Determinação das concentrações plasmáticas de salbutamol pós-nebulização em serviço de emergência pediátrica / Determination of plasma salbutamol concentrations after nebulization in a pediatric emergency department

OBJETIVOS: Validar parcialmente a metodologia para determinação do salbutamol em plasma humano por cromatografia líquida de alta eficiência (detecção por fluorescência). Analisar as concentrações plasmáticas de salbutamol em um grupo de pacientes pediátricos com indicação de nebulizações em sala de emergência. MÉTODO: Estudo transversal, analítico, prospectivo, do tipo série de casos. Foram selecionados consecutivamente 15 pacientes com idade entre 12 e 37meses, com diagnóstico de crise aguda de asma, atendidos no Serviço de Emergência Pediátrica do Hospital da Criança Santo Antônio - Complexo Hospitalar Santa Casa, Porto Alegre, Brasil. Os pacientes foram tratados conforme a rotina da unidade para manejo de crise aguda de asma: nebulização (fluxo 6-8 L/min) com salbutamol (0,15 mg/kg) diluídosem4mL de NaCL 0,9 por cento. A nebulização era administrada seqüencialmente, em intervalos de 20 minutos, por três vezes. Concomitantemente às nebulizações, todos os pacientes recebiam prednisolona via oral (1 mg/kg). RESULTADOS: As concentrações plasmáticas evidenciaram grande variabilidade em portadores de crise aguda de asma que receberam três nebulizações com salbutamol (0,15 mg/kg). Níveis plasmáticos médios foram de 12,09±10,8 ng/mL, com mediana de 8,9 (IQ25-75 por cento 2,75-17,65) e coeficiente de variação da amostra de 92,4 por cento. CONCLUSÕES: As concentrações plasmáticas após inalação de salbutamol apresentam grande dispersão na população pediátrica, a exemplo de outros estudos. As possíveis causas e implicações relacionadas ao achado permanecem alvo de controvérsias e avaliações complementares.

OBJECTIVES: To partially validate the methodology for determining salbutamol in human plasma through high-efficiency liquid chromatography and fluorescence detection. To analyze plasma salbutamol concentrations in a group of pediatric patients with indication for nebulization in the emergency room. METHOD: Analytical, prospective cross-sectional case series. Fifteen patients aged 12 to 37 months with a diagnosis of acute asthma crisis were selected at the Pediatric Emergency Service at Hospital da Criança Santo Antônio - Complexo Hospitalar Santa Casa, Porto Alegre, Brazil. The patients were treated following the unit's routine for the management of acute asthma crises: nebulization with salbutamol (flow rate of 6-8 L/min) (0.15 mg/kg) suspended in 4 mL of 0.9 percent saline solution. Nebulization was administered sequentially, three times, at 20 minute intervals. All patients were given prednisolone orally (1 mg/kg) concurrently with the nebulizations. RESULTS: Plasma concentrations exhibited great variability in acute asthma crisis patients given three nebulizations of salbutamol (0.15 mg/kg). The mean level in plasma was 12.09 ± 10.8 ng/mL, with a median of 8.9 ng/mL (IQ25-75 percent 2.75-17.65). The sample's coefficient of variation was 92.4 percent. CONCLUSIONS: Post-inhalation plasma salbutamol concentrations exhibit great variation in the pediatric population, as seen in other studies. The possible causes and implications of this finding remain the subject of disagreements and of further assessments.

Beneficios clínicos y funcionales de agregar teofilina a la terapia inhalatoria con broncodilatadores de acción corta en pacientes con enfermedad pulmonar obstructiva crónica / Clinical and functional benefits of adding theophylline to a standard treatment with short acting bronchodilators in patients with COPD

Background: Although theophylline is considered a third line bronchodilator drug for the treatment of chronic obstructive pulmonary disease (COPD), it is widely used in Chile, because it is administered orally and has a moderate cost. Aim: To evaluate if theophylline adds clinical and/or functional benefits when associated to standard recommended inhaled bronchodilator therapy. Subjects and methods: Thirty-eight stable COPD patients who accepted to participate in the study approved by the Ethics Committee of our institution were studied. Using a randomized double-blind placebo-controlled study, theophylline (250 mg) or placebo was administered twice a day for 15 days in addition to inhaled salbutamol and ipratropium bromide. Prior to and at the end of the study, patients underwent: a) a spirometry to evaluate changes in dynamic pulmonary hyperinflation using slow vital capacity (SVC) and inspiratory capacity (IC), b) the 6 min walking distance (6 MWD); and c) measurement of maximal inspiratory and expiratory pressures. Dyspnea and quality of life (QoL) were evaluated using appropriate questionnaires. Results: Compared to placebo, patients on theophylline showed significant increases in SVC (p=0.014), IC (p=0.002), and 6 MWD (p=0.005). They also experienced an improvement in dyspnea (p=0.042) and QoL (p=0.011). All patients improved at least one of these parameters with 53% of the patients showing an improvement in 3 or more. Conclusions: Our results indicate that adding theophylline to standard treatment with inhaled bronchodilators provides additional benefits in stable COPD patients by reducing dynamic pulmonary hyperinflation, improving exercise tolerance, dyspnea and QoL.

Theophylline blood levels in Sri Lankan asthmatics: comparison of two methods of assay.

OBJECTIVES: To assay theophylline blood levels in a sample of Sri Lankan chronic asthmatics taking oral theophylline, and to evaluate a simple and cost effective ultraviolet spectrophotometric assay for theophylline levels in blood. SETTING: Chronic asthmatics taking oral theophylline attending medical clinics at the National Hospital of Sri Lanka (NHSL) were recruited for the study. Blood samples were collected from recruited patients on their subsequent clinic visit. DESIGN AND METHODS: A cross-sectional study of theophylline blood levels. Blood samples were assayed for trough theophylline levels using two methods: an automated homogeneous enzyme immunoassay (EMIT), and a low cost ultraviolet spectrophotometric method. RESULTS: Only 2 patients of the 24 had theophylline blood levels in the accepted therapeutic range (10 to 20 micrograms/ml) (3.4); 19 patients had levels under 5 micrograms/ml. A correlation coefficient of 0.99 was obtained in the statistical comparison of the two methods, indicating that the spectrophotometric method has similar accuracy as the reference EMIT assay. CONCLUSIONS: The results signal a need for monitoring of theophylline in asthmatics when accepted clinical indications are present. The ultraviolet spectrophotometric method is ideal to initiate therapeutic drug monitoring (TDM) in the country because of its low cost (about Rs. 55 per assay), requiring only a UV recording spectrophotometer.

Comparative steady-state bioavailability of sustained-release theophylline preparations: Theo-Dur, Uni-Dur and Xanthium.

Steady-state bioavailability of sustained-release theophylline (SRT); Theo-Dur, Uni-Dur and Xanthium were compared in 10 healthy males with theophylline clearance ranged from 0.3 - 0.8 ml/min/kg. Each of 400-mg SRT was administered once daily before breakfast for 7 consecutive days, one-week washout period in a crossover fashion. Serial blood samples were collected over 24 hours on days 6 and 7. Serum theophylline concentrations were determined by fluorescence polarized immunoassay. We found that the oral bloavailability relative to Franol (%F [90% CI]) of Theo-Dur, Uni-Dur and Xanthium were 97 (93-106), 85 (79-96) and 77 (72-87), respectively. Average bioequivalence revealed that the Css(min) (microg/ml) of Uni-Dur (5.07) was higher than Theo-Dur (4.29), and Xanthiume (4.18), while the Css(max) and Css(av) (microg/ml) of Theo-Dur (11.02, 7.87) were statistically higher than Uni-Dur (8.51, 6.91) and Xanthium (7.65, 6.27). The extent of absorption assessed by AUCss(0.24) of Theo-Dur was significantly greater than Uni-Dur and Xanthium. However, fluctuation index (% FI) of Theo-Dur (232) was twofold higher than Uni-Dur (137) and Xanthium (113). The median Tss(max) of Uni-Dur was 12 hours which was significantly longer than Xanthium (7 hours) and Theo-Dur (8 hours). There were no statistically significant differences between Uni-Dur and Xanthium regarding bioavailability, Css(max), Css(av) as well as % FI. Moreover, 400 mg OD of Uni-Dur and Xanthium are suitable for subjects with a theophylline clearance of 0.3-0.55 ml/min/kg while 400 mg OD Theo-Dur can be used in subjects with slower clearance rates of 0.3-0.39 ml/min/kg. Subjects with rapid theophylline clearance rates of 0.65-0.8 ml/min/kg required a higher dose of theophylline and twice-daily dosing was more appropriate.