Pharmacodynamic Estimate of Propofol-Induced Sedation and Airway Obstruction Effects in Obstructive Sleep Apnea-Hypopnea Syndrome

PURPOSE: Sedatives must be carefully titrated for patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) as oversedation may lead to disastrous respiratory outcomes. This study aimed to investigate the relations between the effect-site concentration (Ce) of propofol and sedation and airway obstruction levels in patients with OSAHS. MATERIALS AND METHODS: In 25 patients with OSAHS, sedation was induced by 2% propofol using target-controlled infusion. Sedation and airway obstruction levels were assessed using the Observer's Assessment of Alertness/Sedation Scale and a four-category scale, respectively. The relationships between propofol Ce and sedation and airway obstruction were evaluated using a sigmoid Emax model. Pharmacodynamic modeling incorporating covariates was performed using the Nonlinear Mixed Effects Modeling VII software. RESULTS: Increased propofol Ce correlated with the depth of sedation and the severity of airway obstruction. Predicted Ce50(m) (Ce associated with 50% probability of an effect> or =m) for sedation scores (m> or =2, 3, 4, and 5) and airway-obstruction scores (m> or =2, 3, and 4) were 1.61, 1.78, 1.91, and 2.17 microg/mL and 1.53, 1.64, and 2.09 microg/mL, respectively. Including the apnea-hypopnea index (AHI) as a covariate in the analysis of Ce50(4) for airway obstruction significantly improved the performance of the basic model (p<0.05). CONCLUSION: The probability of each sedation and airway obstruction score was properly described using a sigmoid Emax model with a narrow therapeutic range of propofol Ce in OSAHS patients. Patients with high AHI values need close monitoring to ensure that airway patency is maintained during propofol sedation.

Función suprarrenal en pacientes con síndrome bronquial obstructivo tratados con corticoides sistémicos (Informe Preliminar) / Adrenal function in patients with acute bronchial obstruction treated with systemic corticosteroids: a preliminary report

Introduction: Systemic corticosteroids are widely used in patients with acute bronchial obstruction (ABO). It has been recommended that such treatment last a maximum of 5 days to avoid adverse effects. Suppression of the adrenal axis under these conditions among children has not been evaluated. Objective: Assessment of the hypothalamic pituitary adrenal axis (HHS) function after use of systemic steroids in children after a 5-7 day use of corticoids, utilizing the micro ACTH test. Method: Prospective observational study conducted in the Department of Pediatrics, Hospital Clínico Universidad Católica de Chile. ACTH test used with microdosis (1 mcg/1.73 m²). A normal response was determined if cortisol post-ACTH > 20 mcg/dL. Results: 7 patients were recruited, median age was 4 years 4 months (range 4 months to 8 years). The test was perfomed within an average of 72 hours after discontinuation of prednisone. All patients had normal basal cortisol values, with an average value of 6.5 mcg/dl, range 1 to 9 mcg/dl. The ACTH test yielded a response of cortisol levels with an average value of 13.6 mcg/dL and a range of 3.7 to 20 mcg/dL. Five of the 7 patients presented an abnormal response. Conclusions: Our results suggest that the adrenal response may be reduced in children who have been treated with systemic steroids for ABO even if managed during short periods of time.

Introducción: Los corticoides sistémicos son ampliamente utilizados en pacientes con crisis bronquiales obstructivo (CBO). Se ha recomendado un máximo de 5 días para evitar efectos adversos. No ha sido evaluado si tratamientos por cursos cortos pueden suprimir el eje adrenal. Objetivo: Evaluar la función del eje hipotálamo hipófisis suprarrenal (HHS) mediante la prueba de microdosis de ACTH en pacientes con CBO que recibieron corticoides sistémicos entre 5 a 7 días. Diseño: Estudio observacional prospectivo realizado en el Servicio de Pediatría del Hospital Clínico de la Universidad Católica de Chile. Prueba de ACTH con microdosis (1 mcg/1,73 m²). Se consideró como respuesta normal una respuesta de cortisol postestímulo > 20 mcg/dL. Resultados: Fueron reclutados 7 pacientes, mediana de edad de 4 años 4 meses (rango 4 meses a 8 años). Los resultados fueron obtenidos con una mediana de 72 horas de suspendidos los corticoides (prednisona). Todos los pacientes presentaban valores de cortisol basal normal promedio de 6,5 mcg/dl (rango 1 a 9 mcg/dl). La respuesta de cortisol postestímulo fue de 13,6 mcg/dL (3,7 a 20 mcg/ dL), cinco de los 7 pacientes presentaron respuesta anormal. Conclusiones: La respuesta adrenal puede estar disminuida en pacientes que usan corticoides sistémicos por cursos cortos por CBO.

Efeito da obstrução de vias aéreas nas variações das propriedades resistivas e elásticas do sistema respiratório de asmáticos, mediadas pelo uso de salbutamol / Effects of airway obstruction on albuterol-mediated variations in the resistive and elastic properties of the respiratory system of patients with asthma

OBJETIVO: Investigar os efeitos da obstrução de vias aéreas nas variações das propriedades resistivas e elásticas do sistema respiratório de asmáticos adultos mediadas pelo uso de salbutamol. MÉTODOS: Foram analisados 24 indivíduos controles e 69 asmáticos, todos não tabagistas, divididos em três grupos segundo o nível de obstrução de vias aéreas (leve, moderada e acentuada). Cada grupo foi dividido em dois subgrupos de acordo com a resposta broncodilatadora: resposta broncodilatadora positiva (RB+) ou negativa (RB-). A espirometria foi utilizada para a avaliação da obstrução, e a técnica de oscilações forçadas, para a análise das propriedades resistivas e elásticas, sendo realizadas antes e após a utilização de 300 µg de salbutamol. RESULTADOS: A resistência no intercepto (R0) apresentou maior redução nos grupos com maior obstrução. Essa redução foi mais evidente nos subgrupos RB+ do que nos RB- (p < 0,02 e p < 0,03, respectivamente). Houve diferença significativa entre o grupo controle e a o subgrupo com obstrução acentuada RB+ (p < 0,002). As reduções na elastância dinâmica (Edyn) se acentuaram significativamente com a obstrução, tanto para os subgrupos RB- (p < 0,03), quanto para os RB+ (p < 0,003). As reduções da Edyn foram significativamente maiores nos subgrupos com obstrução moderada RB- (p < 0,008) e com obstrução acentuada RB+ (p < 0,0005) do que no grupo controle. CONCLUSÕES: Em asmáticos, o aumento da obstrução de vias aéreas resulta na elevação das variações em R0 e Edyn com o uso de salbutamol. Pacientes com RB+ apresentam variações mais elevadas que indivíduos com RB-.

OBJECTIVE: To investigate the effects of airway obstruction on albuterol-mediated variations in the resistive and elastic properties of the respiratory system of adult patients with asthma. METHODS: This study comprised 24 healthy controls and 69 patients with asthma, all of whom were nonsmokers. The patients were divided into three groups according to the severity of airway obstruction (mild, moderate or severe). Each of the three groups was divided into two subgroups according to the bronchodilator response (BR): positive (BR+) or negative (BR-). Airway obstruction was determined by means of spirometry, and the resistive and elastic properties were determined by means of the forced oscillation technique. These measurements were conducted before and after albuterol use (300 µg). RESULTS: The resistance at the intercept (R0) presented greater reductions in the groups with higher obstruction. This reduction was more evident in the BR+ subgroups than in the BR- subgroups (p < 0.02 and p < 0.03, respectively). There was a significant difference between the control group and the BR+ subgroup with severe obstruction (p < 0.002). The reductions in dynamic elastance (Edyn) were significantly greater in proportion to the degree of obstruction, in the BR- subgroups (p < 0.03), and in the BR+ subgroups (p < 0.003). The reductions in Edyn were significantly greater in the BR- subgroup with moderate obstruction (p < 0.008) and in the BR+ subgroup with severe obstruction (p < 0.0005) than in the control group. CONCLUSIONS: In patients with asthma, increased airway obstruction results in greater reductions in R0 and Edyn after albuterol use. These reductions are greater among BR+ patients than among BR- patients.

Effects of oral methylprednisolone and inhaled salbutamol in the decrease of wheezing in patients with asthma after tracheal intubation

Airway instrumentation in patients with bronchial hyperreactivity, may evoke life-threatening asthma attack and a good strategy for the prevention of bronchospasm has not been defined. In a randomized, prospective, placebo-controlled study, it was determined whether prophylaxis with either inhaled salbutamol-or combined inhaled salbutamol and oral methylprednisolone improves lung functions and prevents wheezing after intubation. Thirty one patients with partially reversible airway obstruction [airway resistance > 180%, forced expiratory volume in 1 second [FEV1] < 70% of predicted value, and FEV1 increase > 12% after two puffs of salbutamol] were randomized to receive daily either 3-2 puffs [0.2 mg] of salbutamol [n = 16] or 3-2 puffs [0.2 mg] of salbutamol and 40 mg of methylprednisolone [n = 15] orally for 5 days. In all patients lung function was evaluated daily and wheezing changes was assessed before and 5 minutes after tracheal intubation. Both salbutamol and combined inhaled salbutamol and oral methylprednisolone treatment significantly improved airway resistance and FEV1 to a steady state, with no difference between groups. When a single-dose of salbutamol pre-induction or prolonged salbutamol treatment was employed, most patients [8 of 10 and 7 of 9] experienced wheezing after intubation. In contrast, only one patient of those who received both salbutamol and methylprednisolone experienced wheezing [P = 0.0058]. Pretreatment with either salbutamol or combined inhaled salbutamol and oral methylprednisolone significantly improves lung function and decreases the incidence of wheezing after tracheal intubation. Methylprednisolone decreases incidence of wheezing more than salbutamol. Therefore, in patients with bronchial hyper reactivity, preoperative treatment with both methylprednisolone and salbutamol minimizes intubation-evoked broncho-constriction

The effects of low dose leukotriene receptor antagonist therapy on airway remodeling and cysteinyl leukotriene expression in a mouse asthma model

Airway structural changes that occur in patients with asthma in response to persistent inflammation are termed airway remodeling. The cysteinyl leukotrienes (LTC4, D4 and E4) are known to play important roles in the pathobiology of asthma. To evaluate the effect of low dose montelukast (MK) on the development of airway remodeling using a chronic murine model of allergic airway inflammation with subepithelial fibrosis, BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on days 0 and 14, received intranasal OVA periodically on days 14-75. MK treated mice received montelukast sodium intraperitoneally on days 26-75. The OVA sensitized/challenged mice developed an extensive eosinophil cell inflammatory response, goblet cell hyperplasia, mucus occlusion, and smooth muscle hypertrophy of the airways. In addition, in OVA sensitized/challenged mice, dense collagen deposition/fibrosis was seen throughout the lung interstitium surrounding the airways, blood vessels, and alveolar septae. The cysteinyl leukotriene 1 (CysLT1) receptor antagonist, MK significantly reduced the airway eosinophil infiltration, goblet cell hyperplasia, mucus occlusion, and lung fibrosis except airway smooth muscle hypertrophy in the OVA sensitized/challenged mice. The OVA sensitized/challenged mice had significantly increased epithelial desquamation compared with control mice. MK markedly reduced epithelial desquamation of airways in OVA/MK treated animals compared with OVA sensitized/challenged mice. MK treatment did not affect the levels of CysLT in lung tissue. Our results show that the important role of cysteinyl leukotrienes in the pathogenesis of asthma. Lower dose of CysLT1 receptor antagonism has a significant anti-inflammatory effect on allergen-induced lung inflammation and fibrosis but not airway smooth muscle hypertrophy in an animal model of asthma.

A prospective, randomized double-blind study in children comparing two doses of nebulized L-epinephrine in postintubation croup.

OBJECTIVE: To compare the effectiveness and side effects of nebulized l-epinephrine (NLE) at a dose of 0.05 mL/kg versus 0.5 mL/kg in the treatment of postintubation croup in children. MATERIAL AND METHOD: Thirty-nine children, who developed signs and symptoms of upper airway obstruction (UAO) after extubation, were randomized to receive either 0.05 mL/kg or 0.5 mL/kg of NLE. UAO scores, vital signs (VS) and possible side effects were recorded before and at 20 and 40 minutes after the treatment. RESULTS: Twenty-one and 18 patients were allocated to the 0.05 and 0.5 mL/kg groups, respectively. Both groups showed improvements in UAO scores over time. There were no significant differences in UAO scores and VS between the groups at all time points. Side effects of epinephrine were not observed. CONCLUSION: In children with postintubation croup, the administration of NLE at the dose of 0.05 mL/kg results in similar improvements in the UAO scores, compared with the dose of 0.5 mL/kg. No complications were seen in either dose.

Beta 2 agonist in aortic valve disease.

Lung function studies in patients with severe aortic stenosis scheduled for aortic valve replacement [AVR] revealed an obstructive ventilatory pattern. The majority of those operated upon showed a similar pattern postoperatively. A blind study of the effect of placebo and beta[2] agonist [salbutamol] inhalation was performed in two separate groups of patients preoperatively and six months postoperatively, to evaluate the reversibility of airflow obstruction in these patients, using the following flow volume curve, body plethysmographic measurement of airway resistance [Rex] and intrathoracic gas volume [VTG]. The group of patients in the preoperative period showed significant differences between the placebo and the beta2 agonist responses for FEV[1], PEFR, Vmax[50], Rex and VTG [P<0.001], and also in the postoperative group for FEV[1]/FVC and Rex [P<0.01]. We conclude that salbutamol inhalation improves the obstructive impairment in patients with AVR both pre and post-operatively

Terapia inhalatoria ambulatoria en niños / Inhalatory ambulatory therapy in children

La terapia inhalatoria es un tratamiento efectivo en las afecciones bronquiales obstructivas de los niños, en quienes su empleo exige un conocimiento apropiado del procedimiento correspondiente. Se evaluó la forma en que los operadores, por lo general la madre de los pacientes, dispensaban los medicamentos para uso inhalatorio, mediante administración observada de una dosis por inhalación ante dos investigadores en la consulta ambulatoria y se correlacionó la frecuencia y magnitud de los errores cometidos, así como la calidad del procedimiento, con la edad e instrucción del operador, experiencia previa en suministro de terapia por inhaladores y número de hijos. En 60 por ciento de los casos se registraron errores en el método de administración y 36,9 por ciento de los procedimientos fueron calificados como tratamiento de mala calidad, lo que implica que una importante proporción de niños tratados por obstrucción bronquial reciben un manejo farmacológico deficiente por este solo mecanismo. No fue posible relacionar la incidencia de errores con ninguno de los factores específicos estudiados

Variabilidad en la función de jet nebulizadores Hudson: efecto del volumen de llenado / Variability in the function of Hudson jet nebulizer: effect of fill volume

La variablidad en la función de jet nebulizadores de la misma marca y modelo (Hudson UP-DRAFT II, modelo 1730), fue evaluada en relación al gasto o débito (mg/min.) producida al emplear un volumen de llenado de 2 o 4 ml de solución salina normal. La variabilidad intranebulizadores observada en nebulizaciones repetidas no fue significativa. La variabilidad observada en los gastos entre los distintos jet nebulizadores fue estadisticamente significativa (p< 0.05). Sin embargo esta variabilidad fue mayor cuando se emplearon 2 ml de volumen de llenado (p< 0.001). Además se observó una disminución significativa del gasto durante el período de nebulización en todos los nebulizadores estudiados (p< 0.001). Esta disminución fue de mayor magnitud y variabilidad cuando los nebulizadores se emplearon con 2 ml. Este estudio sugiere que parte de la variabilidad observada en los resultados de trabajo clínicos y de laboratorio, que han empleado aerosoles generados por jet nebulizadores, se debería a la variabilidad existente entre los nebulizadores y en las condiciones de manejo de estos dispositivos. Lo anterior refuerza la necesidad de conocer previamente las características de funcionamiento de los sistemas de nebulización. Ambos, el nebulizador y las condiciones de manejo, necesitan ser previamente determinados cuando se evalúa la acción farmacológica de agentes terapéuticos nebulizados generados por jet nebulizadores

Estudio abierto no controlado sobre la eficacia de piroxicam en el tratamiento de los síntomas asociados con inflamación aguda de la vía respiratoria superior / Not controlled open study on the effectiveness of piroxican in the treatment of the symptoms associated with acute inflammation of the superior respiratory tract

Se estudiaron 50 pacientes de edad con proceso inflamatorio agudo del tracto respiratorio superior los que fueron tratados con tabletas dispersables de piroxicam en la dosis de 40 mg diarios durante los dos primeros días seguidos de 20 mg diarios durante los siguientes tres días. La evaluación hecha por el investigador se realizó inmediatamente antes del tratamiento a las 48 horas de iniciado y al 5 día incluyendo una completa historia y exámen clínico y especial valoración de la evolución del enrojecimiento de la faringe de las condiciones de la amigdalitis, de la dificultad al deglutir, dolor en el área de la garganta y fiebre. Los pacientes igualmente hicieron una autoevaluación de su dolor del área de la garganta y su dolor al deglutir. Al final de los 5 días una evaluación final fue realizada por el investigador y los pacientes. Se tomó información sobre la presencia de efectos colaterales como consecuencia del tratamiento. De los 50 pacientes 27 fueron del sexo masculino y 23 del femenino con edades que oscilaron entre 18 y 78 años con una media de 32 años. Los diagnósticos incluyen 29 casos de faringitis, 9 casos de coriza, 8 casos de influenza, dos casos de amigdalitis y dos de faringoamigdalitis. Del total de los 50 pacientes a las 48 horas de iniciado el tratamiento solamente 10 pacientes se encontraban asintomáticos. Pero entre ambas visitas de severidad y el número de los principales síntomas se modificó notoriamente. Por ejemplo: la cefalea presenta originalmnte en 28 pacientes persistencia solo en 7 pacientes (disminución de 75 por ciento); la fiebre desapareció en el 73.3 por ciento de los casos que originalmente la presentaron; la odinofagia cedió en 46.9 por ciento de los casos positivos originalmente. Para el 5º día post-tratamiento solamente seis pacientes (12 por ciento) continuaban sintomáticos...

Teofilinas en el manejo del asma / Theophyllines in the management of bronchial asthma

La tofilina, una metilxantina, es un broncodilatador mayor para el tratamiento del asma bronquial. Su mecanismo de acción es desconocido. Sin embargo, se han determinado numerosas interacciones en diversos pasos metabólicos y celulares que pudieran tener relación con su efecto broncodilatador, como el antagonismo con los receptores de adenosina, su influencia en el metabolismo del calcio y su acción sobre las prostaglandinas. La terapia óptima con teofilina debe producir niveles sanguíneos de 10 a 20 ug/ml (que es su rango terapéutico), lo cual pernmite obtener el máximo efecto broncodilatador con las mínimas reacciones adversas. Las acciones farmacológicas de la teofilina sobre el sistema cardiovascular, el sistema nervioso central, el tubo digestivo, la musculatura lisa y estriada, así como sus efectos beneficiosos sobre el tracto respiratorio deben ser muy bien conocidos por el médico para que así pueda utilizar ésta droga con el mayor beneficio y con la menor cantidad posible de reacciones adversas

Ajuste de volumen en el cálculo del FEF 25 - 75 en la evaluación de la respuesta broncodilatadora / Volume adjustment in the stimation of FEF 25 - 75

Se realiza una pequeña experiencia comparando el efecto broncodilatador medido con determinación de FEF 25-75% basal, post broncodilatador y FEF 25-75% a isovolumen. Se logra determinar que las curvas a isovolumen permiten lograr mayores respuestas broncodilatadoras, con una mayor significación estadística que el método convencional