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Intravenous magnesium as an adjuvant in acute bronchospasm: a meta-analysis |
Alter H J, Koepsell T D, Hilty W M |
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Authors' objectives To evaluate intravenous magnesium sulphate as treatment for acute bronchospasm.
Searching One author searched MEDLINE (from 1966 to 1998) and EMBASE (from 1990 to 1998) with no language restriction using two search algorithms. Additional material was obtained by searching the bibliographies of selected articles, contacting authors of relevant clinical studies, and reviewing the abstracts of four scientific societies.
Study selection Study designs of evaluations included in the reviewRandomised controlled trials (RCTs). Case reports, case series, studies not specifying the clinical condition (i.e. acute versus stable asthma), and those in which magnesium was not delivered intravenously, were excluded from the review.
Specific interventions included in the reviewAdjuvant bolus intravenous magnesium sulphate or placebo. The dosages used were 1.2 to 2 g, or an equivalent paediatric dose, but these were not defined a priori due to the paucity of evidence on dose response mechanics.
Participants included in the reviewParticipants with acute bronchospasm treated in the emergency department.
Outcomes assessed in the reviewThe peak expiratory flow rate, where available, was assesed. All but three studies also reported hospitalisation rates as an outcome.
How were decisions on the relevance of primary studies made?One author identified the trials, but it is probable that more than one author reviewed the studies for inclusion in the review.
Assessment of study quality Study quality was assessed using the method of Jadad et al. (see Other Publications of Related Interest no.1), in which a score of 0 to 5 (0 lowest quality; 5 highest quality) was used to assess randomisation, blinding and follow-up. The authors do not state how the papers were assessed for quality, or how many of the reviewers performed the quality assessment.
Data extraction Two reviewers performed the data extraction. One of the reviewers was blinded to author and journal of publication.
Data were extracted for the categories of: author, country, year and source of publication; number of treatment arms; number of all patients in each arm, their inclusion criteria, and whether all were accounted for; method of blinding; number and dosage of all medications used; outcome measures and approach to assessing them; means and standard deviations (SDs) of the baseline; outcome data for each arm; time of post-treatment measurement; and incidence of complications.
Since several studies reported their results only in graphical form, without corresponding numerical values, the authors enlarged these graphs. The height of the data point and length of the error bars were measured in millimetres from the datum, and this distance was converted to outcome units by measuring the units on the y axes, according to a previously published method (see Other Publications of Related Interest no.2).
In cases where the graph or tables depicted standard error, these were converted to SD by multiplying the root of the number of patients in that study.
Methods of synthesis How were the studies combined?Combined effect sizes (ES) with 95% confidence intervals (CIs) were calculated using Hedges method (see Other Publications of Related Interest no.3). The analyses used a fixed-effect model, although random-effects calculations were also made according to DerSimonian and Laird (see Other Publications of Related Interest no.4).
Publication bias was assessed using a funnel plot, linear regression for quantifying funnel plot asymmetry, and by assessing correlation between ES and the number of patients in each study using Spearman's rank correlation.
How were differences between studies investigated?The Q statistic was used to assess heterogeneity.
Additional one-way sensitivity analyses were performed to assess the influence of study quality and publication bias. The sensitivity analyses used a random-effects model.
Results of the review Nine RCTs were included in the review with 859 participants.
The authors determined that there was little influence of publication bias. All 9 studies were placebo-controlled, and all but one were double-blind. All trials randomly allocated patients to receive placebo or intravenous magnesium sulphate therapy, except for one which used experimental and control treatments on alternate days.
There was a post-treatment ES of 0.162 for patients treated with intravenous magnesium sulphate (95% CI: 0.028, 0.297, P=0.02). The Q statistic for heterogeneity was 13.9 (P=0.084). In sensitivity analyses exploring the effects of study quality and publication bias, the summary effect ranged from 0.127 to 0.206.
The ES of the 6 adult studies was 0.127 (95% CI: -0.016, 0.265, P=0.08) using the random-effects model. This was not statistically significant.
No serious adverse events were reported.
Authors' conclusions The authors state that adjuvant bolus intravenous magnesium sulphate in acute bronchospasm appears statistically beneficial in improving spirometric airway function by 16% of a SD. The clinical significance of this is uncertain, but given the safety of intravenous magnesium sulphate therapy and its relatively low cost, it should be considered, in the absence of contraindications, in patients with moderate-to-severe acute bronchospasm.
CRD commentary This was a reasonable review with a few drawbacks. The authors stated the research question, and inclusion and exclusion criteria. The literature search was reasonably thorough. It is possible that additional relevant studies may have been missed, but the authors tested for, and did not find, publication bias.
The quality of the included studies was formally assessed and used in further analyses in the review. The authors have reported how the articles were selected, and who performed the selection and data extraction. The authors did not state who performed the quality assessment.
The data extraction is reported in tables and discussed in the text of the review. The studies were combined in a statistical meta-analysis using both fixed-effect and random-effects models for comparison, and heterogeneity was assessed.
The authors' conclusions appear to follow from the results but, as the authors themselves state, these should be viewed with caution because of limitations in the quality of the designs of the included studies. In particular, the authors are wary of the precision of their interpretation of graphical, rather than numerical data, and some differences observed between participant characteristics and study design.
Implications of the review for practice and research Practice: The authors state that, given the known safety of the drug and its relatively low cost, the addition of intravenous magnesium sulphate therapy should be considered, in the absence of contraindications, in patients with moderate-to-severe bronchospasm.
Research: The authors state that the recommendations for use of intravenous magnesium sulphate therapy should be refined in the future by an analysis of the cost-effectiveness of such an approach.
Bibliographic details Alter H J, Koepsell T D, Hilty W M. Intravenous magnesium as an adjuvant in acute bronchospasm: a meta-analysis. Annals of Emergency Medicine 2000; 36(3): 191-197 Other publications of related interest 1. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1-12. 2. Littenberg B. Aminophylline treatment in severe, acute asthma: a meta-analysis. JAMA 1988;259:1678-84. 3. Hedges LV, Olkin I. Statistical methods for meta-analysis. San Diego (CA): Academic Press; 1985. 4. DerSimonian R, Laird N. Meta analysis in clinical trials. Control Clin Trials 1986;7:177-88.
Indexing Status Subject indexing assigned by NLM MeSH Acute Disease; Adult; Bias (Epidemiology); Bronchial Spasm /drug therapy; Bronchodilator Agents /administration & Calcium Channel Blockers /administration & Child; Confidence Intervals; Emergency Service, Hospital; Humans; Injections, Intravenous; Magnesium Sulfate /administration & Randomized Controlled Trials as Topic; Safety; Sensitivity and Specificity; Spirometry; Treatment Outcome; dosage /adverse effects /therapeutic use; dosage /adverse effects /therapeutic use; dosage /adverse effects /therapeutic use AccessionNumber 12000001808 Date bibliographic record published 31/10/2001 Date abstract record published 31/10/2001 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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