Rosen & Barkin's 5-Minute Emergency Medicine Consult (360 page)

• Carbon Monoxide Toxicity
  
• Decompression Sickness
  

CODES

• 958.0 Air embolism
  
• 986 Toxic effect of carbon monoxide
  
• 993.3 Caisson disease
  

BASICS

• Severity depends on serum calcium level and rate of increase
  
• 0.1–1% of patients on routine screening
  
• Most cases mild (<12 mg/dL) and asymptomatic
  
• Hypercalcemic crisis, usually >14 mg/dL, causes serious signs and symptoms
  
• Calcium in bloodstream in 3 forms:
  
  • Ionized: 45%
    
  • Bound to protein (primarily albumin): 40%
    
  • Bound to other anions: 15%
    
• Ionized calcium—only physiologically active form
  

• Primary hyperparathyroidism
  
• Malignancy
  
• Miscellaneous
  

DIAGNOSIS

• Neurologic:
  
  • Headache
    
  • Fatigue, lethargy
    
  • Weakness
    
  • Difficulty concentrating
    
  • Confusion
    
  • Depression, paranoia
    
• Renal:
  
  • Polyuria, polydipsia
    
  • Complaints related to oliguric renal failure
    
  • Chronic, complaints related to:
    
    • Renal calculi
      
    • Nephrocalcinosis
      
    • Interstitial nephritis
      
• GI:
  
  • Anorexia
    
  • Nausea, vomiting
    
  • Abdominal pain
    
  • Constipation
    
  • Chronic, complaints related to:
    
    • Peptic ulcer disease
      
    • Pancreatitis
      
• Dermatologic:
  
  • Pruritus
    
  • Mnemonic: “Stones, Bones, Groans, Thrones and Psychiatric Overtones,” “bones” refers to bone pain and “thrones” refers to polyuria.
    

• Failure to thrive
  
• Slow development
  
• Mental retardation may ensue
  

• Neurologic:
  
  • Irritability
    
  • Lethargy
    
  • Stupor
    
  • Coma
    
  • Hyporeflexia
    
• Cardiovascular:
  
  • Hypotension, if severely volume depleted, or HTN
    
  • Sinus bradycardia
    
  • Cardiac arrest with severe hypercalcemia (rare)
    
• Renal:
  
  • Signs of dehydration
    
• Dermatologic:
  
  • Band keratopathy
    
  • Ectopic calcification
    

• Characteristic facies: Pug nose, fat nasal bridge, “cupid’s bow” upper lip
  
• Hypotonia
  

• Ionized and total serum calcium levels, albumin levels:
  
  • Normal total calcium level is <10.5 mg/dL
    
  • Must correct for calcium that is protein bound, primarily to albumin
    
  • Corrected total calcium (mg/dL) = measured total calcium (mg/dL) + 0.8 × [4.0 – albumin concentration (g/dL)]
    
• Electrolytes, BUN/creatinine, glucose
  
  • Possible oliguric renal failure
    
• ECG:
  
  • Shortening of QT interval
    
  • Prolongation of PR interval
    
  • QRS widening
    
  • Accentuated side effects of digoxin
    
  • Sinus bradycardia, bundle branch block, AV block, cardiac arrest with severe hypercalcemia (rare)
    
  • Can cause Osborn J-wave at the end of QRS complex that is usually associated with hypothermia
    

• Phosphate
  
• Protein
  
• Urinalysis
  
• Parathyroid hormone (PTH) level:
  
  • If elevated or high normal, likely primary hyperparathyroidism.
    
  • If <20 pg/mL, consider testing PTH-related peptide and vitamin D metabolites.
    
• Vitamin D metabolites, if suspected
  
  • 25-hydroxy vitamin D (calcidiol):
    
    • If elevated, consider exogenous source (i.e., meds, vitamins, supplements).
      
  • 1,25-dihydroxy vitamin D (calcitriol):
    
    • If elevated, consider lymphoma or sarcoid
      
• Digoxin level, if taking
  
• Thyroid function tests
  

• CT head for altered mental status
  
• Chest x-ray and workup for occult malignancy, if no other cause for hypercalcemia
  

Parathyroidectomy:

• For primary hyperparathyroidism resulting in symptomatic or severe hypercalcemia
  
• Some patients require urgent parathyroidectomy.
  

• Primary hyperparathyroidism:
  
  • Most common cause among outpatients
    
  • Parathyroid adenoma 80%; hyperplasia 15%; carcinoma 5%
    
  • Usually mild, <11.2 mg/dL
    
  • Patients can be asymptomatic or have chronically elevated calcium
    
  • Increased bone resorption, relative decrease in calcium excretion, increased intestinal calcium absorption
    
• Malignancy:
  
  • Most common cause in hospitalized patients
    
  • Usually a rapid rise in serum calcium
    
  • Patients are more often symptomatic
    
  • Higher serum calcium concentrations
    
  • Most common paraneoplastic complication of cancer
    
  • Common tumors causing hypercalcemia: Breast, lung, colon, stomach, cervix, uterus, ovary, kidney, bladder, head and neck, multiple myeloma, and lymphoma
    
  • Most commonly from production of PTH-related protein with similar actions
    
  • May result from production of other bone-resorbing substances by tumor
    
  • May result from local effects of osteolytic skeletal metastasis
    
• Miscellaneous:
  
  • Hypercalcemia associated with granulomatous diseases
    
  • Excessive calcium supplements
    
  • Thiazide diuretics causing increased renal reabsorption
    
  • Familial hypocalciuric hypercalcemia
    
  • Acute vitamin A intoxication
    
  • Exogenous vitamin D intake
    
  • Milk-alkali syndrome from excessive ingestion of calcium and nonabsorbable antacids, such as milk or calcium carbonate
    
  • Long-term lithium therapy
    
  • Renal transplantation
    
  • Hyperthyroidism
    
  • Acute tubular necrosis
    

Differential diagnosis: Differences from adults:

• Primary hyperparathyroidism:
  
  • Less common than in adults
    
• Infantile hypercalcemia:
  
  • Uncertain cause
    
  • Possibly hypersensitivity and in utero excessive exposure to vitamin D
    
• Immobilization hypercalcemia:
  
  • Typically adolescent who is growing rapidly
    
  • Prolonged immobilization, especially in traction, leads to hypercalciuria and then hypercalcemia
    
  • Presumably from increased bone resorption with decreased or arrested bone mineralization
    

TREATMENT

Routine stabilization techniques

• ABCs, IV access, oxygen, cardiac monitor
  
• 0.9% NS 1 L bolus (20 mL/kg) for hypotension or severe dehydration
  
• Naloxone, thiamine, D
  ₅₀
  W (or stat serum glucose measurement) for altered mental status
  

• General:
  
  • Immediate therapy for severe hypercalcemia (corrected total >14 mg/dL) regardless of symptoms, or for symptomatic hypercalcemia
    
  • Asymptomatic, mild hypercalcemia does not require emergency treatment
    
• Restoration of IV volume:
  
  • Isotonic saline:
    
    • 200–300 mL/hr adjusted to maintain urine output 100–150 mL/hr
      
  • Often need 2–5 L/day
    
  • Bedside vigilance necessary to prevent fluid overload
    
  • Correct other electrolyte abnormalities
    
  • Cardiovascular status of patient may necessitate central venous pressure monitoring to adjust fluid administration rates
    
• Renal elimination:
  
  • After volume expansion and if needed to avoid overload, administer loop diuretics (furosemide)
    
  • Avoid thiazide diuretics
    
  • May need peritoneal or hemodialysis against a low calcium dialysate in renal failure
    
• Inhibition of osteoclastic activity:
  
  • Reduce mobilization of calcium from bone
    
  • Administer drug therapy when corrected calcium level >14 mg/dL or signs or symptoms
    
  • First-line drug therapy:
    
    • Bisphosphonates: Pamidronate (more potent and possibly less toxic), etidronate
      
    • Calcitonin: Rapid onset but modest decrease in levels
      
  • Other potential drug therapy:
    
    • Plicamycin: Efficacious but numerous side effects
      
    • Hydrocortisone: Especially useful with malignancies, granulomatous disorders, or vitamin D intoxication
      
  • Encourage ambulation in appropriate patients
    
• Treat underlying disorder:
  
  • Parathyroidectomy for primary hyperparathyroidism resulting in symptomatic or severe hypercalcemia
    
  • Discontinue medication if cause of hypercalcemia