REBEL Core Cast 87.0 – Hypercalcemia

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Definition: A serum calcium level > 10.5 mg/dL. 

Background

Causes

• Malignancy (multiple myeloma, metastases to bone)
• Granulomatous disease (TB, sarcoidosis)
• Endocrine (hyperthyroidism, hyperparathyroidism, adrenal insufficiency, pheochromocytoma)
• Pharmacologic agents (thiazide diuretics, milk-alkali syndrome, PTH therapy for osteoporosis, lithium, Vitamin A)
• Miscellaneous (Dehydration, rhabdomyolysis, prolonged immobilization, dietary, iatrogenic)

Clinical Manifestations

• “Stones (renal), Bones (bone pain), Groans (abdominal pain) + Moans (Psychiatric overtones)” 
• Cardiac Effects 
  • Bradydysrhythmias
  • AV block
  • Sinus Arrest
  • Atrial Fibrillation
  • Ventricular Tachycardia
  • QTc shortening
• Neuropsychiatric Disorders
  • Major: AMS, seizures, weakness, lethargy, coma
  • Minor: Anxiety, depression, confusion, hallucinations
  • Hyporeflexia

Diagnosis

• Serum calcium > 10.5 mg/dL
  • 10.5 – 12.0 mg/dL considered moderate
  • > 14 mg/dL considered severe + potentially life-threatening 
• EKG
  • Short QTc interval (also caused by congenital short QT syndrome and digoxin)
  • Prolonged PR
  • Widened QRS complex
  • AV block

Management

• Supportive Care – ABCs, IV, O₂, Monitor
• Volume Expansion
  • The majority of patients with hypercalcemia have significant dehydration
  • Normal saline administration
    • Mechanism of action: Corrects volume depleted state and inhibits proximal tubule calcium resorption
    • Monitor other electrolytes (potassium, sodium)
    • Dose
      • Bolus to correct hypotension
      • Careful administration while monitoring overall fluid status (patients often have cardiac and/or renal dysfunction making them susceptible to volume overload)
      • Loop diuretics (i.e. furosemide)
        • Mechanism of action: Inhibits reabsorption of Na,K, Cl via the Na⁺-K⁺-2Cl^– cotransporter in the thick ascending loop of henle, thereby also inhibiting Ca²⁺ and Mg²⁺ reabsorption
        • Theoretical benefit of “forced diuresis” not proven in the literature
        • Should NOT be given until volume repletion completed as it can exacerbate hypercalcemia in this situation
• Bisphosphonates
  • Mechanism of action: inhibit osteoclast-mediated bone resorption
  • Zoledronic acid 
    • Preferred in hypercalcemia in the setting of malignancy
    • Dose: 4 mg IV over 15 minutes
  • Other Agents: Pamidronate, Etidronate
• Calcitonin
  • Mechanism of action: inhibits Ca²⁺ absorption in the intestines, inhibits osteoclast activity, stimulates osteoblastic activity, inhibits renal tubular cell reabsorption
  • Dose: 4 IU/kg IM Q12
• Cinacalcet
  • Mechanism of action: increases the sensitivity of Ca²⁺ receptors on parathyroid cells to reduce PTH levels and, thus Ca²⁺ levels
  • Indications: Hypercalcemia in patients with secondary hyperparathyroidism (i.e. CKD on dialysis, parathyroid carcinoma)
• Other
  • Hemodialysis
  • Parathyroidectomy may be considered in patients with hypercalcemia caused by hyperparathyroidism

Take Home Points

• Patients with severe hypercalcemia (> 14 mg/dL) are at risk for severe cardiac dysrhythmias and cardiac collapse
• Treatment centers on volume repletion with normal saline with consideration for the addition of loop diuretics AFTER volume reexpansion is complete
• As the patient begins to diurese, continually monitor electrolytes

References

Pfenning CL, Slovis CM: Electrolyte Disorders; in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 8. St. Louis, Mosby, Inc., 2014, (Ch) 125: p 1636-53.

Read More

• LITFL: QT Interval
• LITFL: Hypercalcemia
• LITFL: Hypercalcemia

Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter: @srrezaie)