What are the acute causes of hypocalcemia?

Acute Causes of Hypocalcemia

The most common acute causes of hypocalcemia include massive blood transfusion, hypoparathyroidism (particularly post-surgical), vitamin D deficiency, acute pancreatitis, and severe hypomagnesemia. 1, 2

Transfusion-Related Causes

• Massive blood transfusion: Each unit of packed red blood cells or fresh frozen plasma contains approximately 3g of citrate, which chelates calcium. During massive transfusion, liver hypoperfusion impairs citrate metabolism, leading to hypocalcemia 1
• Ionized calcium levels below 0.9 mmol/L require prompt correction, as levels below 0.8 mmol/L can cause cardiac dysrhythmias 1
• Hypocalcemia within the first 24 hours of critical bleeding predicts mortality and need for multiple transfusions 1

Endocrine and Metabolic Causes

• Hypoparathyroidism:
  • Post-surgical (75% of cases) - most commonly following thyroid or parathyroid surgery 2, 3
  • Primary (25% of cases) - including genetic disorders like 22q11.2 deletion syndrome 2
• Vitamin D deficiency/disorders:
  • Impaired vitamin D activation in chronic kidney disease 2
  • Decreased intestinal calcium absorption 4
• Hypomagnesemia:
  • Critical for PTH secretion and action
  • Can cause refractory hypocalcemia until magnesium is replaced 2

Critical Illness-Related Causes

• Sepsis syndrome: Commonly associated with hypocalcemia in critically ill patients 5
• Acute pancreatitis: Calcium sequestration in saponification of fat necrosis
• Acute kidney injury: Phosphate retention and decreased vitamin D activation 2
• Biological stress: Surgery, childbirth, or infection can increase hypocalcemia risk 2

Other Acute Causes

• Tumor lysis syndrome: Rapid release of intracellular phosphate binds calcium
• Rhabdomyolysis: Calcium deposition in damaged muscle
• Hungry bone syndrome: Following parathyroidectomy for severe hyperparathyroidism

Clinical Manifestations

• Neuromuscular irritability and tetany
• Seizures
• Cardiac arrhythmias
• Prolonged QT interval (weak association noted, r = -0.12) 5
• Impaired cardiac contractility and systemic vascular resistance 1

Diagnostic Approach

• Measure both total and ionized calcium levels
• Check magnesium levels (hypomagnesemia can cause refractory hypocalcemia)
• Assess parathyroid hormone (PTH) levels to differentiate PTH-mediated from non-PTH-mediated causes 3
• Evaluate vitamin D status (25-OH and 1,25-OH levels)
• Check renal function (phosphate, creatinine)

Management of Acute Hypocalcemia

• For severe symptomatic hypocalcemia: Administer 1-2g IV calcium gluconate (100-200 mg/kg for pediatric patients) immediately, with ECG monitoring 2
• For transfusion-related hypocalcemia: Calcium chloride is preferred (10mL of 10% solution contains 270mg elemental calcium vs. 90mg in calcium gluconate) 1
• Monitor serum calcium every 4-6 hours during intermittent infusions and every 1-4 hours during continuous infusions 2
• Correct underlying causes:
  • Replace magnesium if deficient
  • Administer vitamin D (calcitriol) for vitamin D deficiency or hypoparathyroidism 4
  • Treat underlying conditions (e.g., pancreatitis, sepsis)

Important Considerations

• Hypocalcemia is extremely common in critically ill patients (up to 88%) and correlates with illness severity and mortality 5
• The hazard ratio for death increases by 1.65 for each 0.1 mmol/L decrease in calcium level 5
• Avoid overcorrection, which can lead to hypercalcemia, renal calculi, and renal failure 2
• For chronic hypocalcemia due to hypoparathyroidism, recombinant human PTH may be considered 3, 6

Pitfalls to Avoid

• Laboratory tests may not accurately reflect the impact of hypocalcemia on coagulation, as blood samples are citrated and recalcified before analysis 1
• Failing to check magnesium levels when treating hypocalcemia (hypomagnesemia can cause refractory hypocalcemia)
• Not monitoring cardiac function during rapid calcium correction
• Overlooking the need for vitamin D supplementation in chronic hypocalcemia management