Magnesium for Rapid Atrial Fibrillation Rate-Control in the ED

2017-03-05T14:18:45+00:00

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

    Comment from Mary Ann Howland, PharmD (via email, with permission to post):

    Hi. I have a comment about your article on magnesium for atrial fibrillation. As far as I can tell not one of the articles you quoted actually compared magnesium to the correct dose of diltiazem. The article by Chiladakis comes closest but doesn’t really use two bolus doses before starting an infusion. Also the dose of magnesium they used was 10 g over 6 h. Not an low dose. What was the Mg conc afterward? Your conclusion is to use magnesium before getting a CCB or BB and I am concerned that as far as I am aware none of the articles actually used Mg with a CCB or BB. I am not sure how long the effects of Mg might last but combining with a CCB or BB might be harmful. Perhaps you have more information. Another consideration is that magnesium accumulates in renal dysfunction. Finally magnesium has other effects besides on the heart (neuromuscular junction and CNS etc) and may also interact with drugs used for other purposes.

    • Bryan D. Hayes

      I appreciate your comments on the magnesium post. You’re correct in that there are not studies using magnesium + CCB or BB, only magnesium + digoxin (which takes longer to work). Magnesium bolus therapy only has a moderate reduction in HR (and even that is not seen in all studies). The studies that demonstrated a more pronounced effect were the ones that used much larger doses + infusions, like the Chiladakis one. Interestingly, they did not report serum magnesium levels after that the high dose. The bolus therapy effect tends to be transient (30-60 minutes max) based on available data and unpublished ex previous institution. When combined with standard-dose (https://www.ncbi.nlm.nih.gov/pubmed/27452987) diltiazem or metoprolol, there is the potential for some synergistic HR lowering, which I think is the caution you raised. Based on the incomplete AV nodal blockade with mag, the risk should be minimal, but your point is well taken. Dr. Josh Farkas, an ICU attending at the University of Vermont Medical Center delves into the pharmacology literature a bit more, which is why I linked to his post rather than reiterate it: http://emcrit.org/pulmcrit/magnesium-infusions-for-atrial-fibrillation-torsade/.

      Magnesium can certainly accumulate in renal disease, though a 2 gm dose should only minimally raise the mag level and is only a very small portion of the total body load of this intracellular cation. Magnesium was safe in all of the studies, including the more well-studied patient population in post-cardiac surgery, which included patients with varying levels of renal disease (both acute and chronic). And based on the frequency with which magnesium 2-4 gm IV is ordered on inpatient surgical wards (even with normal magnesium levels), there is little reason to believe a one-time dose would cause harmful neuromuscular effects in a monitored environment such as the ED.

  • Ken Starr

    I’ve used Mg for years in the ER. One night I converted two different patients out of Afib with RvR with Mg alone.

    I’ve recently learned that Mg chloride causes less Headaches than Mg Sulfate. Not sure how important that is in the ER but interesting none the less.

    Thanks Ken Starr MD

    • Bryan D. Hayes

      Dr. Starr, thanks for your comments. I hadn’t heard that about magnesium sulfate causing more headache than magnesium chloride. In fact, several studies have used IV magnesium sulfate for treatment of migraines: https://em.umaryland.edu/educational_pearls/2661/. If you have any references about sulfate vs chloride, please share them. I agree that it could be important in the ED, though maybe less so than controlling the rapid rate.

      • Ken Starr

        Hey Bryan. Yes Magnesium is very effective for migraine headaches. When used as a therapy for migraines it needs to be given fast enough to cause a ” flush” and some symptomatic vasodilation. Typically 2gm over 10 minutes.. When used slowly, how most nurses feel comfortable given it ,like over an hour or more it is ineffective for headache treatment.

        In the ” Definitive Guide for IV Therapy” published by the American College for the Advancement in Medicine. Dr. Schrader discusses infusing Mg for Migraines as well as for other general health purposes. If used as part of a ” stress formula” for general wellness like a ” Myer’s Stress Formula” he’s found like Mg Chloride causes less headaches than Mg Sulfate.

        I’ve only used MgSulfate in the hospital and not even sure Mg Chloride would be available.

        • Bryan D. Hayes

          Thanks Ken. You bring up a great point that I want to highlight: many hospitals only allow magnesium to be infused over an hour for electrolyte repletion. I encourage anyone looking to use magnesium for asthma, migraines, afib, or even eclampsia to review their institutional guideline and make sure it includes indications for faster infusion times (2 gm over 10-20 minutes). Otherwise, it can be difficult to ask nursing to do so in an emergent clinical situation if they haven’t seen the data supporting it.