What is the management of hypocalcemia?

Hypocalcemia: Pathophysiology, Symptoms, and Management

The management of hypocalcemia should be based on severity, with acute symptomatic cases requiring immediate IV calcium administration, while chronic cases need oral calcium supplementation, vitamin D therapy, and treatment of underlying causes to prevent morbidity and mortality. 1

Pathophysiology

Hypocalcemia occurs when serum calcium levels fall below normal (ionized calcium <0.9 mmol/L or serum total corrected calcium <7.5 mg/dL) 1. The pathophysiology involves disruptions in calcium homeostasis, which is normally regulated by:

• Parathyroid hormone (PTH): Increases serum calcium by promoting bone resorption, renal calcium reabsorption, and vitamin D activation
• Vitamin D: Enhances intestinal calcium absorption
• Renal function: Critical for calcium reabsorption and vitamin D metabolism

Common pathophysiological mechanisms include:

1. PTH deficiency or resistance: Hypoparathyroidism (post-surgical, idiopathic, or autoimmune)
2. Vitamin D deficiency or resistance: Reduced intestinal calcium absorption
3. Magnesium deficiency: Impairs PTH secretion and action
4. Hyperphosphatemia: Binds calcium, especially in chronic kidney disease (CKD)
5. Medication effects: Calcium chelation (e.g., citrate in blood products)

Clinical Manifestations

Hypocalcemia can affect multiple organ systems with varying severity 1:

Neuromuscular

• Tetany (increased neuromuscular excitability)
• Perioral numbness and paresthesias
• Carpopedal spasms
• Muscle cramps and twitching
• Chvostek's sign (facial muscle spasm when facial nerve tapped)
• Trousseau's sign (carpal spasm after blood pressure cuff inflation)
• Seizures in severe cases

Cardiovascular

• QT interval prolongation
• Arrhythmias
• Hypotension
• Bradycardia
• Cardiomyopathy (in severe chronic cases)

Neuropsychiatric

• Fatigue
• Irritability
• Confusion
• Memory loss
• Behavioral changes

Diagnostic Approach

Laboratory evaluation should include 1:

• Ionized calcium (more accurate than total calcium)
• Albumin-corrected total calcium
• Parathyroid hormone (PTH) levels
• Magnesium levels
• Phosphorus levels
• 25-hydroxyvitamin D levels
• Renal function tests

Management

Acute Symptomatic Hypocalcemia

1. IV Calcium Administration 1, 2:

   • Calcium chloride: Preferred in emergencies (10 mL of 10% solution contains 270 mg elemental calcium)
   • Calcium gluconate: Alternative (10 mL of 10% solution contains 90 mg elemental calcium)
   • Administer slowly with ECG monitoring, not exceeding 200 mg/minute in adults
   • Target ionized calcium within normal range (1.1-1.3 mmol/L)

2. Monitoring During IV Administration 1:

   • Monitor ionized calcium every 1-4 hours during continuous infusion
   • Every 4-6 hours during intermittent infusions

3. Precautions 1:

   • Avoid mixing calcium with phosphate or bicarbonate-containing fluids
   • Use caution with cardiac glycosides due to arrhythmia risk
   • Avoid administration if phosphate levels are elevated

Chronic Hypocalcemia Management

1. Oral Calcium Supplementation 1, 3:

   • Elemental calcium 1-2 g/day divided into multiple doses
   • Common formulations:
     • Calcium carbonate (40% elemental calcium)
     • Calcium citrate (21% elemental calcium)

2. Vitamin D Therapy 4, 3, 5:

   • For hypoparathyroidism and CKD-related hypocalcemia:
     • Calcitriol (active vitamin D): Starting dose 0.25 μg daily, titrated based on response
   • For vitamin D deficiency:
     • Cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2)

3. Magnesium Replacement 1, 2:

   • Essential if hypomagnesemia is present, as PTH secretion and action require adequate magnesium

4. Specific Therapy Based on Etiology 1, 5:

   • Hypoparathyroidism:
     • Calcium and vitamin D supplementation
     • Recombinant human PTH(1-84) for refractory cases
   • CKD-related hypocalcemia:
     • Manage hyperphosphatemia
     • Calcitriol for secondary hyperparathyroidism
   • Post-parathyroidectomy:
     • Aggressive calcium replacement for hungry bone syndrome

5. Dietary Recommendations 1:

   • Total elemental calcium intake not exceeding 2,000 mg/day
   • Avoid alcohol and carbonated beverages

Monitoring for Chronic Management

• Monitor serum calcium every 2-4 weeks initially
• Then every 3-6 months once stable
• Maintain calcium-phosphorus product <55 mg²/dL 1
• In CKD patients, avoid hypercalcemia while managing hypocalcemia 6

Special Considerations

Hypocalcemia in CKD

• Decisions about phosphate-lowering treatment should be based on persistently elevated serum phosphate 6
• Avoid hypercalcemia in CKD patients (Grade 2C recommendation) 6
• For dialysis patients, use dialysate calcium concentration between 1.25 and 1.50 mmol/L 6
• Restrict calcium-based phosphate binders in CKD patients receiving phosphate-lowering treatment 6

Trauma and Massive Transfusion

• Trauma patients commonly experience hypocalcemia due to citrate in blood products chelating calcium 1
• Close monitoring and calcium replacement necessary during massive transfusion

Pregnancy

• Maternal hypocalcemia increases risk of complications including spontaneous abortion, premature labor, and preeclampsia 1

Common Pitfalls and Caveats

1. Overcorrection: Avoid rapid or excessive correction, which can lead to hypercalcemia, kidney stones, and renal failure 1

2. Untreated Hypomagnesemia: Failure to correct hypomagnesemia can make hypocalcemia refractory to treatment 1, 2

3. Calcium Administration with Hyperphosphatemia: Can lead to calcium phosphate precipitation in tissues 1

4. Ignoring Underlying Cause: Treating symptoms without addressing the primary disorder leads to recurrence 3, 5

5. Aggressive Correction in Asymptomatic Patients: May not be necessary and could cause adverse effects 7

6. Inadequate Monitoring: Failure to monitor calcium levels during treatment can lead to complications 1