Background: Currently, several medications are recommended for the management of atrial fibrillation with rapid ventricular response in the emergency department including calcium channel blockers, beta blockers and digoxin (the optimal choice is still up for debate). Magnesium sulfate may play a role as a supplemental medication based on its ability to decrease the frequency of sinus node depolarization, prolongation of the refractory period of the atrioventricular node, and acting as a calcium antagonist inhibiting calcium currents in cardiomyocytes. In addition, intravenous magnesium is safe and cheap. Most previous trials on the use of magnesium sulfate have rather small sample sizes or were performed in post-cardiac surgery patients. Also, the exact dose of magnesium used in previous studies varied significantly making it difficult to determine which dose would be the most optimal in these patients. Recently, the LOMAGHI study was just published trying to answer the questions behind many of these issues.
What They Did: Prospective, randomized, controlled, double-blind clinical trial at 3 university hospital EDs to determine the benefit of two doses of magnesium sulfate compared to placebo in rate control of rapid atrial fibrillation managed in the ED in addition to atrioventricular (AV) nodal blocking agents
- Low Dose Magnesium Sulfate (LowMg) = IV 4.5g in 100mL of NS
- High Dose Magnesium Sulfate (HiMg) = IV 9.0g in 100mL of NS
- Placebo = 100mL of Saline Infusion
Outcomes:
- Primary: Reduction of baseline ventricular rate at 4hrs to <90 beats/min or reduction of ventricular rate by ≥20% from baseline (Only patients who maintained these changes until the end of the protocol were considered to have achieved a therapeutic response)
- Secondary:
- Resolution time (Elapsed time from start of treatment to therapeutic response)
- Sinus rhythm conversion rate
- Adverse events within the 1st24hrs
Inclusion:
- Age >18 years
- Admitted to the ED for rapid atrial fibrillation (>120 beats/min)
Exclusion:
- Arterial hypotension (SBP <90mmHg)
- Impaired consciousness
- Renal failure (Serum Cr >180umol/L)
- Wide-complex ventricular response
- Contraindication to magnesium sulfate
- Acute myocardial infarction
- Acute congestive heart failure (NYHA Class 3 or 4)
- Sick sinus syndrome
- Rhythm other than atrial fibrillation
Results:
- 450 patients received study medications
- Placebo = 149 patients
- LowMg = 148 patients
- HiMg = 153 patients
- Therapeutic Response Rate at 4 hrs:
- HiMg = 59.5%
- LowMg = 64.2%
- Placebo = 43.6%
- Therapeutic Response Rate at 24hrs:
- HiMg = 94.1%
- LowMg = 97.9%
- Placebo = 83.3%
- Resolution Time:
- HiMg = 5.2 +/- 2.0hrs
- LowMg = 6.1 +/- 1.9hrs
- Placebo = 8.4 +/- 2.5hrs
- Rhythm Control Rate at 24hrs:
- HiMg = 13.0%
- LowMg = 22.9%
- Placebo = 10.7%
- Adverse Effects:
- HiMg = 21 total events (18 pts with flushing, 2 with hypotension, 1 with bradycardia)
- LowMg = 8 total events (6 with flushing, 1 with hypotension, 1 with bradycardia)
- Placebo = 3 total events (1 with flushing, 1 with hypotension, 1 with bradycardia)
Strengths:
- Pharmacists prepared the study packs but were not involved with patient enrollment, data collection or data analysis
- Magnesium sulfate and placebo solutions had identical appearances
- Physicians and patients were both blinded to randomization
- No difference between three treatment groups with respect to baseline demographic or clinical characteristics
- Utilization of rate control medications in the 3 groups were similar between groups
Limitations:
- Additional AV nodal blocking agents given at the same time as magnesium sulfate were left at the discretion of the treating physicians
- There was no a priori standard treatment defined, meaning standard treatment was left to the discretion of the ED physician
- Digoxin was the most commonly used rate control agent in this study, and is not currently the standard agent used in many EDs (i.e. CCBs and BBs are much more common)
- No data collection on patients once they left the ED, therefore no information regarding longer-term variables or complications, therefore it is impossible to make conclusions about longer term ramifications in adding magnesium sulfate to standard care
- There was no correlation of serum magnesium to clinical response
Discussion:
- If atrial fibrillation was diagnosed with certainty as a recent event (i.e. <48hrs) then electrical cardioversion was used instead of standard antiarrhythmic medications
- The most common rate control agent used in this study as usual care was Digoxin (47.5%) and not calcium channel blockers and beta blockers. However in a secondary analysis including only patients receiving beta blockers and calcium channel blockers, the obtained results were not significantly different compared to those in the overall group. Also there is no data on how much of each agent was used. This could simply be due to underdosing of CCBs and BBs.
- According to the authors there have only been 4 randomized controlled double blind trials assessing magnesium sulfate for rate control of rapid atrial fibrillation in cardiac surgery patients, but only 2 of these trials were performed in the ED setting.
- Study excluded patients in extremis (i.e. hemodynamic instability, acute MI, acute CHF) which limits the generalizability of these results to that population. HD instability with atrial fibrillation is often due to underlying other issues but also magnesium sulfate can worsen hypotension, and there is a clear treatment algorithm for unstable patients with atrial fibrillation with RVR (i.e. Cardioversion)
Author Conclusion:“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.”
Clinical Take Home Point: In patients with confirmed atrial fibrillation with RVR, who are not candidates for electrical cardioversion (i.e. <48hrs), the addition of 4.5g of IV magnesium sulfate to standard rate-control agents may more efficiently and more rapidly improves therapeutic response rates with no significant adverse effects compared to placebo and magnesium sulfate 9.0g of IV magnesium sulfate in the emergency department (i.e. Without knowing the exact doses of medications used and the fact that only 50% of patients had a commonly used agent, it is hard to say definitively that magnesium sulfate is effective as an adjunct to standard rate control medications).
References:
- Bouida W et al. LOW dose MAGnesium sulfate versus HIgh dose in early management of rapid atrial fibrillation: randomized controlled double blind study. Acad Emerg Med 2018. PMID: 30025177
For More Thoughts on This Topic Checkout:
- PharmERToxGuy: Low-Dose vs. High-Dose Magnesium in Rapid Afib
Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)
