cardiology papercut lit review

Magnesium in Atrial Fibrillation: Magic or Mush?

May 30, 2024

A 63 yo patient presents to the emergency department at 11pm at night in new atrial fibrillation with a ventricular rate of 167 bpm. There is no past medical history apart from migraine for which the patient is already on metoprolol. Bloods come back essentially normal. A decision is made to see if the patient will self-revert...... all very reasonable.

The next thing that seems to go up always is IV Magnesium and sometimes Potassium. Does magnesium work? Does it add anything? Do you use it? In deciding who to use magnesium on, we need to think about a few things, including patient selection and safety of the drug.

Let's have a look at the evidence. Let's look at the controversy. Spoiler alert; It's a safe drug, causing very few side effects. It may reduce the ventricular rate when given with another rate control agent, but probably doesn't cardiovert.

Atrial fibrillation is the most common arrhythmia we see and will see in the future in the Emergency Department, due to the aging po...

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Atrial fibrillation is the most common arrhythmia we see and will see in the future in the Emergency Department, due to the aging population. Apart from a few circumstances where it may occur due to electrolyte abnormalities or 'holiday heart', it tends to be a condition linked to comorbidites and particularly cardiac medical conditions.

A few facts:

Low magnesium levels may be a risk factor for atrial fibrillation (1)
There is a basis for magnesium as an anti arrhythmic, but mostly based on small or animal studies(2).
When used with other anti arrhythmic medications, magnesium may results in a higher success rate of pharmacological cardioversion (3,4). (Although the medications used in these studies were Ibutilatide and Dofetilide) See the study review below)
Potassium-Magnesium infusions may facilitate a better success rate in electrical cardioversion. (5)
Magnesium may facilitate rate control (when used with digoxin) (6)
Magnesium probably doesn't cardiovert on its own (8)

Below we look at 4 studies:

STUDY 1: The LOMAGHI Study which compared low and high dose IV magnesium to placebo and found a difference in the control of rate, but no difference in rhythm control
STUDY 2: An RCT looking at low dose magnesium alone which found no difference to placebo for rate or rhythm control at 2 hours.
STUDY 3: A systematic review that found that magnesium was effective in both rate and rhythm control
STUDY 4: A systematic review that found that magnesium reduces rate, but is not effective at cardioverting AF patients to sinus rhythm

STUDY 1 (7)

The LOMAGHI Study

"The aim of this study was to investigate the efficacy and tolerance of magnesium sulfate (MgSO4), administered at two different doses, to reduce VR(ventricular rate) in patients admitted to ED with rapid AF."

What They Did

This was a prospective, randomised, Double blind study in 3 emergency departments.

Patients were over 18 years, with rapid AF (>120 beats/min).

Patients were excluded if they had:

Hypotension (systolic arterial pressure < 90 mm Hg)
Impaired consciousness,
Renal failure (serum creatinine > 180 lmol/L),
Wide-complex ventricular response,
Contraindication to MgSO4.
Acute myocardial infarction
Congestive heart failure (New York Heart Associ- ation functional class 3 or 4)
Sick sinus syndrome
Rhythm other than AF.

The anti-arrhythmics that patients were on included calcium channel blockers, beta blockers and Digoxin. We are not given the dosages that patients were on.

N=450

Patients were randomised to receive one of three treatments:

Low Dose Magnesium (4.5 g IV in 100mL normal saline)
High dose Magnesium (9 g IV in 100 mL normal saline)
Placebo (100mL normal saline)

Primary Outcome: Ventricular Rate Control at 4 hours ( ie < 90 bpm or reduced by 20%)

Secondary Outcomes: Time Elapsed, Sinus rhythm conversion rate and adverse events

What They Found

There was a significant difference between both Magnesium Groups and the Placebo group in terms of therapeutic decrease in ventricular rate.
The absolute difference was not different between high and low magnesium groups, although at 24 hours, the therapeutic response was better in the low dose magnesium group.
Conversion to sinus rhythm was not statistically significant between groups at 4 hours.
- Low dose: 12.1%
- High Dose 7.8%
- Placebo 6.7%
At 24 hours conversion to sinus rhythm for patients on beta blockers or calcium channel blockers (given that these are the main medications used ie., not digoxin) was not statistically significant.

My Take On This

This study interestingly shows that low dose magnesium may be better than high dose for rate control, when used synergistically with another rate controlling agent. It may not be as effective for cardioversion to sinus rhythm.

STUDY 2 (8)

"The purpose of this study was to investigate the effect of magnesium sulfate (MgSO4•7H2O, standard hydrated formula) on heart rate and rhythm in patients presenting to the ED with AF of less than 48 hours’ duration and with a ventricular rate greater than 100 beats ⁄ min."

What They Did

This was a double-blinded, placebo-controlled randomised trial, conducted in one emergency department.

Patients were adults with atrial fibrillation of less than 48 hours duration.

Patients were excluded if:

AF was permanent, paroxysmal, and of more than 48 hours’ duration
AF had a wide-complex ventricular response (potential Wolff-Parkinson-White preexcitation syndrome
Systolic blood pressure (sBP) of less than 90 mmHg
Acute pulmonary edema,
ECG evidence of acute myocardial infarction.
Unable to give consent

Primary Objective: Compare heart rate at 2 hours post treatment.

Secondary Objectives: Compare change of heart rate.

Patients received 2.5g of Magnesium or placebo. Patients only received this one drug.

N= 48

What They Found

Mean Heart Rate 2 hours post trial drug:

Magnesium group: Baseline HR=125 and at 2 hours HR=116
Normal Saline group: Baseline HR=140 and at 2 hours HR=114

Conversion to sinus rhythm at 2 hours post trial drug was not statistically significant:

Magnesium 2 patients
Normal saline 6 patients

My Take on This

This is a small study, but looks at the very important question of does magnesium alone lead to cardioversion. The two groups were perhaps not as equal as they should be as the magnesium group were younger with a lower heart rate. Also the time of the study may have been a little short. it would be interesting know what the effect would have been at 4 hours.

The study tells us that on its own, magnesium may not be that good at cardioverting patients into sinus rhythm.

STUDY 3 (9)

This was a systematic review and meta-analysis of randomised controlled trials on the effectiveness of magnesium therapy for the acute management of rapid atrial fibrillation.

Included in this study were:

Adult patients presenting with non-postoperative AF
Patients with chronic or paroxysmal AF with rapid ventricular rate;
RCTs of a parallel or crossover design
Included intervention that consisted of intravenous magnesium compared with routine care or placebo or antiarrhythmic drugs
Double-blind and nonblinded studies were included.

Primary Outcomes: Success in achieving rate and/or rhythm control.

Secondary Outcomes: Time to response and risk of adverse event.

N= Data from 8 RCT's

What They Found

Magnesium was more effective than control treatments for:
- Rate control (OR 1.96, 95% CI, 1.24 to 3.08) and
- Rhythm control (OR 1.60, 95% CI 1.07 to 2.39).
Time to response (in hours) was significantly shorter in the magnesium group than in the control group
Adverse effects were similar in magnesium and placebo groups.
Magnesium was better at rate control compared with the control group.
Magnesium was as effective as amiodarone and diltiazem, for rate control.
IV magnesium was found to be at least 3 time more effective than control treatments for restoring sinus rhythm.

My Take on This

This is a good meta-analysis of RCTs, given that there are not many of these studies available. This study also included patients with chronic atrial fibrillation. It may overestimate the effects of magnesium. Let's compare this to the meta-analysis below.

STUDY 4 (10)

"We hypothesised that intravenous magnesium could be an effective antiarrhythmic agent in patients with acute onset atrial fibrillation. We assessed the potential beneficial and harmful effects of intravenous magnesium, when compared to placebo or an alternative arrhythmic agent, in the setting of acute onset atrial fibrillation (<7 days).... The end-points assessed in this study included rhythm control, ventricular response <100 beats/minute, bradycardia, hypotension, and other side effects."

What They did

This was a meta analysis of 10 trials, with a mixture of settings including emergency departments, ICU and wards.

Outcomes

The proportion of patients with AF converted to sinus rhythm within 24 hours of treatment.
The proportion of patients that ventricular response slowed to less than 100 beats/minute.
Incidence of adverse reactions, which included:
- Flushing, tingling, dizziness
- Bradycardia
- Atrioventricular block
- Hypotension (<100mmHg)
- Patients requiring rescue antiarrhythmics.

What They Found

IV magnesium is more effective than placebo in reducing the fast ventricular response rate when added to digoxin.

In patients with normal serum magnesium levels magnesium but not effective in converting AF to sinus rhythm.

The risk of bradycardia, atrioventricular block or hypotension are less significant than in other medications such as amiodarone. Transient symptoms such as flushing, tingling and dizziness are not uncommon (17%) after the use of IV magnesium.

My Take on This

Here we have a meta-analysis in direct contradiction to the previous one. This is very confusing. In this second study some smaller studies were include, which may affect results. The drug used in combination with magnesium was digoxin; a drug we use far less frequently today.

This article first appeared on www.resus.com.au

References

Khan A M,et al. Low serum magnesium and the development of atrial fibrillation in the community: the Framingham Heart Study. Circulation. 2013;127:33–38.
Delva P. Magnesium and cardiac arrhythmias. Mol Aspects Med. 2003;24:53–62.
Tercius AJ, et al. Intravenous magnesium sulfate enhances the ability of intravenous ibutilide to successfully convert atrial fibrillation or flutter. Pacing Clin Electrophysiol. 2007;30:1331– 1335.
Coleman CI, et al. Dofetilide and Intravenous Magnesium Evaluation (DIME) Investigators. Intravenous magnesium sulfate enhances the ability of dofetilide to suc- cessfully cardiovert atrial fibrillation or flutter: results of the Dofetilide and Intravenous Magnesium Evaluation. Europace. 2009;11:892–895.
Sultan A, et al. Intravenous administra- tion of magnesium and potassium solution lowers energy levels and increas- es success rates electrically cardioverting atrial fibrillation. J Cardiovasc Electrophysiol. 2012;23:54–59.
Davey MJ, Teubner D. A randomized controlled trial of magne- sium sulfate, in addition to usual care, for rate control in atrial fi- brillation. Ann Emerg Med. 2005;45:347–353.
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 2019;26:183-191
Chu K, ey al. Magnesium sulfate versus placebo for paroxysmal atrial fibrillation: a randomized clinical trial. Acad Emerg Med 2009;16:295–300.
Onalan O et al. Meta-Analysis of Magnesium Therapy for the Acute Management of Rapid Atrial Fibrillation. Am J Card. 2007;99:1726-1732.
Ho K M. Use of intravenous magnesium to treat acute onset atrial fibrillation: a meta-analysis. Heart 2007;93:1433-1440.