Hypocalcemia, Emergency Medicine

Basics

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.

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 & Interpretation

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 Ī¼g/day
  - Dihydrotachysterol: 100-400 Ī¼g/day
  - Calcifediol: 50-200 Ī¼g/day
  - Calcitriol: 0.25-0.5 Ī¼g/day: Rapid onset (preferred). Most active metabolite of vitamin D

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)

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 Ī¼g/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

Follow-Up

Disposition

Admission Criteria

Symptomatic or severe ionized hypocalcemia (<3.2 mg/dL)
Continuous IV calcium preparations necessary to maintain calcium levels

Discharge Criteria

Asymptomatic hypocalcemia
Ionized calcium >3.2 mg/dL in healthy patients with no comorbid illness

Followup Recommendations

Close follow-up with an endocrinologist may be necessary for impaired PTH or vitamin D action or synthesis.

Pearls and Pitfalls

Hypocalcemia has many causes
Treatment of hypocalcemia varies with its severity and underlying cause
Patients who are severely symptomatic require rapid correction with IV calcium therapy
To effectively treat hypocalcemia with concurrent magnesium deficiency, magnesium must first be normalized

Additional Reading

Al-Azem H, Khan AA. Hypoparathyroidism. Best Pract Res Clin Endocrinol Metab. 2012;26(4):517-522.
Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcemia. BMJ. 2008;336(7656):1298-1302.
Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930.
Liamis G, Milionis HJ, Elisaf M. A review of drug-induced hypocalcemia. J Bone Miner Metab. 2009;27(6):635-642.

Codes

ICD9

775.4 Hypocalcemia and hypomagnesemia of newborn
275.41 Hypocalcemia
275.5 Hungry bone syndrome

ICD10

E83.51 Hypocalcemia
E83.81 Hungry bone syndrome
P71.1 Other neonatal hypocalcemia

SNOMED

5291005 Hypocalcemia (disorder)
268846006 Neonatal hypocalcemia (disorder)
237883001 Hungry bones syndrome
237884007 drug-induced hypocalcemia (disorder)

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