BACKGROUND:Several randomized controlled trials have examined, with conflicting results, the efficacy of the addition of anticholinergics to beta2 agonists in acute pediatric asthma. The pooling for a larger number of randomized controlled trials may provide not only greater power for detecting group differences and also provide better insight into the influence of patients' characteristics and treatment modalities on efficacy. OBJECTIVES:The aims of this study were to estimate the therapeutic and adverse effects attributable to the addition of inhaled anticholinergics to beta2 agonists in acute pediatric asthma. SEARCH STRATEGY:We searched Medline (1966 to April 2000), Embase (1980 to April 2000), Cinahl (1982 to April 2000) and reference lists of studies. We also contacted drug manufacturers and trialists. SELECTION CRITERIA:Randomised trials comparing the combination of inhaled anticholinergics and beta2 agonists with beta2 agonists alone in children aged 18 months to 17 years with acute asthma. DATA COLLECTION AND ANALYSIS:Assessments of trial quality and data extraction were done by two reviewers independently. MAIN RESULTS:Of the 40 identified trials, 13 were relevant and eight of these were of high quality. The addition of a single dose of anticholinergic to beta2 agonists did not reduce hospital admission [RR=0.93 (95% CI: 0.65, 1.32)]. However, significant group differences in lung function supporting the combination of anticholinergics and beta2-agonists were observed 60 minutes [SMD=0.57 (95% CI:0.21, 0.93)] and 120 minutes [SMD=0.53 (95% CI: 0.17, 0.90)] after the dose of anticholinergic. In contrast, the addition of multiple doses of anticholinergics to beta2 agonists reduced the risk of hospital admission by 25% [RR=0.75 (95% CI: 0.62,0.89)] in children with predominantly moderate and severe exacerbations. Twelve (95% CI: 8, 32) children would need to be treated to avoid one admission. When restricting this strategy to children with severe exacerbations, seven (95% CI: 5, 20) children need to be treated to avoid an admission. At 60 minutes after the last anticholinergic inhalation, a weighted mean group difference of 9.68 in change in % predicted FEV1 [95% CI:5.70, 13.68] favored anticholinergic use. In the two studies where anticholinergics were systematically added to every beta2 agonist inhalation, irrespective of asthma severity, no group differences were observed for the few available outcomes. There was no increase in the amount of nausea, vomiting or tremor in patients treated with anticholinergics. REVIEWER'S CONCLUSIONS:A single dose of an anticholinergic agent is not effective for the treatment of mild and moderate exacerbations and is insufficient for the treatment of severe exacerbations. Adding multiple doses of anticholinergics to beta2 agonists appears safe, improves lung function and would avoid hospital admission in 1 of 12 such treated patients. Although multiple doses should be preferred to single doses of anticholinergics, the available evidence only supports their use in school-aged children with severe asthma exacerbation. There is no conclusive evidence for using multiple doses of anticholinergics in children with mild or moderate exacerbations.

译文

摘要背景:几项随机对照试验已经检验了在急性小儿哮喘中向β2激动剂中添加抗胆碱能药的疗效,但结果相互矛盾。大量随机对照试验的汇集不仅可以提供更大的检测组差异的能力,还可以更好地了解患者的特征和治疗方式对疗效的影响。
目的:本研究的目的是评估在急性小儿哮喘中将吸入性抗胆碱能药添加到β2激动剂中所引起的治疗和不良反应。
搜索策略:我们检索了Medline(1966年至2000年4月),Embase(1980年至2000年4月),Cinahl(1982年至2000年4月)和参考研究清单。我们还联系了药品制造商和试验人员。
选择标准:随机对照试验比较了18个月至17岁急性哮喘儿童中吸入抗胆碱能药和β2激动剂与单独使用β2激动剂的组合。
数据收集与分析:两名审稿人分别对试验质量和数据提取进行评估。
主要结果:在40项确定的试验中,有13项是相关的,其中8项是高质量的。在β2激动剂中添加单剂量抗胆碱药并不能减少住院率[RR = 0.93(95%CI:0.65,1.32)]。然而,观察到60分钟[SMD = 0.57(95%CI:0.21,0.93)]和120分钟[SMD = 0.53(95%CI:0.17,0.90) )]服用抗胆碱药后。相比之下,在以中度和重度急性发作为主的儿童中,向β2激动剂中添加多剂量的抗胆碱能药可使入院风险降低25%[RR = 0.75(95%CI:0.62,0.89)]。需要治疗十二名儿童(95%CI:8、32),以避免一次入院。当将这种策略限制为严重加重的儿童时,需要治疗七名(95%CI:5、20)儿童,避免入院。在最后一次抗胆碱能吸入后60分钟,加权平均组差异9.68的预测FEV1的变化百分比[95%CI:5.70,13.68]有利于抗胆碱能的使用。在两项研究中,每次吸入β2激动剂均系统地添加了抗胆碱药,而与哮喘的严重程度无关,在少数可获得的结果中未观察到组别差异。抗胆碱能药物治疗的患者的恶心,呕吐或震颤没有增加。
评论者的结论:单剂抗胆碱能药对轻度和中度加重无效,对重度加重也无效。在β2激动剂中添加多剂量的抗胆碱药似乎是安全的,可以改善肺功能,并且可以避免12名接受这种治疗的患者中的1名入院。尽管应该比单剂抗胆碱药更优选多剂,但现有证据仅支持将其用于严重哮喘加重的学龄儿童。没有确凿证据表明在轻度或中度加重的儿童中使用多剂量的抗胆碱能药。

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