Review 253
Utility of magnesium sulfate in the treatment of rapid atrial
fibrillation in the emergency department: a systematic review
and meta-analysis
Megan Hoffera, Quincy K. Tranb,c, Ryan Hodgsona, Matthew Atwatera and
Ali Pourmanda
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Atrial fibrillation with rapid ventricular response (Afib/
RVR) is a frequent reason for emergency department (ED)
visits and can be treated with a variety of pharmacological
agents. Magnesium sulfate has been used to prevent and
treat postoperative Afib/RVR. We performed a systematic
review and meta-analysis to assess the effectiveness of
magnesium for treatment of Afib/RVR in the ED. PubMed
and Scopus databases were searched up to June 2021
to identify any relevant randomized trials or observational
studies. We used Cochrane’s Risk-of-Bias tools to assess
study qualities and random-effects meta-analysis for the
difference of heart rate (HR) before and after treatment.
Our search identified 395 studies; after reviewing 11 full
texts, we included five randomized trials in our analysis.
There were 815 patients with Afib/RVR; 487 patients (60%)
received magnesium treatment, whereas 328 (40%) patients
received control treatment. Magnesium treatment was
associated with significant reduction in HR [standardized
mean difference (SMD), 0.34; 95% CI, 0.21–0.47; P < 0.001;
I2 = 4%), but not associated with higher rates of sinus
conversion (OR, 1.46; 95% CI, 0.726–2.94; P = 0.29), nor
higher rates of hypotension and bradycardia (OR, 2.2; 95%
Introduction
In the emergency department (ED), magnesium sulfate
is used to treat multiple emergent medical conditions
including preeclampsia/eclampsia, acute asthma attacks,
migraines, and cardiac dysrhythmias. Among those condi-
tions, magnesium sulfate is the first-line agent for treat-
ment of eclampsia and torsades des pointes (TdP), and is
a secondary agent in asthma exacerbations and migraine
therapy [1,2].
Cardiac dysrhythmias are a common and potentially
life-threatening presenting symptom in the ED setting,
however, magnesium is not currently used routinely for
treatment or prevention of cardiac dysrhythmias except
in the case of TdP. Nonetheless, magnesium sulfate
has been studied extensively in the cardiology litera-
ture for use in the treatment and prevention of cardiac
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CI, 0.62–8.09; P = 0.22). Meta-regressions demonstrated that
higher maintenance dose (corr. coeff, 0.17; P = 0.01) was
positively correlated with HR reductions, respectively. We
observed that magnesium infusion can be an effective rate
control treatment for patients who presented to the ED with
Afib/RVR. Further studies with more standardized forms of
control and magnesium dosages are necessary to assess
the benefit/risk ratio of magnesium treatment, besides to
confirm our observations. European Journal of Emergency
Medicine 29: 253–261 Copyright © 2022 Wolters Kluwer
Health, Inc. All rights reserved.
European Journal of Emergency Medicine 2022, 29:253–261
Keywords: atrial fibrillation, emergency department, magnesium
a
Department of Emergency Medicine, The George Washington University
School of Medicine and Health Sciences, Washington, District of
Columbia,  bDepartment of Emergency Medicine, University of Maryland School
of Medicine and  cProgram in Trauma, The R Adams Cowley Shock Trauma
Center, University of Maryland School of Medicine, Baltimore, Maryland, USA
Correspondence to Ali Pourmand, MD, MPH, RDMS, FACEP, Department of
Emergency Medicine, George Washington University School of Medicine and
Health Sciences, 2120 L St., Washington, DC 20037, USA
Tel: +1 202 741 2911; e-mail: Pourmand@gwu.edu
Received 3 November 2021 Accepted 27 March 2022
dysrhythmias and, in particular, for the treatment of
supraventricular tachycardias including atrial fibrillation.
In the cardiology literature, magnesium sulfate has been
shown to provide antidysrhythmic benefit when given
prophylactically following cardiac surgery. A Cochrane
Review in 2013 concluded that magnesium sulfate was
effective in the prevention of postoperative atrial fibril-
lation [3]. Prophylactic magnesium sulfate has been
demonstrated in several randomized controlled trials
(RCTs) to reduce the risk of supraventricular tachycar-
dias, including atrial fibrillation, atrial tachycardia, and
supraventricular tachycardia postoperatively [4–11].
Similarly, there is evidence that coadministration of mag-
nesium sulfate with other antidysrhythmic medications
reduces the rate of arrhythmias [12,13]. Low serum mag-
nesium has also been associated with a greater risk for
development of cardiac dysrythmias [14]. There is also
evidence that magnesium may decrease early-after-de-
polarizations (EADs) and suppress induced dysrhythmias
[15–23].
DOI: 10.1097/MEJ.0000000000000941
 254  European Journal of Emergency Medicine  2022, Vol 29 No 4
In a cross-sectional analysis of US ED data, there were 3.9
million ED visits from 2007 to 2014 with atrial fibrillation as
a primary diagnosis, resulting in an average 67% admission
rate. The same data indicate an upward trend in ED visits
for atrial fibrillation during that same time period. In a cost
analysis during this time period, there was a 37% increase
in annual adjusted cost of admitted patients with atrial
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fibrillation to a total of 10.1 billion annually in 2014 [24].
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Taking into consideration the apparent benefits of mag-
nesium supplementation in similar inpatient settings
and the high rate that rapid atrial fibrillation is observed
in the ED, it is a question of interest whether the addi-
tion of magnesium may improve our ability to safely and
effectively treat this cardiac dysrhythmia in the ED. This
systemic review and meta-analysis aim to examine the
existing evidence for use of magnesium in the treatment
of rapid atrial fibrillation in the ED.
Methods
Study selection criteria
Prior to the beginning our study, we created a pro-
tocol according to the Preferred Reporting Items for
Systematic Review and Meta-Analysis (PRISMA) proto-
cols statement, and we conducted our study according to
PRISMA guidelines [25].
We used the Patient, Intervention, Comparison,
Outcome framework to guide our inclusion criteria
Population
We included randomized control trials, all observational
studies (prospective and retrospective studies) of adult
patients (age  >  18  years) who presented to EDs with
atrial fibrillation and rapid ventricular responses
Intervention
Patients with atrial fibrillation and rapid ventricular
responses were treated with intravenous magnesium
alone or along with other pharmacological agents.
Comparison
The control group included patients with atrial fibrillation
and rapid ventricular responses but were treated with other
pharmacological agents, without intravenous magnesium.
Outcomes
Our primary outcome was the difference in ventricular
heart rate (HR) before and after treatment at the earli-
est assessment by the authors. Our secondary outcomes
of interest included the percentage of patients who con-
verted from atrial fibrillation to sinus rhythm. We also
investigated the rate of any complications or any major
complications, as defined by the authors.
Search criteria
We searched PubMed and SCOPUS databases from their
conception up to 30 June 2021.
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We excluded studies that did not have full text, and we
also excluded conference abstracts, any reviews, or case
reports. We further excluded studies that did not specify
whether the clinical setting was in the ED. We screened
the bibliographies of included full-text studies for addi-
tional eligible studies but did not find any. We also con-
tacted the corresponding author of an included study to
request further data but did not receive any responses.
This study was registered with PROSPERO, an inter-
national database of prospectively registered systematic
reviews (CRD42021260097).
Search strategy
We used the search (“emergency service, hospital”[MeSH
Terms] OR (“emergency”[All Fields] AND “service”[All
Fields] AND “hospital”[All Fields]) OR “hospital emer-
gency service”[All Fields]) AND (“magnesium”[MeSH
Terms] OR “magnesium”[All Fields] OR “magnesi-
um’s”[All Fields] OR “magnesiums”[All Fields]) AND
(Atrial fibrilation).
We included further detail search terms in Appendix
1, Supplemental digital content 1, http://links.lww.com/
EJEM/A335.
Selection process
After the search, we imported our search results to the
website Covidence (www.covidence.org, Melbourne,
Australia), which helps to manage the screening of our
titles, abstracts, full-text articles, and duplicates. Multiple
reviewers (M.P., C.P., A.P., and Q.K.T.) worked inde-
pendently to screen each title and abstract for eligible
studies. A third investigator adjudicated any differences.
Any title and abstract would need at least two agree-
ments to proceed to the full-text review stage. The same
process again is repeated for the full-text stage. Only full-
text articles receiving agreements from at least two inves-
tigators were included in the final analyses.
Risk of bias assessment
We used the Cochrane’s Risk-of-Bias tool to assess the
quality of the included studies [26]. The Cochrane’s
Risk-of-Bias tool assesses risk of bias in five domains:
randomization, deviations from the study protocol, out-
come measurement, selection of the reported result, and
bias due to missing outcomes data. The overall risk of
bias of the entire study is based on the worst score of any
single domain, which is ranked as low, high, or some con-
cerns. For quality assessment, two investigators graded
the included studies independently. Any discrepancy was
adjudicated by consensus between the two investigators
and a third investigator as an arbiter, if necessary.
Statistical analysis
We presented the information from each study as per-
centage or mean (±SD) as appropriate. When the authors
expressed continuous variables as median (±interquartile

range), we converted median into mean as previously
described, for ease of reporting [27].
Random-effects meta-analysis was performed when any
two studies reported the same outcome. We expressed
the outcome of continuous variables, such as HR before
and after treatment, as standardized difference of means
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(SDM), because some studies reported HR as mean,
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whereas few others reported them as median. We defined
the magnitude of effect between interventions and con-
trol as small if the SDM value was 0.2 or less; an SDM
value of approximately 0.5 was considered a moderate
magnitude of effect, and an SDM value of at least 0.8 was
considered a large magnitude of effect size for the inter-
ventions [28]. We reported the results from random-ef-
fect meta-analysis of categorical outcome (percentages
of patients whose cardiac rhythm converted to sinus
rhythm) as odd ratio (OR) and 95% confidence interval
(CI).
For heterogeneity, we used both the Cochrane’s
Q-statistic and the I2 value. The Q-statistic tests against
the null hypothesis that all studies within our meta-anal-
ysis would share similar effect size. The I2 value shows
whether the variance between studies’ effect size is due
to true difference and not by chance.
We also performed a sensitivity analysis of our primary
outcome by using one-study-removed random-effect
meta-analysis. The one-study-removed sensitivity anal-
ysis systemically removed each individual study, whereas
meta-analysis was performed with the rest of the study.
The sensitivity analysis aimed to identify any single
study that significantly influenced the effect size of the
study. Furthermore, to assess the dose-effect of magne-
sium, we performed exploratory meta-regressions with
continuous independent variables. Our meta-regression
involved baseline serum magnesium at ED presentation,
initial dose of magnesium, and total dosage of magne-
sium as independent variables. For studies that used a
single dose of magnesium, we treated the single dose as
both a loading dose and a maintenance dose.
For publication bias, we used both Egger test and Begg
test. An Egger test’s or Begg test’s P-value > 0.05 would
indicate low risk for publication bias. We did not use
the funnel plot because of the small number of studies
included in our meta-analysis. For another publication
bias assessment, we used the Orwin’s fail-safe N test.
This Orwin’s fail-safe N test would predict the number
of missing or number of future studies that could have
changed the effect size of our primary outcome.
All meta-analysis, sensitivity analysis, meta-regres-
sions, and publication bias assessment were performed
with the Comprehensive Meta-Analysis software (www.
meta-analysis.com, Englewood, New Jersey, USA). Any
variable with two-tailed P-value  <  0.05 was considered
statistically significant.
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Utility of magnesium sulfate Hoffer et al. 255
Results
Study selection
The initial literature search identified 395 studies. We
reviewed 11 full-text articles and included five studies
in the final analysis (Fig. 1). All five studies [29–33] were
RCTs. All five studies reported the change of HR before
and after treatment, when compared with control treat-
ment, although they did not report the proportions of
patients who achieved rate control. Four studies [29–32]
reported the percentages of patients whose rhythms were
converted to sinus rhythm. One study [34] investigated
the effect of magnesium but did not include a control
group, so it was not included in our final analysis.
We identified two additional systematic reviews com-
paring magnesium treatments with other antiarrhythmic
medication [35,36]. However, these studies were not
involving ED settings, so they were excluded.
Risk of bias assessment
All studies included in our meta-analysis were rand-
omized trials. The risk of bias from five included studies
were assessed by the using five qualities of the Cochrane’s
Risk-of-Bias tool (Appendix 2, Supplemental digital con-
tent 1, http://links.lww.com/EJEM/A335). Only one study
from Hays et al. [29] demonstrated some concerns for risk
of bias. The rest of the studies were graded as low risk
for bias.
Summary of studies
Our meta-analysis included 815 patients who presented
to the ED with atrial fibrillation and rapid ventricular
rate, 328 (40%) patients were part of the control group,
whereas 487 patients (60%) received magnesium. One
study [32] contained one control group and two treat-
ment arms: one treatment group was treated with ‘low
dose’ of magnesium, whereas the second treatment group
received ‘high dose’ of magnesium. Since this study
reported separate outcomes for control, ‘low dose’, and
‘high dose’ groups, respectively, we analyzed the effect of
‘low dose’ and ‘high dose’ magnesium compared with the
control group separately [35].
All studies reported treatment of control groups with pla-
cebo up to their first assessments of treatment efficacy.
After the first assessments, any additional antiarrhythmic
medication for both the control groups and the magne-
sium group was left at the discretion of the treating phy-
sicians. Four studies [34–37] used other antidysrhythmic
agents besides magnesium. Digoxin was the most com-
mon antidysrhythmic agent in three studies [29,30,33].
On the other hand, Chu et al. [31] reported that only a
small number of patients in their study received amiodar-
one, while Zouche et al. [33] did not use any additional
antidysrhythmic agents.
Only four studies reported the systolic blood pres-
sure before treatment [29, 31–33], and only two studies
 256  European Journal of Emergency Medicine  2022, Vol 29 No 4

Fig. 1.
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PRISMA flow diagram for study selection. PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analyses.

reported systolic blood pressure after treatment for pla-
cebo group [29,31]. Therefore, we did not perform assess-
ment of blood pressure between control and magnesium
groups.
Four studies [29,30,32,33] reported the prevalence of any
complications from the treatment.
Primary outcome
Five of the RCTs reported the change in HR after treat-
ment with magnesium and control [29–33]. Bouida et al.
[32] reported two separate groups of patients who were
given ‘low dose’ and ‘high dose’ of magnesium, compared
with a control group. As a result, we performed meta-anal-
ysis from these two separate groups [32].
Most studies reported the time intervals for HR reduc-
tion within 4–6 h of magnesium administration [29–33].
However, two studies reported patients’ HRs at 12 h [33]
and 24 h [32] after first administration of magnesium.
The baseline HR for placebo group before treatment was
136 beats per minute, and the group’s HR after treatment
was 119 bpm. On the other hand, baseline HR for mag-
nesium group was 137 bpm. At the first assessment, the

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 Utility of magnesium sulfate Hoffer et al. 257

average HR for the magnesium group after treatment was
108 bpm.
Our random-effects meta-analysis showed a standardized
mean difference (SMD) of HR reduction of 0.34 between
magnesium versus control groups, which was statistically
significant (SMD, 0.34; 95% CI, 0.21–0.47; P  <  0.001)
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magnitude of reduction of HR (SMD, 0.2) to a moder-
ate magnitude of reduction (SMD, 0.5) (Fig.  2a). The
P-value for the Q-statistic was 0.39, which suggested that
the effect size from our study would be similar to the true
effect size. The I2 value was 4%, which demonstrated that
only 4% of variance between our studies’ effect sizes and

(Fig. 2a). Our prediction interval also suggested that, for the true effect size was due to true difference. In other
future studies similar to those included in our analysis, words, there was low likelihood that our study’s findings
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magnesium infusion would be associated with a small would be different from the true effect size.

Fig. 2.

(a) Forest plot of random-effects meta-analysis comparing heart rate difference before and after treatment with magnesium or control. The differ-
ence was expressed as standardized mean difference (SMD). (b) Forest plot of random-effects meta-analysis comparing rates of sinus conversion
between treatment with magnesium or control. (c) Sensitivity analysis of meta-analysis comparing heart rate difference before and after treatment.

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 258  European Journal of Emergency Medicine  2022, Vol 29 No 4
Sensitivity analysis using one-study-removed random-ef-
fects meta-analysis (Fig. 2c) demonstrated that the over-
all SMD of HR reduction between magnesium treatment
and control was consistently between 0.33 and 0.36 and
was well within the 95% CI of the pooled studies. The
analysis showed that no individual studies overly affected
the effect size of our study.
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For our publication bias assessment, the P-values for
both Egger’s test and Begg’s test were 0.38 and 0.45,
respectively. This suggested that our meta-analysis was
associated with low likelihood of having publication bias.
Furthermore, the Orwin’s fail-safe N test demonstrated
that it would take nine missing or future studies with very
small SMD to reduce the effect of magnesium on HR
reduction. In other words, nine missing or future studies
need to have a SMD between magnesium treatment and
control groups of 0.1 (very small effect in HR reduction)
to reduce the effect of magnesium to SMD from 0.34 to
0.2 (small effect in HR reduction).
Secondary outcome: rates of sinus conversion
Only three RCTs reported the rate of conversion to sinus
rhythm [30–32]. Treating patients with magnesium infu-
sion was not statistically associated with higher likelihood
of achieving sinus conversion (OR, 1.46; 95% CI, 0.726–
2.94; P = 0.29) (Fig. 2b). The P-value for the Q-statistic
test was 0.09, which suggested that our study’s effect size
would be similar to the true effect size. Furthermore, the
I2 value was 53%, which demonstrated that up to 53% of
difference between our studies’ effect size and the true
effect size was true difference and not by chance.
Other outcomes: any complications and major
complications
Four studies reported rates of complications [29,30,32,33],
whereas three studies reported the prevalence of major
complications [30,32,33]. Most authors defined major
complications as hypotension or bradycardia. Minor
complications included flushing, headache, nausea, etc.
Patients receiving magnesium infusion were associated
with a five-time higher likelihood of having ANY compli-
cations (OR, 5.33; 95% CI, 2.3–12.3; P < 0.001) (Fig. 3a).
On the other hand, patients receiving magnesium infu-
sion had a similar prevalence of major complications,
when compared with patients receiving control treat-
ment (OR, 2.2; 95% CI, 0.62–8.09; P = 0.22).
Effect of serum magnesium level and magnesium dose
Our exploratory meta-regressions demonstrated that the
baseline (pretreatment) serum magnesium levels were
not related to the SMD of HR reduction after receiving
magnesium treatment (Fig.  3c). In contrast, the initial
loading dose of magnesium [correlation coefficient (corr.
coeff), −0.13; 95% CI, 0.25–0.20; P = 0.02] was negatively
correlated with the magnitude of the SMD of HR reduc-
tion, whereas the maintenance dose of magnesium up to
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6 hours (corr. coeff, 0.17; 95% CI, 0.06–0.28; P = 0.01) was
positively correlated with the magnitude of SMD of HR
reduction. In other words, higher maintenance magne-
sium dose for up to 6  h was associated with larger HR
reductions.
Discussion
Our random-effect meta-analysis demonstrated that mag-
nesium infusion was associated with significant reduction
in HR among patients who presented to ED with atrial
fibrillation and rapid ventricular rates. However, treatment
with magnesium was associated with neither higher rates
of sinus conversion nor higher rates of major complications.
Furthermore, our primary finding was associated with very
low heterogeneity, which suggested that our result might
not be much different from the true effect size.
To our knowledge, this is the first meta-analysis evalu-
ating the use of magnesium to treat atrial fibrillation in
the EDs. A previous meta-analysis by Onalan et al. [35]
involved studies that used magnesium for treatment of
atrial fibrillation; however, it also included other arrhyth-
mias such as supraventricular tachycardia and was not
limited to ED setting. As a result, our study provides fur-
ther evidence for the use of magnesium in the treatment
of patients with atrial fibrillation with rapid ventricular
rates in the ED setting.
The role of magnesium in treating cardiac arrhythmias
is not fully understood but may be attributable to pre-
vention of EADs [37]. Magnesium may abolish or dimin-
ish the amplitude of EAD, by blocking calcium influx
via L-type calcium channels. Thus, EADs are unable to
reach threshold potential, thus preventing the triggering
of dysrhythmias [37,38]. Magnesium also may reduce
dysrhythmias by reducing the inward potassium current,
resulting in fewer EAD [39]. Although more studies
are necessary to confirm our observations, our findings
suggested that magnesium is a good candidate to treat
patients with atrial fibrillation and rapid ventricular
rates, and further, magnesium has a good safety profile
when compared with other frequently used agents such
as metoprolol or diltiazem. Our study demonstrated that
the unadjusted rate of major complications (hypotension
and bradycardia) from magnesium infusion was 11/456
(2.4%) (Fig. 3b). In contrast, a recent study reported that
the rate of hypotension among ED patients treated with
metoprolol or diltiazem was 23 or 39%, respectively [40].
Due to the variabilities in magnesium dosages, further
studies about the dose-effect are necessary to provide
more evidence about the benefit–risk ratios of magnesium
treatments. Our exploratory multivariable meta-regres-
sions demonstrated that higher initial loading dose of mag-
nesium was not correlated with larger reduction of HRs
among patients who received magnesium. This effect was
likely derived from the result of the 2019 Bouida study’s
group of patients who were given the ‘large dose’ of
 Utility of magnesium sulfate Hoffer et al. 259

Fig. 3.
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(a) Forest plot of random-effects meta-analysis comparing the prevalence of any complications as reported by the authors. (b) Forest plot of ran-
dom-effects meta-analysis comparing the prevalence of major complications as reported by the authors such as hypotension and bradycardia.
(c) Results from multivariable meta-regressions measuring association of serum magnesium concentrations and the magnitude of heart rate reduc-
tions before and after treatments.

magnesium. Patients in this group were given up to 9 g of
loading dose of intravenous magnesium, but these patients
did not achieve higher HR reductions at 4 h when com-
pared with those who received the ‘low-dose’ (4.5 g) mag-
nesium infusion. In contrast, a higher maintenance dose
was correlated with an increased HR reduction. Therefore,
we recommended that starting with a small loading dose of
magnesium then eventually reaching 3–4 g over a period
of 4–6  h would be associated with larger HR reductions
while avoiding high rates of major complications.

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 260  European Journal of Emergency Medicine  2022, Vol 29 No 4
Further studies are also necessary to investigate whether
magnesium can either be used as a single therapy for
patients with rapid atrial fibrillation and rapid ventricu-
lar rates, or as an adjunct therapy in addition to other
rate-controlled agents in the ED. Additionally, further
studies are necessary to investigate the benefit/risk ratio
of using magnesium infusion in addition to other agents
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such as metoprolol or diltiazem, given that use of either
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metoprolol or diltiazem is associated with increased risk
of hypotension [40].
Limitations
Our meta-analysis has several limitations. A limited num-
ber of studies were available since we were interested
exclusively in the ED setting in an effort to provide a
more homogenous setting, acuity level, and relevance
to the specialty of Emergency Medicine. Some of these
studies involved smaller patient populations, which
would be at risk of ‘small study effects’, when the effect
sizes are artificially larger than the true effect size.
Furthermore, there was a lack of standardized placebo/
control treatment across all studies. Additionally, vari-
ability in the dosage of magnesium prevented us from
drawing conclusions on the best practice of using mag-
nesium infusion for patients who presented to ED with
atrial fibrillation and rapid ventricular rates. The studies’
authors only reported the ventricular HRs before and
after treatment and not reported the proportion of rate
control. Therefore, although magnesium was associated
with rate reductions, compared with the control group,
some patients still had atrial fibrillation with rapid ven-
tricular rate.
Conclusion
Magnesium sulfate has been used successfully in the
treatment of rapid atrial fibrillation in the ED setting,
both as an independent agent and as an adjunct to other
medication for rate control. Further randomized control
studies in the ED setting using magnesium as a single
agent comparing to other medications are necessary to
confirm our observations.
Acknowledgements
Conflicts of interest
There are no conflicts of interest.
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