magnesium-ivWe love magnesium in the Emergency Department. It’s been said that magnesium is second-line for everything (kind of like doxycycline). But what about rate/rhythm control in atrial fibrillation (AF)? The 2014 AHA/ACC/HRS guideline for the management of patients with AF doesn’t mention magnesium at all.1 Dr. Josh Farkas (@PulmCrit) wrote about magnesium infusions for atrial fibrillation and torsade last year. His post looked at its use for cardioversion, rhythm-control, and rate-control in critically-ill patients. Our post will focus specifically on the IV magnesium data for rate-control in ED-related settings.

Over the years, IV magnesium has been studied for the treatment of rapid AF in several clinical situations, most prominently in post-cardiac surgery patients. However, there are also studies in ED and cardiology patients, both as a primary therapy and as an adjunct. In fact, two meta-analyses from 2007 evaluated the data (mostly the same studies).2,3 Both concluded that magnesium is safe and effective in controlling ventricular rate in rapid AF compared to placebo, the latter in patients also receiving digoxin. A closer look at the meta-analyses reveals that the positive rate-control effect for magnesium seems to be driven by the placebo-controlled trials.4 Similarly, the positive benefit of magnesium in rhythm-control is largely derived from trials versus placebo or traditional rate-control medications (e.g., beta-blockers or calcium channel blockers) rather than amiodarone or other rhythm-control agents. Of the 11 studies cited in the meta-analyses, only five reported rate-control data in ED-related settings. 

Rate-control with IV magnesium in ED-related settings

Citation Setting/Design Comparison Result
Chiladakis 20015 Cardiology department / prospective, randomized Diltiazem (n = 23): 25 mg IV over 15 min, then 12.5 mg/h infusion for 6 h
Magnesium (n = 23): 2.5 g IV over 15 min, then 7.5 g over 6 h
Similar efficacy in reducing ventricular rate at 1 hr (P <0.05)
Davey 20056 ED / prospective, randomized, double-blind, placebo-controlled Control (n = 97): 100 mL 5% dextrose, IV digoxin at the discretion of treating physician
Magnesium (n = 102): 2.5 g over 20 min then 2.5 g over 2 h, IV digoxin at the discretion of treating physician
Magnesium more likely than placebo to achieve a HR <100 bpm (65% vs 34%, RR 1.89; 95% CI 1.38 to 2.59; P <0.0001)
Joshi 19957 ICU / prospective, controlled Verapamil (n = 45): 5 mg IV verapamil, repeat if no response after 15 min
Magnesium (n = 41): 2 g, repeat if no response after 15 min
Verapamil more likely to achieve HR <100 bpm (55.6% vs 19.5%) p < 0.0001
Hays 19948 ED / prospective, randomized, double-blinded, placebo-controlled Control (n = 8): placebo (not defined), 0.5 mg IV digoxin after first 30 min
Magnesium (n = 7): 2 g over 1 min, then 1 g/h for 4 h, IV 0.5 mg digoxin after first 30 min
At 5 minutes, ventricular rates decreased 16 +/- 7% (P <0.02) with MgSO4; this was comparable to rate-control with digoxin (18 +/- 9%) at 4 hours
Gullestad 19939 Unclear / prospective, randomized Verapamil (n = 20): Verapamil 5 mg IV over 5 min, repeat 5 mg if no response after 10 min, followed by 0.1 mg/min infusion
Magnesium (n = 15): 1.2 g over 5 min, repeat if no response after 10 min, followed by infusion 0.04 mmol (0.01 g)/min
Verapamil more likely to achieve HR < 100 bpm at 4 hrs (48% vs 28%) p <0.05

One ED trial has been published since the meta-analyses.10 Twenty-four patients were randomized in a double-blinded, placebo-controlled fashion to receive either magnesium sulfate 2.5 gm (10 mmol) IV or 0.9% saline over 15 minutes.

  • Baseline heart rate (mean +/- standard deviation [SD])
    • Saline group: 140 +/- 21 beats/min
    • MgSO4 group: 125 +/- 24 beat/min
  • Heart rate at 2 hours
    • Saline group: 114 +/- 31 beats/min
    • MgSO4 group: 116 +/- 30 beats/min
  • The heart rate decrease across time did not differ between groups (p=0.124).

Dose

Based on the available date, the magnesium dose should be 2 gm IV over 15 minutes. Repeat boluses or continuous infusions were used in some trials and may be considered. To keep intracellular magnesium levels higher, infusions are theoretically necessary. But, it may not be logistically feasible to maintain a continuous magnesium infusion in the ED, especially considering there is not much available supporting data.

Adverse Effects

The primary adverse effects of IV magnesium administration across the trials were flushing and slight hypotension. All reactions were mild and self-limiting.

Magnesium Deficiency

Hypomagnesemia is often found in patients with rapid AF, but data is conflicting on whether the magnesium level matters.11,12 One study found no difference in magnesium’s effect on heart rate between magnesium deficient and non-deficient patients with rapid AF.

Chronic Atrial Fibrillation

Magnesium does not seem to have an effect on heart rate in patients with chronic AF.13

Bottom Line

Magnesium seems to be safe and moderately effective for reducing heart rate in rapid AF. Even in the studies where magnesium was less effective than an active comparator, it still demonstrated some reduction in HR. Therefore, it seems reasonable to consider administering magnesium 2 gm IV as an adjunctive therapy while you are choosing between a calcium channel blocker or beta blocker as the primary rate-control agent. In some cases, you may find magnesium is enough to achieve lenient HR goals (ie, < 110 bpm). Monitor HR and BP appropriately.

Photo

1.
January C, Wann L, Alpert J, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1-76. [PubMed]
2.
Ho K, Sheridan D, Paterson T. Use of intravenous magnesium to treat acute onset atrial fibrillation: a meta-analysis. Heart. 2007;93(11):1433-1440. [PubMed]
3.
Onalan O, Crystal E, Daoulah A, Lau C, Crystal A, Lashevsky I. Meta-analysis of magnesium therapy for the acute management of rapid atrial fibrillation. Am J Cardiol. 2007;99(12):1726-1732. [PubMed]
4.
Nair G, Morillo C. Magnesium in the acute management of atrial fibrillation: noise or music? Pol Arch Med Wewn. 2007;117(10):446-447. [PubMed]
5.
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. [PubMed]
6.
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. [PubMed]
7.
Joshi P, Deshmukh P, Salkar R. Efficacy of intravenous magnesium sulphate in supraventricular tachyarrhythmias. J Assoc Physicians India. 1995;43(8):529-531. [PubMed]
8.
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. [PubMed]
9.
Gullestad L, Birkeland K, Mølstad P, Høyer M, Vanberg P, Kjekshus J. The effect of magnesium versus verapamil on supraventricular arrhythmias. Clin Cardiol. 1993;16(5):429-434. [PubMed]
10.
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. [PubMed]
11.
Singh R, Manmohan M, Dube K, Singh V. Serum magnesium concentrations in atrial fibrillation. Acta Cardiol. 1976;31(3):221-226. [PubMed]
12.
Eray O, Akça S, Pekdemir M, Eray E, Cete Y, Oktay C. Magnesium efficacy in magnesium deficient and nondeficient patients with rapid ventricular response atrial fibrillation. Eur J Emerg Med. 2000;7(4):287-290. [PubMed]
13.
Frick M, Ostergren J, Rosenqvist M. Effect of intravenous magnesium on heart rate and heart rate variability in patients with chronic atrial fibrillation. Am J Cardiol. 1999;84(1):104-108, A9. [PubMed]
Bryan D. Hayes, PharmD, FAACT, FASHP

Bryan D. Hayes, PharmD, FAACT, FASHP

Chief Science Officer, ALiEM
Creator and Lead Editor, CAPSULES series, ALiEMU
Clinical Pharmacist, EM and Toxicology, MGH
Assistant Professor of EM, Harvard Medical School
Bryan D. Hayes, PharmD, FAACT, FASHP

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