Malnutrition - Magnesium deficiency can be a result of malnutrition especially in those patients with alcoholism. 

Dietary magnesium deficiency - Dietary deficiency, diabetic patients with poor magnesium intake are prone to hypomagnesaemia. A diet high in magnesium including cereals, nuts, meat, fish, vegetables, and fruits may help to restore body stores and prevent depletion. 

Drug induced – Medications can induce renal magnesium wasting.  

Drugs which lower magnesium – platinums, cetuximab, arsenic trioxide, liposomal doxorubicin, cabozantinib, panitumumab, diuretics (loop, osmotic and chronic use of thiazide diuretics), proton pump inhibitors, antibiotics (aminoglycosides, tetracyclines - 4-quinolones, tacrolimus, amphotericin, foscarnet. 

GI –Crohn’s disease, high stoma output, ulcerative colitis, gastroenteritis, extensive bowel resection, short gut syndrome, pancreatitis, cirrhosis.

Endocrine – Diabetic ketoacidosis, hyperaldosteronism, hypoparathyroidism, hyperthyroidism, hungry bone syndrome, SIADH. 

Renal – acute tubular necrosis, renal tubular acidosis, post obstructive diuresis, primary renal magnesium wasting. 

Obstetric – Pregnancy, pre-eclampsia.  

Abnormalities in magnesium may co-exist with other electrolyte abnormalities. Hypocalcaemia in the presence of hypomagnesaemia will not resolve unless the magnesium level is normalised. 

Hypokalaemia in the presence of hypomagnesaemia will not resolve unless the magnesium level is normalised. 

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. 

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

• Correct reversible causes where possible. 
• Review medication and stop, if clinically indicated, drugs that may be contributing to hypomagnesaemia. 
• Encourage magnesium-rich diet e.g. spinach, pumpkin seeds, avocado, almonds, figs, swiss chard.  
• Consider oral magnesium replacement, BUT in patients who are asymptomatic with stable, chronic, hypomagnesaemia consider omitting replacement (particularly in patients with gynaecological cancers, or where magnesium replacement has been associated with troublesome GI side effects).  

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

• In patients who are asymptomatic with stable, chronic, hypomagnesaemia and able to tolerate or absorb oral magnesium supplements consider continuing /increasing oral supplementation and correcting reversible causes where possible. 
• In symptomatic patients and those with a new presentation of hypomagnesaemia administer IV magnesium, and ensure patients discharged with oral supplementation and arrangements are made for monitoring of serum magnesium.  
• Perform an ECG. 
• Encourage  magnesium-rich diet e.g. spinach, pumpkin seeds, avocado, almonds, figs, swiss chard. 

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.  
• Ensure patients discharged with oral supplementation and arrangements are made for monitoring of serum magnesium. 
• In symptomatic hypomagnesaemia, (in some patients e.g., colorectal patients) up to 160mmol of intravenous magnesium infusion over 5 days may be required to correct deficit.

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.

Oral magnesium replacement

Formulary first choice: Magnesium aspartate sachets (10mmol of magnesium per sachet): one sachet two to three times a day based on patient tolerability.  Dissolve sachet in 50-200 mL water, tea or orange juice and take immediately.  

Cautions: Avoid in renal impairment, if eGFR < 30 ml/minute. Diabetic patients, each sachet of magnesium aspartate contains 3g of sugar (use magnesium glycerophosphate tablets).  Caution in patients with hyperphosphataemia as tablets contain phosphate  

Alternative oral product: Magnesium glycerophosphate 4 mmol tablets can be used if sachets are not tolerated.  The usual starting dose is one tablet three times daily. The dose should be adjusted according to magnesium level. The tablets may be chewed or crushed.  

Interactions: Magnesium may lower levels of tetracyclines and quinolones. Doses should be separated as much as possible (e.g., 4 hours). See SPC for full list of interactions.   

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

Side effects: Magnesium salts are not well absorbed for the GI tract and may cause diarrhoea – If diarrhoea develops, consider reducing the dose/clinical need for replacement.  

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

Magnesium level: 0.3–0.5 mmol/L (Grade 2/3) and not able to tolerate or absorb oral magnesium supplements - IV magnesium sulphate 20-30 mmol per day for up to 3 days (10mL–15mL of magnesium sulphate 50%) in 500ml glucose 5% or sodium chloride 0.9% over 6 hours. Prolong infusion time if possible, to 12-24 hours to aid better absorption. There may be clinical circumstances when a shorter duration infusion would be desirable.  

Magnesium level <0.3 (Grade 4) or symptomatic hypomagnesaemia:  On the first day of therapy up to 40mmol magnesium sulphate in 500ml of glucose 5% or sodium chloride 0.9% given over 12 to 24 hours is recommended. A faster rate may be considered for subsequent infusions as appropriate. In symptomatic hypomagnesaemia, (in some patients e.g., colorectal patients) up to 160mmol of intravenous magnesium infusion over 5 days may be required to correct deficit.  

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

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.