Hypermagnesaemia

Hypermagnesaemia is a serum magnesium concentration over 1.10 mmol/L. It is uncommon because healthy kidneys excrete magnesium efficiently, so it nearly always reflects a large magnesium load in a patient with reduced kidney function, or deliberate magnesium treatment in pre-eclampsia. Toxicity blocks neuromuscular and cardiac conduction, and the dangerous end points are respiratory paralysis, heart block and cardiac arrest.

Clinical relevance. Mild hypermagnesaemia occurs in up to 10% of hospital patients, mostly with chronic kidney disease. Severe cases follow magnesium containing laxatives, antacids or enemas in older adults or patients with kidney failure, bowel obstruction or ileus, and overdose of magnesium sulphate in obstetric care.

Physiology. Magnesium blocks release of acetylcholine at the neuromuscular junction, competes with calcium at voltage gated channels, and reduces excitability of cardiac conduction tissue and vascular smooth muscle. The kidney excretes the load, so any fall in glomerular filtration or tubular function, or an excessive load, produces accumulation.

Classification by severity (serum magnesium).

• Mild: 1.10 to 2.00 mmol/L (nausea, flushing, headache, often no symptoms).
• Moderate: 2.01 to 3.50 mmol/L (loss of deep tendon reflexes, drowsiness, hypotension, bradycardia, PR and QRS prolongation).
• Severe: 3.51 to 5.00 mmol/L (muscle paralysis, respiratory depression, complete heart block, coma).
• Life threatening: over 5.00 mmol/L (cardiac arrest).

Classification by cause.

• Excess intake or administration: magnesium containing laxatives, antacids, enemas (milk of magnesia, Epsom salts), magnesium sulphate treatment, parenteral nutrition, dialysate errors, and ingestion of magnesium salts or sea water.
• Reduced excretion: acute kidney injury, chronic kidney disease, and drugs that reduce renal handling.
• Redistribution and release: rhabdomyolysis, tumour lysis, diabetic ketoacidosis, and burns.
• Endocrine and other: adrenal insufficiency, hypothyroidism, familial hypocalciuric hypercalcaemia, lithium therapy, and neonatal exposure from maternal treatment.

Key distinctions. Loss of the patellar reflex is the first reliable clinical sign and appears at about 2.0 to 3.5 mmol/L. Respiratory depression appears at over 3.5 mmol/L, so reflex testing is the bedside guard during magnesium infusions.

History.

• Magnesium exposure: laxatives, antacids, magnesium enemas, supplements, intravenous magnesium (obstetric or arrhythmia treatment), overdose, and recent bowel preparation.
• Kidney disease or oliguria, diabetes, adrenal or thyroid disease, and lithium use.
• Symptoms: nausea, vomiting, flushing, headache, drowsiness, weakness, double vision, difficulty breathing, palpitations, and confusion.
• Bowel obstruction, ileus, constipation, and inflammatory bowel disease (increased absorption).
• In neonates: maternal magnesium infusion for pre-eclampsia or tocolysis.

Examination.

• Level of consciousness, reflexes (reduced or absent), muscle tone and power, respiratory rate and effort.
• Pulse, blood pressure (hypotension), skin (flushing), pupils (fixed and dilated at high levels), and abdomen (distension, ileus).
• Urine output and volume status.
• ECG: prolonged PR interval, wide QRS, peaked T waves, bradycardia, atrioventricular block, and cardiac arrest.

Red flags.

• Loss of tendon reflexes with reduced respiratory rate (under 12 breaths/min) or reduced oxygen saturation.
• Bradycardia, hypotension, atrioventricular block, or QRS widening.
• Reduced consciousness or paralysis.
• Magnesium over 3.5 mmol/L, or any level with symptoms.
• Acute kidney injury or oliguria with ongoing magnesium exposure.
• Ongoing magnesium infusion in a woman with pre-eclampsia and reduced urine output (under 25 mL/hour) or raised creatinine.
• Ileus or obstruction with magnesium containing laxatives.

Special groups. Patients with kidney failure and older adults are at highest risk. Women receiving magnesium sulphate for pre-eclampsia and their newborns are at risk. Neonates may have hypotonia, poor feeding and respiratory depression. Children given magnesium laxatives are at risk with dehydration.

Causes of hypermagnesaemia.

• Iatrogenic: magnesium sulphate for pre-eclampsia, eclampsia, torsades de pointes, asthma, or tocolysis; magnesium in parenteral nutrition; dialysis fluid error.
• Over the counter and oral intake: magnesium containing antacids, laxatives, bowel preparations, supplements, Epsom salts, and magnesium enemas.
• Kidney failure: acute kidney injury and advanced chronic kidney disease (eGFR under 30 mL/min).
• Endocrine: adrenal insufficiency, hypothyroidism, and hyperparathyroidism.
• Cell breakdown: rhabdomyolysis, tumour lysis syndrome, severe burns, and diabetic ketoacidosis at presentation.
• Other: familial hypocalciuric hypercalcaemia, lithium, and neonatal exposure.

Conditions that mimic or accompany hypermagnesaemia. Opioid or sedative overdose, myasthenia gravis, botulism, Guillain-Barre syndrome, hypocalcaemia, hyperkalaemia, hypothermia, hypothyroid myxoedema coma, stroke, sepsis, and other causes of bradycardia and heart block. Hypermagnesaemia commonly coexists with hypocalcaemia, hyperkalaemia and acidosis in kidney failure.

Step 1. Assess airway, breathing and circulation, and check reflexes, respiratory rate and level of consciousness. Obtain an ECG at once.

Step 2. Laboratory tests: magnesium, calcium (corrected or ionised), potassium, phosphate, sodium, urea, creatinine and eGFR, glucose, bicarbonate or blood gas, creatine kinase, lactate, thyroid function, and morning cortisol or short synacthen test where adrenal disease is suspected.

Step 3. Identify the source: medication list, over the counter products, enemas, supplements, infusion records, and dialysate composition. Urine magnesium and a 24 hour urine collection help only when the cause is unclear.

Step 4. Further tests when the cause is not clear: PTH and calcium to creatinine clearance ratio (for familial hypocalciuric hypercalcaemia), abdominal radiograph or CT for ileus or retained magnesium containing material, and lithium level.

Interpretation. A magnesium of 2.0 mmol/L or more with absent reflexes, hypotension or bradycardia needs immediate treatment. A level over 3.5 mmol/L with respiratory depression is an emergency.

Limitations. Serum levels correlate loosely with symptoms; reflex testing and respiratory rate are the practical guides. Concomitant hypocalcaemia and hyperkalaemia increase toxicity and are checked together. Point of care analysers for magnesium vary.

Principles. Stop all magnesium intake and infusions, protect the airway and heart with intravenous calcium, increase renal excretion, and use dialysis for severe or symptomatic hypermagnesaemia, kidney failure or cardiac toxicity. Mild asymptomatic hypermagnesaemia with normal kidney function resolves on removing the source.

Immediate measures.

• Stop magnesium sulphate, laxatives, antacids, enemas and supplements, and remove unabsorbed magnesium from the gut where it is feasible and safe (bowel evacuation with non-magnesium agents in patients without obstruction).
• Monitor continuously: ECG, oxygen saturation, blood pressure, respiratory rate, reflexes every 15 to 30 minutes, and urine output hourly. Give oxygen and prepare for ventilation.
• Ventilatory support (bag mask ventilation, then intubation and mechanical ventilation) for respiratory depression or paralysis, until magnesium falls.

Antagonise the cardiac and neuromuscular effects (moderate to severe, or any ECG change, bradycardia, hypotension or respiratory depression).

• Calcium gluconate 10% 10 to 20 mL (1 to 2 g; 2.2 to 4.4 mmol) IV over 5 to 10 minutes with continuous ECG monitoring. Repeat after 10 minutes if signs persist, to a maximum of 3 doses, and follow with an infusion of calcium gluconate 10% 50 mL in 500 mL of 0.9% saline over 4 to 6 hours if toxicity recurs. The effect starts in minutes and lasts 30 to 60 minutes, which only buys time.
• Calcium chloride 10% 5 to 10 mL (3.4 to 6.8 mmol) IV over 10 minutes through a central vein in cardiac arrest.
• Cautions: digoxin treated patients (give slowly, with monitoring), extravasation (tissue necrosis, particularly with calcium chloride), and do not mix with bicarbonate or phosphate.
• Atropine 0.5 to 1 mg IV every 3 to 5 minutes (maximum 3 mg) for symptomatic bradycardia, and temporary transvenous pacing for high degree block that does not respond.
• Hypotension: isotonic crystalloid 250 to 500 mL boluses and vasopressors (noradrenaline 0.05 to 0.5 micrograms/kg/minute IV, titrated to mean arterial pressure over 65 mmHg).

Increase excretion (kidney function preserved).

• Isotonic saline 0.9% 1 to 2 litres IV over 1 to 2 hours, then 200 to 300 mL/hour, aiming for urine output over 100 mL/hour, with monitoring of volume status, sodium and potassium.
• Furosemide 40 to 80 mg IV (higher in reduced kidney function, up to 160 mg), repeated every 6 hours as needed, once the patient is volume replete. Monitor urine output, potassium, calcium, magnesium and creatinine every 4 to 6 hours. Furosemide also lowers calcium, so replace calcium as needed.

Dialysis. Haemodialysis (with a magnesium free or low magnesium dialysate) for kidney failure, serum magnesium over 4 to 5 mmol/L, respiratory failure, heart block, severe symptoms, or failure of other measures. Magnesium falls by 50 to 70% in a 4 hour session, and levels may rebound after dialysis, so repeat the level at 2 and 6 hours. Peritoneal dialysis is an option where haemodialysis is not available. Continuous renal replacement therapy in unstable patients.

Pre-eclampsia and obstetric patients. Stop the magnesium sulphate infusion at once when reflexes are lost, respiratory rate falls under 12 breaths/min, urine output is under 25 mL/hour or creatinine is rising. Give calcium gluconate 10% 10 mL (1 g) IV over 10 minutes, supportive ventilation if needed, and foetal and neonatal monitoring. Seizure control while the infusion is interrupted: lorazepam 4 mg IV (0.1 mg/kg, maximum 4 mg, repeated once after 10 minutes).

Neonates and children. Calcium gluconate 10% 100 mg/kg (1 mL/kg) IV over 10 minutes with ECG monitoring, ventilatory support, hydration, and exchange transfusion or dialysis in severe cases under specialist care.

Cause specific.

• Adrenal insufficiency: hydrocortisone 100 mg IV then 50 mg IV every 6 hours, with isotonic saline.
• Hypothyroidism: levothyroxine, with specialist advice.
• Rhabdomyolysis and tumour lysis: isotonic saline to maintain urine output over 200 mL/hour, treat hyperkalaemia and hyperphosphataemia, and renal replacement therapy as needed.
• Remove contributing drugs: lithium (specialist advice), magnesium containing products, and review all supplements.
• Treat constipation and ileus with non-magnesium laxatives (macrogol, senna).

Monitoring. Magnesium every 2 to 4 hours until falling, then every 6 to 12 hours until normal; calcium, potassium, phosphate, creatinine and bicarbonate every 6 hours; ECG and respiratory monitoring continuously until stable; reflexes hourly; and urine output hourly.

Referral and escalation. Critical care for respiratory depression, cardiac conduction disturbance, hypotension or magnesium over 3.5 mmol/L. Nephrology for dialysis. Obstetrics and neonatology for magnesium sulphate toxicity. Toxicology for overdose. Endocrinology for adrenal or thyroid disease.

Admission criteria. Magnesium over 2.0 mmol/L with symptoms or kidney impairment, over 3.0 mmol/L at any level, abnormal reflexes, ECG changes, respiratory depression, hypotension, acute kidney injury, or ongoing exposure. Mild asymptomatic hypermagnesaemia (1.10 to 1.50 mmol/L) with normal kidney function can be rechecked in 48 to 72 hours after stopping the source.

Discharge and safety netting. Discharge when magnesium is under 1.10 mmol/L, symptoms have resolved, reflexes are normal, and the source has been removed, with magnesium and creatinine checked in 1 week. Written advice to avoid magnesium containing laxatives, antacids and supplements in kidney disease. Patients return for weakness, drowsiness, slow pulse, breathlessness, fainting or reduced urine output.