Powell Colin, Dwan Kerry, Milan Stephen J, Beasley Richard, Hughes Rodney, Knopp-Sihota Jennifer A, Rowe Brian H
Department of Child Health, Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK.
Cochrane Database Syst Rev. 2012 Dec 12;12:CD003898. doi: 10.1002/14651858.CD003898.pub5.
Asthma exacerbations can be frequent and range in severity from relatively mild to status asthmaticus. The use of magnesium sulfate (MgSO(4)) is one of numerous treatment options available during acute exacerbations. While the efficacy of intravenous MgSO(4) has been demonstrated, little is known of the role of inhaled MgSO(4).
To determine the efficacy of inhaled MgSO(4) administered in acute asthma on pulmonary functions and admission rates.
To quantify the effects of inhaled MgSO(4) i) in addition to inhaled β(2)-agonist, ii) in comparison to inhaled β(2)-agonist alone or iii) in addition to combination treatment with inhaled β(2) -agonist and ipratropium bromide.
Randomised controlled trials were identified from the Cochrane Airways Group register of trials in September 2012. These trials were supplemented with trials found in the reference list of published studies, studies found using extensive electronic search techniques, as well as a review of the grey literature and conference proceedings.
Randomised (or pseudo-randomised) controlled trials including adults or children with acute asthma were eligible for inclusion in the review. Studies were included if patients were treated with nebulised MgSO(4) alone or in combination with β(2)-agonist and/or ipratropium bromide and were compared with β(2)-agonist alone or inactive control.
Trial selection, data extraction and risk of bias were assessed independently by two review authors. Efforts were made to collect missing data from authors. Results are presented as standardised mean differences (SMD) for pulmonary function and risk ratios (RR) for hospital admission; both are displayed with their 95% confidence intervals (CI).
Sixteen trials (21 references) of unclear and high risk of bias were eligible and included 896 patients who were randomised (838 patients completed). Seven of the 16 included studies involved adults exclusively, three included adults and paediatric patients, four studies enrolled paediatric patients and in the remaining two studies the age of participants was not stated.The design, definitions, intervention and outcomes were different in all 16 studies; this heterogeneity made direct comparisons difficult (see additional tables 1-3).The overall risk of bias among the included studies was variable and this is reflected in the 'Summary of findings' table with most outcomes being judged as only moderate or less.Inhaled magnesium sulfate in addition to inhaled β(2)-agonistThere was no statistically significant improvement in pulmonary function when inhaled MgSO(4) and β(2)-agonist was compared with β(2)-agonist alone (SMD 0.23; 95% CI -0.27 to 0.74; three studies, n = 188); however, there was considerable between study heterogeneity. There was no clear advantage in terms of hospital admissions (RR 0.76 95% CI 0.49, 1.16; four studies, n = 249), and there were no serious adverse events reported.Inhaled magnesium sulfate versus inhaled β(2)-agonistThe results of pulmonary function in three studies that compared inhaled MgSO(4) versus β(2)-agonist were too heterogeneous to combine; however, two of the studies found poorer lung function on MgSO(4). There was no significant difference in terms of hospital admissions in a single small study when MgSO(4) was compared to β(2)-agonist (RR 0.53 95% CI 0.05, 5.31; one study, n = 33), and there were no serious adverse events reported.Inhaled magnesium sulfate in addition to inhaled β(2)-agonist and ipratropiumA further comparison has been included in the 2012 update of this review of MgSO(4) given in addition to inhaled ipratropium and β(2)-agonist therapy (as recommended by the GINA guidelines). However, there is not yet enough data for this outcome to come to any definite conclusions, but both small studies in adults with severe asthma exacerbation found improvements in pulmonary function with additional inhaled MgSO(4).
AUTHORS' CONCLUSIONS: There is currently no good evidence that inhaled MgSO(4) can be used as a substitute for inhaled β(2)-agonists. When used in addition to inhaled β(2)-agonists (with or without inhaled ipratropium), there is currently no overall clear evidence of improved pulmonary function or reduced hospital admissions. However, individual study results from three trials suggest possible improved pulmonary function in those with severe asthma exacerbations (FEV1 less than 50% predicted). Heterogeneity among trials included in this review precludes a more definitive conclusion. Further studies should focus on inhaled MgSO(4) in addition to the current guideline treatment for acute asthma (inhaled β(2) -agonist and ipratropium bromide). As the evidence suggests that the most effective role of nebulised MgSO(4) may be in those with severe acute features and this is where future research should be focused. A set of core outcomes needs to be agreed upon both in adult and paediatric studies to allow improved study comparison in future.
哮喘急性发作可能频繁发生，严重程度从相对轻微到哮喘持续状态不等。硫酸镁（MgSO₄）的使用是急性发作期间众多可用治疗选择之一。虽然静脉注射MgSO₄的疗效已得到证实，但吸入MgSO₄的作用却鲜为人知。
确定急性哮喘中吸入MgSO₄对肺功能和入院率的疗效。
量化吸入MgSO₄的效果，i）除吸入β₂激动剂外；ii）与单独吸入β₂激动剂相比；iii）除与吸入β₂激动剂和异丙托溴铵联合治疗外。
从2012年9月Cochrane气道组试验注册库中识别随机对照试验。这些试验通过已发表研究的参考文献列表中找到的试验、使用广泛电子检索技术找到的研究以及灰色文献和会议记录的综述进行补充。
包括成人或儿童急性哮喘患者的随机（或准随机）对照试验有资格纳入本综述。如果患者单独接受雾化MgSO₄治疗或与β₂激动剂和/或异丙托溴铵联合治疗，并与单独使用β₂激动剂或无活性对照进行比较，则纳入研究。
两名综述作者独立评估试验选择、数据提取和偏倚风险。努力从作者处收集缺失数据。结果以肺功能的标准化均值差（SMD）和入院的风险比（RR）表示；两者均显示其95%置信区间（CI）。
16项偏倚风险不明确和高的试验（21篇参考文献）符合条件，包括896名随机分组的患者（838名患者完成试验）。16项纳入研究中有7项仅涉及成人，3项包括成人和儿科患者，4项研究纳入儿科患者，其余2项研究未说明参与者的年龄。所有16项研究的设计、定义、干预和结局均不同；这种异质性使得直接比较变得困难（见附加表1 - 3）。纳入研究中的总体偏倚风险各不相同，这在“结果总结”表中有所体现，大多数结局仅被判定为中等或更低。
除吸入β₂激动剂外吸入硫酸镁
当将吸入MgSO₄和β₂激动剂与单独使用β₂激动剂进行比较时，肺功能没有统计学上的显著改善（SMD 0.23；95% CI -0.27至0.74；三项研究，n = 188）；然而，研究间存在相当大的异质性。在入院方面没有明显优势（RR 0.76，95% CI 0.49，1.16；四项研究，n = 249），并且没有报告严重不良事件。
吸入硫酸镁与吸入β₂激动剂比较
三项比较吸入MgSO₄与β₂激动剂的研究中肺功能结果过于异质，无法合并；然而，其中两项研究发现使用MgSO₄时肺功能较差。在一项小型研究中比较MgSO₄与β₂激动剂时，入院方面没有显著差异（RR 0.53，95% CI 0.05，5.31；一项研究，n = 33），并且没有报告严重不良事件。
除吸入β₂激动剂和异丙托溴铵外吸入硫酸镁
本综述2012年更新版中纳入了另一项比较，即除吸入异丙托溴铵和β₂激动剂治疗外给予MgSO₄（如全球哮喘防治创议（GINA）指南所推荐）。然而，对于该结局尚无足够数据得出任何明确结论，但两项针对重度哮喘急性发作成人的小型研究均发现额外吸入MgSO₄可改善肺功能。
目前没有充分证据表明吸入MgSO₄可替代吸入β₂激动剂。当与吸入β₂激动剂（无论是否联合吸入异丙托溴铵）联合使用时，目前没有总体明确证据表明肺功能得到改善或入院率降低。然而，三项试验的个体研究结果表明，重度哮喘急性发作（预计第一秒用力呼气容积（FEV₁）低于50%）患者的肺功能可能得到改善。本综述纳入试验间的异质性妨碍了得出更明确的结论。进一步的研究应聚焦于除当前急性哮喘指南治疗（吸入β₂激动剂和异丙托溴铵）外的吸入MgSO₄。由于证据表明雾化MgSO₄最有效的作用可能在于具有严重急性特征的患者，这也是未来研究应关注的重点。需要在成人和儿科研究中商定一套核心结局，以便未来能更好地进行研究比较。
