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Background: Patients with chronic neck pain have a number of factors that could constitute a predisposition for respiratory dysfunction. However, the existing evidence is limited and not well established, and many questions such as the association of neck pain deficits with respiratory function remain unanswered. Thus, the aim of this study was to investigate whether patients with chronic neck have accompanying respiratory dysfunction and which are the neck pain deficits which principally predispose to these respiratory disturbances.Methods: In this case-control observational study, 45 patients with chronic idiopathic neck pain (>6 months, at least once per week) and 45 healthy age-, gender-, height- and weight-matched controls were voluntarily recruited. A third group of 10 patients with chronic non-spinal musculoskeletal pain was also used, but only for future reference. Participants' neck muscle strength and endurance were measured by an isometric neck dynamometer and craniocervical flexion test respectively. Range of movement was assessed by using an ultrasound-based motion analysis system. Forward head posture was assessed by obtaining lateral photographs and calculating the craniovertebral angle. Disability and neck pain intensity were assessed through the Neck Disability Index and Visual Analogue Scale. Psychological assessment was performed by using the Hospital Anxiety and Depression Scale, the Pain Catastrophizing Scale and the Tampa Scale for Kinesiophobia. Spirometry was used for assessing pulmonary volumes, flows and maximal voluntary ventilation. Respiratory muscle strength was assessed by using a mouth pressure meter. Finally, PaCO2 was assessed by using transcutaneous blood gas monitoring.Results: Patients with chronic neck pain were found to have weaker respiratory muscles than healthy controls (p<0.05). Their pulmonary volumes and maximal voluntary ventilation were also found to be reduced (p<0.05). Their mean respiratory flows were found to be unaffected (p>0.05), whereas their peak flows were reduced (p<0.05). Their partial pressure of carbon dioxide was also found to be affected (p<0.05), revealing existence of hypocapnia (PaCO2<35mmHg). The neck pain deficits that were found to be mostly correlated with these respiratory parameters were the neck muscle strength, neck muscle endurance, kinesiophobia, catastrophizing and pain intensity (r>0.3, p<0.05). Finally, the regression models revealed that neck pain deficits and especially neck muscle strength can provide a quite generalizable accurate estimation of this respiratory dysfunction (R2=0.28-0.52).Conclusions: Patients with chronic neck pain present dysfunction of their respiratory system which can be mainly manifested as respiratory weakness and/or hypocapnia. Pain intensity, neck muscle weakness, fatigue and kinesiophobia seem to be the most important deficits predisposing to this respiratory dysfunction. The understanding of this dysfunction could have a great impact on various clinical aspects notably patient assessment, rehabilitation and drug prescription. However, further research is suggested mainly directed towards optimizing treatment protocols and developing classification systems improving clinical reasoning.

A hypothetical causal link between ventilatory regulation of carbon dioxide anddevelopment of syncope during orthostatic challenges is reduction in arterial partialpressure of carbon dioxide and resultant reduction in cerebral blood flow. We performedtwo experiments to investigate the ventilatory sensitivity to carbon dioxide and factorsaffecting cerebral autoregulation (CA). We also studied the nonlinear phase couplingbetween cardio-respiratory parameters before syncope.For experiment one, in 30 healthy adults, we stimulated chemo and baro reflexesby breathing either room-air or room-air with 5 percent carbon dioxide in a pseudorandom binary sequence during supine and 70 degree head up tilt (HUT). Six subjectsdeveloped presyncope during tilt.To determine whether changes in ventilatory control contribute to the observeddecrease in PaCO2 during HUT, we assessed ventilatory dynamic sensitivity to changesin PaCO2 during supine and 70 degrees HUT. The sensitivity of the ventilatory controlsystem to perturbations in end tidal carbon dioxide increased during tilt.To investigate nonlinear phase coupling between cardio-respiratory parametersbefore syncope, bispectra were estimated and compared between presyncopal andnon-presyncopal subjects. Our results indicate that preceding presyncope, nonlinearphase coupling is altered by perturbations to baro and chemo reflexes.To investigate the effects of gender in CA, we selected 10 men and 10age-matched women and used spectral analysis to compare differences in CA betweenmen and women. Our results showed that gender-related differences in CA did exist andgender may need to be considered as a factor in investigating CA.To investigate the influence of induced hypocapnia on CA in absence ofventilatory variability, we performed experiment two in which subjects were randomlyassigned to a Control (under normocapnia) or Treatment (under hypocapnia) group. Bothgroups voluntarily controlled their breathing pattern yet two groups breathed in air withdifferent levels of carbon dioxide. Our results show that changes in mean blood pressureat middle cerebral artery level were less transferred into mean cerebral blood flow in theTreatment group than in the Control group, suggesting better CA under hypocapniarelative to under normocapnia.

Etablir le diagnostic d'une réaction d'hypersensibilité aiguë (RHA) peropératoire est difficile du fait de l'incidence supérieure des diagnostiques différentiels. Les facteurs de risques en sont mal établis. Il n'existe pas de signe clinique fiable aidant à un diagnostic rapide. Alors que 25% des explorations immunologiques classiques ne mettent pas en évidence un mécanisme IgE-médié, des études animales et humaines suggèrent un rôle des IgG dans ces RHA non caractérisées. Ce travail s'est basé sur deux cohortes de patients : la première pour étudier des phénotypes en lien avec l'apparition d'un bronchospasme, la seconde pour analyser des marqueurs diagnostiques au bloc opératoire et explorer un mécanisme alternatif impliquant les IgG. La survenue d'un bronchospasme au cours d'une RHA peropératoire n'est pas associée à un antécédent d'asthme mais au curare comme agent étiologique. La mise en évidence de la valeur diagnostique d'une hypocapnie inférieure à 20 mmHg dans le caractère sévère de la RHA devrait aider les cliniciens à l'établissement rapide du diagnostic. La présence d'IgG spécifiques anti-curares était associée à la survenue d'une RHA sévère suggérant une participation des IgG à la gravité de la RHA en association avec les IgE. En fonction du curare administré, le mécanisme de la RHA semble différent : implication d'anticorps (IgE et/ou IgG) dans 90% pour succinylcholine et rocuronium mais uniquement 50% pour atracurium suggérant une importante contribution de l'histamino-libération dans ces réactions. L'ensemble de ces travaux devraient permettre d'améliorer les performances diagnostiques en temps réel et à distance lors de la survenue d'une RHA peropératoire. / Diagnosis of intra-anesthetic acute hypersensitivity reactions (AHR) is challenging because of elevated incidences of differential diagnoses. Risk factors remain mostly unknown and there is no reliable clinical sign to help physicians in establishing a rapid diagnosis. In 25% of cases, immunologic exploration cannot identify the culprit agent through the exploration of the IgE-mediated pathway. Several animal and human studies suggest a role of IgG in the physiopathology of anaphylaxis, which could explain these uncharacterized AHR. This PhD has focused on two cohorts of patients: the first cohort allowed the exploration of phenotypic links in relation to bronchospasm occurrence; the second cohort analyzed clinical markers of severe AHR and the alternative pathway involving IgG against neuromuscular blocking agents (NMBA). Analysis of risk factors identified a NMBA as the culprit agent of the intra-anesthetic AHR to be the only factor statistically associated with bronchospasm. We propose that a hypocapnia below 20 mmHg may be a novel and useful tool for physicians for the rapid diagnosis of severe intra-anesthetic AHR. Among the second cohort of patients, NMBA-specific IgG were identified and associated with clinical severity, suggesting that they may participate in the severity of NMBA-AHR in association with IgE. The chemical structure of a given NMBA may dictate the mechanism of anaphylaxis to this particular NMBA: an IgE/IgG-pathway for succinylcholine and rocuronium, whereas atracurium may be rather linked to spontaneous histamine release mechanisms. Altogether, our results might improve diagnosis efficacy at the time of the AHR and during immunologic explorations.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23755号 / 医博第4801号 / 新制||医||1056(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 川上 浩司, 教授 小濱 和貴, 教授 平井 豊博 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Introdução: A ventilação manual é um aspecto chave que determina a eficiência da ressuscitação neonatal e pode ser realizada por várias categorias de profissionais utilizando diferentes equipamentos. Objetivos: Comparar os efeitos da ventilação manual realizada por diferentes profissionais envolvidos na assistência neonatal, médicos, enfermeiros e fisioterapeutas, utilizando dois equipamentos: Peça T e balão autoinflável. Métodos: Coelhos adultos foram submetidos à ventilação manual utilizando Peça T ou balão autoinflável, 10 minutos com cada dispositivo, operado por médicos, fisioterapeutas e enfermeiros, num total de 21 indivíduos. A escolha do primeiro dispositivo utilizado por cada voluntário foi realizada por randomização. Os dados de mecânica respiratória (volume corrente, volume minuto, frequência respiratória, tempos inspiratório e expiratório, pressão inspiratória e pressão expiratória final positiva) foram obtidos de maneira contínua através de um sistema informatizado de aquisição de dados, cega para os operadores. Amostras de sangue arterial foram obtidas por cateterização da carótida antes e depois de cada ventilação manual para determinação da PaCO2 e do pH. Foram comparados os dispositivos entre si, assim como o desempenho dos grupos de profissionais com cada dispositivo. Resultados: Quando analisados todos os profissionais em conjunto (n = 21) os animais ventilados com o balão autoinflável apresentaram maior volume minuto, menor frequência respiratória, menor tempo inspiratório e maiores valores de pH após o período de 10 minutos de ventilação. Quando analisados separadamente cada um dos três grupos de profissionais, os animais ventilados com o balão autoinflável no grupo Enfermeiras (n = 7) apresentaram maior volume minuto (390±108 vs 766±410 mL/min, p < 0,05) em relação ao grupo Fisioterapeutas (n = 7) (418±192 vs 886±787 mL/min) e grupo Médicos (n = 7) (438±206 vs 705±434 mL/min). Resultados similares foram encontrados em relação ao pH após 10 minutos de ventilação manual, sendo observada no grupo Enfermeiras a ocorrência de alcalose respiratória (7,40±0,11 vs 7,61±0,02, p < 0,05, 7,37±0,10 vs 7,52±0,23, 7,36±0,07 vs 7,40±0,18 mL/min, respectivamente) e de hipocapnia (32,4±6,9 vs 23,4±7,5 mmHg, p < 0,05; 40,4±10,8 vs 28,0±15,2 mmHg, 38,0±13,8 vs 42,6±18,1 mmHg) respectivamente. Conclusão: O balão autoinflável resultou em hipocapnia e alcalose respiratória no grupo Enfermeiras, a ventilação manual utilizando a Peça T resultou em menor volume corrente e menor volume minuto / Introduction: Manual ventilation is a key aspect that determines the efficiency of neonatal resuscitation and can be performed by several categories of professionals using different equipment. Objectives: To compare the effects of manual ventilation performed by different professionals involved in neonatal care, physicians, nurses and physiotherapists, using two devices: T-piece and self-inflating bag. Methods: Adult rabbits were submitted to manual ventilation using T-piece or self-inflating bag, 10 minutes with each device, operated by physicians, physiotherapists and nurses, in a total of 21 individuals. The choice of the first device used by each volunteer was by randomization. Respiratory mechanics data (tidal volume, minute volume, respiratory rate, inspiratory and expiratory time, inspiratory pressure and positive end expiratory pressure) were obtained continuously through a computerized data acquisition system, blind to operators. Arterial blood gas samples were obtained through carotid catheterization before and after each manual ventilation for determination of PaCO2 and pH. The devices were compared to each other as well as the performance of groups of professionals with each device. Results: When all the professionals (n = 21) were analyzed together, the animals ventilated with the self-inflating bag presented higher minute volume, lower respiratory rate, shorter inspiratory time and higher pH values after 10 minutes of ventilation. When the three groups of professionals were analyzed separately, the animals ventilated with the self-inflating bag in the Nurse group (n = 7) had a higher minute volume (390±108 vs 766±410 mL/min, p < 0.05) compared to the Physiotherapists group (n = 7) (418±192 vs 886±787 mL/min) and the Physicians group (n = 7) (438±206 vs. 705±434 mL/min). Similar results were found in relation to pH after 10 minutes of manual ventilation, with the occurrence in the Nurses group of respiratory alkalosis (7.40±0.11 vs 7.61±0.02, p < 0.05, 7.37±0.10 vs 7.52±0.23, 7.36±0.07 vs 7.40±0.18 mL/min, respectively) and hypocapnia (32.4±6.9 vs 23.4±7.5 mmHg, p < 0.05; 40.4±10.8 vs 28.0 ± 15.2 mmHg, 38.0±13.8 vs. 42.6±18.1 mmHg) respectively. Conclusion: The self-inflating bag resulted in hypocapnia and respiratory alkalosis in the Nurses group, manual ventilation using T-piece resulted in lower tidal volume and minute volume

Introdução: A ventilação manual é um aspecto chave que determina a eficiência da ressuscitação neonatal e pode ser realizada por várias categorias de profissionais utilizando diferentes equipamentos. Objetivos: Comparar os efeitos da ventilação manual realizada por diferentes profissionais envolvidos na assistência neonatal, médicos, enfermeiros e fisioterapeutas, utilizando dois equipamentos: Peça T e balão autoinflável. Métodos: Coelhos adultos foram submetidos à ventilação manual utilizando Peça T ou balão autoinflável, 10 minutos com cada dispositivo, operado por médicos, fisioterapeutas e enfermeiros, num total de 21 indivíduos. A escolha do primeiro dispositivo utilizado por cada voluntário foi realizada por randomização. Os dados de mecânica respiratória (volume corrente, volume minuto, frequência respiratória, tempos inspiratório e expiratório, pressão inspiratória e pressão expiratória final positiva) foram obtidos de maneira contínua através de um sistema informatizado de aquisição de dados, cega para os operadores. Amostras de sangue arterial foram obtidas por cateterização da carótida antes e depois de cada ventilação manual para determinação da PaCO2 e do pH. Foram comparados os dispositivos entre si, assim como o desempenho dos grupos de profissionais com cada dispositivo. Resultados: Quando analisados todos os profissionais em conjunto (n = 21) os animais ventilados com o balão autoinflável apresentaram maior volume minuto, menor frequência respiratória, menor tempo inspiratório e maiores valores de pH após o período de 10 minutos de ventilação. Quando analisados separadamente cada um dos três grupos de profissionais, os animais ventilados com o balão autoinflável no grupo Enfermeiras (n = 7) apresentaram maior volume minuto (390±108 vs 766±410 mL/min, p < 0,05) em relação ao grupo Fisioterapeutas (n = 7) (418±192 vs 886±787 mL/min) e grupo Médicos (n = 7) (438±206 vs 705±434 mL/min). Resultados similares foram encontrados em relação ao pH após 10 minutos de ventilação manual, sendo observada no grupo Enfermeiras a ocorrência de alcalose respiratória (7,40±0,11 vs 7,61±0,02, p < 0,05, 7,37±0,10 vs 7,52±0,23, 7,36±0,07 vs 7,40±0,18 mL/min, respectivamente) e de hipocapnia (32,4±6,9 vs 23,4±7,5 mmHg, p < 0,05; 40,4±10,8 vs 28,0±15,2 mmHg, 38,0±13,8 vs 42,6±18,1 mmHg) respectivamente. Conclusão: O balão autoinflável resultou em hipocapnia e alcalose respiratória no grupo Enfermeiras, a ventilação manual utilizando a Peça T resultou em menor volume corrente e menor volume minuto / Introduction: Manual ventilation is a key aspect that determines the efficiency of neonatal resuscitation and can be performed by several categories of professionals using different equipment. Objectives: To compare the effects of manual ventilation performed by different professionals involved in neonatal care, physicians, nurses and physiotherapists, using two devices: T-piece and self-inflating bag. Methods: Adult rabbits were submitted to manual ventilation using T-piece or self-inflating bag, 10 minutes with each device, operated by physicians, physiotherapists and nurses, in a total of 21 individuals. The choice of the first device used by each volunteer was by randomization. Respiratory mechanics data (tidal volume, minute volume, respiratory rate, inspiratory and expiratory time, inspiratory pressure and positive end expiratory pressure) were obtained continuously through a computerized data acquisition system, blind to operators. Arterial blood gas samples were obtained through carotid catheterization before and after each manual ventilation for determination of PaCO2 and pH. The devices were compared to each other as well as the performance of groups of professionals with each device. Results: When all the professionals (n = 21) were analyzed together, the animals ventilated with the self-inflating bag presented higher minute volume, lower respiratory rate, shorter inspiratory time and higher pH values after 10 minutes of ventilation. When the three groups of professionals were analyzed separately, the animals ventilated with the self-inflating bag in the Nurse group (n = 7) had a higher minute volume (390±108 vs 766±410 mL/min, p < 0.05) compared to the Physiotherapists group (n = 7) (418±192 vs 886±787 mL/min) and the Physicians group (n = 7) (438±206 vs. 705±434 mL/min). Similar results were found in relation to pH after 10 minutes of manual ventilation, with the occurrence in the Nurses group of respiratory alkalosis (7.40±0.11 vs 7.61±0.02, p < 0.05, 7.37±0.10 vs 7.52±0.23, 7.36±0.07 vs 7.40±0.18 mL/min, respectively) and hypocapnia (32.4±6.9 vs 23.4±7.5 mmHg, p < 0.05; 40.4±10.8 vs 28.0 ± 15.2 mmHg, 38.0±13.8 vs. 42.6±18.1 mmHg) respectively. Conclusion: The self-inflating bag resulted in hypocapnia and respiratory alkalosis in the Nurses group, manual ventilation using T-piece resulted in lower tidal volume and minute volume

Cerebral autoregulation is an intrinsic physiological response that maintains a constant cerebral blood flow (CBF) despite dynamic changes in the systemic blood pressure. Autoregulation is achieved through changes in the resistance of the small blood vessels in the brain through reflexive vasodilatation and vasoconstriction. Cerebrovascular reactivity (CVR) is a measure of this response. CVR is defined as a change in CBF in response to a given vasodilatory stimulus. CVR therefore potentially reflects the vasodilatory reserve capacity of the cerebral vasculature to maintain a constant cerebral blood flow. A decrease in CVR (which is interpreted as a reduction in the vasodilatory reserve capacity) in the vascular territory downstream of a larger stenosed supply artery correlates strongly with the risk of a hemodynamic stroke. As a result, the use of CVR studies to evaluate the state of the cerebral autoregulatory capacity has clinical utility. Application of CVR studies in the clinical scenario depends on a thorough understanding of the normal response. The goal of this thesis therefore was to map CVR throughout the brain in normal healthy individuals using Blood Oxygen Level Dependant functional Magnetic Resonance Imaging (BOLD MRI) as an index to CBF and precisely controlled changes in end-tidal partial pressure of carbon dioxide (PETCO2) as the global flow stimulus.

Cerebral autoregulation is an intrinsic physiological response that maintains a constant cerebral blood flow (CBF) despite dynamic changes in the systemic blood pressure. Autoregulation is achieved through changes in the resistance of the small blood vessels in the brain through reflexive vasodilatation and vasoconstriction. Cerebrovascular reactivity (CVR) is a measure of this response. CVR is defined as a change in CBF in response to a given vasodilatory stimulus. CVR therefore potentially reflects the vasodilatory reserve capacity of the cerebral vasculature to maintain a constant cerebral blood flow. A decrease in CVR (which is interpreted as a reduction in the vasodilatory reserve capacity) in the vascular territory downstream of a larger stenosed supply artery correlates strongly with the risk of a hemodynamic stroke. As a result, the use of CVR studies to evaluate the state of the cerebral autoregulatory capacity has clinical utility. Application of CVR studies in the clinical scenario depends on a thorough understanding of the normal response. The goal of this thesis therefore was to map CVR throughout the brain in normal healthy individuals using Blood Oxygen Level Dependant functional Magnetic Resonance Imaging (BOLD MRI) as an index to CBF and precisely controlled changes in end-tidal partial pressure of carbon dioxide (PETCO2) as the global flow stimulus.