilizing a novel 3D-HRM assembly and a novel 3D-eSleeve concept based on finding the axial maximum of the radial minimum pressures at each sensor ring along the sleeve segment. Our findings suggest that this approach is more accurate than standard HRM and other methods that utilize a radially averaged pressure within the EGJ. Although we can only speculate on how much this will improve clinical management, 3D-HRM will certainly improve the accuracy of EGJ relaxation measurements and this will certainly impact research endeavors focused on modeling EGJ function during swallowing and reflux.

The aim of this thesis is to present a complex information about the etiology, diagnosis and treatment of gastroesophageal reflux disease (GERD) and to further elucidate the function of the diaphragm as the external esophageal sphincter and as a part of the antireflux barrier in patients with GERD. The study included 87 patients with verified GERD. Patients were subjected to a set of postural and respiratory maneuvers - caudal position of chest, abdominal breathing and measuring of the maximal respiratory pressures, all performed on the basis of tolerance to position and maneuver. The high-resolution manometry (HRM) was chosen to record the changes in pressure in the lower esophageal sphincter and for the measurement of respiratory pressures was used the spirometric system MasterScope. It was found that postural and respiratory maneuvers, that activate the diaphragm, increase the pressure in the EGJ. The most significant increase occurred during the maximal inspiratory maneuver, which increased LES pressure up to 261.2 %. The results also show that patients with GERD have reduced the strength of respiratory muscles, especially inspirational muscles. Reaching only 66.5 % of predicted PImax. We have demonstrated that patients with GERD have significantly lower diaphragm muscle strength, what...

Introduction The main aim of this study is to present a complex review comprising etiological factors, diagnostic options and therapeutic methods related to globus pharyngeus, a persistent or intermittent sensation of a lump or foreign body in the throat. The second purpose is to investigate the reciprocal relationship between motor control with musculoskeletal system and pressure changes in the esophagus, especially in the upper esophageal sphincter. Methods 37 patients participated in the study. 24 of them suffered globus pharyngeus and 13 were patients with GERD but without the symptoms of globus pharyngeus. Because of the complex physiology of esophageal function and the inability of conventional manometry to fully describe this complexity, we found High-Resolution Manometry as a useful device for accomlishing the referred task. Patients were examined in four different postural situations which had to be modified when the attitude wasn't tolerated. The examination was followed by manual physiotherapy and exercises targeted to influence postural alignment. 10 patients with globus pharyngeus who agreed with a control manometry examination were familiarized with the results as a form of biofeedback. Results On the basis of the results of this research, it can be concluded that a high pressure...

Multiorgan dysfunction syndrom is the major driving pathophysiological mechanism of morbidity and mortality in critically ill patients. Gastrointestinal dysfunction usually develops as a result critical illness and it is believed to play a key role in the development and progression of multiple organ dysfunction. Moreover, any primary disorder of the gastrointestinal tract, if severe enough, can lead to a critical state and secondary multiorgan dyfunction. Despite intensive experimental and clinical research, reliable tools for monitoring and evaluation of the severity of gastrointestinal dysfunction remain unknown. In the same line, therapy of this complex pathology remains largely supportive. The aim of this thesis was first to explain the severity of the most common and most serious nosocomial infection of the digestive tract, second to elucidate the safety and effectiveness of the endoscopic dual enteral probe insertion in ventilated critically ill patients, and, third to evaluate new diagnostic tools of the gastrointestinal dysfunction. Finally, we present an ongoing project aimed at investigating esophageal dysfunction in mechanically ventilated critically ill patients.

Multiorgan dysfunction syndrom is the major driving pathophysiological mechanism of morbidity and mortality in critically ill patients. Gastrointestinal dysfunction usually develops as a result critical illness and it is believed to play a key role in the development and progression of multiple organ dysfunction. Moreover, any primary disorder of the gastrointestinal tract, if severe enough, can lead to a critical state and secondary multiorgan dyfunction. Despite intensive experimental and clinical research, reliable tools for monitoring and evaluation of the severity of gastrointestinal dysfunction remain unknown. In the same line, therapy of this complex pathology remains largely supportive. The aim of this thesis was first to explain the severity of the most common and most serious nosocomial infection of the digestive tract, second to elucidate the safety and effectiveness of the endoscopic dual enteral probe insertion in ventilated critically ill patients, and, third to evaluate new diagnostic tools of the gastrointestinal dysfunction. Finally, we present an ongoing project aimed at investigating esophageal dysfunction in mechanically ventilated critically ill patients.