The overall aim of the present thesis was to study aspects of patient safety in critically ill patients with special focus on airway management, respiratory complications and nursing procedures. Study I describes a method called pharyngeal oxygen administration during intubation in an experimental acute lung injury model. The study showed that pharyngeal oxygenation prevented or considerably increased the time to life-threatening hypoxemia at shunt fractions by at least up to 25% and that this technique could be implemented in airway algorithms for the intubation of hypoxemic patients. In study II, we investigated short-term disconnection of the expiratory circuit from the ventilator during filter exchange in critically ill patients. We demonstrated that when using pressure modes in the ventilator, there was no indication of any significant deterioration in the patient's lung function. A bench test suggests that this result is explained by auto-triggering with high inspiratory flows during the filter exchange, maintaining the airway pressure. Study III was a clinical observational study of critically ill patients in which adverse events were studied in connection with routine nursing procedures. We found that adverse events were common, not well documented, and potentially harmful, indicating that it is important to weigh the risks and benefits of routine nursing when caring for unstable, critically ill patients. In study IV, we conducted a retrospective database study in patients with pelvis fractures treated in the intensive care unit. We found that the incidence of respiratory failure was high, that the procedure involved in surgical stabilization affected the respiratory status in patients with lung contusion, and that the mortality was low and probably not influenced by the respiratory condition. In conclusion, the results obtained in the present thesis have increase our knowledge in important areas in the most severely ill patients and have underlined the need for improvements in the field of patient safety.

Thesis (M.Tech.: Emergency Medical Care)-Dept. of Emergency Medical Care and Rescue, Durban University of Technology, 2008. xii, 301 leaves, Annexures A-0 to A-7 / Paramedic clinical decision making (CDM) surrounding emergency airway management of the critically ill or injured patient in the pre-hospital environment is poorly understood. In order to deliver pre-hospital care effectively it is necessary to understand how paramedics make clinical decisions in this area and determine what influences clinical practice. This study primarily investigated the factors influencing paramedic CDM in the context of advanced emergency airway management with specific focus on the newly introduced skill of rapid sequence intubation (RSI). An evaluation of the correct application of RSI guidelines, the determination of the need for their review and the identification of measures to enhance CDM around RSI were secondary research questions.

BACKGROUND:Airway hyperresponsiveness (AHR), a primary characteristic of asthma, involves increased airway smooth muscle contractility in response to certain exposures. We sought to determine whether common genetic variants were associated with AHR severity.METHODS:A genome-wide association study (GWAS) of AHR, quantified as the natural log of the dosage of methacholine causing a 20% drop in FEV1, was performed with 994 non-Hispanic white asthmatic subjects from three drug clinical trials: CAMP, CARE, and ACRN. Genotyping was performed on Affymetrix 6.0 arrays, and imputed data based on HapMap Phase 2, was used to measure the association of SNPs with AHR using a linear regression model. Replication of primary findings was attempted in 650 white subjects from DAG, and 3,354 white subjects from LHS. Evidence that the top SNPs were eQTL of their respective genes was sought using expression data available for 419 white CAMP subjects.RESULTS:The top primary GWAS associations were in rs848788 (P-value 7.2E-07) and rs6731443 (P-value 2.5E-06), located within the ITGB5 and AGFG1 genes, respectively. The AGFG1 result replicated at a nominally significant level in one independent population (LHS P-value 0.012), and the SNP had a nominally significant unadjusted P-value (0.0067) for being an eQTL of AGFG1.CONCLUSIONS:Based on current knowledge of ITGB5 and AGFG1, our results suggest that variants within these genes may be involved in modulating AHR. Future functional studies are required to confirm that our associations represent true biologically significant findings.

Background: Careful airway management, including tracheal intubation, is important when performing anaesthesia in order to achieve safe tracheal intubation. Aim: To study airway management in anaesthesia care from both the professional and patient perspectives. Methods: 11 RNAs performed three airway tests in 87 patients, monitored in a study-specific questionnaire. The tests usefulness for predicting an easy intubation was analysed (Study I). 68 of 74 anaesthesia departments in Sweden answered a self-reported questionnaire about the presence of airway guidelines (Study II). 20 anaesthesiologists were interviewed; a phenomenographic analysis was performed to describe how anaesthesiologists' understand algorithms for management of the difficult airway (Study III). 13 patients were interviewed; content analysis was performed to describe patients' experiences of being awake fiberoptic intubated (Study IV). Results: The Mallampati classification is a good screening test for predicting easy intubation and intubation can be safely performed by RNAs (Study I). The presence of airway guidelines in Swedish anaesthesia departments is poorly implemented (Study II). Algorithms can be understood as law-like rules, a succinct plan to follow in difficult airway situations, an action plan kept in the back of one's mind while creating flexible and versatile personal algorithms, or as consensus guidelines based on expert opinion in order to be followed in clinical practice (Study III). One theme emerged describing experiences of being awake intubated; feelings of being in a vulnerable situation but cared for in safe hands, described in five categories: a need for tailored information, distress and fear of the intubation, acceptance and trust of the staff's competence, professional caring and support, and no hesitation about new awake intubation (Study IV). Conclusions: The Mallampati classification is a good screening test for predicting easy intubation, when the airway assessment is performed in a structured manner by RNAs. The presence of airway guidelines in Swedish anaesthesia departments was poorly implemented and should receive higher priority. Algorithms need to be simple and easy to follow and based on the best available scientific evidence. Tailored information about what to expect, ensuring eye contact, and giving breathing instructions during the procedure may reduce patients' feeling distress.

Increased bulk of smooth muscle mass around the airways is a typical feature of asthma. Several mediators act in concert or antagonistically to regulate airway smooth muscle (ASM) cell proliferation. This thesis focuses on fibroblast growth factor (FGF)2 and transforming growth factor (TGF)[béta]1 which are known to be sequentially upregulated in the lung following allergic challenge and have recently been shown to synergize together in ASM cell proliferation. Emphasis is put toward the conflicting studies documenting the mitogenic effect of TGF[béta]1 in vitro and to its seemingly potent effect in vivo. Thereafter, different asthma mediators, such as IL-4 and IL-13, are introduced and how their mitogenic potential toward ASM cells could be altered by FGF2 is presented. Finally, how the controversial issue between in vitro and in vivo data regarding the mitogenic effect of leukotrienes could be reconciliated and how it could be related to FGF2 and TGF[béta]1 proliferative synergism is discussed.

BACKGROUND: Operation Giving Back (OGB) of the American College of Surgeons (ACS) and various other surgical missions in the developing world have become more popular and provide a valuable way of reducing the surgical burden worldwide. While most cases are "bread and butter" general surgery, difficult surgeries are often encountered. MATERIALS AND METHODS: Description of a total thyroidectomy for super giant goiter extending to chest inferiorly, lateral neck and behind both ears, compressing the trachea and causing chronic difficulties breathing. The surgical team was unable to intubate, but performed surgery under local anesthesia and sedation with Ketamine injection. RESULTS: Total thyroidectomy, as a life-saving procedure, was performed under local anesthesia and Ketamine with mild sedation. Once thyroid was removed, the outside diameter of trachea was assessed to be 4mm. Patient tolerated the procedure well and had no postoperative complication. Her breathing improved significantly post-operatively. Five years later, she is doing well. CONCLUSION: Total thyroidectomy for giant goiters can be done under local anesthesia with Ketamine and proper sedation. Surgeons and anesthesiologists participating in surgical missions may have to perform major surgery under local anesthesia. (C) 2015 The Authors. Published by Elsevier Ltd. on behalf of Surgical Associates Ltd.

Introduction: Little is known about the impact of spousal involvement on continuous positive airway pressure (CPAP) adherence. The aim of this study was to determine whether spouse involvement affects adherence with CPAP therapy, and how this association varies with gender. Methods: 194 subjects recruited from Apnea Positive Pressure Long Term Efficacy Study (APPLES) completed the Dyadic Adjustment Scale (DAS). The majority of participants were Caucasian (83%), and males (73%), with mean age of 56 years, mean BMI of 31 kg/m2. & 62% had severe OSA. The DAS is a validated 32-item self-report instrument measuring dyadic consensus, satisfaction, cohesion, and affectional expression. A high score in the DAS is indicative of a person’s adjustment to the marriage. Additionally, questions related to spouse involvement with general health and CPAP use were asked. CPAP use was downloaded from the device and self-report, and compliance was defined as usage > 4 h per night. Results: There were no significant differences in overall marital quality between the compliant and noncompliant subjects. However, level of spousal involvement was associated with increased CPAP adherence at 6 months (p=0.01). After stratifying for gender these results were significant only among males (p=0.03). Three years after completing APPLES, level of spousal involvement was not associated with CPAP compliance even after gender stratification. Conclusion: Spousal involvement is important in determining CPAP compliance in males in the 1st 6 months after initiation of therapy but is not predictive of longer-term adherence. Involvement of the spouse should be considered an integral part of CPAP initiation procedures. Support: HL068060

Master of Science / Department of Kinesiology / Craig A. Harms / Obesity and asthma often coexist in the same people. Both are characterized by the presence of low-grade systemic inflammation. A high-fat diet may contribute to concurrent development of both conditions by promoting a pro-inflammatory postprandial environment leading to a transient accumulation of blood lipids (postprandial lipemia; PPL) and acute airway inflammation. Previous results from our lab have shown an ~20% increase in airway inflammation two hours after consuming a high-fat meal (HFM) that was significantly associated with increased plasma triglycerides. While acute exercise has been shown to attenuate PPL, it is unknown whether these protective effects will translate to reduced airway inflammation after a high-fat meal. PURPOSE: To determine the effects of an acute bout of exercise on airway inflammation after a HFM. We tested the hypothesis that an acute bout of exercise 12 hours before a high-fat meal would protect against subsequent airway inflammation in healthy men and would be related to the decreased PPL and systemic inflammatory markers. METHODS: In a randomized cross-over study, 12 healthy college-aged men consumed a HFM (1g fat/1kg body weight) 12 hours following exercise (EX; 60 min at 60% VO2max) or without exercise (CON). Exhaled nitric oxide (eNO; measure of airway inflammation), blood lipid profiles (venous sample; total cholesterol, HDL, LDL, triglycerides, glucose), inflammatory markers (hsCRP, TNF-[alpha], IL-6) and pulmonary function tests (PFT) (forced expiratory volume in 1-s,forced vital capacity, forced expiratory flow at 25-75% of vital capacity) were measured pre-HFM, two hours, and four hours post-HFM. RESULTS: Baseline eNO was not different (p>0.05) between trials. eNO increased (p<0.05) post HFM at two hours in the both CON and EX conditions. eNO between trials was not different (p>0.05). Triglycerides were significantly increased two and four hours post HFM but were not different (p>0.05) between conditions. There was no relationship (p>0.05) between eNO and triglycerides or systemic inflammatory markers for any time point in either condition. Pulmonary function did not differ (p>0.05) between any condition. CONCLUSION: These results demonstrate that an acute bout of moderate intensity exercise 12 hours before a HFM does not attenuate postprandial airway inflammation or lipemia in healthy college-aged men.

A asma é uma doença heterogênea caracterizada por inflamação crônica das vias aéreas. A prevalência de asma tem aumentado nas últimas décadas principalmente em países ocidentais, sobrecarregando os sistemas de saúde. A teoria da higiene sugere que a exposição a infecções na infância pode proteger contra o desenvolvimento de asma e outras doenças alérgicas. Estudos prévios demonstram que o tratamento com Saccharomyces cerevisiae UFMG A-905 protegeu camundongos contra infecções intestinais, preveniu translocação bacteriana e aumentou a produção de IL-10. Em um modelo animal de asma, a S. cerevisiae UFMG A-905 atenuou as principais características da asma reduzindo a hiper-responsividade brônquica (HRB), eosinofilia no lavado broncoalveolar (LBA), a inflamação peribrônquica, a produção de muco e os níveis de IL-4, IL-5 e IL-13. Paraprobióticos são microrganismos inativados que conferem benefícios a saúde do hospedeiro. Os objetivos deste trabalho foram avaliar os efeitos da administração do paraprobiótico S. cerevisiae UFMG 905 na prevenção da asma e os mecanismos envolvidos. Camundongos Balb/c machos de 6 a 8 semanas foram sensibilizados com injeções de ovalbumina (OVA), com uma semana de intervalo, e desafiados com OVA intranasal diariamente por três dias consecutivos. A levedura foi inativada por calor a 121°C por 20 minutos. Os camundongos receberam S. cerevisiae UFMG A-905 inativadas por gavagem diariamente, iniciando dez dias antes da primeira sensibilização, seguindo continuamente até o último desafio. Vinte e quatro horas após o último desafio, os animais foram anestesiados, ventilados com um ventilador para pequenos animais FlexVent® (Sicreq, Montreal, Canadá) e realizadas medidas in vivo da HRB na condição basal e após a administração de concentrações crescentes de um broncoconstritor (metacolina). Após, a inflamação foi avaliada no lavado broncoalveolar (LBA) pela contagem total e diferencial de células, dosagem das citocinas IL-4, IL-5, IL-10, IL-13, IL-17A e INF-y no LBA e homogenato pulmonar, por avaliação histológica do tecido pulmonar, produção de muco, e pela avaliação dos níveis de IgE. O grupo OVA, quando comparado ao grupo SAL, apresentou um aumento significativo na HRB (p<0,001), número total de células (p<0,001) e eosinófilos (p<0,001) no LBA, nos níveis de IgE (p<0,001), inflamação peribrônquica (p<0,001) e produção de muco (p<0,001). Quando comparado ao grupo OVA, a administração do paraprobiótico S. cerevisiae UFMG A-905 reduziu significativamente a quantidade de eosinófilos (p<0,001) no LBA, os níveis de IL-5 (p<0,05), IL-13 (p<0,05), e IgE (p<0,001) e a produção de muco (p<0,01), além disso, a administração aumentou os níveis de IL-17A (p<0,001), e não alterou a HRB. Conclui-se que a administração do paraprobiótico S. cerevisiae UFMG A-905 atenuou a inflamação das vias aéreas em modelo animal de asma. / Asthma is a heterogeneous disease characterized by chronic inflammation of the airways. The prevalence of asthma has increased in the last decades mainly in western countries, overloading health systems. Hygiene theory suggests that exposure to infections can protect against the development of asthma and other allergic diseases.. Studies have shown that treatment with S. cerevisiae UFMG A-905 protected mice against intestinal infections, prevented bacterial translocation and increased IL-10 production. In an animal model of asthma Saccharomyces cerevisiae UFMG A-905 attenuated the main characteristics of asthma reducing bronchial hyperresponsiveness (BHR), eosinophilis in bronchoalveolar lavage (BAL), peribronchial inflammation, mucus production, important inflammatory cytokines in asthma such IL-4, IL-5 and IL-13. Paraprobiotics are inactivated microorganisms that confer benefits to host health. The objectives of this study were to evaluate the effects of the administration of paraprobiotic S. cerevisiae UFMG 905 on the prevention of asthma and the mechanisms involved. Male Balb/c from 6 to 8 weeks were sensitized twice with ovalbumin (OVA), with one week apart between applications, and challenged intranasally with OVA daily for three consecutive days. The yeast was heatinactivated at 121°C for 20 minutes. Mice received by gavage S. cerevisiae UFMG A- 905 inactivated daily, starting ten days prior to the first sensitization, continuously until the last challenge. Twenty-four hours after the last challenge, the animals were anesthetized, ventilated with a ventilator for small animals FlexVent® (Sicreq, Montreal, Canada) and measurements were performed in vivo HRB at baseline and after administration of increasing concentration of a brochoconstrictor (methacholine). The inflammation was assessed by couting total and differential cells present in BAL analysis of the cytockines IL-4, IL-5, IL-10, IL-13, IL-17 e INF-y in BAL and pulmonary homogenate by ELISA, by histological assessment of lung tissue, mucus production and levels of IgE. There was significant increase in BHR between the OVA/PBS and SAL/PBS (p<0,001), total number of cells (p<0,001) and eosinophils (p<0,001), peribronchial inflammation (p<0, 001) and mucus production (p<0,001). When compared to the OVA/PBS group, administration of paraprobiotic Saccharomyces cerevisiae UFMG A-905 significantly reduced the amount of eosinophils (p<0,001) in BAL, IL-5 (p<0,001) and IL-13 (p<0,01) cytokines, levels of IgE (p<0,01) and mucus production (p<0,01), also increased levels of IL-17A (p<0,001), and did not change the BHR. In conclusion, oral administration of paraprobiotic S. cerevisiae UFMG A-905 attenuated the inflammation of the airways in an animal model of asthma.

A prevalência de asma tem aumentado em crianças e nas comunidades que adotam um estilo de vida ocidental e se tornam mais urbanizadas. A teoria da higiene sugere que a exposição a infecções e contato não higiênicos na infância pode proteger contra o desenvolvimento de asma. Probióticos são micro-organismos vivos que conferem um benefício à saúde do hospedeiro. O tratamento com Saccharomyces cerevisiae UFMG 905 protegeu camundongos contra infecções intestinais, preveniu a translocação bacteriana e aumentou a produção de IL-10. Até o momento, não há descrição do uso de Saccharomyces cerevisiae UFMG 905 na prevenção e/ou tratamento da asma. Os objetivos deste trabalho foram avaliar os efeitos da administração de Saccharomyces cerevisiae UFMG 905 na prevenção da asma e os mecanismos envolvidos. Camundongos Balbc machos de 6 a 8 semanas foram sensibilizados duas vezes com ovalbumina (OVA), com uma semana de intervalo, e desafiados com OVA diariamente por três dias consecutivos. Os camundongos receberam por gavagem Saccharomyces cerevisiae UFMG 905 diariamente, dez dias antes da primeira sensibilização e durante todo o período de sensibilização e desafios, totalizando 27 administrações. O grupo controle recebeu apenas salina ou PBS. Assim quatro grupos, de 6 a 8 camundongos, foram estudados: Prev. SAL/PBS, Prev. OVA/PBS, Prev. SAL/Sac e Prev. OVA/Sac. Após a sensibilização e desafios, os animais foram anestesiados, ventilados com um pequeno ventilador para animais FlexiVent® (Scireq, Montreal, QC, Canadá) e submetidos a medidas in vivo da mecânica pulmonar na condição basal e após a administração de concentrações crescentes de aerossóis com metacolina. Após, o lavado broncoalveolar (LBA) foi coletado para contagem total e diferencial de células. As citocinas IL-4, IL-5, IL-10, IL-13 e IFN- foram dosadas no LBA e homogenato pulmonar. Foi realizada histoquímica para visualização e quantificação de inflamação e colágeno. Observamos que o grupo Prev. OVA/PBS apresentou aumento significativo na hiper-responsividade brônquica (RRS: p<0,0001; RN: p<0,01 e G: p<0,05), o número total de células (p<0,0001), número de eosinófilos (p<0,001), e nos níveis de IL-4 (p<0,05) e IL-13 (p<0,05) quando comparado ao grupo Prev. SAL/PBS. O grupo Prev. OVA/Sac, em comparação ao grupo Prev. OVA/PBS apresentou redução na hiper-responsividade brônquica (RRS: p<0,001; RN: p<0,01; G: p<0,05), no número total de células (p<0,05), número de eosinófilos (p< 0,001) e níveis de IL-4 (p<0,05) no LBA. Em comparação com o grupo Prev. OVA/PBS, a administração de Saccharomyces cerevisiae UFMG 905 reduziu os níveis de IL-5 (p<0,05) e IL-13 (p<0,05) no homogenato do pulmão, e as células inflamatórias no pulmão (p<0,001). Adicionalmente, houve aumento nos níveis de IL-10 (p<0,05) no tecido pulmonar do grupo OVA/Sac em comparação ao grupo Prev. OVA/PBS. Conclui-se que a Saccharomyces cerevisiae UFMG 905 atenuou as principais características da asma em um modelo animal e, consequentemente, pode ter um efeito benéfico na prevenção da asma. / The prevalence of asthma has increased in children and communities that adopt a Western lifestyle and become more urbanized. The hygiene hypothesis suggests that exposure to infections early in life can reduce the risk of asthma and other allergic diseases. Probiotics are live micro-organisms that confer a health benefit to the host. Treatment with Saccharomyces cerevisiae UFMG 905 protected mice against intestinal infections, prevented bacterial translocation and increased IL-10 production. There is no study of Saccharomyces cerevisiae in the prevention or treatment of asthma. The objective of this study was to evaluate the effects of viable Saccharomyces cerevisiae UFMG 905 administration in the prevention and treatment of asthma and the mechanisms involved. Male Balb/c mice were sensitized twice with ovalbumin (OVA) intraperitoneally, one week apart, and challenged with OVA intranasally for three days. Mice were treated by gavage with Saccharomyces cerevisiae UFMG 905 10 days before OVA sensitization and during challenges. Control mice received saline or PBS on the same days. After challenge, mice were ventilated with a small animal ventilator (FlexiVent®) and in vivo measurements of bronchial hyperresponsiveness were performed with increasing concentrations of methacoline aerosol (6.25, 12.5, 25 and 50 mg/ml). Bronchoalveolar lavage(BAL) was collected to quantify total and differential cell counts. Levels IL-4, IL-5, IL-10, IL-13 and IFN- in BAL and lung homogenate were measured by ELISA. Inflammatory cell number and collagen deposition were assed in lung tissues. Oral treatment with Saccharomyces cerevisiae UFMG 905 significantly decreased airway hyperresponsiveness, measured by total resistance (p<0,0001), central airway resistance(p<0,001) and tissue resistance (p<0,05). Saccharomyces cerevisiae UFMG 905 significantly attenuated total cell number (p<0,05) and the influx of eosinophil (p<0,001) to the airway lumen. Furthermore, inflammatory cell number in lung peripheral (p<0,001 and levels of IL-4 (p<0,05) in BAL and IL-5 (p<0,05) and IL-13 (p<0,05) in lung homogenate were significantly diminished by Saccharomyces cerevisiae UFMG 905.Of note, Saccharomyces cerevisiae UFMG 905 restored IL-10 (p<0,05) levels in lung tissue. In conclusion, oral administration of Saccharomyces cerevisiae 905 UFMG attenuated major asthma-like characteristics in a mouse model. These results showed that Saccharomyces cerevisiae UFMG 905 might have potential for prevention of asthma.