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Date: February 7th, 2019

Reference: Bouida et al. LOw dose MAGnesium sulfate versus HIgh dose in the early management of rapid atrial fibrillation: randomised controlled double-blind study. AEM February 2019.

Guest Skeptic: Dr. Corey Heitz is an emergency physician in Roanoke, Virginia. He is also the CME editor for Academic Emergency Medicine.

Case: You are working in your local freestanding emergency department (ED). This is an ED not physically attached to a hospital, for the non-American listeners. A 64-year-old male patient presents with a feeling of “palpitations” for about one week. His heart rate is 130-140 beats per minute, irregular, and his EKG shows atrial fibrillation with rapid ventricular response (RVR). You want to control his rate and have recently heard some of your colleagues talking about using intravenous magnesium in addition to their typical rate control agents.

Background: Atrial fibrillation is the most frequent cardiac arrhythmia. Patients often present to the ED with increased heart rates, chest pain and weakness among other presentations.

Rate control vs. rhythm control is a debate that has gone on for many years. The management in the USA tends to be rate control while in Canada they tend to do more rhythm control.

In Canada, we tend to cardiovert patients with recent onset of atrial fibrillation (less than 48 hours). There is an aggressive protocol out of Ottawa using procainamide and electricity to rapidly cardiovert and discharge patients with these arrhythmias. A study by Stiell et al showed that the vast majority of patients (97%) were discharged home from the ED with 93% in normal sinus rhythm using this protocol (SGEM#88).

In patients with chronic atrial fibrillation or unknown time of onset and a rapid ventricular response (RVR), rate control and consideration of anticoagulation therapy are the standard ED approach.

Dr. Anand Swaminathan and I reviewed a RCT comparing diltiazem vs. metoprolol in the management of atrial fibrillation or flutter with rapid ventricular rate in the ED (SGEM#133). The SGEM bottom line was that the best available evidence shows that diltiazem will achieve more rapid rate control in patients with atrial fibrillation than metoprolol (NNT 2).

Magnesium has been investigated as an alternative or adjunct for to rate control patients with rapid atrial fibrillation. Prior analyses have suggested that it is a safe and effective alternative strategy, however it has not been well studied in the ED, and the best dosing has been unclear.

Clinical Question: Can IV magnesium sulfate reduce the ventricular rate safely and effectively in ED patients with rapid atrial fibrillation?

Reference:Bouida et al. LOw dose MAGnesium sulfate versus HIgh dose in the early management of rapid atrial fibrillation: randomised controlled double-blind study. AEM February 2019.

  • Population: Emergency department patients older than 18 years of age with rapid atrial fibrillation (>120 bpm).
    • Exclusions: Hypotension (SBP < 90 mm Hg), impaired consciousness, renal failure (serum creatinine > 180 mmol/L), wide-complex ventricular response, or contraindication to MgSO4, acute myocardial infarction, acute congestive heart failure (New York Heart Association functional class 3 or 4), sick sinus syndrome, or rhythm other than atrial fibrillation.
  • Intervention: 9g IV Magnesium sulfate (MgS) infused over 30 minutes.
  • Comparison: 5g IV Magnesium sulfate or placebo infused over 30 minutes.
  • Outcome:
    • Primary Outcome: Reduction of baseline ventricular rate to 90 beats per minute or less, or reduction of ventricular rate by 20% or greater from baseline.
    • Secondary Outcomes: Resolution time, sinus rhythm conversion rate and adverse events within 24 hours.

This is an SGEMHOP episode which means we should have an author on the show. However, the research group was from Tunisia and for a variety of reasons we were not able to have them on the show.

Authors’ Conclusions: “Intravenous MgS appears to have a synergistic effect when combined with other AV nodal blockers resulting in improved rate control. Similar efficacy was observed with the 4.5 and 9g of MgS but a dose of 9g was associated with more side effects.”

Quality Checklist for Randomized Clinical Trials:

  1. The study population included or focused on those in the emergency department. Yes
  2. The patients were adequately randomized. Yes
  3. The randomization process was concealed. Yes
  4. The patients were analyzed in the groups to which they were randomized. Yes
  5. The study patients were recruited consecutively (i.e. no selection bias). Yes
  6. The patients in both groups were similar with respect to prognostic factors. Yes
  7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes
  8. All groups were treated equally except for the intervention. Unsure
  9. Follow-up was complete (i.e. at least 80% for both groups). Yes
  10. All patient-important outcomes were considered. Yes
  11. The treatment effect was large enough and precise enough to be clinically significant. Unsure

Key Results: They enrolled 450 patients into the trial with 1/3 in each group. The mean age was 67 years and 60% were women. Rate control agents used were digoxin (47%), diltiazem (31%) and beta-blockers (22%).

Magnesium sulfate improved rate control in patients with atrial fibrillation with rapid ventricular response.

  • Primary Outcome:
    • Low dose (4.5g MgS) placebo: absolute difference 20.5%, risk ratio 2.31, 95% CI 1.45-3.69
    • High dose (9g MgS) placebo: absolute difference 15.8%, risk ratio 1.89, 95% CI 1.20-2.99
    • 5g vs. 9g MgS: absolute difference 4.7%, risk ratio 0.81, 95% CI 0.51-1.30

  • Secondary Outcomes: Magnesium groups had faster time to resolution, low dose had a higher sinus rhythm conversion rate and rhythm control at 24 hours. However, adverse events (flushing) were higher in patients treated with magnesium.
    • Mean resolution time: 8.4 +5 hours placebo, 6.1 +1.9 hours low dose, 5.2 + 2 hours high dose
    • Sinus rhythm conversion at 4 hours 6.7% placebo, 12.1% low dose, 7.8% high dose
    • Rhythm control at 24 hours 10.7% placebo, 22.9% low dose, 13.0% high dose
    • Adverse events higher with MgS (flushing in 24 patients, transient hypotension in 4 patients – 2 high dose, 1 low dose, one placebo, bradycardia in one patient/group)

1) Both Groups Treated Equally: The choice of AV nodal blocking agents was up to the discretion of the treating physician. This could have impacted the results. It would have been cleaner to have specified an AV nodal blocker to use.

2) AV Nodal Blocker: Digoxin was the most commonly used agent, with almost 50% of patients receiving this as their AV nodal blocker. In the US and Canada, this would likely be the least commonly chosen, with a calcium channel blocker such as diltiazem, or a beta blocker, being the most likely. This could impact the external validity of the results.

Their success rate at four hours (HR <90 bpm or ventricular rate reduction of >20%) was only about 60% in the intervention groups. We covered a study with Swami on SGEM#133 that showed diltiazem had a success rate (HR <100 bpm) of 96% at 30 minutes. Again, we question the external validity of this trial to our experience.

3) Target Heart Rate: The primary endpoints for therapeutic response was a reduction of baseline ventricular rate to 90 bpm or less, or reduction of ventricular rate by 20% or greater from baseline.Some practitioners would be more liberal with the heart rate, allowing 100-110 bpm. As stated earlier, the Fromm et al trial had a target of <100 bpm

4) Disease-Oriented Outcome: The primary outcome was an object number, but it was also a disease-oriented outcome. While it may be statistically significant, is the decrease in heart rate clinically significant? Why not have a more patient-oriented outcome like death, admission to hospital, stroke, MI, length of stay in the ED or hospital, or readmission rate?

This also relates to the potential benefit vs. potential harm of using magnesium as an adjunct for rate control. Is the 16-20% absolute benefit of a disease-oriented surrogate outcome worth the increased risk of side effects like flushing and hypotension? If yes, what would patients say?

5) Low Dose vs. High Dose: The low dose magnesium group had greater efficacy in achieving rate control, time to resolution, sinus rhythm at four hours and rhythm control at 24 hours compared to high dose magnesium. We wonder why there was not a dose response noted or is it that MgS has a ceiling effect and a dose higher than 4.5g does not provide additional benefit.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusion.

SGEM Bottom Line: In patients receiving rate control for atrial fibrillation in the ED, magnesium may (may not) be a useful adjunct but can be associated with more side effects. 

Case Resolution: You decide to give your patient diltiazem for rate control and within one hour, the ventricular rate is approximately 95-100 bpm.

Dr. Corey Heitz

Clinical Application: When giving rate control medications for rapid atrial fibrillation, specifically digoxin, magnesium can be considered as an adjunctive agent, with the caveat that minor side effects may be increased.

What Do I Tell My Patient? Your heart rate is very high and irregular. We are going to treat you with a medication that should bring it down over the next few hours. If that doesn’t work, there are other options we may consider.

Keener Kontest: Last weeks’ winner was Claudia Martin a Respiratory Therapist.  She knew that if your patient was poisoned with the herbicide paraquat, supplying oxygen if they are not hypoxic is known to increase mortality.

Listen to the SGEM podcast to hear this the new keener question. If you know the answer send an email to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

Other FOAMed:

SGEMHOP: Now it is your turn SGEMers. What do you think of this episode? Tweet your comments using #SGEMHOP. What questions do you have about using MgS for rapid atrial fibrillation control? Ask them on the SGEM blog. The best social media feedback will be published in AEM.

Also, don’t forget those of you who are subscribers to Academic Emergency Medicine can head over to the AEM home page to get CME credit for this podcast and article. We will put the process on the SGEM blog:

  • Go to the Wiley Health Learning website
  • Register and create a log in
  • Search for Academic Emergency Medicine – “February”
  • Complete the five questions and submit your answers
  • Please email Corey (coreyheitzmd@gmail.com) with any questions or difficulties.

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.