HYPOMAGNESEMIA 

Definition

Hypomagnesemia is defined as:

  • Serum magnesium < 1.7 mg/dL/< 0.7 mmol/L/< 1.4 mEq/L

⚠️ Important: Serum magnesium represents <1% of total body magnesium → normal serum levels do not exclude intracellular depletion.

Normal Magnesium Physiology

Total Body Magnesium

  • Total body content: ~24 g (1000 mmol)
  • Distribution:
    • Bone: ~60%
    • Muscle & soft tissue: ~39%
    • Extracellular fluid: <1%

Serum Magnesium Fractions

Fraction

Percentage

Ionized (active)

~55–70%

Protein-bound (albumin)

~20–30%

Complexed (phosphate, citrate)

~5–15%

Magnesium Homeostasis

Intestinal Absorption (30–50%)

  • Mainly in ileum & colon
  • Passive paracellular absorption
  • Active transcellular (TRPM6 channels)

Renal Handling (Key Regulator)

Nephron Segment

% Reabsorbed

Mechanism

Proximal tubule

15–20%

Passive

Thick ascending limb (TAL)

60–70%

Paracellular (claudin-16, ROMK)

Distal convoluted tubule (DCT)

5–10%

Active (TRPM6)

DCT is the final checkpoint → no reabsorption beyond this

Etiology of Hypomagnesemia

1. Reduced Intake / Absorption

  • Poor nutrition
  • Starvation
  • Chronic alcoholism
  • Malabsorption syndromes
  • Celiac disease
  • Crohn disease
  • Short bowel syndrome
  • Chronic diarrhea
  • Proton pump inhibitors (PPIs) (↓ TRPM6)

2. Gastrointestinal Losses

  • Chronic diarrhea
  • Laxative abuse
  • High-output stomas
  • Nasogastric suction
  • Biliary or pancreatic fistulae

3. Renal Magnesium Wasting (MOST COMMON in ICU)

Drugs

Drug Class

Examples

Diuretics

Loop > thiazides

Aminoglycosides

Gentamicin, amikacin

Amphotericin B

Tubular toxicity

Cisplatin

DCT injury

Calcineurin inhibitors

Tacrolimus, cyclosporine

Digoxin

↑ urinary Mg loss

PPIs

↓ intestinal absorption

Renal Tubular Disorders

  • Gitelman syndrome
  • Bartter syndrome
  • Post-AKI diuretic phase
  • Post-transplant tubular dysfunction
  • Recovery phase of ATN

4. Redistribution (Shift into Cells)

  • Refeeding syndrome
  • Insulin therapy (DKA)
  • Acute pancreatitis
  • Hungry bone syndrome
  • Catecholamine surge
  • Respiratory alkalosis

5. Endocrine / Metabolic Causes

  • Uncontrolled diabetes mellitus (osmotic diuresis)
  • Hyperaldosteronism
  • Hyperparathyroidism
  • SIADH (dilutional)

ICU-Specific Risk Factors

  • Sepsis
  • Massive transfusion (citrate binding)
  • CRRT
  • DKA / HHS
  • Alcohol withdrawal
  • Prolonged ICU stay
  • Poor enteral nutrition

Pathophysiology

Key Cellular Roles of Magnesium

  • Cofactor for >300 enzymatic reactions
  • Regulates:
    • Na⁺-K⁺-ATPase
    • Calcium channels
    • Potassium transport
    • ATP metabolism
    • Neuromuscular stability

Electrolyte Interactions 

Hypomagnesemia → Refractory Hypokalemia

  • Mg deficiency → ↑ ROMK activity
  • ↑ renal K⁺ wasting
  • Potassium will not correct unless Mg is replaced

Hypomagnesemia → Hypocalcemia

  • ↓ PTH secretion
  • End-organ resistance to PTH

Clinical Manifestations

Neuromuscular

  • Tremors
  • Muscle weakness
  • Fasciculations
  • Tetany
  • Carpopedal spasm
  • Seizures
  • Hyperreflexia

Cardiovascular

  • Ventricular arrhythmias
  • Torsades de pointes
  • Atrial fibrillation
  • Prolonged QT
  • Digitalis toxicity (↑ sensitivity)

Neuropsychiatric

  • Apathy
  • Delirium
  • Depression
  • Confusion
  • Agitation

Metabolic

  • Refractory hypokalemia
  • Hypocalcemia
  • Insulin resistance

ECG Changes

  • Prolonged QT interval
  • Flattened T waves
  • ST depression
  • Ventricular ectopy
  • Polymorphic VT (torsades)

Diagnosis

Laboratory

  • Serum Mg <1.7 mg/dL
  • Check:
    • Potassium
    • Calcium
    • Phosphate
    • Albumin

Distinguishing Renal vs Non-Renal Loss

24-Hour Urinary Magnesium

  • 24 mg/day → renal loss

Fractional Excretion of Magnesium (FeMg)

FeMg=(PMg ×UCr )(UMg ×PCr ) ×100

FeMg

Interpretation

<2%

GI loss

>4%

Renal wasting

Severity Classification

Serum Mg (mg/dL)

Severity

1.2–1.7

Mild

0.9–1.2

Moderate

<0.9

Severe

Management

General Principles

  • Treat symptoms, not just numbers
  • Correct Mg before K⁺ or Ca²⁺
  • Monitor ECG in severe cases

Magnesium Replacement

IV Magnesium (Preferred in ICU)

Drug

  • Magnesium sulfate (MgSO₄)
    1 g = 8 mEq Mg²⁺

Oral Magnesium (Stable Patients)

Preparation

Elemental Mg

Mg oxide

High Mg, poor absorption

Mg citrate

Better absorption

Mg lactate

Well tolerated

Special Situations

Renal Failure

  • Use 50% dose
  • Slow infusion
  • Frequent Mg monitoring

Torsades de Pointes

  • MgSO₄ IV , regardless of Mg level
  • May repeat

Alcohol Withdrawal

  • Prophylactic Mg replacement recommended

DKA / Refeeding Syndrome

  • Monitor Mg daily
  • Early aggressive replacement

Monitoring

  • Serum Mg every 12–24 h
  • ECG monitoring if:
    • Mg <1.2 mg/dL
    • Arrhythmias
    • Concomitant hypokalemia

Complications of Overcorrection

  • Hypotension
  • Bradycardia
  • Loss of DTRs
  • Respiratory depression
  • Cardiac arrest (very high levels)