Interpretation and Management of Abnormal Serum Magnesium Levels
Defining Abnormal Magnesium Levels
Hypomagnesemia is defined as serum magnesium <0.85 mmol/L (2.07 mg/dL or 1.7 mEq/L), and treatment should be initiated at this threshold to prevent chronic latent magnesium deficit and associated health risks. 1, 2
- Values <1.3 mEq/L are "undisputedly low" and confirm clinically significant hypomagnesemia 1
- Severe hypomagnesemia is defined as <0.50 mmol/L (<1.2 mg/dL) and requires urgent intervention 1, 3
- Hypermagnesemia occurs at levels >2.5 mmol/L, with life-threatening toxicity developing at 6–10 mmol/L 1
- Normal serum magnesium does not exclude intracellular depletion, as serum levels are maintained by releasing magnesium from body stores 4
Initial Assessment and Diagnosis
Immediate Clinical Evaluation
Obtain an ECG immediately in any patient with hypomagnesemia who has cardiac risk factors, concurrent QT-prolonging medications, heart failure, digoxin therapy, or arrhythmias. 1
- ECG changes include prolonged QT interval, T-wave flattening, ST-segment depression, and prominent U waves 1
- Neuromuscular hyperexcitability is the hallmark of hypomagnesemia, with cardiac arrhythmias representing the most life-threatening complication 1
- Symptoms typically do not arise until serum magnesium falls below 1.2 mg/dL 3
Determine the Etiology
Calculate fractional excretion of magnesium (FEMg) and urinary calcium-creatinine ratio to distinguish gastrointestinal from renal losses. 3
- FEMg <2% indicates appropriate renal conservation due to gastrointestinal losses or inadequate intake 3
- FEMg >2% in a patient with normal kidney function indicates renal magnesium wasting 3
Common causes of hypomagnesemia include:
Gastrointestinal losses:
- Chronic diarrhea, short bowel syndrome, malabsorption syndromes, high-output stomas (each liter contains ~100 mmol/L sodium and proportionate magnesium) 1
Renal losses:
- Loop and thiazide diuretics (most common medication cause) 1
- Proton pump inhibitors, aminoglycosides, amphotericin B, cisplatin, calcineurin inhibitors (tacrolimus, cyclosporine), pentamidine, foscarnet 1
- Gitelman syndrome (associated with hypocalciuria) vs. Bartter syndrome (associated with hypercalciuria) 3
Treatment Algorithm
Step 1: Assess Volume Status and Correct Depletion FIRST
Before initiating any magnesium supplementation, correct sodium and water depletion with IV isotonic saline to eliminate secondary hyperaldosteronism, which perpetuates renal magnesium wasting. 1, 5
- This is the most common therapeutic pitfall—failure to correct volume depletion first leads to continued magnesium losses despite supplementation 1
- Assess orthostatic vital signs and urinary sodium (<10 mEq/L indicates volume depletion) 1
Step 2: Identify and Address Concurrent Electrolyte Abnormalities
Always replace magnesium BEFORE attempting to correct hypocalcemia or hypokalemia, as these abnormalities are refractory to treatment until magnesium is normalized. 1
- Hypomagnesemia impairs PTH secretion and potassium transport mechanisms, increasing renal potassium excretion 1
- Calcium normalization typically follows within 24–72 hours after magnesium repletion begins 1
Step 3: Choose Route and Dose Based on Severity
Life-Threatening Presentations (Torsades de Pointes, Ventricular Arrhythmias, Seizures, Cardiac Arrest)
Give 1–2 g magnesium sulfate IV bolus over 5 minutes IMMEDIATELY, regardless of baseline serum magnesium level. 6, 1
- This is a Class I recommendation from the American Heart Association 1
- Follow with continuous infusion of 1–4 mg/min if needed 1
- Have calcium chloride available to reverse magnesium toxicity if needed 1
Severe Symptomatic Hypomagnesemia (<0.50 mmol/L or <1.2 mg/dL)
Administer 1–2 g magnesium sulfate IV bolus over 5–15 minutes, followed by continuous infusion. 1, 7
- FDA-approved dosing: For severe hypomagnesemia, up to 250 mg/kg (approximately 2 mEq/kg) may be given IM within 4 hours, or 5 g (40 mEq) added to 1 liter of fluid for slow IV infusion over 3 hours 7
- Monitor for magnesium toxicity: loss of patellar reflexes, respiratory depression, hypotension, bradycardia 1
- Maximum rate of IV injection should not exceed 150 mg/minute except in severe eclampsia with seizures 7
Mild to Moderate Hypomagnesemia (0.50–0.85 mmol/L)
Start oral magnesium oxide 12 mmol (approximately 480 mg elemental magnesium) at night as first-line therapy. 1, 5
- Night-time dosing exploits slower intestinal transit during sleep for maximal absorption 1, 5
- If serum magnesium remains low after 1–2 weeks, increase to 24 mmol daily (single or divided doses) 1, 5
- Magnesium oxide is preferred because it contains the highest elemental magnesium content and is converted to magnesium chloride in gastric acid 5
- Most magnesium salts are poorly absorbed and may worsen diarrhea or stoma output 1, 5
Alternative oral formulations:
- Organic magnesium salts (aspartate, citrate, lactate) have higher bioavailability than magnesium oxide but may still cause gastrointestinal side effects 5
Step 4: Manage Refractory Cases
For patients who fail oral therapy after maximal dosing (24 mmol daily), add oral 1-α-hydroxy-cholecalciferol starting at 0.25 µg daily and titrating up to 9 µg. 1, 5
- Monitor serum calcium weekly to avoid hypercalcemia 1, 5
- This enhances magnesium balance by increasing jejunal absorption 1
For severe malabsorption or short bowel syndrome:
- Consider subcutaneous magnesium sulfate (4–12 mmol added to saline bags) administered 1–3 times weekly 1, 5
- Reduce excess dietary lipids, which worsen magnesium malabsorption 5
Step 5: Address Underlying Causes
Discontinue or adjust offending medications when possible:
- Consider adding a potassium-sparing diuretic (amiloride 5–10 mg daily or spironolactone 25–50 mg daily) to conserve magnesium in patients requiring loop or thiazide diuretics 1
- Monitor potassium closely (target 4.5–5.0 mEq/L) to avoid hyperkalemia, especially with concurrent ACE inhibitors 1
For digoxin-treated patients:
- Aggressive magnesium repletion (target serum magnesium ≥2 mEq/L) is mandatory, as deficiency markedly increases digoxin toxicity risk 1
Monitoring and Follow-Up
Monitor serum magnesium, potassium, calcium, and creatinine every 6–12 hours during IV magnesium replacement. 1
- Target serum magnesium within normal range (1.8–2.2 mEq/L or >0.85 mmol/L) 5, 2
- Observe for resolution of clinical symptoms (neuromuscular irritability, arrhythmias) 1
- In patients with severe renal insufficiency (eGFR <30 mL/min), maximum magnesium dose is 20 g over 48 hours with frequent serum monitoring 1, 7
Management of Hypermagnesemia
Clinical Presentation
Severe hypermagnesemia (>2.5 mmol/L) presents with progressive neurological symptoms (weakness, paralysis, ataxia, drowsiness, confusion), cardiovascular effects (vasodilation, hypotension, bradycardia, arrhythmias), and respiratory compromise. 1
- Life-threatening toxicity develops at 6–10 mmol/L, particularly in patients with GFR <30 mL/min receiving magnesium-containing medications 1
- Loss of deep tendon reflexes occurs at ~10 mEq/L, with respiratory paralysis and heart block at this or higher levels 7
Immediate Management
Discontinue all magnesium-containing medications immediately and administer IV calcium (calcium chloride 10% 5–10 mL or calcium gluconate 10% 15–30 mL IV over 2–5 minutes) for severe symptomatic hypermagnesemia. 1
- Calcium ions competitively antagonize cardiac and neuromuscular effects of excess magnesium 1
- Initiate urgent hemodialysis or continuous renal replacement therapy for life-threatening presentations 1
- Prepare for mechanical ventilation if hypoventilation or respiratory depression develops 1
Critical Pitfalls to Avoid
Never start oral magnesium without first correcting volume depletion in patients with gastrointestinal fluid losses—secondary hyperaldosteronism will prevent effective repletion 1, 5
Never attempt to correct hypocalcemia or hypokalemia before normalizing magnesium—these will be refractory to treatment 1
Do not separate calcium and magnesium supplements by less than 2 hours—they inhibit each other's absorption 1
Separate oral magnesium from fluoroquinolone antibiotics by at least 2 hours to avoid reduced antibiotic efficacy 1
In pregnant women receiving magnesium sulfate for preeclampsia/eclampsia, do not continue beyond 5–7 days—prolonged use can cause fetal abnormalities 7
Avoid over-correction in patients with 22q11.2 deletion syndrome—can lead to iatrogenic hypercalcemia, renal calculi, and renal failure 1