|
IV
MAGNESIUM
FOR SEVERE ACUTE
ASTHMA: YES,
BUT ONLY FOR
SOME
EDMONTON, ALBERTA, AND SEATTLE--Two new meta-analyses suggest that intravenous magnesium sulfate may be a useful adjunct to standard therapy in the management of acute asthma.[1,2] The effect of intravenous magnesium is modest and appears to be limited to patients with severe attacks. In such patients, however, magnesium may improve pulmonary function and decrease the need for hospitalization.
These
findings are sufficient evidence to make intravenous magnesium
an accepted treatment for severe acute asthma, and its administration
should be incorporated into clinical practice guidelines,
asserts Brian H. Rowe, MD, lead author of one of the meta-analyses.[1]
In fact, Canada has already included this recommendation
in its national acute asthma guidelines, he said in an interview
with PULMONARY REVIEWS.
Physicians in the United States have been slow to add intravenous magnesium to their list of asthma treatments, he added, because many American asthma experts believe that a large clinical trial is necessary to confirm its effectiveness. "But the question is, how much evidence is enough?" asked Dr. Rowe, an Associate Professor and Research Director in the Division of Emergency Medicine at the University of Alberta, in Edmonton. "A large trial would take years and cost millions just to produce the same findings. Is it really ethical to withhold this treatment for the next five years while we wait for the results?"
A large trial would be wise, he said, if intravenous magnesium were expensive or had many dangerous side effects. "But it costs virtually nothing and is incredibly safe, especially in the doses we use for acute asthma," he pointed out.
DUELING ANALYSES
Dr. Rowe and colleagues searched the Cochrane Airways Review Group (ARG) register, a large collection of studies and review papers on asthma therapies.[1] The ARG register is the result of a comprehensive search of the EMBASE, MEDLINE, and CINAHL databases. However, the researchers also included the results of a hand search of 20 respiratory journals and updates from the Cochrane Controlled Trials Register, an international database of studies and reviews of treatments for many illnesses.
The group found seven relevant studies involving 668 adults and children. To be included in the meta-analysis, studies had to be randomized, placebo-controlled trials of intravenous magnesium for acute asthma. Each study also had to report hospital admission rates, results of pulmonary function tests (particularly absolute peak expiratory flow rate [PEFR], absolute forced expiratory volume in one second [FEV1], and the percentage of predicted PEFR or FEV1), vital signs (heart rate, respiratory rate, and blood pressure), and/or adverse outcomes and side effects.
The other meta-analysis, conducted by Harrison J. Alter, MS, MD, and colleagues in the Division of Emergency Medicine at the University of Washington, in Seattle, contained nine studies with 859 adult and pediatric patients with either asthma or chronic obstructive pulmonary disease (COPD).[2] Both diseases were included because COPD and asthma-related bronchospasm are often indistinguishable, the researchers explained.
They obtained their data by searching MEDLINE and EMBASE and by reviewing the bibliographies of the citations they found. To locate unpublished studies, they reviewed abstracts from five years of scientific meetings held by the Society for Academic Emergency Medicine, the American Thoracic Society, the American College of Chest Physicians, and the European Respiratory Society.
The subjects in each study had to meet three inclusion criteria: acute illness in the emergency department or an equivalent setting; acute bronchospasm; and random assignment to intravenous boluses of magnesium or placebo. The researchers selected PEFR as their main outcome measurement.
Because the two meta-analyses used different criteria for inclusion, their results are somewhat different. However, their primary conclusions are strikingly similar.
BENEFIT IN SEVERE CASES
In both
meta-analyses, the typical dose of intravenous magnesium
was found to be 2 g in adults and between 25 and 100 mg/kg
in children; administration usually occurred over 20 minutes.
Patients also received standard interventions for acute
asthma, such as ß-agonists
and intravenous or oral corticosteroids. Some also received
a methylxanthine or ipratropium bromide.
When they
included all of the asthma patients in their analysis, Dr.
Rowe's group found no statistically significant difference
in hospital admission rates between those given magnesium
and those receiving placebo; the only benefit seen with
intravenous magnesium was a small but nonsignificant improvement
in pulmonary function. However, when the analysis was restricted
to patients with severe acute asthma, magnesium was shown
to markedly reduce the risk of hospital admission (odds
ratio, 0.10) and to improve both PEFR (weighted mean difference
[WMD], 52 L/min) and the percentage of predicted FEV1 (WMD,
10%).
In the
statistical analysis by Alter et al, intravenous magnesium
produced a posttreatment summary effect size of 0.162 for
PEFR. In other words, it improved PEFR by 16.2% of its standard
deviation in a given population. That translates to a mean
increase of 16.4 L/min, for example, in the six adult studies
with a pooled standard deviation for PEFR of about 101 L/min.
Neither
meta-analysis detected major side effects from intravenous
magnesium administration. However, minor side effects, such
as burning at the injection site, flushing, and fatigue,
were common in at least one study. Overall, vital signs
remained stable in the period immediately after intravenous
magnesium administration, Rowe et al noted.
The clinical
significance of the improvement in pulmonary function the
drug produced is uncertain, both groups of investigators
acknowledged. The reason is simply that no one yet knows
how much change in lung function test results is required
to produce a clinically significant improvement in patients
with severe acute asthma.
Nevertheless,
both groups recommended the use of intravenous magnesium--Rowe
et al for severe acute asthma and Alter et al for moderate
and severe acute bronchospasm--because of its safety and
low cost. The drug works by relaxing airway smooth muscle,
both teams noted. The fact that it operates independently
of the ß 2-adrenergic receptor suggests an adjunctive
role, they added.
PROCEDURAL
DIFFERENCES
"The
two meta-analyses have interesting procedural differences,"
commented Robert L. Wears, MD, MS, a Professor of Emergency
Medicine at the University of Florida Health Sciences Center
in Jacksonville, in a recent interview. He also discussed
these differences in an editorial that accompanied the two
meta-analyses.[3] Not only did the two meta-analyses contain
slightly different data sets (despite examining the same
issue), but there were also significant variations between
the meta-analyses in the quality ratings they assigned to
some studies.
"But
it is important that, despite their differences, they produced
about the same conclusions," said Dr. Wears. They both
agree that magnesium can benefit patients with severe asthma,
but its effect is modest, not dramatic. He added, "There
would be serious questions about meta-analysis if two groups
using most of the same data came up with opposing findings.
The fact that they did not tells me the results of meta-analysis
are very reliable and not altered much by who does the analysis
or what technique they choose, as long as the methods are
valid."
--Timothy
Begany
References
1. Rowe BH, Bretzlaff JA, Bourdon C, et al. Intravenous
magnesium sulfate treatment for acute asthma in the emergency
department: a systematic review of the literature. Ann
Emerg Med. 2000;36:181-190.
2. Alter HJ, Koepsell TD, Hilty WM. Intravenous magnesium
as an adjuvant in acute bronchospasm: a meta-analysis. Ann
Emerg Med. 2000;36:191-197.
3. Wears RL. Dueling meta-analyses [editorial]. Ann Emerg
Med. 2000;36:234-236.
Return
to table of contents
|
