What are the indications, recommended dosing, adverse effects, and contraindications of magnesium supplementation in adults?

Magnesium: Clinical Indications, Dosing, Adverse Effects, and Contraindications

Critical Cardiac Indications

Magnesium may be considered for torsades de pointes (polymorphic VT with long QT interval), but routine use in cardiac arrest is not recommended. 1

Cardiac Arrest and Arrhythmias

• The routine use of magnesium for VF/pVT cardiac arrest is NOT recommended (Class III: No Benefit), as multiple RCTs showed no improvement in ROSC, survival to hospital discharge, or neurologic outcomes 1
• For torsades de pointes specifically, give 1-2 g magnesium sulfate IV over 5-15 minutes regardless of serum magnesium level (Class IIb recommendation) 1, 2
• Magnesium acts to prevent reinitiation of torsades rather than pharmacologically convert the rhythm 1
• In life-threatening presentations (cardiac arrest, ventricular arrhythmias, seizures), administer 1-2 g IV bolus over 5 minutes immediately 3, 2

Common pitfall: Magnesium was studied in 4 small RCTs totaling only 444 patients, and consistently showed no benefit for cardiac arrest with any rhythm 1. The evidence supporting its use in torsades comes from only 2 observational studies 1.

Magnesium Deficiency Correction

The most critical first step is correcting volume depletion with IV saline to eliminate secondary hyperaldosteronism—failure to do this first will result in continued renal magnesium wasting despite supplementation. 3, 4

Assessment and Initial Management

• Volume depletion triggers secondary hyperaldosteronism, which increases renal retention of sodium at the expense of both magnesium and potassium 3, 4
• Administer IV normal saline (2-4 L/day initially) to restore sodium and water balance before starting magnesium supplementation 3, 4
• Check magnesium, potassium, calcium, phosphate, and renal function at baseline 3, 4

Oral Magnesium Replacement

• Start with magnesium oxide 12 mmol at night (approximately 480 mg elemental magnesium), increasing to 24 mmol daily if needed 3, 4
• Magnesium oxide is preferred because it contains more elemental magnesium than other salts and is converted to magnesium chloride in the stomach 3
• Administer at night when intestinal transit is slowest to maximize absorption 3, 4, 5
• For chronic constipation, the American Gastroenterological Association suggests starting at 400-500 mg daily and titrating to 1.5 g/day based on response 4

Intravenous Magnesium Replacement

• Severe symptomatic hypomagnesemia (<0.50 mmol/L or <1.2 mEq/L) requires 1-2 g magnesium sulfate IV over 15 minutes, followed by continuous infusion or repeated doses 3, 2
• For mild deficiency, give 1 g (8.12 mEq) IM every 6 hours for 4 doses 2
• For severe hypomagnesemia, up to 250 mg/kg (approximately 2 mEq/kg) may be given IM within 4 hours, or 5 g added to 1 L fluid for slow IV infusion over 3 hours 2
• The rate of IV injection should generally not exceed 150 mg/minute (1.5 mL of 10% solution), except in severe eclampsia with seizures 2

Special Clinical Scenarios

For refractory hypokalemia due to hypomagnesemia, always correct magnesium first or simultaneously—potassium supplementation will fail until magnesium is normalized. 3, 4

• Hypomagnesemia causes dysfunction of multiple potassium transport systems and increases renal potassium excretion 3, 4
• For hypomagnesemia with hypocalcemia, magnesium replacement must precede calcium supplementation 3
• In short bowel syndrome with high-output stomas, rehydration to correct secondary hyperaldosteronism is the most crucial first step 3, 4

Monitoring and Follow-Up

• Check magnesium levels 2-3 weeks after starting oral supplementation or after any dose adjustment 3, 4
• Target serum magnesium within normal range (1.8-2.2 mEq/L or 0.70-1.10 mmol/L), with minimum target >0.6 mmol/L 3, 4
• Always check and correct potassium, calcium, and phosphate levels concurrently 3
• For patients on continuous renal replacement therapy, use dialysis solutions containing magnesium to prevent hypomagnesemia 4

Adverse Effects

The adverse effects of parenteral magnesium are primarily manifestations of magnesium intoxication. 2

• Flushing and sweating 2
• Hypotension and circulatory collapse 2
• Depressed reflexes and flaccid paralysis 2
• Hypothermia 2
• Cardiac and CNS depression proceeding to respiratory paralysis 2
• Hypocalcemia with signs of tetany (reported in eclampsia treatment) 2
• Oral magnesium: diarrhea, abdominal distension, and gastrointestinal intolerance occur in 11-37% of patients 4, 5

Contraindications and Precautions

Magnesium supplementation is absolutely contraindicated when creatinine clearance is <20 mL/min due to risk of life-threatening hypermagnesemia. 3, 4

Absolute Contraindications

• Creatinine clearance <20 mL/min 3, 4
• Severe renal insufficiency (maximum 20 g/48 hours with frequent monitoring if absolutely necessary) 2

Relative Contraindications and Cautions

• Use extreme caution with creatinine clearance 20-30 mL/min; avoid unless life-threatening emergency 4
• Reduce doses with close monitoring when creatinine clearance 30-60 mL/min 4
• Avoid in patients with myocardial damage when considering use for paroxysmal atrial tachycardia 2
• Continuous maternal administration beyond 5-7 days in pregnancy can cause fetal abnormalities 2

Drug Interactions

• Increased sensitivity to digoxin toxicity in magnesium deficiency 4
• Enhanced electrolyte depletion when loop diuretics combined with thiazides or metolazone 4
• Regional citrate anticoagulation during CRRT increases hypomagnesemia risk 4

Physiological Roles and Disease Prevention

Magnesium is the fourth most abundant mineral in the body and acts as a cofactor for >300 enzymatic reactions 6, 7, 8, 9. It is essential for:

• DNA and RNA synthesis, protein synthesis, and ATP metabolism 6, 8, 9
• Regulation of muscular contraction, nerve transmission, and neuromuscular conduction 6, 8
• Cardiac excitability, vasomotor tone, and blood pressure regulation 6, 8, 9
• Insulin metabolism and glucose homeostasis 6, 9

Critical caveat: Serum magnesium levels remain a poor predictor of tissue magnesium content, as >99% of magnesium is intracellular and <1% is in blood 7, 10. Normal serum levels can coexist with significant intracellular depletion 4.

Low magnesium levels have been associated with chronic diseases including type 2 diabetes, hypertension, cardiovascular disease, stroke, migraine headaches, Alzheimer's disease, and ADHD 6, 9.