We look at it daily on routine ICU bloods, it is used to help various acute conditions, it is always checked in the setting of cardiac arrhythmia….it burns with a glowing flame!

We seem to obsess with keeping it’s serum level at the higher end of normal….is the fuss justified?

It is true that hypomagnesaemia predisposes to arrhythmias, but it has been described as the “jack of all trades”, when it comes to the treatment of specific arrhythmias and the treatment of many other arrhythmias in the ICU setting.  The rationale being that low levels of magnesium predispose to arrhythmias (particularly ventricular) or at least predispose an already existing arrhythmia to become uncontrolled.

What does it do physiologically?

  • Normal lavel = 0.7-1.0 mmol/L
  • High = >2.5 mmol/L

It is a crucial cofactor in the sodium-potassium-ATPase enzyme system, which contributes to the sodium and potassium flux across cell membranes. This determines the potential needed for depolarization of cardiac muscle. Of note, digitalis blocks the sodium-potassium-ATPase enzyme system; it has been shown in the dog model that hypomagnesemia facilitated digitalis-toxic arrhythmias and that most of these arrhythmias were terminated with intravenous magnesium sulfate. This explains why trials have been done using both of these drugs.

Too much causes:

  • General – skin flushing, lightheadedness.
  • Muscular – weakness.
  • CVS – hypotension, vasodilatation, bradycardia, arrhythmias (asystole, AF, intraventricular conduction delay), cardiac arrest.
  • RS – bronchodilatation, respiratory depression, failure to wean.
  • CNS – disappearance of tendon reflexes, sedation, stupor, coma.
  • GI – diarrhoea, nausea, vomiting.
  • Interaction – prolongation of neuromuscular blockade due to decreased Ach levels at the neuromuscular junction.
  • Blood – impaired coagulation due to platelet clumping and delayed thrombin formation.
  • ECG – prolonged PR interval, broad QRS complexes, heart block.

Immediate Management:

  • 100% O2…ABC.
  • Intubate as necessary.
  • 10 mL 10% calcium gluconate over 10 mins, plus repeat if necessary.
  • 50 mL 50% dextrose and 10IU human actrapid over 1 hour.
  • Infuse normal saline, initially 1 litre per hour induce diuresis using furosemide 20-40 mg, plus repeat as necessary.
  • Dialysis can be initiated in life threatening situations with magnesium free dialysate.

Visible Sign

Magnesium Level (mmol/L)

Abolition of knee jerk 3.0-5.5
Respiratory arrest 5.0-7.5
All deep tendon reflex abolition >10
Cardiac arrest >15

Too little causes:

  • General – anxiety, confusion, weakness, muscle cramps, vertigo, depression
  • CVS – palpitations, hypertension and angina, arrhythmias (VT/VF, torsade de pointes, SVT, AF).
  • RS – stridor.
  • CNS – seizures, ataxia, dysarthria, dysphagia, myoclonus, Trousseau’s sign, Chvostek’s sign, hyper-reflexia, coma.
  • Bone – osteoporosis, osteomalacia.
  • Interaction – increased risk of digoxin toxicity.
  • ECG – prolonged PR interval, broadened QRS, inverted T waves, ST depression, U waves.

Immediate Management:

  • 100% O2…ABC.
  • Treat seizures with diazemuls 5-10 mg.
  • Acute severe asthma / dysrhythmias: magnesium sulphate 10mmol (2.5g) IV in 100 mL N saline over 10 min.
  • Followed by 50-100 mmol (12-25g) over the next 24h.
  • PIH/Eclampsia: load with 16 mmol (4g) IV in 100 mL N saline over 30 min.
  • Followed by  4 mmol/h (1g/h) over the next 24h after last seizure. If another seizure recurs in this time, give 8-16mmol (2-4g) over 5 min.
  • Aim for therapeutic level of 2-4 mmol/L.

The Evidence behind it all in arrhythmia therapy…

A recent article in the European Heart Journal Cardiovascular Pharmacotherapy reviews the literature, highlighting the current knowledge base on magnesium and it’s therapeutic potential.

The potential for magnesium supplementation to prevent and treat arrhythmias has been recognised for years and includes:

Prevention of post-operative atrial fibrillation

25-40% of patients undergoing cardiac surgery develop post-operative atrial fibrillation (POAF). This results in prolonged length of hospital stay, increased risk of stroke and higher healthcare associated costs.

There is an association between low pre-operative intracellular magnesium concentrations and an elevated risk of POAF. So, it is plausible that the prophylactic use of magnesium has the potential to correct deficiencies and reduce the risk of POAF.

However, there have been mixed results from the large number of clinical trials (most in cardiac surgical patients) and meta-analyses evaluating the impact of perioperative magnesium supplementation on the rates of POAF. This is certainly due in part to the heterogeneity amongst the published research, inclusion of studies with small sample sizes, varying magnesium doses, variation in timing of administration, differing study designs and quality.

A meta-analysis investigating the effectiveness of prophylactic magnesium at preventing POAF concluded that there was no benefit to using magnesium prophylactically (OR .94, 95% CI 0.61 to 1.44).

Treatment of acute atrial and ventricular arrhythmias

Atrial fibrillation

Atrial fibrillation is the most common supraventricular arrhythmia and is associated with an increased risk of stroke and mortality.

Lower serum magnesium levels have been found in patients with AF compared to healthy controls, therefore out is unsurprising that treatment of new onset AF (NOAF) can involve magnesium therapy.

Trial evidence has shown that IV magnesium is effective for controlling ventricular response in AF and IV magnesium used in combination with digoxin resulted in significant reductions in heart rates.

A randomised controlled trial of 190 patients presenting with rapid atrial fibrillation to the emergency department found that IV magnesium sulfate was:

  • more likely than placebo to achieve a pulse rate of less than 100 beats / min (63 [65%] of 97 versus 32 [34%] of 93, relative risk [RR] 1.89; 95% confidence interval [CI] 1.38 to 2.59; P<.0001)
  • more likely to convert to sinus rhythm (25 [27%] of 94 patients versus 11 [12%] of 91 patients; RR 2.20; 95% CI 1.15 to 4.21; P=.01).

Two meta-analyses investigated the efficacy of IV magnesium in the acute treatment of rapid AF.

The first meta-analysis found that magnesium was:

  • effective in achieving rate control (OR 1.96, 95% CI 1.24 to 3.08)
  • effective in controlling rhythm (OR, 1.60, 95% CI 1.07 to 2.39)
  • reducing time to response (weighted mean difference, −6.98; 95% CI −9.27 to −4.68)

Whereas, the second meta-analysis revealed that:

  • IV magnesium was not effective in converting acute onset AF to sinus rhythm compared to placebo or an alternative anti-arrhythmic drug
  • adding IV magnesium to digoxin did increase the proportion of patients with a ventricular response <100 beats/min (58.8% vs 32.6%; odds ratio [OR] 3.2, 95% confidence interval [CI] 1.93-5.42; p<0.00001) compared to placebo

Finally, although IV magnesium was less effective than calcium antagonists or amiodarone, in reducing the ventricular response (21.4% vs 58.5%; OR 0.19, 95%CI 0.09-0.44; p<0.0001). It was less likely to cause significant bradycardia or atrioventricular block (0% vs 9.2%; OR 0.13, 95%CI 0.02-0.76; p=0.02).

In addition to this, there have been studies performed to assess the role of magnesium in the conversion of AF to normal sinus rhythm.

Parenteral magnesium sulfate versus amiodarone in the therapy of atrial tachyarrhythmia demonstrated that IV magnesium via continuous infusion led to a larger number of conversions of atrial tachyarrhythmias (including AF) to normal sinus rhythm than amiodarone at 24 hours (p<0.05).

This was further corroborated by meta-analysis data that showed that patients treated with IV magnesium were more likely to convert to sinus rhythm than other agents, including placebo and calcium channel blockers (OR 1.60, 95% CI 1.07 to
2.39).

Supraventricular tachycardia (SVT)

The evidence to support the use of magnesium to terminate SVT is less robust and frankly contradictory.

A case report highlighted the effectiveness of IV magnesium in the conversion of SVT refractory to IV adenosine. While a small trial demonstrated the anti-arrhythmic properties of IV magnesium sulfate during bouts of SVT but with only moderate efficacy.

On the other hand, a study evaluating the effects of IV magnesium sulfate compared to adenosine triphosphate (ATP) in patient with SVT, found that ATP was significantly better than magnesium at terminating tachycardias (14 of 14 vs 6 of 14, p < 0.0001).

As a result, the current data does not support the routine use of IV magnesium for the rapid termination of SVT.

Ventricular arrhythmias

A study carried out in a municipal hospital found that, serum magnesium levels were lower and urine magnesium excretion was greater, in patients with complex ventricular arrhythmias. It was also found that IV magnesium resulted in significant reduction in the number of ventricular ectopic beats (P < 0.0001), couplets (P < 0.003) and episodes of non-sustained ventricular tachycardia (P < 0.01)

The primary and well-established use of magnesium is to terminate polymorphic VT / Torsades de Pointes (TdP). Guidelines recommend the immediate administration of magnesium as the first-line treatment of TdP.

This recommendation was based on data from a case series in which torsade de pointes resolved in 9 of 12 patients (75%), following a single bolus of 2g IV magnesium sulfate.

So, in conclusion…

It is clear that magnesium has a number of beneficial effects on the cardiovascular system, in particular, it’s anti-arrhythmic properties. These benefits are probably due to correcting the intracellular magnesium deficiencies found in patient populations presenting with arrhythmias.

So although, there is some merit to using magnesium in the management of various tachyarrhythmias, it does not appear to be the cure-all that it is made out to be!

 

Written by Dr R Pertwee (ITU Social Media & Research Fellow)

Edited by Dr Jonny Wilkinson

 

Other things to look at:

Magnesium physiology

Magnesium and the Heart

Magnesium deficiency