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Level 2 of 6Must-remember

Disorders of calcium and magnesium

Assess, manage and stay safe — enough on its own

The card — assess, manage, caution

Assessment— look, ask, measure

  • Never interpret a total calcium without a simultaneous albumin: normal total plasma calcium is 2.1–2.6 mmol/L (8.5–10.5 mg/dL), only the free ionised fraction (normally 1.16–1.31 mmol/L, 4.6–5.3 mg/dL) is active, and corrected calcium (mmol/L) = measured calcium + 0.02 × (40 − albumin in g/L), or in conventional units corrected calcium (mg/dL) = measured calcium + 0.8 × [4.0 − albumin in g/dL].Not available at your setup — Serum electrolytes.
  • Know the calcium cut-offs: hypocalcaemia is a corrected total calcium below 2.1 mmol/L or an ionised calcium below 1.16 mmol/L, becoming dangerous below an ionised calcium of about 1.0 mmol/L; hypercalcaemia is a corrected calcium above 2.6 mmol/L, severe above 3.0 mmol/L, and hypercalcaemic crisis above 3.5 mmol/L, with coma and cardiac arrest at 3.7–4.5 mmol/L (14.8–18 mg/dL).
  • Know the magnesium cut-offs: normal plasma magnesium is 0.7–1.0 mmol/L (1.7–2.4 mg/dL, different sources quoting upper limits between 1.0 and 1.1); hypomagnesaemia is below 0.7 mmol/L with symptoms unusual above 0.5 mmol/L; hypermagnesaemia becomes clinically toxic above about 2 mmol/L, causes coma and respiratory depression above 4 mmol/L, and approaches asystole near 10 mmol/L.
  • A normal serum magnesium does not exclude depletion: only about 1% of the body's 25 g of magnesium is extracellular (half is in bone, almost all the rest intracellular), and hypomagnesaemia when present usually signifies a whole-body deficit of 0.5–1 mmol/kg.
  • Send calcium, albumin, magnesium, phosphate, potassium, urea and creatinine on every such patient, on the same sample — the commonest reason a patient fails to improve is that one cation has been corrected and the other ignored.Not available at your setup — Serum electrolytes.
  • Look for hypocalcaemic neuromuscular irritability: perioral and acral paraesthesiae, muscle cramps, myalgia and irritability early; then overt tetany with carpopedal spasm (the main d'accoucheur posture — flexion of the metacarpophalangeal joints, extension of the interphalangeal joints, adduction of the thumb); pedal spasm occurs less often.
  • Use Trousseau's sign, not Chvostek's: Trousseau's (a cuff inflated 20 mmHg above systolic pressure for up to three minutes producing carpal spasm) is positive in over 90% of hypocalcaemic patients and only about 1% of normocalcaemic ones, whereas Chvostek's (facial twitching on tapping anterior to the tragus) is positive in around 70% of hypocalcaemic patients but also in up to 15% of entirely normal people — never diagnose hypocalcaemia on Chvostek's alone.
  • Identify the lethal hypocalcaemic manifestations: laryngospasm, which can obstruct the airway completely within minutes and is especially dangerous when a recurrent laryngeal nerve palsy coexists after thyroid surgery; arrhythmia on a prolonged QT; seizures in roughly one in ten symptomatic patients; and a reversible cardiomyopathy.
  • Recognise hypercalcaemia by bones, stones, abdominal groans and psychic moans, with fatigue overtones: polyuria and nocturia from nephrogenic diabetes insipidus, polydipsia, dehydration, renal colic, nephrocalcinosis; anorexia, nausea, vomiting, constipation, abdominal pain, peptic ulceration, pancreatitis; fatigue, depression, poor concentration, lethargy through confusion and stupor to coma; short QT, bradyarrhythmia, heart block, hypertension and marked sensitivity to digoxin; bone pain, osteoporosis and fracture.
  • Recognise hypomagnesaemia: tremor, ataxia, hyper-reflexia, fasciculation, carpopedal spasm indistinguishable from that of hypocalcaemia, personality change, confusional and hallucinatory states, vertical nystagmus and seizures — with torsades de pointes as the cardiac hallmark, and broad flattened T waves, prolonged PR and QRS intervals and occasional ST shortening on the ECG.
  • The two most useful clues to magnesium depletion are entirely biochemical: a hypokalaemia or a hypocalcaemia that refuses to correct despite adequate replacement. Any patient with torsades de pointes should be assumed magnesium-depleted until proved otherwise.
  • Recognise hypermagnesaemia by its orderly descending sequence: above about 2 mmol/L nausea, facial flushing, cutaneous vasodilatation and — the earliest reliable physical sign — loss of the deep tendon reflexes, of which the knee jerk is the most convenient to follow; then hypotension, weakness, drowsiness, ileus, urinary retention and pupillary dilatation; above about 4 mmol/L coma, complete areflexia and progressive respiratory depression through hypoventilation to apnoea; then prolonged PR, QRS widening, QT prolongation, complete heart block and asystole approaching 10 mmol/L.
  • In any patient on a magnesium infusion, loss of the patellar reflex or a falling respiratory rate is magnesium toxicity until proved otherwise — this is most often the obstetric patient receiving magnesium sulphate for eclampsia.
  • Take a 12-lead ECG and measure the QTc: long QTc means low calcium, low magnesium or low potassium; short QT with bradycardia or heart block means high calcium; long PR with broad QRS and long QT in a renal patient means high magnesium (check the potassium too). Serial QTc is the best bedside index of response.
  • Red flags demanding immediate treatment irrespective of the number: stridor or any suggestion of laryngospasm; seizure or reduced conscious level; torsades de pointes, sustained ventricular arrhythmia, complete heart block or profound bradycardia; a measured QTc above 500 ms; a falling respiratory rate or loss of the deep tendon reflexes in any patient exposed to magnesium; hypercalcaemia with oliguria or a rising creatinine; and hypercalcaemia in a patient taking digoxin.
  • Beware the two interpretive traps: a low total calcium with a normal corrected or ionised calcium in an asymptomatic patient requires no calcium at all — treating it produces iatrogenic hypercalcaemia; and hyperventilation-induced respiratory alkalosis reproduces tetany perfectly at a normal total calcium, so in an anxious hyperventilating patient coach the breathing rather than reach for a syringe.

Management— do this, in order

  • Severe symptomatic hypocalcaemia — secure the airway first, because laryngospasm is the immediate threat, then give intravenous calcium gluconate, the agent of choice. Remember the arithmetic: 10% calcium gluconate 10 mL = 1 g = 2.2 mmol = 90 mg elemental calcium = 4.65 mEq.Doctor / Nurse
  • Adult hypocalcaemia dose: 10–20 mL of 10% calcium gluconate diluted in 50–100 mL of 5% glucose or 0.9% sodium chloride intravenously over 10–20 minutes with continuous cardiac monitoring — give the first 10 mL over 10 minutes, and a second 10 mL may follow over a further 10 minutes and be repeated until tetany ceases.Doctor / Nurse
  • Then start an infusion, because a bolus raises the calcium for only 1–2 hours and the tetany will return: prepare 100 mL of 10% calcium gluconate in 1 litre of 5% glucose and run at 50–100 mL/hour; equivalently 11 g of calcium gluconate made up to 1000 mL in 5% glucose (about 1 mg elemental calcium/mL) infused at 0.5–2.0 mg elemental calcium/kg/hour, titrated to the lower end of the normal range, rechecking calcium every 4–6 hours.Doctor / NurseNot available at your setup — Infusion pump. carefully counted gravity drip with hourly volume checks if a pump is unavailable
  • Child and neonate: 10% calcium gluconate 0.5 mL/kg (0.11 mmol/kg elemental calcium), maximum 20 mL, diluted, over 10 minutes with continuous ECG monitoring, repeated if tetany persists, then a maintenance infusion titrated to serum calcium; in a neonate give 0.5 mL/kg by slow intravenous injection through a large secure vein because extravasation causes severe tissue injury.Doctor / Nurse
  • If calcium gluconate is unavailable use calcium chloride: 10% calcium chloride 10 mL = 6.8 mmol calcium, roughly three times the calcium of the same volume of gluconate, but far more sclerosant — give only through a large vein that flushes freely, or a central line.Doctor / NurseNot available at your setup — Central venous access. a large peripheral vein that flushes freely, if a central line is unavailable
  • Give magnesium concurrently in hypocalcaemia — hypocalcaemia with magnesium depletion will not correct until magnesium is replaced, and this is the commonest reason for apparently refractory hypocalcaemia.Doctor / Nurse
  • Convert to oral therapy once tetany has settled and the QTc normalised: oral calcium supplying 1–2 g of elemental calcium daily in divided doses with meals (calcium carbonate is 40% elemental calcium, 500–1000 mg twice daily a usual start, and needs gastric acid; calcium citrate at 21% elemental calcium is absorbed with or without food and is preferred on proton pump inhibitors or H2-receptor antagonists), plus an activated vitamin D analogue started at the same time — calcitriol 0.25 microgram orally each morning titrated to a usual maintenance of 0.5–4 micrograms/day in two divided doses, or alfacalcidol 0.5–3 micrograms/day.
  • Severe hypercalcaemia — fluid first, always, and in volume: 0.9% sodium chloride at least 4–6 litres over the first 24 hours in an adult without heart failure, then 3–4 litres daily for several days; in shock or profound dehydration start with 1 litre over the first hour and reassess; in the elderly, cardiac or renal patient give 250–500 mL boluses with clinical reassessment after each; in a child give 20 mL/kg over 1 hour, then maintenance plus deficit.Doctor / Nurse
  • Monitor urine output and replace potassium and magnesium, which saline diuresis strips out.
  • Then a bisphosphonate, after rehydration: pamidronate 30–90 mg in 500 mL of 0.9% sodium chloride intravenously over 2–4 hours (60–90 mg for a corrected calcium above 3.0 mmol/L), or zoledronic acid 4 mg in 100 mL of 0.9% sodium chloride over at least 15 minutes, which is more potent in malignancy-associated hypercalcaemia.Doctor / NurseNot available at your setup — Infusion pump. carefully counted gravity drip with hourly volume checks if a pump is unavailable
  • Hypercalcaemia adjuncts by cause and urgency: calcitonin 4–8 units/kg intramuscularly or subcutaneously every 6 hours (alternatively 200 units intravenously 6-hourly) works within hours rather than days; prednisolone 30–60 mg orally daily or hydrocortisone 100 mg/day intravenously for myeloma, lymphoma, leukaemia, sarcoidosis and other granulomatous disease and vitamin D or A intoxication, with the calcium falling over 2–5 days; denosumab 120 mg subcutaneously for bisphosphonate-refractory malignant hypercalcaemia; cinacalcet from about 30 mg orally daily; and renal replacement therapy with a low-calcium dialysate where oliguric AKI or established renal failure coexists.Doctor / NurseNot available at your setup — Dialysis / renal replacement. calcitonin, corticosteroid or cinacalcet where dialysis is unavailable
  • Stop the aggravating drugs, mobilise the patient and withhold digoxin: thiazides, lithium, calcium supplements, vitamin D and A preparations and calcium-containing antacids all come off.
  • Hypomagnesaemia with torsades de pointes or seizure (adult): magnesium sulphate 2 g (8 mmol) diluted in 10 mL of 5% glucose intravenously over 10–15 minutes whatever the measured magnesium; in cardiac arrest the same 2 g is given as a bolus, repeated once if torsades recurs. Remember 50% magnesium sulphate: 2 mL = 1 g = 4 mmol magnesium.Doctor / Nurse
  • Symptomatic hypomagnesaemia without arrhythmia (adult): magnesium sulphate 1–2 g intravenously over 5–60 minutes, diluted.Doctor / Nurse
  • Replete the stores, because a bolus alone is never enough: magnesium sulphate 24 mmol (6 g) in 500 mL of 0.9% sodium chloride or 5% glucose intravenously over 24 hours, or magnesium chloride 50 mmol in 1 litre of 5% glucose or other isotonic fluid over 12–24 hours, repeated daily and continued for at least 2 days after the plasma magnesium has normalised; in chronic kidney disease reduce the dose by up to 75%, and check magnesium every 12–24 hours during replacement.Doctor / NurseNot available at your setup — Infusion pump. carefully counted gravity drip with hourly volume checks if a pump is unavailable
  • Child with hypomagnesaemia: magnesium sulphate 25–50 mg/kg (0.1–0.2 mmol/kg), maximum 2 g, intravenously over 20 minutes, followed by a maintenance infusion. Mild asymptomatic depletion in an adult: oral magnesium salts totalling 20–30 mmol/day in divided doses, for example magnesium oxide 250–500 mg once or twice daily.Doctor / Nurse
  • Hypermagnesaemia — stop every source immediately (infusion, antacid, laxative, enema, purgative) and antagonise with calcium: 10 mL of 10% calcium gluconate (1 g, 2.2 mmol calcium) intravenously over 2–10 minutes, repeated as required, with cardiac monitoring; in obstetric magnesium toxicity the accepted regimen is calcium gluconate 1 g intravenously over 2 minutes; the paediatric dose is 0.5 mL/kg of the 10% solution by slow intravenous injection.Doctor / Nurse
  • Then promote excretion and support the patient: intravenous 0.9% sodium chloride with furosemide 20–40 mg intravenously guided by urine output if the kidneys still work; glucose and insulin shift magnesium intracellularly exactly as for hyperkalaemia, which frequently coexists in the renal patient; support ventilation, since neuromuscular blockade causes hypoventilation and then apnoea; and arrange haemodialysis early rather than late in severe hypermagnesaemia with renal failure.Doctor / NurseNot available at your setup — Dialysis / renal replacement. furosemide-guided diuresis and ventilatory support where dialysis is unavailable

Caution— what harms

  • Never push intravenous calcium — rapid administration causes bradycardia, hypotension and asystole. Dilute it, give it over at least 10 minutes, and monitor the rhythm throughout.
  • Never run calcium into a line containing bicarbonate or phosphate — it precipitates. Calcium chloride extravasation causes tissue necrosis, and in a neonate even calcium gluconate extravasation causes severe tissue injury.
  • In a digitalised patient hypercalcaemia potentiates digoxin toxicity: if calcium is unavoidable, dilute 10 mL of 10% calcium gluconate in 100 mL of 5% glucose and infuse over 20–30 minutes with continuous monitoring. Withhold digoxin in hypercalcaemia.
  • Do not give a loop diuretic to a dehydrated hypercalcaemic patient — furosemide is not first-line, has little value except in genuinely life-threatening hypercalcaemia and only after full rehydration, and given to a dehydrated patient it worsens the hypercalcaemia; use furosemide 20–40 mg intravenously only if the patient becomes fluid-overloaded.
  • Do not expect the bisphosphonate to rescue anybody: the calcium will not fall for 24–72 hours and the effect then lasts around two weeks — the fluid is the rescue. Do not repeat the dose prematurely.
  • Avoid intravenous bisphosphonates at an eGFR below approximately 35 mL/min/1.73 m², reduce the dose and slow the infusion in lesser renal impairment, and watch for the transient acute-phase reaction and for hypocalcaemia and hypophosphataemia after the calcium falls; denosumab causes prolonged and sometimes severe hypocalcaemia.
  • Do not treat a low total calcium with a normal corrected or ionised calcium in an asymptomatic patient — this is hypoalbuminaemia, the commonest cause of a low total calcium, and treating it produces iatrogenic hypercalcaemia.
  • Do not mistake hyperventilation for hypocalcaemia: respiratory alkalosis lowers ionised calcium at a normal total calcium and reproduces tetany exactly — coach the breathing instead. Remember acidosis raises ionised calcium and alkalosis lowers it.
  • Do not give oral calcium and oral phosphate together — they precipitate before absorption. Correct hypocalcaemia before giving intravenous phosphate for coexisting hypophosphataemia, and keep the calcium × phosphate product below 4.4 mmol²/L² (55 mg²/dL²) to avoid metastatic calcification.
  • Aim for the low end of normal, not the middle: in hypoparathyroidism the maintenance target is approximately 2.0–2.15 mmol/L (8–8.6 mg/dL), because these patients lack PTH-driven tubular calcium reabsorption and are prone to hypercalciuria and nephrolithiasis (hydrochlorothiazide 25 mg daily reduces hypercalciuria). Over-replacement causes hypercalciuria, nephrolithiasis and renal impairment.
  • A single magnesium bolus does not replete the stores — only 50–70% of an intravenous dose is retained and the intracellular deficit is 0.5–1.5 mmol/kg; continue for at least two days beyond normalisation of the plasma level.
  • Excessive magnesium repletion recreates hypermagnesaemia: monitor deep tendon reflexes and respiratory rate throughout any infusion — they are the earliest signs of overshoot. Davidson's advises not exceeding 0.5 mmol/kg in the first 24 hours, so cap the fixed 24 mmol regimen at 0.5 mmol/kg in anyone under about 50 kg or with renal impairment, and reduce by up to 75% in chronic kidney disease.
  • Avoid intramuscular magnesium for repletion — the injections are painful and 2 mL of the 50% solution delivers only 4 mmol. Oral magnesium is limited by diarrhoea, which unchecked worsens the deficit.
  • Aggressive saline resuscitation causes pulmonary oedema in the elderly and cardiac patient, and potassium and magnesium depletion in everyone — hence 250–500 mL boluses with reassessment in those groups, and replacement of both cations.

Refer / escalate

Escalate or transfer urgently for stridor or laryngospasm, seizure or reduced conscious level, torsades de pointes or any sustained ventricular arrhythmia, complete heart block or profound bradycardia, a QTc above 500 ms, areflexia or a falling respiratory rate in any patient exposed to magnesium, a corrected calcium of 3.5 mmol/L or above (treated immediately whatever the symptoms), hypercalcaemia with oliguria or a rising creatinine, and any severe hypermagnesaemia with renal failure needing dialysis.

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