📉 Hypomagnesemia

Recognition and Management of Magnesium Deficiency

🚨 EMERGENCY RECOGNITION: Hypomagnesemia

1 Clinical Suspicion: Tetany, seizures, or torsades de pointes with normal Ca/K levels
2 High-Risk Patients: Chronic alcoholism, diuretics, PPI use, malabsorption
3 Associated Deficiencies: Check K, Ca, PO4 - often concurrent (60% hypokalemic)
4 Treatment Priority: Must correct Mg FIRST - K refractory until Mg repleted

📊 Definition and Clinical Significance

Hypomagnesemia Definition

  • Serum Magnesium: <1.8 mg/dL (0.75 mmol/L)
  • Mild: 1.2-1.8 mg/dL (0.5-0.75 mmol/L)
  • Moderate: 0.8-1.2 mg/dL (0.35-0.5 mmol/L)
  • Severe: <0.8 mg/dL (<0.35 mmol/L)
  • Critical Insight: Normal serum levels don't exclude total body depletion
  • Prevalence: 2-15% hospitalized, up to 65% ICU patients

🎯 Causes of Hypomagnesemia

Category Specific Causes Key Clinical Features Mechanism
Nutritional/GI Chronic alcohol use disorder Multiple nutrient deficiencies, withdrawal risk ↓Absorption, ↑losses, poor intake
Malabsorption syndromes Diarrhea, weight loss, steatorrhea ↓Intestinal absorption
Bariatric surgery (RYGB) Post-surgical, rapid weight loss ↓Absorptive surface area
Renal Losses Loop diuretics Dose-dependent, concurrent hypokalemia ↓TAL reabsorption
Proton pump inhibitors Long-term use (>1 year) ↓TRPM6/TRPM7 channels
Aminoglycosides Duration-dependent nephrotoxicity Tubular toxicity
Endocrine Diabetes mellitus Poor glycemic control, osmotic diuresis ↑Renal losses
Primary aldosteronism Hypertension, concurrent hypokalemia ↑Distal tubule flow
Genetic Gitelman syndrome Hypocalciuria, hypokalemia NCCT mutations

🔍 Clinical Manifestations

Neuromuscular Manifestations

  • Early signs: Fatigue, weakness, irritability
  • Progressive: Muscle cramps, fasciculations
  • Chvostek/Trousseau signs: May be positive
  • Severe: Tetany, seizures, altered mental status
  • Key: Symptoms usually absent until <1.2 mg/dL

Cardiovascular Complications

  • Arrhythmias: Atrial and ventricular
  • Life-threatening: Torsades de pointes
  • Enhanced digitalis toxicity: ↑Na+ cellular accumulation
  • Vascular effects: Coronary spasm, hypertension
  • ECG changes: QT prolongation, U waves

Metabolic Consequences

  • Hypokalemia: 60% of patients concurrent
  • Hypocalcemia: PTH resistance/↓secretion
  • Hypophosphatemia: Impaired PTH action
  • Vitamin D metabolism: ↓1α-hydroxylase activity
  • Insulin resistance: ↓Glucose tolerance

🧮 Hypomagnesemia Risk and Replacement Calculator




Replacement Protocol: Enter values to calculate dosing

🔬 Diagnostic Workup

Initial Laboratory Assessment

  • Serum magnesium (fasting): <1.8 mg/dL diagnostic
  • Ionized magnesium: More accurate but limited availability
  • Concurrent electrolytes: K, Ca, PO4, albumin
  • Intact PTH: Suppressed in severe deficiency
  • 25(OH)D level: Impaired activation

Determine Etiology

  • 24-hour urine Mg: <120 mg/day in deficiency
  • Fractional excretion: >2% suggests renal wasting
  • Medication review: Diuretics, PPIs, antibiotics
  • GI assessment: Diarrhea, malabsorption history

Specialized Testing

  • Mg tolerance test: Gold standard for body stores
  • Genetic testing: Suspected inherited disorders
  • Alcohol use screening: CAGE, quantity assessment
  • Nutritional evaluation: Comprehensive assessment

📐 Fractional Excretion of Magnesium (FEMg)

Formula: FEMg = (UMg × SCr) / (0.7 × SMg × UCr) × 100

  • Normal response to deficiency: <2% (renal conservation)
  • Renal wasting: >2% despite hypomagnesemia
  • Clinical utility: Distinguish renal vs. extrarenal losses

🧪 Ionized Magnesium Testing

  • Normal range: 0.45-0.60 mmol/L
  • Advantages: Not affected by protein binding
  • Clinical utility: Better correlation with intracellular stores
  • Limitations: Limited availability, expensive
  • Consider when: Normal total Mg with strong clinical suspicion
  • Research evidence: May detect deficiency earlier than total Mg

💊 Treatment Strategies

Acute Severe Hypomagnesemia (<1.0 mg/dL)

1 IV Loading Dose: 1-2 grams (4-8 mmol) MgSO4 in 50-100 mL NS over 1-2 hours
2 Continuous Infusion: 6 grams (24 mmol) MgSO4 in 1000 mL NS over 24 hours
3 Monitoring: Serum Mg every 6-8 hours, check DTRs, renal function
4 Concurrent K replacement: Required for successful K repletion

Oral Magnesium Supplementation

  • Preferred forms: Chloride, citrate, gluconate, glycinate
  • Highly recommended: Magnesium chloride (25% elemental, excellent absorption)
  • Avoid: Magnesium oxide (poor absorption, diarrhea)
  • Dosing: 400-800 mg daily elemental Mg, divided doses
  • Duration: Weeks to months depending on etiology
  • Side effects: Diarrhea (dose-limiting, less with chloride form)

Chronic Parenteral Therapy

  • Indications: Malabsorption, ongoing losses
  • Dosing: 2-4 grams MgSO4 weekly or twice-weekly
  • Administration: Outpatient infusion centers
  • Monitoring: Monthly serum levels, clinical symptoms

Treatment of Underlying Conditions

  • Medication review: Discontinue/modify offending agents
  • Alcohol cessation: Comprehensive addiction treatment
  • GI disorders: Specific therapy for malabsorption
  • Endocrine disorders: Hormone replacement/suppression

💊 Oral Magnesium Formulations

Formulation Elemental Mg Content Bioavailability GI Tolerance Clinical Notes
Magnesium Oxide 60% 4% (Poor) Poor - Diarrhea Avoid - despite high Mg content
Magnesium Citrate 16% 25-30% (Good) Good Preferred oral form
Magnesium Gluconate 5.4% 25-30% (Good) Excellent Well tolerated, lower Mg per pill
Magnesium Glycinate 14% 35-40% (Excellent) Excellent Chelated form, optimal absorption
Magnesium Lactate 12% 25-30% (Good) Good Alternative to citrate
Magnesium Chloride 25% 30-35% (Excellent) Very Good Highly bioavailable, well-tolerated

⚠️ Special Clinical Considerations

PPI-Induced Hypomagnesemia

  • Mechanism: ↓TRPM6/TRPM7 intestinal channels
  • Time course: Usually >1 year of therapy
  • High risk: Concurrent thiazides, elderly
  • Management: PPI discontinuation often required
  • Alternatives: H2 blockers don't affect Mg absorption

Alcohol Use Disorder

  • Multiple mechanisms: ↓Intake, ↓absorption, ↑losses
  • Withdrawal risk: ↑Seizure susceptibility
  • Nutritional rehab: Thiamine, folate, B12 deficiencies
  • Higher requirements: During detoxification
  • Comprehensive care: Addiction medicine referral

Diuretic-Induced Deficiency

  • Loop diuretics: Greatest Mg wasting (TAL)
  • Thiazides: Gitelman syndrome phenocopy
  • Dose-dependent: >80 mg furosemide daily high risk
  • Prevention: K-sparing diuretics may help
  • Monitoring: Baseline, 1-2 weeks, then q3-6 months

🔄 Critical Electrolyte Interactions

Magnesium-Potassium Relationship

  • Physiologic interdependence: Mg deficiency impairs renal K conservation
  • Clinical significance: 60% of hypomagnesemic patients have hypokalemia
  • Treatment priority: Must correct Mg FIRST - K refractory otherwise
  • Mechanism: ↓Na-K-ATPase activity, ↑K channel activity
  • Dosing: Simultaneous replacement more effective than sequential

Magnesium-Calcium-PTH Axis

  • PTH synthesis: Mg required for hormone production
  • PTH secretion: Severe Mg deficiency (<1.0 mg/dL) suppresses PTH
  • PTH resistance: ↓Target organ responsiveness in Mg deficiency
  • Vitamin D metabolism: Mg cofactor for 1α-hydroxylase
  • Clinical result: Hypocalcemia refractory to Ca replacement until Mg corrected

📊 Monitoring and Follow-up

Acute Treatment Monitoring

  • Serum Mg: Every 6-8 hours during IV replacement
  • Renal function: Creatinine, avoid overload
  • Deep tendon reflexes: Clinical improvement marker
  • Cardiac monitoring: If arrhythmias present

Chronic Management

  • Target level: >1.8 mg/dL, ideally 2.0-2.4 mg/dL
  • Follow-up frequency: Weekly initially, then monthly
  • Symptom assessment: Muscle cramps, weakness resolution
  • Concurrent electrolytes: K, Ca, PO4 normalization

🎯 Key Learning Points

  • Recognition: Consider in alcohol use disorder, chronic diuretics, PPI therapy, malabsorption
  • Clinical Clues: Refractory hypokalemia, unexplained tetany, torsades de pointes
  • Diagnostic Limitation: Normal serum Mg doesn't exclude total body depletion
  • Treatment Priority: Must correct magnesium BEFORE potassium will respond
  • Oral Forms: Chloride, citrate, gluconate, glycinate preferred; avoid oxide
  • IV Replacement: 1-2g loading dose, then 6g/24h for severe deficiency
  • PPI Association: Long-term PPI use can cause refractory hypomagnesemia
  • Electrolyte Interactions: Affects K, Ca, PO4 - comprehensive replacement needed
  • Prevention: Monitor high-risk patients, consider prophylactic supplementation