CORE EM: Hypercalcemia

Originally published at CoreEM.net, dedicated to bringing Emergency Providers all things core content Emergency Medicine available to anyone, anywhere, anytime. Reposted with permission.

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Written by: Anand Swaminathan, MD

Background

• Exists in two states
  • Free ionized form (approx. 50%)
  • Bound to other molecules (primarily albumin)
• Ionized Ca²⁺ concentration is inversely proportional to pH

  

  Calcium Metabolism – what-when-how.com

• Ca²⁺ Metabolism
  • Vitamin D: aids in intestinal Ca²⁺absorption
  • Parathyroid hormone (PTH)
    • Increases renal Ca²⁺reabsorption
    • Arbitrates Vit D stimulated intestinal Ca²⁺absorption
    • Mobilizes Ca²⁺ from bone
  •  Calcitonin
    • PTH antagonist
    • Inhibits renal Ca²⁺ reabsorption
    • Inhibits Ca²⁺ mobilization from bone
• Ca²⁺ plays numerous critical roles including muscle contraction (skeletal and smooth), clotting factor activity and nerve conduction

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
  • 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 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.

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