Travers Andrew H, Jones Arthur P, Camargo Carlos A, Milan Stephen J, Rowe Brian H
Department of Emergency Medicine and Community Health and Epidemiology, Emergency Health Services, Nova Scotia, Canada.
Cochrane Database Syst Rev. 2012 Dec 12;12(12):CD010256. doi: 10.1002/14651858.CD010256.
Inhaled beta(2)-agonist therapy is central to the management of acute asthma. For rapid bronchodilation in severe cases, penetration of inhaled drug to the affected small conducting airway may be impeded, and the intravenous (IV) rather than inhaled administration of bronchodilators may provide an earlier response. IV beta(2)-agonist agents and IV aminophylline may also be considered as additional interventions in this setting and this review compares IV beta-agonist agents and IV aminophylline in the treatment of people with acute asthma.
To compare the benefit of IV beta(2)-agonists versus IV aminophylline for acute asthma treated in the emergency department and in patients admitted to hospital with acute severe asthma.
Randomised controlled trials (RCTs) were identified using the Cochrane Airways Group Register, which is compiled from systematic searches of bibliographic databases as well as handsearching of respiratory journals and conference abstracts. The latest search was run in September 2012. We searched bibliographies from included studies and known reviews were also searched. Primary authors and content experts were contacted to identify eligible studies.
We included RCTs of patients who presented to the emergency department with acute asthma, and patients admitted to hospital with acute severe asthma, and were treated with IV beta(2)-agonists versus IV aminophylline. Two review authors independently selected potentially relevant articles and selected articles for inclusion. Methodological quality was independently assessed using two scoring systems and two review authors.
Data were extracted independently by two review authors. Missing data were obtained from authors or calculated from data present in the papers. Trials were combined using a random-effects model for odds ratios (OR) or mean differences (MD) and reported with 95% confidence intervals (95% CI).
Eleven studies met our inclusion criteria and in total they included 350 patients. However, opportunities to combine these studies in meta-analyses were limited by the variations in the range of outcomes reported in the trials.Length of stayTwo studies reported length of stay. They were both paediatric trials (with one in paediatric intensive care unit), and there was no significant difference between the two groups (MD 23.19 hours; 95% CI -2.40 to 48.77 hours; 2 studies; N = 73). Individual separate MD analyses for the two studies also indicated no significant difference between the aminophylline and beta(2)-agonist on this outcome. However, this finding should be interpreted with caution owing to the small number of trials and participants the analysis.Pulmonary functionThere were no significant differences in the sequential or summative pulmonary function demonstrated across the studies.Heart rateData for serial heart rates were reported in three studies at various points from 15 to 60 minutes and in each case there were no significant differences between people in the IV aminophylline or beta(2)-agonist groups. The difference between the two groups with respect to final heart rate was statistically significant (MD 10.00; 95% CI 0.99 to 19.01), although these data are from a single, small study and should be interpreted with caution.Adverse effectsThe analyses for giddiness (OR 59.22; 95% CI 2.80 to 1253.05; 1 study; N = 30), nausea/vomiting (where reported as a combined outcome) (OR 14.18; 95% CI 1.62 to 124.52; 2 studies; N = 96) and nausea (OR 6.53; 95% CI 1.60 to 26.72; 2 studies; N = 49) all significantly favoured beta(2)-agonists. In view of the very small number of studies and number of patients contributing to these analyses these results should be interpreted with caution. A closely related review considering the possible benefits of adding IV aminophylline to beta-agonists in adults with acute asthma also indicates a higher incidence of adverse effects associated with IV aminophylline.
AUTHORS' CONCLUSIONS: In the included RCTs there was no consistent evidence favouring either IV beta(2)-agonists or IV aminophylline for patients with acute asthma. The opportunity to draw clear conclusions is limited by the heterogeneity of outcomes evaluated and the small sample sizes in the included studies. It is recommended that these data should be viewed carefully alongside the conclusions from separate Cochrane reviews comparing IV beta(2)-agonists plus inhaled beta(2)-agonists versus inhaled beta(2)-agonists alone and IV aminophylline plus inhaled beta(2)-agonists versus inhaled beta(2)-agonists alone.
吸入β₂受体激动剂疗法是急性哮喘治疗的核心。对于重症病例的快速支气管扩张,吸入药物向受影响的小传导气道的渗透可能会受到阻碍,而静脉注射(IV)而非吸入支气管扩张剂可能会提供更早的反应。静脉注射β₂受体激动剂和静脉注射氨茶碱也可被视为这种情况下的额外干预措施,本综述比较了静脉注射β受体激动剂和静脉注射氨茶碱在急性哮喘患者治疗中的效果。
比较静脉注射β₂受体激动剂与静脉注射氨茶碱对急诊科治疗的急性哮喘患者以及因急性重度哮喘入院患者的疗效。
使用Cochrane Airways Group Register识别随机对照试验(RCT),该注册库是通过对书目数据库的系统检索以及对呼吸杂志和会议摘要的手工检索编制而成。最新检索于2012年9月进行。我们检索了纳入研究的参考文献,也检索了已知的综述。联系了主要作者和内容专家以识别符合条件的研究。
我们纳入了因急性哮喘就诊于急诊科的患者以及因急性重度哮喘入院且接受静脉注射β₂受体激动剂与静脉注射氨茶碱治疗的患者的RCT。两位综述作者独立选择潜在相关文章并选择纳入文章。使用两个评分系统和两位综述作者独立评估方法学质量。
数据由两位综述作者独立提取。缺失数据从作者处获取或根据论文中的数据计算得出。试验使用随机效应模型合并以计算比值比(OR)或均值差(MD),并报告95%置信区间(95%CI)。
11项研究符合我们的纳入标准,总共纳入了350名患者。然而,由于试验中报告的结果范围存在差异,将这些研究纳入荟萃分析的机会有限。
两项研究报告了住院时间。它们均为儿科试验(其中一项在儿科重症监护病房),两组之间无显著差异(MD 23.19小时;95%CI -2.40至48.77小时;2项研究;N = 73)。对这两项研究分别进行的MD分析也表明氨茶碱和β₂受体激动剂在该结果上无显著差异。然而,由于试验和参与者数量较少,该发现应谨慎解释。
各项研究中序贯或综合肺功能均无显著差异。
三项研究在15至60分钟的不同时间点报告了连续心率数据,每种情况下静脉注射氨茶碱组或β₂受体激动剂组患者之间均无显著差异。两组最终心率的差异具有统计学意义(MD 10.00;95%CI 0.99至19.01),尽管这些数据来自一项单一的小型研究,应谨慎解释。
关于头晕(OR 59.22;95%CI 2.80至1253.05;1项研究;N = 30)、恶心/呕吐(合并结果报告时)(OR 14.18;95%CI 1.62至124.52;2项研究;N = 96)和恶心(OR 6.53;95%CI 1.60至26.72;2项研究;N = 49)的分析均显著支持β₂受体激动剂。鉴于参与这些分析的研究和患者数量非常少,这些结果应谨慎解释。一项密切相关的综述考虑了在成人急性哮喘患者中β受体激动剂加静脉注射氨茶碱的可能益处,也表明与静脉注射氨茶碱相关的不良反应发生率更高。
在纳入的RCT中,没有一致的证据表明静脉注射β₂受体激动剂或静脉注射氨茶碱对急性哮喘患者更有利。由于评估结果的异质性以及纳入研究的样本量较小,得出明确结论的机会有限。建议将这些数据与Cochrane单独的综述结论一起仔细看待,这些综述比较了静脉注射β₂受体激动剂加吸入β₂受体激动剂与单独吸入β₂受体激动剂以及静脉注射氨茶碱加吸入β₂受体激动剂与单独吸入β₂受体激动剂的效果。