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Hypocalcemia, Emergency Medicine

Basics

Description

- 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

- 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

- Hypotension - Impaired contractility (heart failure) - ECG changes: - Bradycardia - QT and ST prolongation - T-wave abnormalities

- Ocular: - Papilledema - Cataracts - May occur in patients with acute onset hypocalcemia

- 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

- Calcium complex formation or sequestration: - Hyperphosphatemia - Ethylene glycol, ethylenediaminetetraacetic acid (EDTA), citrate (from transfusion) - Pancreatitis, rhabdomyolysis - Alkalosis (i.e., hyperventilation)

- Malignancies: - Prostate cancer - Breast cancer - Lung cancer - Chondrosarcoma

- 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

- 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

- 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

  • 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 circulationIntravascular 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, jitterinessTachypneaApneic spells with cyanosisVomiting

Diagnosis

Signs and Symptoms

  • Occur when ionized calcium <3.2 mg/dL
  • Dependent upon absolute calcium concentration and rate at which it falls
  • Neuromuscular:ParesthesiasHyperreflexiaMuscle spasmTetany:Neuromuscular irritabilityUncommon unless ionized calcium <4.3 mg/dLLatent tetanyChvostek 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 stridorSeizuresChoreoathetosis
  • Cardiovascular:Dysrhythmias:Torsades de pointesHeart blockHypotensionImpaired contractility (heart failure)ECG changes:BradycardiaQT and ST prolongationT-wave abnormalities
  • Psychiatric:Irritability/anxietyPsychosisDepressionConfusionDelusionsChoreaParkinsonisms
  • Ocular:PapilledemaCataractsMay 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 hypoparathyroidismDecrease in phosphate associated with vitamin D deficiency
  • PTH:Very high levels of PTH associated with pseudohypoparathyroidismHigh levels of PTH associated with vitamin D deficiencyLow 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 cancerAutoimmune disease (typically presents in childhood)Congenital hypoparathyroidismNeonatal secondary to maternal hyperparathyroidismPseudohypoparathyroidism (resistance to PTH)Infiltrative (amyloidosis, sarcoidosis, metastases, iron overload)HIV infection
  • Impaired vitamin D synthesis or action:Nutritional malabsorption or poor intakeRenal diseasePronounced hypophosphatemia
  • Sepsis or severe burns:Impaired secretion of PTH and calcitriolEnd-organ resistance to the action of PTH
  • Calcium complex formation or sequestration:HyperphosphatemiaEthylene glycol, ethylenediaminetetraacetic acid (EDTA), citrate (from transfusion)Pancreatitis, rhabdomyolysisAlkalosis (i.e., hyperventilation)
  • Hypomagnesemia:Causes end-organ PTH resistanceDecreased PTH secretionSeen in chronic and/or critical illnessMust give magnesium to correct hypocalcemia
  • Medications:Mithramycin, plicamycin, phosphate, calcitonin, bisphosphonatesPhenobarbital, phenytoinCisplatinCadmium, colchicineFluoride, citrate, PPI
  • Malignancies:Prostate cancerBreast cancerLung cancerChondrosarcoma
  • "Hungry bone syndrome"¯:After parathyroid removalRapid 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% dextroseInfuse over 20 minFaster IV rates can cause cardiac dysrhythmiasCalcium salts are irritating to veins.IM calcium gluceptate or calcium gluconate if IV access not availableBolus dose increases ionized calcium for only 1-2 hr, therefore, must be followed by an infusionCalcium infusion:Calcium infusion rate: 0.5-1.5 mg/kg/hrDo not mix with bicarbonate or phosphate or precipitation of salts may form.Administer cautiously in patients taking digitalis-may initiate and exacerbate digitalis toxicityResponse 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 minIn 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 supplementation1.5-2 g/day of Calcium in div. doses. May need up to 4 g/day in patients with malabsorption.Vitamin D:Enhances intestinal absorptionInitiate with calcium supplementation-alone not sufficient to restore calcium levels.600 IU for ages 19-50 yr600 IU for ages 51-70 yr800 IU for ages 71 and olderMultivitamins contain variable amounts of vitamin DVitamin D preparations:Ergocalciferol: 125 Ī¼g/dayDihydrotachysterol: 100-400 Ī¼g/dayCalcifediol: 50-200 Ī¼g/dayCalcitriol: 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 mgCheddar cheese, 1 oz = 200 mgCalcium-fortified cereal, 1 cup = 300 mgCalcium-fortified orange juice, 1 cup = 270 mgShrimp, 3 oz = 50 mgPeanuts = 130 mgOrange = 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.

See Also (Topic, Algorithm, Electronic Media Element)

  • Hypercalcemia
  • Hyperparathyroidism
  • Hypoparathyroidism

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)