What is the recommended protocol for correcting hypomagnesemia, including oral and intravenous magnesium dosing, monitoring parameters, and management of underlying causes?

Magnesium Correction Protocol

For mild-to-moderate hypomagnesemia, start with oral magnesium oxide 12 mmol (480 mg elemental magnesium) nightly, escalating to 24 mmol daily if needed; for severe symptomatic cases or life-threatening arrhythmias, give 1–2 g magnesium sulfate IV over 5–15 minutes immediately, regardless of measured serum level. 1

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Step 1: Assess Severity and Correct Volume Depletion First

Define Severity

• Mild hypomagnesemia: serum Mg 0.50–0.70 mmol/L (1.2–1.7 mg/dL) 1
• Severe hypomagnesemia: serum Mg <0.50 mmol/L (<1.2 mg/dL) 1
• Life-threatening: torsades de pointes, ventricular arrhythmias, seizures, or cardiac arrest 1

Correct Volume Depletion Before Magnesium Supplementation

• Administer IV normal saline 2–4 L/day initially to restore sodium and water balance in patients with gastrointestinal losses (diarrhea, high-output stoma, jejunostomy) 1, 2
• Volume depletion triggers secondary hyperaldosteronism, which increases renal magnesium excretion and prevents effective oral repletion 1, 2
• Check urinary sodium: <10 mEq/L confirms volume depletion with secondary hyperaldosteronism 2
• Critical pitfall: Starting oral magnesium without correcting volume status allows ongoing renal magnesium wasting despite supplementation 1, 2

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Step 2: Oral Magnesium Replacement (Mild-to-Moderate Cases)

First-Line Oral Regimen

• Magnesium oxide 12 mmol (480 mg elemental magnesium) once nightly 1, 2
• Night-time dosing exploits slower intestinal transit during sleep for maximal absorption 1, 2
• If serum magnesium remains low after 1–2 weeks, escalate to 24 mmol daily (single or divided doses) 1, 2

Alternative Oral Formulations

• Organic magnesium salts (aspartate, citrate, lactate, glycinate) have higher bioavailability and cause less diarrhea than magnesium oxide 1, 2
• Use organic salts when gastrointestinal side effects limit magnesium oxide tolerance 1, 2
• Avoid magnesium hydroxide or magnesium sulfate orally—they are potent laxatives with poor absorption 2

Refractory Oral Cases

• Add oral 1-alpha hydroxy-cholecalciferol (starting 0.25 µg daily, titrating up to 9 µg) to improve magnesium balance when oral magnesium alone fails 1, 2
• Monitor serum calcium weekly to avoid hypercalcemia 1, 2
• Consider subcutaneous magnesium sulfate 4–12 mmol added to saline bags, administered 1–3 times weekly, for patients with short bowel syndrome or severe malabsorption 1, 3

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Step 3: Intravenous Magnesium Replacement (Severe or Symptomatic Cases)

Life-Threatening Presentations (Immediate IV Bolus)

• Torsades de pointes, ventricular arrhythmias, seizures, or cardiac arrest: give 1–2 g magnesium sulfate IV bolus over 5 minutes regardless of baseline magnesium level 1, 4
• This is a Class I recommendation from the American Heart Association 1
• Follow with continuous infusion 1–4 mg/min if needed 1

Severe Symptomatic Hypomagnesemia (Non-Emergent)

• Serum Mg <0.50 mmol/L (<1.2 mg/dL) with symptoms: give 1–2 g magnesium sulfate IV over 15 minutes 1, 4
• Alternatively, add 5 g (40 mEq) magnesium sulfate to 1 L of 5% dextrose or 0.9% saline and infuse over 3 hours 4
• For mild deficiency: 1 g (8.12 mEq) IM every 6 hours for 4 doses (total 32.5 mEq/24 hours) 4

Maximum Infusion Rate and Renal Dosing

• Do not exceed 150 mg/minute IV (1.5 mL of 10% solution), except in severe eclampsia with seizures 4
• In severe renal insufficiency (CrCl <30 mL/min): maximum dose is 20 g over 48 hours with frequent serum monitoring 1, 4
• Absolute contraindication: CrCl <20 mL/min due to life-threatening hypermagnesemia risk 1, 2

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Step 4: Correct Associated Electrolyte Abnormalities

Magnesium Must Be Corrected First

• Hypokalemia and hypocalcemia are refractory to supplementation until magnesium is normalized 1, 2
• Hypomagnesemia impairs potassium transport systems and increases renal potassium excretion 1, 2
• Hypomagnesemia impairs parathyroid hormone (PTH) secretion, causing hypocalcemia 1

Sequence of Electrolyte Replacement

1. Correct volume depletion with IV saline 1, 2
2. Replace magnesium first (oral or IV depending on severity) 1, 2
3. Then replace potassium and calcium—expect calcium normalization within 24–72 hours after magnesium repletion begins 1

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Step 5: Identify and Address Underlying Causes

Common Causes of Renal Magnesium Wasting

• Loop and thiazide diuretics (most common medication cause) 1, 5
• Proton pump inhibitors, calcineurin inhibitors (tacrolimus, cyclosporine) 1, 5
• Aminoglycosides, cisplatin, pentamidine, amphotericin B, foscarnet 1, 5
• Diabetes mellitus, alcoholism 5

Gastrointestinal Causes

• Chronic diarrhea, short bowel syndrome, high-output stoma, malabsorption 1, 2, 5
• Each liter of jejunostomy output contains ~100 mmol/L sodium and substantial magnesium 1, 2

Diagnostic Approach

• Measure fractional excretion of magnesium (FEMg): <2% indicates gastrointestinal loss; >2% indicates renal wasting 6
• Check 24-hour urine magnesium in patients with ongoing losses to assess total body status 2
• Discontinue offending medications when possible (e.g., switch from PPI to H2-blocker) 2

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Step 6: Monitoring Parameters

Initial Monitoring

• Baseline: serum magnesium, potassium, calcium, creatinine 1, 2
• During IV replacement: monitor Mg, K, Ca, creatinine every 6–12 hours 1
• Watch for magnesium toxicity: loss of patellar reflexes, respiratory depression, hypotension, bradycardia 1
• Have calcium chloride available to reverse magnesium toxicity if needed 1

Oral Supplementation Monitoring

• Recheck magnesium 2–3 weeks after starting or after any dose adjustment 2
• Once stable: monitor every 3 months 2
• More frequent monitoring if high GI losses, renal disease, or on magnesium-wasting medications 2

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Special Clinical Scenarios

Cardiac Patients

• Maintain magnesium >2 mg/dL in patients with QTc prolongation >500 ms or on QT-prolonging medications 1, 2
• Digoxin therapy: magnesium deficiency markedly increases digoxin toxicity risk—target serum Mg ≥2 mEq/L 1

Diuretic Therapy

• Add potassium-sparing diuretic (amiloride 5–10 mg daily or spironolactone 25–50 mg daily) to conserve magnesium in patients on loop or thiazide diuretics 1
• Monitor potassium closely: risk of hyperkalemia when combined with ACE inhibitors or potassium supplements 1

Continuous Renal Replacement Therapy (CRRT)

• Use dialysis solutions containing magnesium to prevent ongoing losses 1, 2
• Hypomagnesemia occurs in 60–65% of critically ill patients on CRRT 1

Pregnancy (Preeclampsia/Eclampsia)

• Initial dose: 4–5 g IV over 3–4 minutes, then 4–5 g IM into alternate buttocks every 4 hours 4
• Alternatively: 1–2 g/hour continuous IV infusion after initial bolus 4
• Do not exceed 5–7 days of continuous magnesium sulfate in pregnancy—fetal abnormalities can occur 4

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Critical Pitfalls to Avoid

1. Never start oral magnesium without correcting volume depletion first in patients with GI losses—secondary hyperaldosteronism will prevent effective repletion 1, 2

2. Never attempt to correct hypokalemia or hypocalcemia before normalizing magnesium—these are refractory until magnesium is repleted 1, 2

3. Do not assume normal serum magnesium excludes deficiency—less than 1% of total body magnesium is in blood; intracellular depletion can coexist with normal serum levels 2, 5

4. Avoid magnesium supplementation in severe renal insufficiency (CrCl <20 mL/min) except in life-threatening emergencies (torsades de pointes), and then only with extreme caution 1, 2, 4

5. Most magnesium salts worsen diarrhea in patients with GI disorders—start low and titrate slowly 1, 2

6. Separate magnesium from fluoroquinolone antibiotics by at least 2 hours to avoid reduced antibiotic absorption 2

7. Do not co-administer calcium and magnesium supplements together—separate by at least 2 hours to avoid absorption interference 1