Low-dose vs. High-dose Magnesium in Rapid Afib

Magnesium sulfate has been used as an adjunct medication for the treatment of atrial fibrillation (AF) due to its ability to lessen sinus node depolarization via calcium antagonism. Prior studies investigating magnesium in rapid AF administered varying dosages, often targeted post-surgical patients, and had small sample sizes. Dr. Bryan Hayes summarized previous studies on Academic Life in Emergency Medicine in 2016, focusing on IV magnesium for rate-control in ED-related settings and concluded it to be safe and moderately effective for reducing heart rate in rapid AF.

A new 2018 study by Bouida and colleagues aimed to determine the benefit of two different magnesium doses vs. placebo to control ventricular rate in ED patients with AF, when used with an AV nodal blocking agent.

What They Did

• Prospective randomized, controlled, double-blind study in three Tunisian EDs
• Intervention (administered within 30 minutes of ED arrival):
  • 4.5 grams IV magnesium in 100 mL NS (Low-dose group), or
  • 9 grams IV magnesium in 100 mL NS (High-dose group), or
  • 100 mL IV NS (placebo group)
• Primary outcome: reduction of ventricular rate to 90 beats/min or less, or reduction of rate by ≥20% from baseline
• Secondary outcomes: resolution time, sinus rhythm conversion rate, and adverse events within the first 24 hours

Inclusion criteria

• Age >18 yo
• AF with HR >120 beats/min

Exclusion criteria

• SBP <90mmHg
• Altered mental status
• Renal failure
• Wide-complex ventricular response, sick sinus syndrome, rhythm other than AF
• Acute MI
• CHF (class 3 or 4)
• Contraindication to magnesium

What They Found

Sample size: 149 in placebo group, 148 in low-dose group, and 153 in high-dose group

Rate control agents utilized as primary therapy

	Placebo	Low-dose	High-dose
Digoxin n (%)	71 (47.7)	75 (50.7)	68 (44.5)
Diltiazem n (%)	45 (30.2)	43 (29.0)	51 (33.3)
Beta-blockers n (%)	33 (22.1)	30 (20.3)	34 (22.2)
Based on discretion of the treating physicians and not mandated by the study protocol

Therapeutic response rates (primary outcome)

	Placebo	Low-dose Magnesium	High-dose Magnesium
4 Hours	43.6% [35.7-51.6]	64.2% [56.5-71.9]*	59.5% [57.1-67.3]*
24 Hours	83.3% [77.2-89.2]	97.9% [95.7-100]	94.1% [90.4-97.8]
* p≤0.05 vs Placebo Therapeutic response = HR ≤ 90 beats/min or reduction of ventricular response by at least 20%

Absolute difference in therapeutic response when compared to placebo

	Low-dose Magnesium	High-dose Magnesium
4 Hours	20.5% [RR 2.31, 95% CI 1.45-3.69]*	15.8% [RR 1.89, 95% CI 1.20-2.99]*
24 Hours	14.1% [RR 9.87, 95% CI 2.87-17.05]*	10.3% [RR 3.22, 95% CI 1.45-7.17]
* p≤0.05 vs Placebo

Secondary endpoints

• Mean AF resolution time (hours): 8.4 ± 2.5 for placebo, 6.1 ± 1.9 for low-dose, 5.2 ± 2.0 for high-dose
  • Statistically significant between placebo and both high-and low-dose magnesium groups
• Conversion to sinus rhythm at 4 hour: 6.7% for placebo, 12.1% for low-dose, 7.8% for high-dose
  • Not statistically significant between any group
• Rhythm control at 24 hours: 10.7% for placebo, 22.9% for low-dose, 13.0% for high-dose
  • Statistically significant between low-dose group and placebo (p=0.005)
  • Statistically significant between low-dose group and high-dose group (p=0.03)
• Adverse reactions:
  • Flushing (n = 25), occurring most frequently in the high-dose group
  • Transient hypotension in 4 patients (2 in High dose group, 1 in Low dose group, and 1 in placebo group) and bradycardia observed in 3 patients, one in each group

Author’s conclusions

Magnesium appears to have a synergistic effect when combined with other AV nodal blockers and should be combined with usual rate-control agents to obtain efficient and more rapid action. Additionally, magnesium at a dose of 9 grams was not associated with greater efficacy on rate control compared to 4.5 grams.

Application to Clinical Practice

1. Greater decreases in heart rate throughout the 24-hour study period were achieved with the addition of magnesium. This is important because it may not be immediately evident during an ED stay if magnesium is helping, especially when using digoxin which takes longer to work (sometimes several hours).
2. The most common AV nodal blocking agent in the study was digoxin. This is not reflective of general practice in the U.S. It is encouraging that in patients who received diltiazem or beta blockers, there was not an increased risk of bradycardia or hypotension. We need a study with magnesium + the AV nodal blocking agents used in the U.S.
3. There was no difference in efficacy between the low- and high-dose group but less side effects were experienced in the low-dose group.
4. In light of the Previous magnesium data and this new study, we suggest considering the addition of magnesium 4 grams IV in patients with rapid AF in the ED setting as an adjunct to traditional AV nodal blocks. We traditionally have used 2 gm, but 4 gm seems to be what may work in the highest-quality study to date. 4 gm is easier to prepare than 4.5 gm (4 gm is often available as a premixed preparation).

Reference

Bouida W, et al. Low dose magnesium sulfate versus high dose in the early management of rapid atrial fibrillation: randomised controlled double blind study. Acad Emerg Med. 2018 Jul 19. Epub ahead of print. PMID 30025177