Causes of hypomagnesaemia

Hypomagnesaemia can occur in patients due to:

• decreased intake of magnesium
• intestinal loss such as diarrhoea
• medication side effects
• renal loss such as metabolic alkalosis
• transcellular shift

Consider reviewing medicines that can cause hypomagnesaemia such as:

• aminoglycosides
• loop diuretics
• proton pump inhibitors
• tacrolimus
• thiazide diuretics

Classification of hypomagnesaemia

Hypomagnesaemia is defined as less than 0.7mmol/L of serum magnesium.

Mild

0.5 to 0.7mmol/L serum magnesium.

Clinical signs

No symptoms or non-specific symptoms, such as lethargy, muscle cramps, or muscle weakness.

Severe

Less than 0.5mmol/L serum magnesium.

Clinical signs

Severe neurologic symptoms such as nystagmus, tetany, seizures, and cardiac arrhythmias.

Management of hypomagnesaemia

The reference range for serum magnesium and dosing recommendations may vary locally. Healthcare professionals should work in line with their organisation’s medicines policy.

Identify and treat the underlying causes of hypomagnesaemia.

Correct any other electrolyte disturbances. Hypomagnesaemia is often associated with hypocalcaemia and hypokalaemia.

The dose, dosing schedule and duration of treatment will depend on your patient’s serum magnesium level and symptoms.

Lower doses may be required in renal impairment due to the risk of hypermagnesaemia.

Mild

Use oral magnesium replacement. Give intravenous (IV) magnesium sulfate in a hospital setting if the oral route is not available.

Dose

Give a total daily oral dose of 10 to 24mmol of magnesium in divided doses.

Give an initial IV dose of 1 to 5g (4 to 20mmol) of magnesium depending on serum level in patients who cannot receive treatment via the oral or enteral route.

Repeat the oral or IV dose depending on serum magnesium level.

Severe

IV magnesium sulfate should be given in a hospital setting.

Dose

Give an initial IV dose of 5g (20mmol) of magnesium for severe or symptomatic hypomagnesaemia.

Repeat the dose depending on serum magnesium level.

Up to 40g (160mmol) of IV magnesium over 5 days may be required to correct deficiency.

Duration of therapy

There are no published guidelines on the recommended duration of magnesium therapy. It is common practice to prescribe oral magnesium replacement for up to 7 days and then repeat the serum magnesium level.

Continue treatment for 1 to 2 days after magnesium levels normalise. While serum magnesium levels typically rise quickly with therapy, replenishing intracellular stores takes longer.

Medication induced hypomagnesaemia

If hypomagnesaemia is believed to be induced by medication, consider alternative treatments.

Proton Pump Inhibitors

Consider histamine 2 receptor antagonists, like famotidine or nizatidine, for patients who need an alternative to proton pump inhibitors.

Diuretics

Consider potassium-sparring diuretics, like amiloride or spironolactone, for patients who need an alternative to a loop or thiazide diuretic.

Side effects

Oral magnesium salts are poorly absorbed and can cause diarrhoea in large doses.

Start with a low dose, such as 1 tablet per dose, and gradually increase to a maximum tolerated dose. Advise patients to take oral magnesium with meals and in divided doses.

If diarrhoea occurs, reduce the dose or temporarily withhold treatment until symptoms improve. If diarrhoea persists or the patient becomes symptomatic, IV magnesium replacement may be necessary.

Renal impairment

Seek specialist advice before prescribing magnesium replacement to patients with the following:

• severe kidney disease (CKD 4 or 5)
• acute kidney injury
• receiving dialysis
• a kidney transplant

There are no published data to guide treatment in such patients.

For patients with mild to moderate kidney disease (CKD 1 to 3), use IV magnesium with caution. Consider reducing the initial magnesium dose by 25 to 50%. No dose adjustments are needed for oral magnesium replacement.

Choice of oral magnesium replacement

Consult your local formulary for first line product choice.

The following salts are licensed in the UK for the treatment of hypomagnesaemia:

• magnesium aspartate oral powder sachets (contain 10mmol magnesium)
• magnesium citrate tablets (contain 4mmol magnesium)
• magnesium glycerophosphate tablets, chewable tablets, capsules (contain 1.6 to 4mmol magnesium)
• magnesium glycerophosphate oral solutions (contain 4 to 5mmol magnesium in 5mL)

There are no significant differences in bioavailability between oral magnesium salts. If the first line choice is ineffective or not tolerated, consider a different oral magnesium salt.

Oral magnesium may not be suitable for patients who:

• have severe hypomagnesaemia
• are nil by mouth
• have no or limited gastrointestinal absorption
• are unable to tolerate oral medicines
• require immediate correction of magnesium blood levels.

Choice of IV magnesium replacement

Consult local guidelines in first instance.

Consider the following when you are choosing IV magnesium products.

Magnesium sulfate strengths may be expressed as a % w/v, g/mL or mmol per mL. Each 1g of magnesium sulphate is equivalent to 4mmols of magnesium.

Expression

Magnesium sulfate can be expressed in the following way:

• magnesium sulfate 10% w/v (0.1g/mL), contains 0.4mmol/mL magnesium
• magnesium sulfate 20% w/v (0.2g/mL), contains 0.8mmol/mL magnesium
• magnesium sulfate 50% w/v (0.5g/mL), contains 2mmol/mL magnesium

Concentration

Magnesium sulfate 50% (0.5g/mL or 2mmol/mL) must always be diluted before use. Undiluted magnesium sulfate 50% has high osmolarity over 1,000mOsm/L and can cause extravasation or significant tissue damage.

Do not exceed a concentration of 20% (0.2g/mL or 0.8mmol/mL) of IV magnesium through a central line.

Do not exceed a concentration of 5% (0.05g/mL or 0.2mmol/mL) to 10% (0.1g/mL or 0.4mmol/mL) of IV magnesium through a peripheral line.

Dilute to the required concentration according to local policy.

Rate

The usual rate of IV magnesium is 1 to 2g/hour (4 to 8mmol/hour) and should not exceed 9g/hour (36mmol/hour).

Monitoring

Repeat the serum magnesium level 7 days after starting oral therapy and again after 1 to 3 months, depending on the cause of hypomagnesaemia.

Monitor the serum magnesium level after each IV dose.

Other monitoring parameters during magnesium replacement should include:

• serum calcium and potassium
• renal function
• blood pressure with IV magnesium
• ECG monitoring with IV magnesium in patients with severe symptoms such as tetany, seizures and arrhythmias

Other parameters will depend on individual patient circumstances.