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Abril 2016

ARTÍCULOS DE INVESTIGACIÓN The effect of benzodiazepines on bronchoconstriction in asthma patients - M. Miric et al Commission for Steel and Coal (Jonasset, 1960). Functional assessment of the respiratory system is done with the help of spirometer of the “Jaeger” calibration pump and physical plethysmograph of the “Jaeger” Werzburg. Intrathoracic gas volume and resistance airway was measured by body plethysmography18. In order to detect changes in airflow after inducing methacholine in patients with asthma, the index of bronchial reactivity was calculated. Bronchial reactivity index was defined as the log of the percent decline in FEV1/log final histamine dose after adding 10 to eliminate negative values19. Bronchial reactivity was tested by using aerosol of methacholine (Acetyl-β-methylcholine chloride) as inhalation test,manufactured by Sigma - Aldrich Chemie GmbH, Product Number: A2251. Methacholine 436 was used as a solution for inhalation, at room temperature, as recommended elsewhere17. The group of 12 asthmatic patients, which were treated by aerosol of methacholine was investigated in the course of two consecutive days: First day: After determining the initial values of pulmonary function, dose response curve were made for the following doses of methacholine until a maximum response: 0.2, 0.6 , 2.0, 6.0, and 20.0 mg/mL20. After the last dose, when at least a 20% drop of the initial FEV1 value was achieved, we measured VC , FEV1, 7, 15 and 30 minutes after provocation. Patients were in seated position and inhaled methacholine as a nebulization through the mouth. The nose was sealed with cotton wool. Each inhalation lasted two minutes and the device used for inhalation was the “Inhalet” type INHO2 (IEVT). The air flow during inhalation was 5 L/min and size of the particles obtained spray, ranged from 0.5 to 5.0 Nm. The flow of dispersed liquid was 0,2 ml/min. After each dose of inhaled methacholine, the same parameters of lung function were determined in the patients. The provocative dose (PD), by definition, is the dose that results in the desired response and represents a reflection of the sensitivity of airways. The dose of provocative substance which caused at least a 35% change in RT and SRt (proposal of the European Society for Clinical Respiratory Physiology SEPCR) was considered clinically significant21. Second day: The inhalation of aerosol particles, which comprised at least 10 percent by weight of diazepam (Apaurin, Krka) and less than 90 percent by weight of water, was given to the same group of patients. Vials of 10 mg/2 mL were used. The nose was closed with soft plastic clips like clothespins, which pinched the nostrils together. Benzodiazepines containing aerosols were delivered using the inhalation device “Inhalet” type INHO2 (IEVT). The device consisted of three elements: an element for heating a benzodiazepine containing composition to form a vapor; an element allowing the vapor to cool, thereby providing a condensation aerosol; and, an element permitting the patient to inhale the aerosol. The air flow during inhalation was 5 L/min and size of the particles obtained spray, ranged from 0.5 to 6.0 Nm. The flow of dispersed liquid was 0,2 ml/ min. A typical dosage of a benzodiazepine aerosol is either administered as a single inhalation or as a series of inhalations taken within 5 minutes or less (dosage equals sum of inhaled amounts). After the inhalation, parameters of lung function were measured again. Then, we repeated methacholine inhalation in increased doses, in the same manner as on the previous day. Statistical analysis of the results included the calculation of the mean value (X), standard deviation (SD) and standard error (SE) for all measured lung function parameters. To determine statistical significance, data were tested by t-test, a threshold value included changes in the level of statistical significance of p < 0.05. Results The population examined consisted of 12 patients with well controlled asthma in which we examined the response of the airways to increasing doses of methacholine with inhalative application of diazepam. The anthropometric data and lung function parameters are given in Table 1 and 2. Seven patients were women and five men. Their age ranged from 32 to 59 years. Only patients which FEV1 declined in more then 20% after inhalation of one of the doses of methacholine were analyzed. After application of methacholine dose of 0.6 mg/ mL, six (50%) subjects responded with an increase of resistance of more than 20%,after application of methacholine dose of 0.2 and 6.0 mg/ml, four patients had the same response, and two patients (16.6%) had significant bronchoconstriction to methacholine dose of 2.0 mg/mL. The characteristic response to increasing doses Rev Med Chile 2016; 144: 434-441


Abril 2016
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