Hypomagnesaemia

Causes of hypomagnesaemia

INADEQUATE INTAKE: prolonged fasting, dietary magnesium deficiency, malnutrition in chronic alcoholism

GI LOSS: Chronic diarrhoea, vomiting, excessive laxative use, high stoma output, extensive bowel resection, inflammatory bowel disease (including Crohn’s disease and ulcerative colitis), gastroenteritis, cirrhosis, pancreatitis

RENAL LOSS: Acute tubular necrosis, renal tubular acidosis, post obstructive diuresis, primary renal magnesium wasting

ENDOCRINE: Diabetic ketoacidosis, hyperaldosteronism, hypoparathyroidism, hyperthyroidism, hungry bone syndrome, SIADH

OBSTETRIC: Pregnancy, pre-eclampsia

DRUG INDUCED:

Systemic anti-cancer therapies

1. Platinum-based chemotherapy

Eg. cisplatin. carboplatin and oxaliplatin

2. Epidermal Growth Factor Receptor (EGFR) inhibitors

· Monoclonoal antibodies Eg. cetuximab and panitumumab

· TKI inhibitors E.g cabozantinib, afatinib, erlotinib, gefitinib

· Human EGFR-2 (HER2) inhibitors E.g trastuzumab and pertuzumab

Non-cancer drug therapies

1. Antimicrobials: aminoglycosides, tetracyclines, amphotericin B, foscarnet

2. Proton pump inhibitors

3. Tacrolimus

4. Diuretics (loop, osmotic and chronic use of thiazide diuretics)

5. Insulin

Symptoms of hypomagnesaemia

Magnesium is mainly an intracellular ion, so serum concentrations are not an exact measurement of total body stores. Patients with mild deficiency (>0.5 mmol/L) are usually asymptomatic.

Patients with severe depletion and symptomatic the condition can be life threatening. When serum magnesium levels drop significantly (<0.5 mmol/L) most patient have nonspecific symptoms, but they may go on to develop:

Cardiac or muscle-related symptoms such as weakness, cramping, tachycardia/palpitations.
Neurological symptoms such as vertigo, ataxia, depression and in severe case seizures or altered mental state.
ECG changes – arrhythmias, extrasystoles, torsades de pointes, VT, VF, widening of QRS complex, prolongation of QT interval, peaking T waves. If depletion worsens the T wave is diminished

Symptomatic hypomagnesaemia is often associated with hypocalcaemia and hypokalaemia.

Management of hypomagnesaemia

General Principles:

Monitor risk of re-feeding syndrome in patients with malnutrition - refer to local refeeding syndrome guidelines
Diet rich in magnesium is often encouraged in the management of hypomagnesium– examples of this include spinach, pumpkin seeds, avocado, almonds, figs and swiss chard

Grade 1 - Magnesium level: 0.5–0.7 mmol/L or to prevent recurrence of deficit.

Correcting reversible causes where possible including stopping medication that may contribute to hypomagnesaemia in clinically indicated
Encourage magnesium-rich diet
Consider oral magnesium replacement
In asymptomatic, chronic hypomagnesemia – only consider magnesium replacement if benefits outweight risk, particularly in patients with gynaecological cancer as magnesium replacement has been associated with troublesome GI side effects

Grade 2 - Magnesium level: 0.4–0.5 mmol/L.

Correcting reversible causes where possible including stopping medication that may contribute to hypomagnesaemia in clinically indicated
Encourage magnesium-rich diet
Correct any other electrolyte imbalance
In asymptomatic patients with stable & chronic hypomagnesaemia who are tolerating or absorbing oral magnesium supplements, consider continuing / increasing oral supplementation
In symptomatic patients or those with a new presentation of hypomagnesaemia, treat as grade 3.

Grade 3 - Magnesium level 0.3–0.4 mmol/L, patients with symptomatic hypomagnesaemia or those with a new presentation of grade 2 hypomagnesaemia.

Administer IV magnesium.
Monitor serum magnesium concentrations (daily in renal impairment). Blood samples should be taken at least 2 hours after infusion has stopped from the opposite arm. This may be performed the next day when required
Correct any other electrolyte imbalance
Perform an ECG if considering iv replacement
Ensure patients discharged with oral supplementation and arrangements are made for monitoring of serum magnesium

Grade 4 - Magnesium levels <0.3 mmol/L

Admit for IV magnesium as per grade 3 (above)
In severe cases, particularly if abnormal ECG, consider HDU/ITU referral for cardiac monitoring if rapid rate replacement is needed.

Treatment guidelines

Oral magnesium replacement

Formulary choice in order

Dose

Caution/ Note

1

Magnesium aspartate

(10 mmol of Mg 2+) sachet

One sachet two to three times a day based on tolerability.

Dissolve in 50-200ml water, tea, or orange juice and take immediately

1. Avoid in renal impairment if eGFR <30ml/min

2. Each sachet contains 2.7 grams of sucrose.

2

Magnesium Glycerophosphate

4 mmol chewable tablet

Starting dose is one tablet three times daily.

The dose should be adjusted according to magnesium level. Tablet could be broken into quarters, chewed or crushed

1. First choice in diabetic patients

2. Avoid in hyperphosphatemia

3. Contains aspartame, avoid in phenylketonuria.

Prescribing note:

· Interactions: Magnesium could lower level of tetracyclines and quinolones due to chelation. Dose should be separated for two to three hours. See SPC for full list of interactions

· Side effects: Magnesium salts are not well absorbed from GI tract and diarrhoea is a common, dose-dependent side effect. If diarrhoea develops, consider reducing the dose or review clinical need for replacement

· Treatment Duration: Hypomagnesaemia may persist for many months after the completion of SACT. Patients should continue replacement therapy as clinically appropriate.

· Monitoring: Magnesium levels should be checked prior to the next cycle of SACT, or by GP as appropriate.

· Other: Supplementation with other electrolytes such as potassium and calcium may also be required. Due to increased magnesium losses a dose adjustment of magnesium replacement sachets may be necessary with concurrent drugs which lower magnesium levels.

IV magnesium replacement

Dose

Administration

GRADE 2/3

0.3 – 0.5 mmol/L and not tolerating / absorbing oral magnesium supplement

Give 20-30 mmol of IV magnesium sulphate per day for up to 3 days

Add 10mL – 15mL of magnesium sulphate 50% to a 500ml infusion bag of Glucose 5% / Sodium Chloride 0.9% over 6 hours.

Prolong infusion time to 12-24 hours to aid better absorption if possible. A faster rate may be considered for subsequent infusions as appropriate.

GRADE 4

<0.3 mmol/L

On Day 1, give up to 40mmol of IV magnesium sulphate, then recheck magnesium level daily.

To correct symptomatic magnesium deficits in specific populations (e.g., colorectal patients), intravenous replacement of up to 160 mmol over five days may be required.

Add up to 20mL of magnesium sulphate 50% to a 500 ml infusion bag of Glucose 5%/ Sodium chloride 0.9% and infuse over 12 - 24 hours.

Recommended maximum infusion rate: 8mmol/hour (higher rate may require cardiac monitoring).

Prescribing note:

· Side effects: Flushing, hypotension, nausea, vomiting, muscle weakness, bradycardia, coma, respiratory depression, and cardiac arrest may occur with rapid administration.

· Monitoring: Arrange a repeat magnesium level and advise on further management between SACT visits and/or prior to the next cycle of chemotherapy.

IV magnesium replacement in renal impairment (eGFR <50ml/min):

Renal impairment – reduce total dose by 50%

Recommended dose: 20-30mmol over 24 hours on day 1 then 10mmol over 24 hours daily for a further 2-5 days according to serum magnesium levels.

Monitoring: Serum magnesium should be monitored after each dose as appropriate – this can be measured within 24 hours after the end of infusion. ECG monitoring is sometimes indicated in high-risk patients.

Referral routes for intravenous magnesium administration

NHS Lothian:
- Edinburgh Cancer Centre, Western General Hospital: Cancer Assessment Unit, WGH. Tel 0131 537 4050
- St Johns Hospital: SJH Chemotherapy Unit. Email: SJH.Oncologydc@nhslothian.scot.nhs.uk
NHS Fife:
- Planned Investigation Unit, QMH. Tel: 01383 623 623 Ext 27011. If urgent: Acute Medical Assessment Unit at Victoria Hospital, Kirkcaldy.
NHS Borders:
- Macmillan Unit, BGH. Tel 01896 826 333 or 01896 826 888 bleep 3041.
- oncologynurses@borders.scot.nhs.uk. If urgent, Medical Assessment Unit Borders General Hospital.
NHS Dumfries & Galloway:
- Ambulatory care arranged by disease specific CNS. If urgent – combined assessment unit arranged via Medical Reg on-call. Both via switchboard on 01387246246.