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Combined inhaled anticholinergics and beta2-agonists for initial treatment of acute asthma in children

  • Review
  • Intervention

Authors

  • Laurie Plotnick,

    Corresponding author
    1. The Montreal Children's Hospital, McGill University, Department of Paedriatrics, Montreal, Quebec, Canada
    • Laurie Plotnick, Department of Paedriatrics, The Montreal Children's Hospital, McGill University, Room C538E, 2300 Tupper Street, Montreal, Quebec, H3H 1P3, Canada. drplotnick@sympatico.ca.

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  • Francine Ducharme

    1. McGill University Health Centre, Department of Pediatrics, Montreal, Quebec, Canada
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Abstract

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 methods

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] favoured 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.

Authors' 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.

摘要

背景

合併使用吸入性抗乙醯膽鹼藥劑(anticholinergics)及第二型乙型交感神經興奮劑(beta2agonists)治療孩童急性氣喘

多項隨機對照實驗(randomized controlled trials) 曾針對第二型乙型交感神經興奮劑附加抗乙醯膽鹼藥劑治療孩童急性氣喘的效果做過研究調查,然而得到的結果卻有所衝突。匯集大量的隨機對照試驗結果,不但可能提供較有力的證據以分辨各組差異,也更能分析了解患者的特徵及各治療方式的療效。

目標

此研究的目的在評估第二型乙型交感神經興奮劑附加抗乙醯膽鹼藥劑治療孩童急性氣喘的治療效果及負面影響。

搜尋策略

我們搜尋MEDLINE (1966 to April 2000)、EMBASE (1980 to April 2000)、CINAHL (1982 to April 2000) 以及各研究列舉的參考文獻。同時也聯繫藥物製造者及試驗者。

選擇標準

隨機對照實驗對於患有急性氣喘者接受第二型乙型交感神經興奮劑附加抗乙醯膽鹼藥劑或單獨接受第二型乙型交感神經興奮劑治療的18個月大至17歲兒童作比較。

資料收集與分析

由兩個檢閱者獨立進行試驗品質的評估及資料的擷取。

主要結論

在40項試驗中,13項符合主題要求,其中8項品質較佳。第二型乙型交感神經興奮劑附加單一劑量抗乙醯膽鹼藥劑並不會減少住院時間[RR=0.93 (95% CI: 0.65, 1.32)]。然而,在不同的群組間觀察到明顯的肺功能差異(給予抗乙醯膽鹼藥劑60分鐘後[SMD=0.57 (95% CI:0.21, 0.93)] 及120分鐘後[SMD=0.53 (95% CI: 0.17, 0.90)] )證實了第二型乙型交感神經興奮劑附加單一劑量抗乙醯膽鹼藥劑的功效。相對的,第二型乙型交感神經興奮劑附加多劑量抗乙醯膽鹼藥劑可使中度至嚴重發作的孩童減少25%需住院的風險[RR=0.75 (95% CI: 0.62,0.89)]。每12個小孩接受治療可以避免一個住院病例(95% CI: 8, 32),當限制條件為嚴重發作的孩童時,則每7個小孩接受治療可以避免一個住院病例(95% CI: 5, 20)。在吸入抗乙醯膽鹼藥劑60分鐘後,會有9.68的加權平均群組差異(weighted mean group difference) 改變百分比預測一秒最大呼氣量(% predicted FEV1)[95% CI:5.70, 13.68]支持抗乙醯膽鹼藥劑的使用。在2個研究中,不論患者氣喘嚴重度,給予吸入性第二型乙型交感神經興奮劑及系統性得附加抗乙醯膽鹼藥劑,結果並無明顯的群組間差異。給予抗乙醯膽鹼藥劑的患者並無增加噁心、嘔吐及震顫的現象。

作者結論

單一劑量抗乙醯膽鹼藥劑對輕度及中度氣喘發作並非有效的治療方式,對嚴重患者則不適當。第二型乙型交感神經興奮劑附加多劑量抗乙醯膽鹼藥劑是安全的,且能改善肺部功能及每12個接受治療病童可減少一住院病例。雖然多劑量抗乙醯膽鹼藥劑較單一劑量佳,但現有證據只支持使用在嚴重發作的學齡孩童。並無確切證據支持輕度及中度發作患者使用多劑量抗乙醯膽鹼藥劑。

翻譯人

本摘要由國泰綜合醫院劉怡敏翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan) 統籌。

總結

給予正確劑量的抗乙醯膽鹼藥劑附加於第二型乙型交感神經興奮劑可以減緩孩童嚴重的氣喘症狀及因肌肉痙攣產生的呼吸道狹窄。支氣管擴張劑(reliever inhalers)能鬆弛呼吸道肌肉,進而打開呼吸道使能輕鬆呼吸。抗乙醯膽鹼藥劑對肌肉也有同樣效果,因此有時可用在嚴重氣喘發作的孩童身上作為支氣管擴張劑。在文獻的回顧中發現同時使用此兩類藥物能改善嚴重氣喘發作孩童的預後,雖然並無明顯證據對輕度及中度發作患者有效。儘管此額外的藥物是安全的,但更多研究以找出可能的藥物不良反應是必要的。

Plain language summary

Combined inhaled anticholinergics and beta2-agonists for initial treatment of acute asthma in children

In an asthma attack, the airways (passages to the lungs) narrow from muscle spasms. Bronchodilators (reliever inhalers) relax the muscles in the airways, opening the airways so breathing is easier. Anti-cholinergic drugs can also affect these muscles, and so are sometimes used as well as bronchodilators when children have severe asthma attacks. The review of trials found using both drugs together improves outcomes for children with severe asthma attacks, although there is not enough evidence about effects for children with mild or moderate attacks. More research on possible adverse effects of the extra drug is needed, although it seems safe.

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