Rodrigo C, Rodrigo G
Centro de Tratamiento Intensivo, Asociación Española Primera de Socorros Mutuos, Montevideo, Uruguay.
Am J Emerg Med. 1998 Nov;16(7):637-42. doi: 10.1016/s0735-6757(98)90164-4.
The objectives of this study were to compare the efficacy of salbutamol delivered by either metered-dose inhaler plus spacer (MDI-spacer) or by wet nebulization (NEB), and to determine the relationships between physiologic responses and plasma salbutamol concentrations. Asthmatic patients presenting to the emergency department (ED) with acute severe asthma (forced expiratory volume in the first second [FEV1] less than 50% of predicted) were enrolled in a randomized, double-blind, parallel-group study. The MDI-spacer group received salbutamol, delivered via MDI into a spacer device, in four puffs actuated in rapid succession at 10-minute intervals (2.4 mg/h). The NEB group was treated with nebulized salbutamol, 1.5 mg, via nebulizer at 15-minute intervals (6 mg/h). Doses were calculated on the basis of the percentage of total dose that reaches the lower airway with both methods. The protocol involved 3 hours of this treatment. Mean peak expiratory flow rate (PEFR) and FEV1 improved significantly over baseline values for both groups (P=.01). However, there were no significant differences between both groups for PEFR and FEV1 at any point studied. The examination of the relationships between cumulative dose of salbutamol and change in FEV1 showed a significant linear relationship (P=.01) for both methods (MDI r=.97; NEB r=.97). The regression equations showed that for every 1 mg of salbutamol by MDI-spacer, 2.5 mg are needed from nebulization to have equal therapeutic response. At the end of treatment, the salbutamol plasma levels were 10.1+/-1.6 ng/ml for the MDI-spacer group and 14.4+/-2.3 ng/ml for the NEB group (P=.0003). Both groups showed a nonsignificant heart rate decrease. A significant group-by-time interaction means that differences between groups increased with time (P=.04). Additionally, the NEB group presented a higher incidence of tremor (P=.03) and anxiety (P=.04), reflecting larger systemic absorption of salbutamol. These data indicate that when doses used are calculated on the basis of the percentage of total drug that reaches the lower airway, there was equivalent bronchodilatation after salbutamol administered by either MDI-spacer or nebulization in patients with acute severe asthma. However, nebulizer therapy produced greater side effects related to the increase in salbutamol absorption and higher plasma level.
本研究的目的是比较定量吸入器加储雾罐(MDI-储雾罐)或湿化雾化(NEB)方式给予沙丁胺醇的疗效,并确定生理反应与血浆沙丁胺醇浓度之间的关系。因急性重度哮喘(第一秒用力呼气容积[FEV1]低于预测值的50%)到急诊科(ED)就诊的哮喘患者被纳入一项随机、双盲、平行组研究。MDI-储雾罐组通过MDI将沙丁胺醇喷入储雾罐装置,每隔10分钟快速连续按压4次(2.4毫克/小时)。NEB组通过雾化器每隔15分钟给予雾化沙丁胺醇1.5毫克(6毫克/小时)。剂量根据两种方法到达下呼吸道的总剂量百分比计算。该方案包括3小时的这种治疗。两组的平均呼气峰值流速(PEFR)和FEV1均较基线值显著改善(P = 0.01)。然而,在任何研究时间点,两组的PEFR和FEV1均无显著差异。对沙丁胺醇累积剂量与FEV1变化之间关系的研究表明,两种方法均呈现显著的线性关系(P = 0.01)(MDI组r = 0.97;NEB组r = 0.97)。回归方程显示,通过MDI-储雾罐给予每1毫克沙丁胺醇,雾化给药需要2.5毫克才能产生同等治疗反应。治疗结束时,MDI-储雾罐组的血浆沙丁胺醇水平为10.1±1.6纳克/毫升,NEB组为14.4±2.3纳克/毫升(P = 0.0003)。两组心率均有非显著性下降。显著的组×时间交互作用意味着组间差异随时间增加(P = 0.04)。此外,NEB组震颤(P = 0.03)和焦虑(P = 0.04)的发生率更高,这反映了沙丁胺醇更大的全身吸收。这些数据表明,当根据到达下呼吸道的总药物百分比计算所用剂量时,急性重度哮喘患者通过MDI-储雾罐或雾化给予沙丁胺醇后支气管扩张效果相当。然而,雾化治疗因沙丁胺醇吸收增加和血浆水平升高产生了更多副作用。