What is hypocalcemia and how is it treated?

Hypocalcemia: Diagnosis and Management

For severe symptomatic hypocalcemia, immediate treatment with 1-2g IV calcium gluconate administered slowly with ECG monitoring is essential to prevent life-threatening complications. 1, 2

Definition and Clinical Presentation

Hypocalcemia is defined as a total serum calcium level below 8.5 mg/dL (2.12 mmol/L) or ionized calcium below 0.9 mmol/L 1, 3. Clinical manifestations vary widely depending on severity:

• Mild hypocalcemia: Often asymptomatic
• Moderate hypocalcemia: Neuromuscular irritability, paresthesias, muscle cramps
• Severe hypocalcemia (ionized calcium <0.8 mmol/L): Tetany, seizures, cardiac dysrhythmias, impaired cardiac contractility 1, 4

Common Causes

1. Hypoparathyroidism

   • Postsurgical (75% of cases) - most common overall cause of chronic hypocalcemia 3
   • Primary/idiopathic (25% of cases) 5
   • Genetic disorders (e.g., 22q11.2 deletion syndrome) 1

2. Vitamin D deficiency or resistance

   • Inadequate intake, absorption, or metabolism
   • Renal failure (decreased 1,25-dihydroxyvitamin D production) 1

3. Acute causes

   • Massive blood transfusion (citrate chelation)
   • Acute pancreatitis
   • Severe hypomagnesemia
   • Critical illness 1

4. Chronic kidney disease

   • Phosphate retention
   • Decreased vitamin D activation
   • Skeletal resistance to PTH 1

5. Medication-induced

   • Bisphosphonates
   • Cisplatin
   • Antiepileptics
   • Aminoglycosides
   • Proton pump inhibitors 6

Diagnostic Approach

1. Laboratory assessment:

   • Serum calcium (total and ionized)
   • Serum phosphate (typically elevated in hypoparathyroidism)
   • Serum magnesium (hypomagnesemia can cause functional hypoparathyroidism)
   • Parathyroid hormone (PTH) levels
   • Vitamin D levels (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D)
   • Renal function tests 1, 3

2. Interpretation:

   • Low calcium with low/inappropriately normal PTH → hypoparathyroidism
   • Low calcium with high PTH → secondary hyperparathyroidism (vitamin D deficiency, CKD)
   • Check magnesium levels, as hypomagnesemia can impair PTH secretion and action 1

Treatment Algorithm

1. Acute Symptomatic Hypocalcemia

• Immediate intervention: 1-2g IV calcium gluconate (100-200 mg/kg for pediatric patients) administered slowly with ECG monitoring 1, 2
• For transfusion-related hypocalcemia, calcium chloride may be preferred due to higher elemental calcium content 1
• Monitor serum calcium every 4-6 hours during intermittent infusions and every 1-4 hours during continuous infusions 1
• Caution: Avoid overcorrection which can lead to hypercalcemia, renal calculi, and renal failure 1

2. Chronic Hypocalcemia Management

For Hypoparathyroidism:

1. Calcium supplementation:

   • Oral calcium (typically 1-3g elemental calcium daily in divided doses)
   • Titrate to maintain serum calcium in low-normal range to minimize hypercalciuria 4

2. Vitamin D therapy:

   • Active vitamin D analogs (calcitriol) typically 0.25-2.0 mcg daily
   • Adjust dose to maintain serum calcium while avoiding hypercalciuria 3

3. Additional measures:

   • Thiazide diuretics to reduce urinary calcium excretion
   • Phosphate binders if hyperphosphatemia is present
   • Low-salt and low-phosphorus diet 7

For Vitamin D Deficiency:

• High-dose vitamin D replacement (ergocalciferol or cholecalciferol)
• Calcium supplementation
• Treat underlying cause of vitamin D deficiency 3

For Hypomagnesemia:

• Correct magnesium deficiency before attempting to normalize calcium
• Magnesium replacement is essential for patients with seizures or neurological symptoms 1

3. Special Considerations for CKD Patients

• Avoid hypercalcemia in CKD G3a to G5D patients 8
• For dialysis patients, use dialysate calcium concentration between 1.25 and 1.50 mmol/L (2.5 and 3.0 mEq/L) 8
• Restrict calcium-based phosphate binders in patients receiving phosphate-lowering treatment 8
• Individualized approach for hypocalcemia during calcimimetic treatment 8

Monitoring and Follow-up

• Regular monitoring of calcium, phosphorus, vitamin D, and bone mineral status in at-risk patients 1
• Monitor for complications of treatment:
  • Hypercalciuria
  • Nephrocalcinosis
  • Renal impairment
  • Soft tissue calcification 4, 7
• Assess for symptoms of hypocalcemia or hypercalcemia
• Monitor magnesium levels in patients at risk for deficiency 1

Important Caveats

• Calcium levels must be interpreted in the context of albumin levels (for total calcium) or measured directly as ionized calcium
• Hypocalcemia risk increases during biological stress (surgery, childbirth, infection) 1
• Carbonated beverages and alcohol can worsen hypocalcemia 1
• Laboratory tests may not accurately reflect the impact of hypocalcemia on coagulation 1
• The safety of calcium gluconate for long-term use has not been established 2