Addition of intravenous aminophylline to beta2-agonists in adults with acute asthma

 

Abstract

Background

Aminophylline has been used extensively in acute asthma, but its role is unclear especially with respect to any additional benefit when added to beta2-agonists.

Objectives

To determine the magnitude of effect of the addition of intravenous aminophylline to beta2-agonists in adult patients with acute asthma treated in the emergency setting.

Search methods

Studies were identified from the following sources: The Cochrane Airways Group register (derived from MEDLINE, EMBASE, CINAHL standardised searches), hand searched respiratory journals and meeting abstracts. Potentially relevant articles were obtained, and their bibliographic lists were hand searched for additional articles. The search included searches of the database up to 1999.

Selection criteria

Randomised controlled trials comparing intravenous aminophylline versus placebo in adults with acute asthma and treated with beta-adrenergic agonists. Patients could be treated with or without corticosteroids or other bronchodilators.

Data collection and analysis

A total of 210 abstracts were identified. Two independent reviewers selected a total of 27 eligible studies for possible inclusion, in which quality assessment was performed and a third reviewer was used to adjudicate disagreements. Peak expiratory flow (PEFR) and forced expiratory volume in the first second (FEV1) data were extracted and entered in Review Manager from these studies. Information not obtained from the authors was estimated from graphs. All data were entered and double checked by two reviewers. Results are reported as weighted mean differences (WMD) or odds ratio (OR), both with 95% confidential intervals (CI).

Main results

Fifteen studies were included. Overall, the quality of the studies was only moderate; concealment of allocation was assessed as clearly adequate in only seven (45%) of the trials. The doses of aminophylline and other medications and the severity of asthma varied between studies.

There was no statistically significant effect of aminophylline on airflow outcomes at any time period. The aminophylline treated group had higher values of PEFR at 12 (PEFR 8 L/min or 2.3%) and 24 hours (PEFR 22 L/min or 6.4%), but these were not significant (p>0.05). Two subgroup analyses were performed by grouping studies according to mean baseline airflow limitation (n = 11 studies) and the use of any steroids (n = 9 studies). There was no relationship between baseline airflow limitation nor the use of steroids on the effect of aminophylline. Aminophylline treated patients reported more palpitations/arrhythmias (OR: 2.9; 95% CI: 1.5 to 5.7) and vomiting (OR: 4.2; 95% CI 2.4 to 7.4), but no difference was found in tremor or hospital admissions.

Authors' conclusions

In acute asthma, the use of intravenous aminophylline did not result in any additional bronchodilation compared to standard care with beta-agonists. The frequency of adverse effects was higher with aminophylline. No subgroups in which aminophylline might be more effective could be identified. These results should be added to consensus statements and guidelines.

 

Plain language summary

The effects of intravenous aminophylline when added to bronchodilator drugs for acute asthma

In an asthma attack, the airways (passages to the lungs) narrow from muscle spasms and swelling (inflammation), which can cause breathing problems, wheezing and coughing. Attacks can be fatal. The main drugs used to relieve a major asthma attack are bronchodilators (reliever inhalers to open up the lungs and airways) for the spasms, and corticosteroids for the swelling. The drug aminophylline has also been used intravenously (through the veins). However, the review of trials found that aminophylline is no better than other bronchodilator drugs, and has more adverse effects.

 

摘要

背景

以Beta2作用劑加靜脈注射aminophylline治療急性氣喘成人

Aminophylline廣泛使用於急性氣喘的治療，但角色不明，尤其當添加到beta2作用劑時，是否產生額外的效益，目前並不清楚。

目標

確定－在急診室使用beta2作用劑治療急性氣喘成人時，添加靜脈注射aminophylline的有效程度。

搜尋策略

從以下資料庫找出研究：Cochrane Airways Group register (MEDLINE、EMBASE、CINAHL標準化搜尋)、人工搜尋呼吸道期刊及會議摘要。取得可能相關文章後，再以人工搜尋其參考資料表以找出更多的文章。本次搜尋資料庫時間到1999年為止。

選擇標準

對於接受乙型腎上腺作用劑治療的成年急性氣喘患者，比較靜脈注射aminophylline或安慰劑的隨機對照試驗。病患可能有或沒有接受皮質類固醇或其他支氣管擴張劑治療。

資料收集與分析

共找到210篇摘要。兩位審查員選取共27篇可能納入的適當研究，進行品質評估；有爭議時則交給第三位審查員仲裁。從這些研究中擷取尖峰吐氣流量(PEFR)和第1秒用力吐氣量(FEV1)數據，輸入Review Manager。無法從作者那裡取得的資料則由圖形推估而來。輸入所有數據，並由兩位審查員仔細檢查。以加權平均差(WMD)或危險對比值(OR)(兩者都附有95%信賴區間 [CI])呈現報告結果。

主要結論

共選入15篇研究。整體而言，這些研究的品質只是中等。其中只有七篇(45%)試驗符合分組隱匿(concealment of allocation)的標準。各個研究的aminophylline和其他藥物的劑量、氣喘的嚴重程度各不相同。無論在哪一時期，aminophylline對呼吸道氣流的影響結果都沒有統計學上的意義。Aminophylline治療組在12小時(PEFR 8 公升/分鐘，或2.3%)和24小時(PEFR 22公升/分鐘，或 6.4%)的PEFR值較高，但不具意義(p>0.05)。 根據平均基礎氣流限制(n = 11項研究)和類固醇的使用(n = 9項研究)進行分組研究，並作兩項次組分析。無論是基礎氣流限制或類固醇的使用，都與aminophylline的作用沒有關係。aminophylline治療組有較多的心悸/心律不整(危險對比值：2.9；95% 信賴區間：1.5 到 5.7)和嘔吐(危險對比值：4.2；95% 信賴區間：2.4 到 7.4)。在震顫或住院率方面則沒有差異。

作者結論

對急性氣喘患者，靜脈注射aminophylline與使用乙型作用劑的標準治療相比，並不會產生額外的支氣管擴張作用。副作用頻率在aminophylline組較高。也沒有任何次組分析顯示：aminophylline可能比較有效。 這些結果應該被加入共識聲明和指引中。

翻譯人

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

總結

對於因氣喘發作被送到醫院急診室的病患，靜脈注射aminophylline不但沒有比其他支氣管擴張劑來得有效，而且還會產生較多的副作用。氣喘發作時，呼吸道因肌肉痙攣和腫脹(發炎)而變得狹窄，造成呼吸困難、哮喘和咳嗽。發作可能是致命的。用於舒緩氣喘發作的主要藥物是－支氣管擴張劑(具紓解功能的吸入器[Reliever Inhaler]，以打開肺臟和呼吸道)治療痙攣，以及皮質類固醇治療腫脹。Aminophylline 這一類藥物也曾經由靜脈注射使用。然而，本回顧發現：aminophylline非但沒有比其他支氣管擴張劑有效，而且還有較多的副作用。