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Three Part Question

In [atrial fibrillation with rapid ventricular response] is [intravenous magnesium] effective in[cardioversion to sinus rhythm]?

Clinical Scenario

A sixty-five year old man attends the Emergency Department with a twelve hour history of palpitations. An ECG confirms that he is in atrial fibrillation with a ventricular rate of 130 beats per minute. He has no cardiovascular compromise. You have heard that intravenous magnesium may be an effective and safe way of converting him back to sinus rhythm and wish to review the relevant literature.

Search Strategy

MEDLINE Pubmed 1950- May 2010
EMBASE 1980- May 2010
Current Controlled Trials (www.controlled-trials.com) May 2010
Cochrane Central Register of Controlled Trials May 2010
National Institute for Health May 2010
Google Scholar May 2010

[{(Magnesium) ti,ab} OR {(mgso4) ti,ab}] AND [{(Atrial Fibrillation) ti,ab} OR ((Atrial) AND (Fibrillation)) ti,ab} OR {(Atrial tachyarrhythmia*) ti,ab}] NOT [{(postoperative) ti} OR {(perioperative) ti} OR {(cardiac surgery) ti} OR {(bypass) ti} OR {(graf*) ti}], LIMIT to Human

Search Outcome

145 unique papers of which 8 relevant. One further paper identified on reference search.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Brodsky et al 1994 USA	18 Outpatients with symptomatic AF duration <7 days and ventricular response 100-200bpm; Mg 2g over 15 mins then 8g over 6 hours IV plus digoxin by weight (0.375 to 0.625mg) then up to 3 more doses (0.125-0.375mg) versus dextrose placebo with digoxin regime identical	Randomized double-blind study	Mean ventricular rate <90 for over 60 mins; Conversion to SR	100% pts in Mg group reached end point vs. 50% in control group (p<0.05); 60% Mg group converted to SR vs. 38% control group (p>0.05)	Poorly defined population and symptom duration, small study, no detail of randomisation or blinding
Chiladakis et al 2001 Greece	46 new medical admissions with continuous AF <12 hours and ventricular rate >100bpm; Mg 2.5g bolus IV over 15 mins then 7.5g infusion over 6 hours versus diltiazem: 25mg bolus IV over 15 mins then 12.5mg/hr infusion over 6 hours	Randomized single-blind study	Conversion to sinus rhythm within 6 hours of trial start	Conversion to SR in 57% Mg group vs. 22% diltiazem group (p<0.03)	Single blinded, no explanation of randomisation, no placebo group
Chu et al 2009 Australia	24 patients >18yrs attending ED with paroxysmal AF <48 hours with sustained ventricular response >100bpm; Mg 2.5g in 100ml N saline, infused over 15 mins versus placebo: N Saline 5ml in 100ml N saline over 15 mins	Randomized double-blind study	Heart rate, rhythm, BP at baseline and every 15 mins to 2 hours	No difference between groups in HR decrease (p=0.124) or rate of cardioversion (p=0.25) at 2 hours	Recruitment bias, HR measurement inappropriate
Davey et al 2005 Australia	199 patients >18yrs attending ED with AF and ventricular response >120bpm; Mg 5g IV with half given over 20 mins then half over next 2 hours versus placebo: Equivalent volume of 5% dextrose IV at same rates of infusion	Randomized double-blind study	HR <100/min; Mean changes in HR at 30/60/90/120/150 mins; Conversion to SR	27% Mg group converted to SR vs.12% control group (p<0.01)	Recruitment bias No AF duration specified No standardised protocol for "usual care", suboptimal data collection, short follow up period
Gullestad et al 1993 Norway	57 patients with atrial fibrillation, flutter or paroxysmal SVT of duration <7days and ventricular response >100bpm; Mg 1.2g over 5 mins and further 1.2g after 10 mins if primary outcome not met then infusion 0.04 mmol/min up to 24h versus verapamil: 5mg over 5 mins and 5mg after 10 mins if primary outcome not met then infusion 0.1mg/min to 24h	Randomized single-blind study	Conversion to SR/ HR<100/min within 4hr; Conversion to SR within 24h	58% Mg group converted to SR in 4h compared with 19% Verapamil group (p<0.01); 48% Verapamil group had HR <100/min at 4h vs. 28% Mg group (p<0.05)	Study population setting not defined, not restricted to AF, no placebo
Hays et al 1994 USA	15 patients presenting to ED with AF and ventricular response >99bpm; Mg 2g bolus then continuous infusion of 1g/hour for 4 hours plus IV digoxin infusion versus placebo: (composition/regime not specified) plus IV digoxin infusion	Randomized double-blind study	Ventricular rate; Conversion to SR also noted.	3 pts (37.5%) in placebo group converted to SR vs. 1 pt (14.3%) in Mg group	Small study, max AF duration not properly defined, placebo and schedule not defined, blinding/randomisation not defined, data from excluded pts not included in analysis
Joshi et al 1995 India	86 patients admitted to general ICU showing AF with ventricular response >160bpm (AF as subgroup of SVTs studied); Mg 2g IV, same dose at 15 mins if HR >100/min versus verapamil: 5mg IV, Same dose at 15 mins if HR >100/min	Randomized unblinded study	HR; Rhythm; Systolic/diastolic BP effect; Respiratory rate; Symptoms	19.5% Mg group converted to SR vs. 55.5% Verapamil group (p=0.0006)	ICU population, inclusion ventricular response very high, AF duration not defined, comorbidities not well defined
Moran et al 1995 Australia	42 patients admitted to general ICU with atrial tachyarrhythmia for >1hr, ventricular response >120bpm and Potassium at least 4.0mmol/L; Mg 37mg/kg over 5 mins then infusion 0.025mg/kg/24hrs versus amiodarone: 5mg/kg loading dose over 15-20 mins then infusion 10mg/kg/24hrs	Randomized unblinded study	Conversion to SR within 24h; Change in HR/SBP	Mg group significantly more likely to cardiovert by 24h	ICU population, non-consecutive recruitment, unblinded study, no placebo
Walker et al 1996 Australia	41 patients attending ED with atrial fibrillation or flutter <48h duration and ventricular response >120bpm; Mg 5g over 30 mins then digoxin as indicated versus placebo: 20ml N saline over 30 mins then digoxin as indicated	Randomized double-blind study	Conversion to SR; Ventricular rate <100/min; Adverse symptoms	No difference between groups in cardioversion at 4 hours	Not just atrial fibrillation, small sample size, strict exclusion criteria, inadequate description of randomization/blinding

Comment(s)

Search strategy was amended as a result of a large body of evidence surrounding AF in cardiac surgery, which was not felt to be directly relevant to the clinical scenario in this case. Four studies demonstrate, with statistical significance, a more rapid conversion to sinus rhythm in the magnesium group, generally as an adjunct to "usual care", in particular with digoxin. However there is little evidence to support its use as a sole agent as no robust, large study of magnesium alone versus placebo exists.

Editor Comment

KMJ

Clinical Bottom Line

The evidence available to date does not support the use of magnesium as a sole agent for effective rhythm control in fast AF without haemodynamic compromise. It is however demonstrably effective as an adjunct to other agents such as digoxin in both rate and rhythm control, particularly in hypomagnesemic patients.

References

1. Brodsky M, Orlov M, Capparelli E, Allen B, Iseri L, Ginkel M. et al. Magnesium therapy in new-onset atrial fibrillation. Am J Cardiol 1994; 73(16): 1227-1229
2. Chiladakis J, Stathopoulos C, Davlouros P, Manolis A. Intravenous magnesium sulfate versus diltiazem in paroxysmal atrial fibrillation. Int J Cardiol 2001; 79(2-3): 287-291
3. Chu K, Evans R, Emerson G, Greenslade J, Brown A. Magnesium sulfate versus placebo for paroxysmal atrial fibrillation: A randomized clinical trial. Acad Emerg Med. 2009; 16(4): 295-300
4. Davey M, Teubner D. A randomized controlled trial of magnesium sulfate, in addition to usual care, for rate control in atrial fibrillation. Ann Emerg Med 2005; 45(4): 347-353
5. Gullestad L, Birkeland K, Molstad P, Hoyer M, Vanberg P, Kjekshus J. The effect of magnesium versus verapamil on supraventricular arrhythmias. Clin Cardiol 1993; 16(5): 429-34
6. Hays J, Gilman J, Rubal B. Effect of magnesium sulfate on ventricular rate control in atrial fibrillation. Ann Emerg Med 1994; 24(1):61-64
7. Joshi P, Deshmukh P, Salkar R. Efficacy of intravenous magnesium sulphate in supraventricular tachyarrhythmias. J Ass Phys Ind 1995; 43(8):529-31
8. Moran J, Gallagher J, Peake S, Cunningham D, Salagaras M, Leppard P. Parenteral magnesium sulfate versus amiodarone in the therapy of atrial tachyarrhythmias: a prospective randomized study. Crit Care Med 1995; 23(11):1816-1824
9. Walker S, Taylor J, Harrod R. The acute effects of magnesium in atrial fibrillation and atrial flutter with a rapid ventricular rate. Emerg Med 1996; 8:207-213