The Pre-brief
- Atrial Fibrillation (AF) is the most prevalent arrhythmia in the U.S., and it is estimated that 12.1 million people will be affected by 2030.
- Accounts for 16-26 billion in annual expenditures and more than 454,000 hospitalizations each year in the U.S.
- Death attributed to AF has been rising for more than two decades, currently accounting for 158,000 deaths annually
- Prevalence increases with age
- Women are more likely to experience AF than men
- Nearly 4 million visits to the emergency department (ED) annually are for AF, most of which are for stable rapid AF.
- Defined as: HR >110 bpm at rest without hemodynamic instability.
- Acute management includes:
- HR control with beta-blockers, non-dihydropyridine calcium channel blockers, or digoxin
- Consideration for pharmacologic rhythm control (antiarrhythmic therapy including amiodarone) or electrical cardioversion
- Consideration of anticoagulation based on stroke risk assessment
- Treatment of any underlying acute triggers to prevent hemodynamic compromise (e.g. fever, hypoxia, ischemia, infection/sepsis, heart failure, etc.)
- IV magnesium has been investigated as an adjunct to achieve rate and/or rhythm control
Adjunctive IV magnesium for rate control
Magnesium works to reduce sinus node rate by blocking slow, inward L-type calcium channels and prolonging the atrioventricular conduction time and refractory period. It is an attractive adjunctive therapy option in rapid AF due to its minimal negative inotropic effects, potential to synergize with standard AF treatment, low cost, and low risk for adverse events.
IV magnesium has been studied as part of the management of rapid AF. Previous meta-analyses determined that IV magnesium in combination with standard of care was more effective than placebo in achieving rate, but not rhythm, control in AF. However, most studies included were small and characterize outcomes in the cardiac surgery population.
In the LOMAGHI study, 450 patients presenting to the ED with rapid AF (HR >120 bpm) were randomized to receive either high-dose IV magnesium (9 g/100 mL saline), low-dose IV magnesium (4.5 g/100 mL saline), or placebo within 30 minutes. The majority of patients received digoxin for rate control (47.5%). A statistically significant increase in ventricular response at 4 hours, defined as HR ≤90 bpm or ≥20% reduction from baseline, was achieved in patients receiving high-dose (59.5%) or low-dose (64.2%) IV magnesium compared to placebo (43.6%), p ≤0.05. Patients receiving IV magnesium were more likely to have sustained ventricular rate response at 24 hours compared to placebo.
Interestingly, this study demonstrated a significant increase in rhythm control with low-dose IV magnesium compared to placebo which indicates the benefits of magnesium may extend beyond heart rate control. Overall, both magnesium regimens were well-tolerated, but significantly more flushing occurred in the high-dose group.
A recent systematic review and meta-analysis by Ramesh et al. included 745 patients pooled from six randomized trials comparing IV magnesium to placebo for control of rapid AF. IV magnesium doses ranged from 3-10 g and standard of care primarily comprised of digoxin, followed by calcium channel blockers and beta-blockers. IV magnesium was superior in achieving rate control (63% vs. 40%, OR 2.49, 95% CI 1.80-3.45) and rhythm control (21% vs. 14%, OR 1.75, 95% CI 1.08-2.84) compared to placebo.
Less is more?
Low-dose (≤5 g) IV magnesium in the aforementioned meta-analysis was associated with significantly increased rhythm control compared to high-dose (>5 g). High-dose IV magnesium was also associated with increased rates of transient flushing. In the case of IV magnesium as an adjunct to standard of care for AF control – yes, less is more!
How much, how fast?
Magnesium comes premixed as 4 g/100 mL. Generally speaking, the rate should not exceed 150 mg/min… this equates to a 27 minute infusion. However, in the setting of continuous cardiac monitoring it is reasonable to administer over 15-20 minutes such as in eclampsia. Hypotension is a potential complication from rapid magnesium administration. Consider more conservative infusion times (e.g. over 30 minutes) in patients with hemodynamic stability.
The Debrief
- IV magnesium when combined with standard HR control (beta-blockers, non-dihydropyridine calcium channel blockers, or digoxin) is associated with achieving significantly increased rate and rhythm control.
- Magnesium doses <5 g were associated with increased rhythm control and less risk of flushing compared to higher doses
- Consider dosing magnesium 4 g IV over 15-20 minutes in the setting of continuous cardiac monitoring for rapid AF
References
- Atrial fibrillation. Centers for Disease Control and Prevention. Accessed 17 August 2021, https://www.cdc.gov/heartdisease/atrial_fibrillation.htm
- Chugh SS, Havmoeller R, Narayana K, et al. Worldwide epidemiology of atrial fibrillation: a global burden of disease 2010 study. Circulation. 2014; 129(8):837-847.
- Ramesh T, Lee PYK, Mitta M, et al. Intravenous magnesium in the management of rapid atrial fibrillation: A systematic review and meta-analysis. J Cardiol. 2021; Jun 20:S0914-5087(21)00151-9. Epub ahead of print.
- Bouida W, Beltaief K, Msolli MA, et al. Low-dose Magnesium Sulfate Versus High Dose in the Early Management of Rapid Atrial Fibrillation: Randomized Controlled Double-blind Study (LOMAGHI Study). Acad Emerg Med. 2019; 26(2):183-191.
Question: Do we need to know Mag level – Does Mg level really matter?
If the serum magnesium level is low, of course this supports giving more mag. However, even normal serum magnesium levels may underestimate intracellular magnesium concentrations. Therefore, I would still give the magnesium as described above even if the serum level is normal.
Thanks a lot, I believe that any intracellular cation cannot have normal levels if you are intracellularly depleted just based on physiology. Like Potassium it has to be intracellularly repleted before you can see higher extracellular levels.