DESCRIPTION
- Hypocalcemia is defined as a total plasma calcium level <8.7 mg/dL:
- Ionized calcium may be normal and, therefore, have no clinical manifestations.
- Normal total serum calcium concentrations are 8.7–10.5 mg/dL.
ETIOLOGY
- Incidence in the general population is 0.6%.
- Mechanism:
- From either increased loss of calcium from the circulation or decreased entry into the circulation
- Intravascular calcium circulates in 3 forms:
- Bound to proteins (mainly albumin): 45–50%
- Bound to complexing ions (citrate, phosphate, carbonate): 5–10%
- Ionized (free) calcium (physiologically active form): 45–50%
- Serum levels of calcium are primarily controlled by 3 hormones:
- Parathyroid hormone (PTH)
- Decrease in calcium levels leads to an increase in PTH secretion (increasing bone resorption, renal absorption, intestinal absorption, urinary phosphate excretion).
- Vitamin D (1,25-dihydroxyvitamin D):
- Decrease in calcium level activates vitamin D (increasing bone resorption and intestinal absorption).
- Calcitonin:
- Causes a direct inhibition of bone resorption with increased calcium levels
- Hypoalbuminemia—the most common cause:
- Each 1 g/dL decrease in serum albumin decreases protein-bound serum calcium by 0.8 mg/dL.
- Ionized (free) calcium levels do not change.
Pediatric Considerations
- Children have higher values of normal calcium (9.2–11 mg/dL).
- Neonatal hypocalcemia: Total serum calcium concentrations <7.5 mg/dL or serum-ionized calcium levels <4 mg/dL
- Symptoms of hypocalcemia in infancy:
- Hyperactivity, jitteriness
- Tachypnea
- Apneic spells with cyanosis
- Vomiting
DIAGNOSIS
SIGNS AND SYMPTOMS
- Occur when ionized calcium <3.2 mg/dL
- Dependent upon absolute calcium concentration and rate at which it falls
- Neuromuscular:
- Paresthesias
- Hyperreflexia
- Muscle spasm
- Tetany:
- Neuromuscular irritability
- Uncommon unless ionized calcium <4.3 mg/dL
- Latent tetany
- Chvostek sign (finger taps of parotid gland over the facial nerve causes facial muscle spasm)
- Trousseau signs (an inflated blood pressure cuff over the arm causes carpopedal spasm)
- Laryngeal stridor
- Seizures
- Choreoathetosis
- Cardiovascular:
- Dysrhythmias:
- Torsades de pointes
- Heart block
- Hypotension
- Impaired contractility (heart failure)
- ECG changes:
- Bradycardia
- QT and ST prolongation
- T-wave abnormalities
- Psychiatric:
- Irritability/anxiety
- Psychosis
- Depression
- Confusion
- Delusions
- Chorea
- Parkinsonisms
- Ocular:
- Papilledema
- Cataracts
- May occur in patients with acute onset hypocalcemia
ESSENTIAL WORKUP
Serum-ionized calcium level confirms the diagnosis
DIAGNOSIS TESTS & NTERPRETATION
Lab
- Arterial blood gas:
- Change from normal pH of 0.1 U equals a reciprocal change in ionized calcium of ∼1.7 mg/dL.
- Serum albumin
- Electrolytes, BUN/creatinine, glucose
- Magnesium
- Phosphate:
- Increase in phosphate associated with hypoparathyroidism
- Decrease in phosphate associated with vitamin D deficiency
- PTH:
- Very high levels of PTH associated with pseudohypoparathyroidism
- High levels of PTH associated with vitamin D deficiency
- Low levels of PTH associated with hypoparathyroidism
- Serum calcidiol or calcitriol
Diagnostic Procedures/Surgery
ECG:
- Prolonged QT interval
- Heart block
DIFFERENTIAL DIAGNOSIS
- Impaired PTH action or secretion:
- Parathyroid or thyroid surgery or radical neck surgery and/or irradiation for head and neck cancer
- Autoimmune disease (typically presents in childhood)
- Congenital hypoparathyroidism
- Neonatal secondary to maternal hyperparathyroidism
- Pseudohypoparathyroidism (resistance to PTH)
- Infiltrative (amyloidosis, sarcoidosis, metastases, iron overload)
- HIV infection
- Impaired vitamin D synthesis or action:
- Nutritional malabsorption or poor intake
- Renal disease
- Pronounced hypophosphatemia
- Sepsis or severe burns:
- Impaired secretion of PTH and calcitriol
- End-organ resistance to the action of PTH
- Calcium complex formation or sequestration:
- Hyperphosphatemia
- Ethylene glycol, ethylenediaminetetraacetic acid (EDTA), citrate (from transfusion)
- Pancreatitis, rhabdomyolysis
- Alkalosis (i.e., hyperventilation)
- Hypomagnesemia:
- Causes end-organ PTH resistance
- Decreased PTH secretion
- Seen in chronic and/or critical illness
- Must give magnesium to correct hypocalcemia
- Medications:
- Mithramycin, plicamycin, phosphate, calcitonin, bisphosphonates
- Phenobarbital, phenytoin
- Cisplatin
- Cadmium, colchicine
- Fluoride, citrate, PPI
- Malignancies:
- Prostate cancer
- Breast cancer
- Lung cancer
- Chondrosarcoma
- “Hungry bone syndrome”:
- After parathyroid removal
- Rapid accretion of calcium as bone is remineralized
TREATMENT
INITIAL STABILIZATION/THERAPY
ABCs:
- Establish IV catheter access.
- Cardiac monitor
ED TREATMENT/PROCEDURES
- Acute management:
- Treat symptomatic hypocalcemia as a medical emergency with parenteral calcium administration.
- Calcium IV bolus:
- Calcium gluconate 1–2 g in 50 mL of 5% dextrose
- Infuse over 20 min
- Faster IV rates can cause cardiac dysrhythmias
- Calcium salts are irritating to veins.
- IM calcium gluceptate or calcium gluconate if IV access not available
- Bolus dose increases ionized calcium for only 1–2 hr, therefore, must be followed by an infusion
- Calcium infusion:
- Calcium infusion rate: 0.5–1.5 mg/kg/hr
- Do not mix with bicarbonate or phosphate or precipitation of salts may form.
- Administer cautiously in patients taking digitalis—may initiate and exacerbate digitalis toxicity
- Response to therapy:
- Individual responses vary.
- Monitor calcium concentrations q1–4h during therapy.
- Titrate treatment to symptoms or ECG changes.
- Consider hypomagnesemia if the patient fails to respond to calcium therapy—correct hypomagnesemia with Mg 2 g IVPB 10% solution over 10 min
- In the setting of acidosis, correct calcium 1st; alkalosis will further reduce ionized calcium.
- Side effects of IV calcium include: Nausea, vomiting, hypotension, and dysrhythmias
- Chronic management:
- Oral calcium supplementation
- 1.5–2 g/day of Calcium in div. doses. May need up to 4 g/day in patients with malabsorption.
- Vitamin D:
- Enhances intestinal absorption
- Initiate with calcium supplementation—alone not sufficient to restore calcium levels.
- 600 IU for ages 19–50 yr
- 600 IU for ages 51–70 yr
- 800 IU for ages 71 and older
- Multivitamins contain variable amounts of vitamin D
- Vitamin D preparations:
- Ergocalciferol: 125 μg/day
- Dihydrotachysterol: 100–400 μg/day
- Calcifediol: 50–200 μg/day
- Calcitriol: 0.25–0.5 μg/day: Rapid onset (preferred). Most active metabolite of vitamin D
Pregnancy Considerations
Calcitriol requirements may double or triple toward the end of pregnancy.
MEDICATION
- IV calcium:
- Calcium chloride: 1 g in 10 mL (1 g = 360 mg [13.6 mEq] elemental calcium)
- Calcium gluceptate (IV/IM): 1 g in 5 mL (1 g = 90 mg [4.5 mEq] elemental calcium)
- Calcium gluconate: 1 g in 10 mL (1 g = 90 mg [4.5 mEq] elemental calcium)
- Oral calcium:
- Calcium carbonate: 350–1,500 mg tablets (1 g = 400 mg)
- Calcium citrate: 950 mg tablets (1 g = 211 mg elemental calcium)
- Calcium glubionate: 18 g/5 mL of syrup (1 g = 65 mg elemental calcium)
- Calcium gluconate: 500—1,000 mg tablets (1 g = 90 mg elemental calcium)
- Calcium lactate: 350–1,000 mg tablets (1 g = 130 mg elemental calcium)
Pediatric Considerations
- Initial calcium bolus with 10% calcium gluconate should be 9–18 mg of elemental calcium/kg or 1–2 mL/kg not to exceed 5 mL in premature infants or 10 mL in term infants.
- Calcitriol dose in children ranges from 0.1–3 μg/day.
- MISCELLANEOUS:
- Calcium content of common foods:
- Milk or yogurt, 8 oz = 300 mg
- Cheddar cheese, 1 oz = 200 mg
- Calcium-fortified cereal, 1 cup = 300 mg
- Calcium-fortified orange juice, 1 cup = 270 mg
- Shrimp, 3 oz = 50 mg
- Peanuts = 130 mg
- Orange = 50 mg
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