Intravenous aminophylline for acute severe asthma in children over two years receiving inhaled bronchodilators

 

Abstract

Background

Since the advent of inhaled ß₂ -agonists, anticholinergic agents and glucocorticoids, the role of aminophylline in paediatric acute asthma has become less clear. There remains some consensus that it is beneficial in children with acute severe asthma, receiving maximised therapy (oxygen, inhaled bronchodilators, and glucocorticoids).

Objectives

To determine if the addition of intravenous aminophylline produces a beneficial effect in children with acute severe asthma receiving conventional therapy.

Search methods

The Cochrane Airways Group register of trials was used to identify relevant studies. The latest search was carried out in February 2007.

Selection criteria

Randomised-controlled trials comparing intravenous aminophylline with placebo in addition to usual care in children met the inclusion criteria.

Data collection and analysis

Two reviewers independently assessed studies and extracted data. Disagreement in the selection of trials was resolved by consensus. Attempts were made to contact authors to verify accuracy of data.

Main results

Seven trials met the inclusion criteria (380 participants). Methodological quality was high. All studies recruited children with acute severe asthma and requiring hospital admission. Six studies sought participants who were unresponsive to nebulised short-acting beta-agonist and administered systemic steroids to study participants. In two studies where some children were able to perform spirometry, baseline FEV₁ was between 35 and 45% predicted. The addition of aminophylline to steroids and ß₂-agonist significantly improved FEV₁% predicted over placebo at 6-8 hours, 12-18 hours and 24 hours. Aminophylline led to a greater improvement in PEF% predicted over placebo at 12-18 hours. There was no significant difference in length of hospital stay, symptoms, frequency of nebulisations and mechanical ventilation rates. There were insufficient data to permit aggregation for oxygenation and duration of supplemental oxygen therapy. Aminophylline led to a three-fold increase in the risk of vomiting. There was no significant difference between treatment groups with regard to hypokalaemia, headaches, tremor, seizures, arrhythmias and deaths.

Authors' conclusions

In children with a severe asthma exacerbation, the addition of intravenous aminophylline to ß₂-agonists and glucocorticoids (with or without anticholinergics) improves lung function within 6 hours of treatment. However there is no apparent reduction in symptoms, number of nebulised treatment and length of hospital stay. There is insufficient evidence to assess the impact on oxygenation, PICU admission and mechanical ventilation. Aminophylline is associated with a significant increased risk of vomiting.

 

Plain language summary

Intravenous aminophylline for acute severe asthma in children over two years receiving inhaled bronchodilators

Acute asthma is a common paediatric emergency prevalent in many countries. Treatment aims to reverse asthma by opening up the airways and targeting the underlying inflammation of the airways. Beta-agonists, anticholinergic agents and glucocorticoids are currently the most commonly used strategies. In the past, aminophylline has been extensively used for the management of acute asthma, despite side effects. However, its use has declined with the availability of effective inhaled bronchodilators and glucocorticoids. The purpose of this review was to assess whether the use of intravenous aminophylline in children receiving maximised inhaled bronchodilators and glucocorticoids produced additional beneficial effects. We identified a small number of good quality trials which compared aminophylline with placebo in children given inhaled bronchodilators and glucocorticoid therapy. This review found evidence that children treated with aminophylline had a greater improvement in lung function than children treated with placebo, when both groups received inhaled bronchodilators and steroids and they responded incompletely to these initial therapies. However, aminophylline use also resulted in greater risk of vomiting. Aminophylline use in children may be appropriate if children have a role in severe acute exacerbations of asthma where response to maximised therapy (inhaled bronchodilators and glucocorticoids) is poor. These results are based on small numbers and further work in this area is required.

 

摘要

背景

靜脈注射aminophylline用於治療接受了超過兩年吸入性支氣管擴張劑治療的急性重症氣喘兒童

由於吸入性乙二型交感神經興奮劑，抗膽鹼激導性劑和糖化皮質類固醇的出現，氨茶鹼的作用在兒童急性氣喘的治療角色已變得不那麼清楚。但對盡量增加接受治療(氧氣、吸入性支氣管擴張劑和糖化皮質類固醇)是有利於兒童急性重症氣喘的治療上仍有一些共識。

目標

確定在急性重症氣喘兒童病患接受傳統療法外，增加靜脈注射氨茶鹼治療會產生有益的影響，。

搜尋策略

使用the Cochrane Airways Group register of trials來找出相關的研究。最新的檢索是於2007年2月進行。

選擇標準

收案標準:隨機對照試驗比較了除了通常的兒童治療外，額外加入靜脈注射氨茶鹼與安慰劑的效果。

資料收集與分析

兩名審查員獨立的評估研究和分析數據。在試驗的選擇上有不同意見，則以協商解決。審查員嘗試聯繫作者以確認資料的正確性。

主要結論

7個試驗符合收案標準(380名受試者)。方法學的品質很好。所有的研究均招募了急性嚴重氣喘且需要住院兒童患者。六項研究尋求需對霧化短效乙二型交感神經興奮劑和系統性給予類固醇沒有反應的受試者。在兩個研究中，一些兒童進行肺功能量計的測量且預期FEV1基線在35至45％之間。在類固醇和乙二型交感神經興奮劑治療外加上氨茶鹼，相較於服用安慰劑時，在6 – 8小時、12 – 18小時和24小時，明顯改善FEV1％預測值。相較於服用安慰劑時，氨茶鹼在使用12 – 18小時，對PEF％預測值有更大的改善。住院時間、症狀、霧化頻率和機械性呼吸量上無顯著差異。沒有足夠的數據可以分析氧氣治療的聚合時間和補充氧氣治療的時間長短。氨茶鹼導致了3倍的嘔吐風險。治療組之間，在有關低血鉀，頭痛，tremour，癲癇，心律不整和死亡的比率上，無顯著差異。

作者結論

對於嚴重氣喘惡化的兒童，在乙二型交感神經興奮劑和糖化類固醇(有或沒有抗膽鹼激導性劑)外增加靜脈注射氨茶鹼可於治療後6小時內改善肺功能。不過，目前沒有發現症狀，噴霧治療的次數和住院時間是有明顯減少的。沒有足夠的證據可用以評估氧氣治療、PICU的住院和機械式呼吸的效果。氨茶鹼與顯著增加的嘔吐風險有關。

翻譯人

本摘要由臺北醫學大學萬芳醫院劉怡敏翻譯。

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

總結

急性氣喘是一種常見的兒科急診病症並普及於許多國家。治療的目的是經由暢通呼吸道以反轉氣喘症狀，並針對潛在的呼吸道發炎病症。使用乙二型交感神經興奮劑、抗膽鹼激導性劑和糖化皮質類固醇治療是目前最常用的策略。在過去，氨茶鹼已被廣泛用於管理急性氣喘，雖然是有副作用的。然而，它的使用率在下降因為有效的吸入支氣管擴張劑和糖化皮質類固醇是可被取得的。這次審查的目的是評估是否在接受最大化吸入支氣管擴張劑和糖化皮質類固醇的兒童使用靜脈注射氨茶鹼可以產生額外的有利影響。我們發現少數品質良好的試驗將接受吸入支氣管擴張劑和糖化皮質類固醇治療的兒童給予氨茶鹼是並與使用安慰劑相比較。這次審查發現有證據顯示使用氨茶鹼治療兒童，肺功能有較大的改善，相對於使用安慰劑治療的兒童，當兩組均使用吸入支氣管擴張劑和類固醇而且對對這些初步的治療方法產生的不完全的反應。然而，氨茶鹼的使用也導致嘔吐的風險加重。氨茶鹼使用於兒童身上可能是適當的，如果兒童在使用最大化治療(吸入支氣管擴張劑和糖化皮質類固醇)氣喘時，有嚴重急性惡化情況。這些結果是建立於很少的試驗基礎上，於此領域的進一步的研究是必需的