Hypomagnesaemia and hypermagnesaemia

• Hypomagnesaemia is a serum magnesium concentration below 0.70 mmol/L (1.8 mg/dL), and hypermagnesaemia is any concentration above 1.05 mmol/L (2.6 mg/dL).
• Low magnesium is common in people with alcohol use disorder, chronic diarrhoea, malabsorption, long-term proton pump inhibitor use, and treatment with loop or thiazide diuretics, cisplatin, amphotericin B or aminoglycosides. It is also common in uncontrolled diabetes.
• Magnesium deficiency usually comes with hypokalaemia and hypocalcaemia that will not correct until the magnesium is replaced, together with neuromuscular irritability (tremor, tetany, seizures) and arrhythmia, including torsades de pointes.
• Severe or symptomatic hypomagnesaemia is treated with intravenous magnesium sulphate; milder deficiency is treated with oral magnesium salts, which are limited by diarrhoea.
• Hypermagnesaemia is almost always due to kidney failure, often after magnesium-containing antacids or laxatives, and occasionally after magnesium sulphate given for pre-eclampsia; it announces itself through loss of reflexes, respiratory depression and (if severe) cardiac arrest, and is reversed with calcium gluconate and dialysis.

By the end of this page you should be able to:

1. Define hypomagnesaemia and hypermagnesaemia and state their thresholds.
2. List the common causes of hypomagnesaemia grouped by mechanism, including drugs, PPIs, diuretics, alcohol, diarrhoea, malabsorption, diabetes, Gitelman syndrome and refeeding.
3. Explain why hypomagnesaemia produces hypokalaemia and hypocalcaemia that resist correction, and how it predisposes to arrhythmia and neuromuscular irritability.
4. Plan management of severe hypomagnesaemia (IV magnesium sulphate dosing, rate, monitoring) and of milder deficiency (oral replacement, with the diarrhoea caution).
5. Recognise hypermagnesaemia, grade its severity, and use calcium gluconate, diuresis and dialysis appropriately.
6. Read the ECG changes of the major electrolyte disorders of this chapter and apply a practical approach in a low-resource setting.

Most of the body's magnesium (about 99%) is intracellular or in bone; less than 1% is in serum. Reference ranges differ between laboratories and sources, roughly 0.7 to 1.0 mmol/L, with narrower intervals such as 0.75 to 0.95 mmol/L quoted for healthy populations. Because only a tiny fraction is extracellular, a normal serum level does not exclude depleted stores, and a low serum level in someone who has just received magnesium may not yet reflect tissue stores. ^[7]

Severity for hypomagnesaemia is clinical rather than biochemical, but practical cut-offs help: deficiency is usually asymptomatic until serum magnesium falls below 1.2 mg/dL (below 0.50 mmol/L), and many references treat levels persistently below 1.25 mg/dL (below 0.50 mmol/L), or any symptomatic case, as grounds for treatment. ^[1] Severity bands for magnesium are not well standardised, so judge the patient and the speed of the fall rather than the number alone.

Symptom-based bands for hypermagnesaemia come mainly from the serum concentration: ECG changes appear at 2.5 to 5 mmol/L (6 to 12 mg/dL), deep tendon reflexes disappear as the level approaches 5.0 mmol/L (12 mg/dL), and cardiac arrest can occur above 6.0 to 7.5 mmol/L (above 15 mg/dL). ^[2]

Hypomagnesaemia has a reported incidence of about 2% in the general population, and is far more common in hospital patients, particularly in intensive care. Suboptimal intake is common: one review cites roughly three-quarters of Americans falling short of the recommended daily allowance. Measured levels also tend to be lower after endurance exercise and in the third trimester of pregnancy. ^[7]

Magnesium deficiency is also more common in diabetes. In one summary, 13.5 to 47.7% of patients with type 2 diabetes had hypomagnesaemia, against 2.5 to 15% of those without diabetes, and lower levels tracked worse glycaemic control. Mouthing these figures loosely, a diabetic patient with new arrhythmia, resistant hypokalaemia or hypocalcaemia should make you think of magnesium. ^[7]

Hypermagnesaemia is rare with normal kidney function. It is most often seen when kidney function is reduced and a magnesium-containing preparation (antacid, laxative, or cathartic) has been swallowed, or when large intravenous magnesium doses have been given (for example in pre-eclampsia). ^[2]

Magnesium homeostasis is shared between three organs: the small intestine (absorption), bone (the major reservoir) and the kidneys (excretion). Under normal conditions 90 to 95% of filtered magnesium is reabsorbed, mainly in the thick ascending limb of the loop of Henle and to a lesser extent in the distal convoluted tubule. ^[7]

Four mechanisms produce hypomagnesaemia:

1. Decreased intake or absorption (poor diet, alcohol, short bowel, malabsorption). ^[1][7]
2. Shift from extracellular to intracellular fluid (refeeding, treatment of diabetic ketoacidosis, hungry bone syndrome after parathyroid or thyroid surgery, acute pancreatitis). ^[1][7]
3. Gastrointestinal loss (chronic diarrhoea, vomiting, nasogastric suction, fistulas, small bowel bypass, and proton pump inhibitor effect on absorption). ^[1][7]
4. Renal wasting (inherited tubular defects, loops/thiazides, nephrotoxic drugs, alcohol tubular dysfunction, hypercalcaemia). ^[1][7]

Hypermagnesaemia is usually a single mechanism: failure to excrete magnesium because kidney function has fallen, combined with an extra (often over-the-counter) load.

Why deficiency hurts: magnesium modulates calcium channels and the sodium–potassium ATPase. Low magnesium depolarises cell membranes, causing hyper-excitability. On the kidney side it removes the intracellular block of the ROMK channel in the collecting duct, producing renal potassium wasting, and it impairs parathyroid hormone secretion and end-organ responsiveness, producing hypocalcaemia. Both of these make the deficiency refractory: hypokalaemia and hypocalcaemia will not correct until magnesium is replaced. ^[7]

Use the table of causes to group them by clinical picture. ^[1]

Decreased intake and malabsorption. Poor diet, starvation, alcohol dependence (intake drops and renal losses rise together), parenteral nutrition, and short-bowel or bypass surgery.

Gastrointestinal losses. Chronic diarrhoea (including laxative abuse), steatorrhoea, vomiting, nasogastric suction, enteric fistulas and small bowel bypass. ^[1][7]

Proton pump inhibitors. Chronic (more than one year) PPI use is a well recognised cause; the mechanism is thought to be impaired intestinal active transport through the TRPM6/TRPM7 channels. PPIs carry a relative risk of hypomagnesaemia of 1.43 in observational data, and cases often recover magnesium levels about a week after stopping the drug. ^[7]

Renal losses: inherited. Bartter and Gitelman syndromes, and familial hypomagnesaemia with hypercalciuria and nephrocalcinosis. In these, renal wasting is the problem and oral or IV replacement is the only available treatment. ^[7]

Renal losses: acquired. Loop and thiazide diuretics inhibit magnesium reabsorption in the thick ascending limb; the potassium-sparing diuretics actually reduce magnesium loss. ^[7] Nephrotoxic drugs do the same lower in the nephron: aminoglycosides, amphotericin B, cisplatin, pentamidine, tacrolimus and cyclosporine. Cisplatin can cause severe, persistent losses even after the drug is stopped. ^[1][7] Alcohol produces hypomagnesaemia in about 30% of chronic users, mostly through tubular dysfunction and excess urinary excretion. ^[7] Hypercalcaemia also competes: the extra filtered calcium reduces magnesium reabsorption in the loop of Henle. ^[7] Gitelman syndrome itself is the inherited cause in which hypomagnesaemia accompanies hypocalcaemia and hypokalaemia. ^[1]

Redistribution. Refeeding syndrome (possibly from intracellular movement with carbohydrate feeding), correction of diabetic ketoacidosis (which drives magnesium into cells), hungry bone syndrome after parathyroidectomy or thyroidectomy, and acute pancreatitis (saponification of magnesium in necrotic fat, analogous to the hypocalcaemia of pancreatitis). ^[1][7]

Diabetes. Hypomagnesaemia is common in type 2 diabetes (13.5 to 47.7% in one summary) and worsens glycaemic control. Screening is reasonable in diabetic patients on long-term PPIs or diuretics. ^[7]

• Kidney failure is the dominant cause; symptomatic hypermagnesaemia is rare when renal excretion works. ^[2]
• Magnesium-containing medicines: antacids, laxatives and purgatives (magnesium hydroxide, magnesium sulphate). ^[2]
• Pre-eclampsia and eclampsia treatment, because magnesium sulphate is the drug of choice and is given in substantial intravenous doses, especially when renal function is impaired. ^[7]
• Occasionally in diabetic ketoacidosis, hypothyroidism and hyperparathyroidism (the last sometimes with hypercalcaemia, note the association with familial hypocalciuric hypercalcaemia). ^[2][4]
• Excessive oral or parenteral intake in someone with reduced renal clearance.

Magnesium deficiency is often silent until the level is low (serum under 1.2 mg/dL, or under 0.50 mmol/L). When present, features fall into three groups. ^[1][7]

Neuromuscular hyper-excitability. The earliest effects are tremor, fasciculation, tetany (Chvostek and Trousseau signs, carpopedal spasm), hyperreflexia, muscle cramps and headache. Severe deficiency can cause generalised tonic-clonic seizures, particularly in children. ^[1][7]

Electrocardiographic and arrhythmic effects. With modest depletion, the QRS complex widens and T waves are peaked; with severe depletion, PR prolongation, progressive QRS widening and diminution of T waves occur. Torsades de pointes, a polymorphic ventricular tachycardia linked to QT prolongation, is the classic dangerous rhythm; intravenous magnesium is the drug of choice. Digoxin toxicity is more likely, because the sodium–potassium ATPase that digoxin inhibits is magnesium-dependent. A low magnesium also predisposes to hypertension (partly through vasoconstriction) and to coronary spasm. ^[7]

Biochemical consequences: hypokalaemia and hypocalcaemia. Hypokalaemia occurs in many patients and will not correct until magnesium is replaced, because low magnesium keeps the ROMK channel open and wasting potassium. Hypocalcaemia is frequent with moderate to severe deficiency and responds to magnesium replacement alone: calcium and vitamin D will not fix it, because magnesium is needed for parathyroid hormone secretion and action. ^[7] Up to 2.5 g of the next day's potassium can be wasted; the practical message is: do not keep pouring potassium in without checking magnesium. ^[7]

Other associations include altered glucose homeostasis and diabetic complications (low magnesium impairs insulin secretion and sensitivity), osteoporosis, nephrolithiasis and asthma exacerbations, but these are associations rather than direct indications for treatment. ^[7]

Symptoms and signs include hyporeflexia (reflexes disappear as the level approaches 12 mg/dL, 5.0 mmol/L), hypotension, respiratory depression and narcosis, and finally cardiac arrest at levels above 15 mg/dL (6.0 to 7.5 mmol/L). Bradycardia, a wide paced QRS in pacemaker patients and, rarely, heart block can be early cardiac clues. ^[2]

ECG changes appear at moderate levels: PR prolongation, widening of the QRS complex and increased T-wave amplitude, progressing to high-grade atrioventricular block, bradyarrhythmia and asystole. ^[2]

Hypomagnesaemia is most often caught by investigating another problem: a patient who is "hypokalaemic and will not correct", "hypocalcaemic and will not correct", "has tetany on a normal calcium", or "has an odd arrhythmia". The table compares the major electrolyte disorders in this chapter on ECG grounds. Serum sodium disorders usually cause neurological symptoms (confusion, seizures) rather than characteristic ECG changes, so they are not in the ECG column. ^{[2][5][4][3][1]}

• Serum magnesium concentration. The standard quick test, with a usual reference interval of roughly 0.7 to 1.0 mmol/L (check the local laboratory range). Remember that it is a poor reflector of total body or intracellular stores: a level between 0.50 and 0.70 mmol/L with a compatible clinical picture is already suggestive, and depletion can exist with a "normal" result when the index of suspicion is high. ^[1][7]
• Urine studies. To separate renal from intestinal loss: a 24-hour urinary magnesium excretion above 10 to 30 mg, or a fractional excretion of magnesium above 2%, in a patient with normal kidney function suggests renal wasting; a low value suggests intake or malabsorption. ^[7]
• Other electrolytes. Always measure potassium, calcium, sodium, chloride, bicarbonate and creatinine alongside magnesium. ^[1]
• ECG. As graded in the table above; essential in moderate to severe deficiency and in any case with arrhythmia.
• Drug and history review. PPI use beyond one year, diurectics, aminoglycosides, amphotericin, cisplatin, cyclosporine or tacrolimus, alcohol, chronic diarrhoea, malabsorption, past thyroid or parathyroid surgery, diabetic ketoacidosis treatment and refeeding are the usual triggers. ^[1][7]

There is no further criterion beyond the serum magnesium and the clinical picture. Hypomagnesaemia is diagnosed by a serum magnesium below 0.70 mmol/L; hypermagnesaemia by a serum magnesium above 1.05 mmol/L. ^[1][2]

For practice, degrees of low magnesium can be used as working guides: a level below 0.50 mmol/L (1.25 mg/dL) is generally where symptoms appear, and treatment is indicated when deficiency is symptomatic or the magnesium is persistently below 1.25 mg/dL. ^[1] Diagnose on clinical grounds as well when testing is not available or the result has not returned: refractory hypokalaemia or hypocalcaemia, tetany on a normal calcium, seizures with risk factors, or an unexplained arrhythmia all justify empirical magnesium until proven otherwise. ^[1]

Treat the cause as well as the number: stop or swap the offending drug, treat diarrhoea, address alcohol, improve diabetic control, and use a potassium-sparing (magnesium-sparing) drug such as amiloride when a diuretic cannot be withdrawn. Magnesium excretion and potassium excretion rise and fall together through the thick ascending limb, so when both are being lost a magnesium-sparing strategy helps both. ^[7]

Always correct concurrent hypokalaemia and hypocalcaemia: they will stay abnormal until magnesium is replete, and isolated calcium correction alone will not fix hypocalcaemia caused by magnesium deficiency. ^[1][7] One caution: intravenous magnesium sulphate can worsen hypocalcaemia, because sulphate binds ionized calcium. Recheck ionized calcium after IV dosing, particularly in patients who are already hypocalcaemic. ^[1]

Oral magnesium is the preferred route when the patient is stable and can swallow. A practical regimen is magnesium salts in divided doses, for example magnesium gluconate 500 to 1000 mg orally three times a day for three to four days; the total daily elemental dose is product-specific (some local guidelines cite up to about 24 mmol/day), so follow the product label and local protocol. ^[1] Oral treatment is limited by diarrhoea: magnesium is an osmotic laxative when given in excess, so many patients cannot tolerate the doses needed, and oral bioavailability varies between salts. Organic salts (citrate, lactate, gluconate) are generally better absorbed but still cause diarrhoea at higher doses. ^[7] If diarrhoea develops, split the dose further, take it with food, or switch to parenteral replacement.

For severe, symptomatic hypomagnesaemia, such as serum magnesium below 0.50 mmol/L with seizures or other severe symptoms, give 2 to 4 g of magnesium sulphate intravenously over 5 to 10 minutes; if seizures persist, repeat up to a total of 10 g over the next six hours. Once the acute event settles, 10 g in 1 L of 5% dextrose in water can be infused over 24 hours, followed by up to 2.5 g every 12 hours to replace whole-body stores and prevent further drops. ^[1]

When the magnesium is 1.25 mg/dL (0.50 mmol/L) or lower but symptoms are less severe, give magnesium sulphate intravenously in 5% dextrose in water at 1 g per hour as a slow infusion for up to 10 hours. Gradual repletion over 3 to 5 days is then used for less severe cases. ^[1] Whenever intravenous magnesium is needed, the infusion should run slowly over 12 to 24 hours, because a rapid rise in plasma magnesium drives urinary loss of roughly half the infused dose. ^[7]

A longer-acting alternative for very low stores in alcohol use disorder is a single parenteral dose (and thereafter oral therapy), because adherence is often poor; oral magnesium salts 500 to 1000 mg three times a day for three to four days is the routine course otherwise. ^[1]

Treatment of severe magnesium toxicity (around 5.0 mmol/L, 12 mg/dL) means supporting the circulation and ventilation and giving 10 to 20 mL of 10% calcium gluconate intravenously. Calcium transiently reverses many magnesium-induced changes, including respiratory depression, by antagonising the membrane effects. ^[2]

Remove the excess magnesium by:

• Stopping every magnesium source (oral, antacid, laxative, IV). ^[2]
• Intravenous furosemide, with careful maintenance of volume, if renal function is adequate. ^[2]
• Haemodialysis when severe or when kidney function is insufficient: about 70% of blood magnesium is not protein-bound and is dialysable. Peritoneal dialysis is the option when haemodynamic compromise makes haemodialysis impractical. ^[2]

Monitor deep tendon reflexes, respiratory rate, oxygenation, blood pressure, heart rate and the ECG throughout; cardiac arrest risk rises above 15 mg/dL (6.0 to 7.5 mmol/L). ^[2]

• Pregnancy. Magnesium sulphate given intravenously for pre-eclampsia or eclampsia roughly halves the risk of eclampsia (Magpie randomised trial) and is now the drug of choice. Hypermagnesaemia from high doses is more likely when renal clearance is reduced, so the treatment effect is monitored clinically (reflexes, respiratory rate, urine output) and calcium gluconate is kept available. ^[7]
• Children. Severe hypomagnesaemia can cause generalised tonic-clonic seizures. Inherited tubular defects (Bartter, Gitelman) present in childhood with growth failure alongside renal losses. ^[1][7]
• Older adults. Long-term PPI use is an under-recognised cause; include older adults on diuretics. ^[1]
• Renal impairment. Avoid magnesium replacement in chronic kidney disease without close monitoring; use smaller or parenteral doses only with senior input, and dialyse hypermagnesaemia if severe. ^[1][2]

• Arrhythmia, including torsades de pointes, ventricular tachycardia and fibrillation, plus an increased risk of digoxin toxicity in hypomagnesaemia. ^[7]
• Refractory electrolyte disturbance: hypokalaemia and hypocalcaemia that do not correct until magnesium is repleted. ^[1][7]
• Neuromuscular irritability with tremor, tetany, seizures and rhabdomyolysis. ^[1][7]
• Hypermagnesaemia complications: loss of reflexes, respiratory depression, hypotension and cardiac arrest. ^[2]
• Long-term: osteoporosis, calcium-containing stones in hypomagnesuric calcium nephrolithiasis, altered glucose handling in diabetes. ^[7]

Most symptomatic hypomagnesaemia improves quickly once magnesium is replaced; hypokalaemia and hypocalcaemia may take days to fully normalise. ^[1] In hospital, outcome depends on the underlying cause and on how early severe deficiency is recognised. Hypermagnesaemia, by contrast, can kill within hours if ventilation fails or the heart arrests; it is fully reversible if treated promptly and the kidney recovers or dialysis is given. ^[2]

• Maintain an intake of magnesium-rich foods (green leafy vegetables, legumes, nuts, seeds, whole grains), particularly when risk is high (diabetes, alcohol misuse, diuretics). ^[7]
• Review the need for long-term PPIs periodically, and check serum magnesium before starting or during long-term treatment. ^[1][7]
• Monitor serum magnesium and potassium in patients on loop or thiazide diuretics, cisplatin, amphotericin or aminoglycosides, and after alcohol-related admission. ^[1][7]
• Patients with chronic kidney disease should avoid magnesium-containing antacids and laxatives, and read labels on over-the-counter products. ^[2]

• Serum magnesium and urine magnesium may not be available. Suspect hypomagnesaemia in refractory hypokalaemia or hypocalcaemia, tetany on normal or borderline calcium, unexplained arrhythmia (especially torsades de pointes), seizures with risk factors, and alcohol-related presentations. ^[1][7]
• Where testing is unavailable but deficiency is likely, treat empirically with magnesium (oral if the patient can swallow; IV magnesium sulphate when severe or for arrhythmia) while monitoring the clinical signs. ^[1]
• Oral replacement with available magnesium salts and food sources, in divided doses, plus control of diarrhoea, is the backbone of treatment in stable patients. IV magnesium sulphate should follow the same safety limits as above: 2 to 4 g over 5 to 10 minutes for acute severe disease, 1 g per hour as a slow infusion otherwise. Give it slowly because a rapid infusion is lost in the urine. ^[1][7]
• Hypermagnesaemia is usually recognised clinically (loss of reflexes, drowsiness, respiratory depression, hypotension) and confirmed by kidney failure. Stop magnesium sources immediately. Calcium gluconate may not be available; then prioritise urgent transfer and supportive care until dialysis can be arranged. ^[2]
• For pre-eclampsia, magnesium sulphate should be given where possible, with the dose effect monitored clinically (reflexes, respiration, urine output), and patients with rising levels or falling urine output referred early. ^[7]
• Teach patients with chronic kidney disease to avoid magnesium antacids and laxatives, and to ask a pharmacist before buying over-the-counter remedies. ^[2]

• Hypomagnesaemia is a serum magnesium below 0.70 mmol/L (1.8 mg/dL); hypermagnesaemia is above 1.05 mmol/L (2.6 mg/dL). Serum magnesium is a poor guide to total body stores.
• Common causes of low magnesium are alcohol use disorder, chronic diarrhoea, malabsorption, proton pump inhibitors (more than one year), loop and thiazide diuretics, cisplatin, amphotericin B, aminoglycosides and uncontrolled diabetes; inherited (Gitelman, Bartter) and redistributive (refeeding, DKA treatment) causes are also recognised.
• Magnesium deficiency explains hypokalaemia and hypocalcaemia that will not correct: low intracellular magnesium leaves the ROMK channel open and impairs parathyroid hormone secretion and action.
• Neuromuscular signs (tremor, tetany, Chvostek and Trousseau signs, seizures) and arrhythmia, especially torsades de pointes, are the dangerous presentations of hypomagnesaemia.
• Severe or symptomatic hypomagnesaemia: 2 to 4 g magnesium sulphate IV over 5 to 10 minutes; repeat up to 10 g over 6 hours for recurring seizures; then 10 g in 1 L 5% dextrose over 24 hours and up to 2.5 g every 12 hours.
• Milder deficiency: oral magnesium salts in divided doses, e.g. magnesium gluconate 500 to 1000 mg three times a day for 3 to 4 days, stopping or reducing the dose if diarrhoea limits tolerance.
• Always replace potassium and calcium at the same time, but note that IV magnesium sulphate can transiently worsen hypocalcaemia.
• Hypermagnesaemia is almost always renal failure plus a magnesium load (antacids, laxatives, IV magnesium, including for pre-eclampsia); watch for loss of reflexes, respiratory depression, hypotension and cardiac arrest.
• ECG changes of hypermagnesaemia appear at 2.5 to 5 mmol/L (PR prolongation, widened QRS, increased T waves); reflexes go at about 5 mmol/L and cardiac arrest risk rises above 6 to 7.5 mmol/L.
• Hypermagnesaemia is reversed by calcium gluconate 10 to 20 mL of 10% IV, IV furosemide with volume repletion, and dialysis when severe.
• In the table: hyperkalaemia gives tall peaked T waves and a sine wave; hypokalaemia gives ST sagging and prominent U waves; hypercalcaemia shortens QTc; hypocalcaemia prolongs QTc; sodium disorders mainly cause neurological rather than ECG change.
• Pre-eclampsia/eclampsia: magnesium sulphate is the drug of choice and roughly halves the risk of eclampsia, but needs clinical monitoring for hypermagnesaemia.

Plain text names only, because the following topics are placeholders until separately written and verified: hypokalaemia; hyperkalaemia; hypocalcaemia; hypercalcaemia; hyponatraemia; hypernatraemia; Bartter and Gitelman syndromes; renal tubular acidosis; primary aldosteronism; Cushing syndrome; diabetic ketoacidosis; refeeding syndrome; pre-eclampsia; alcohol use disorder; acute kidney injury; chronic kidney disease. Add formal links once those topics are published.