Magnesium Replacement: Recommended Forms and Administration
Direct Recommendation
For mild to moderate hypomagnesemia, use oral magnesium oxide 12-24 mmol daily (approximately 480-960 mg elemental magnesium) as first-line therapy, administered at night when intestinal transit is slowest. 1 For severe or symptomatic hypomagnesemia, use intravenous magnesium sulfate 1-2 g over 15 minutes for acute cases, or 4-5 g added to one liter of fluid infused over 3 hours. 1, 2
Treatment Algorithm by Severity
Step 1: Assess Severity and Clinical Context
Mild hypomagnesemia (asymptomatic, Mg >0.50 mmol/L):
- Start oral magnesium oxide 12-24 mmol daily (480-960 mg elemental magnesium) 1
- Administer at night when intestinal transit is slowest to maximize absorption 1, 3
- Divide into 2-3 doses if gastrointestinal side effects occur 3
Severe hypomagnesemia (symptomatic or Mg <0.50 mmol/L):
- Use parenteral magnesium sulfate as first-line 1
- For acute severe deficiency: 1-2 g IV over 15 minutes 1
- For ongoing replacement: 4-5 g (40 mEq) in 1 liter of fluid over 3 hours 2
- Maximum rate: 150 mg/minute except in severe eclampsia with seizures 2
Life-threatening situations (torsades de pointes, severe arrhythmias):
- Give 1-2 g magnesium sulfate IV bolus over 5 minutes regardless of measured serum level 1
- For pulseless torsades: 25-50 mg/kg (maximum 2 g) as immediate bolus 1
Form Selection: Oral Preparations
First-Line: Magnesium Oxide
Magnesium oxide is the recommended first-line oral preparation despite lower bioavailability because it provides the highest elemental magnesium content per dose and has the most guideline support. 1, 3
- Dosing: 12-24 mmol daily (480-960 mg elemental magnesium) 1
- Formulation: Typically given as 4 mmol (160 mg) gelatin capsules 3
- Timing: Administer at night when intestinal transit is slowest 1, 3
- Caveat: Poorly absorbed (fractional absorption ~4%) and may worsen diarrhea in patients with gastrointestinal disorders 1, 4
Alternative: Organic Magnesium Salts (Better Bioavailability)
For patients with malabsorption or those intolerant to magnesium oxide, use organic salts (citrate, aspartate, lactate) which have superior bioavailability. 3, 5, 4
- Magnesium citrate: Superior bioavailability in research studies, increases serum and salivary magnesium more than oxide 5
- Magnesium aspartate: Equivalent bioavailability to citrate and lactate 4
- Magnesium lactate: Equivalent bioavailability to aspartate and chloride 4
- Dosing: 250-500 mg elemental magnesium daily, divided doses 6
- Advantage: Better tolerated, less diarrhea than oxide 3, 6
Important Nuance in the Evidence
There is contradictory evidence regarding bioavailability: one study found magnesium oxide increased intracellular magnesium more than citrate 7, while another found citrate had superior bioavailability 5. However, guidelines consistently recommend magnesium oxide as first-line because the higher elemental magnesium content (60% vs 16% for citrate) compensates for lower absorption in clinical practice. 1, 3
Form Selection: Parenteral Preparations
Intravenous Magnesium Sulfate (Standard)
Magnesium sulfate is the only recommended parenteral form. 1, 2
- Mild deficiency: 1 g (8.12 mEq) IM every 6 hours for 4 doses 2
- Severe deficiency: 5 g (40 mEq) in 1 liter IV over 3 hours 2
- Maximum rate: 150 mg/minute (1.5 mL of 10% solution) except in emergencies 2
- Concentration: Must dilute to ≤20% for IV use; 50% solution acceptable for IM in adults 2
Subcutaneous Administration (Refractory Cases)
For patients with short bowel syndrome or severe malabsorption who fail oral therapy, subcutaneous magnesium sulfate may be necessary. 1, 3
- Dosing: 4-12 mmol added to saline bags, 1-3 times weekly 1
- Indication: Reserved for patients unable to maintain levels with oral therapy 3
Critical Pre-Treatment Steps
Correct Volume Depletion First
Before initiating magnesium replacement, correct sodium and water depletion with IV saline to eliminate secondary hyperaldosteronism, which increases renal magnesium wasting. 1, 3
- This is particularly crucial in patients with high-output stomas, diarrhea, or gastrointestinal losses 1
- Each liter of jejunostomy fluid contains ~100 mmol/L sodium 1
- Failure to correct volume status first will result in continued magnesium losses despite supplementation 3
Check Renal Function
Avoid magnesium supplementation if creatinine clearance <20 mL/min due to life-threatening hypermagnesemia risk. 3, 6
Special Clinical Scenarios
Short Bowel Syndrome/Malabsorption
- Start with oral magnesium oxide 12-24 mmol daily at night 1, 3
- If oral fails, add 1-alpha hydroxy-cholecalciferol 0.25-9.00 μg daily (monitor calcium to avoid hypercalcemia) 1, 3
- If still refractory, use subcutaneous magnesium sulfate 4-12 mmol in saline 1-3 times weekly 1
Continuous Renal Replacement Therapy
- Use dialysis solutions containing magnesium to prevent ongoing losses 1, 3
- Hypomagnesemia occurs in 60-65% of critically ill patients on CRRT 1
Post-Transplant Patients on Calcineurin Inhibitors
- Attempt increased dietary intake first, but typically requires supplementation 1
- Monitor calcium, phosphorus, and magnesium per transplant protocols 1
Monitoring for Toxicity
Monitor for signs of magnesium toxicity during IV replacement: 1
- Loss of patellar reflexes (first sign)
- Respiratory depression
- Hypotension and bradycardia
- Have calcium chloride available to reverse toxicity if needed 1
Common Pitfalls
Attempting magnesium replacement without correcting volume depletion first - this leads to continued renal losses via hyperaldosteronism 1, 3
Not correcting magnesium before treating hypocalcemia or hypokalemia - calcium and potassium supplementation will be ineffective until magnesium is repleted 1
Using magnesium oxide in patients with diarrhea - the poor absorption worsens gastrointestinal symptoms; switch to organic salts 1, 6
Supplementing in renal insufficiency - absolute contraindication when CrCl <20 mL/min 3, 6
Rapid IV infusion - causes hypotension and bradycardia; respect maximum rate of 150 mg/minute 1, 2