Hypocalcemia

Michelle Sergel (p

Rosen & Barkins 5-Minute Emergency Medicine Consult

4th Edition Jeffrey J. Schaider, MD Roger M. Barkin, MD Stephen R. Hayden, MD Richard E. Wolfe, MD Adam Z. Barkin, MD, MPH Philip Shayne, MD, FACEP Peter Rosen, MD

Lippincott Williams&Wilkins, Philapdelphia, USA. 2011. Basics

Description

Hypocalcemia is defined as a total plasma calcium level <8.7 mg/dL: o Ionized calcium may be normal and, therefore, have no clinical manifestations occurring. Normal total serum calcium concentrations are 8.710.5 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 o Intravascular calcium circulates in 3 forms: Bound to proteins (mainly albumin): 4550% Bound to complexing ions (citrate, phosphate, carbonate): 510% Ionized (free) calcium (physiologically active form): 4550% o 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). o Vitamin D (1,25-dihydroxyvitamin D): Decrease in calcium level activates vitamin D (increasing bone resorption and intestinal absorption). o Calcitonin: Causes a direct inhibition of bone resorption with increased calcium levels Hypoalbuminemiathe most common cause: o Each g/dL decrease in serum albumin decreases protein-bound serum calcium by 0.8 mg/dL. o Will not change ionized (free) calcium

Pediatric Considerations

Children have higher values of normal calcium (9.211 mg/dL). Neonatal hypocalcemia: Total serum calcium concentrations <7.0 mg/dL or serumionized calcium levels <4.4 mg/dL Symptoms of hypocalcemia in infancy: o Hyperactivity, jitteriness o Tachypnea o Apneic spells with cyanosis o Vomiting

Diagnosis
Signs and Symptoms

Occur when ionized calcium <3.2 mg/dL Depends on both the absolute and the rate of fall in calcium concentration Neuromuscular: o Paresthesias o Hyperreflexia o Muscle spasm o Tetany:

Neuromuscular irritability Uncommon unless ionized calcium <4.3 mg/dL o Latent tetany (Chvostek and Trousseau signs) o Laryngeal stridor o Seizures o Choreoathetosis Cardiovascular: o Dysrhythmias: Torsades de pointes Heart block o Hypotension o Impaired contractility (CHF) o ECG changes: Bradycardia QT and ST prolongation T-wave abnormalities Psychiatric: o Irritability/anxiety o Psychosis o Depression o Confusion o Delusions o Chorea o Parkinsonisms Ocular: o Papilledema o Cataracts o May occur in patients with acute onset hypocalcemia

Essential Workup
Serum-ionized calcium level confirms the diagnosis

Diagnostic Tests & Interpretation

Lab

Arterial blood gas: o Change from normal pH of 0.1 units equals a reciprocal change in ionized calcium of approximately 1.7 mg/dL. Serum albumin Electrolytes, BUN/creatinine, glucose Magnesium Phosphate: o Increase in phosphate associated with hypoparathyroidism o 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
o o o

Diagnostic Procedures/Surgery ECG:

Prolonged QT interval Heart block

Differential Diagnosis

Impaired PTH action or secretion: o Parathyroid or thyroid surgery or radical neck surgery and/or irradiation for head and neck cancer o Autoimmune disease (typically presents in childhood) o Congenital hypoparathyroidism o Neonatal secondary to maternal hyperparathyroidism o Pseudohypoparathyroidism (resistance to PTH) o Infiltrative (amyloidosis, sarcoidosis, metastases, iron overload) o HIV infection Impaired vitamin D synthesis or action: o Nutritional malabsorption or poor intake o Renal disease o Pronounced hypophosphatemia Sepsis or severe burns: o Impaired secretion of PTH and calcitriol o End-organ resistance to the action of PTH Calcium complex formation or sequestration: o Hyperphosphatemia o Ethylene glycol, ethylenediaminetetraacetic acid (EDTA), citrate (from transfusion) o Pancreatitis, rhabdomyolysis o Alkalosis (ie, hyperventilation) Hypomagnesemia: o Causes end-organ PTH resistance o Decreased PTH secretion o Seen in chronic and/or critical illness o Must give magnesium to correct hypocalcemia Medications: o Mithramycin, plicamycin, phosphate, calcitonin, bisphosphonates o Phenobarbital, phenytoin o Cisplatin

Cadmium, colchicine Fluoride, citrate Malignancies: o Prostate cancer o Breast cancer o Lung cancer o Chondrosarcoma Hungry bone syndrome: o After parathyroid removal o Rapid accretion of calcium as bone is remineralized

o o

Treatment
Initial Stabilization/Therapy
ABCs:

Establish IV catheter access. Cardiac monitor

ED Treatment/Procedures

Acute management: o Treat symptomatic hypocalcemia as a medical emergency with parenteral calcium administration. o Calcium IV bolus: Calcium gluconate 12 g in 50 mL of 5% dextrose Infuse over 1020 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 12 hr, therefore, must be followed by an infusion o Calcium infusion: Calcium infusion rate: 0.51.5 mg/kg/h Do not mix with bicarbonate or phosphate or precipitation of salts may form. Administer cautiously in patients taking digitalismay initiate and exacerbate digitalis toxicity o Response to therapy: Individual responses vary. Monitor calcium concentrations q14h during therapy. Titrate treatment to symptoms or ECG changes.

Consider hypomagnesemia if the patient fails to respond to calcium therapycorrect 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: o Oral calcium supplementation o 14 g/d of elemental calcium in divided doses o Vitamin D: Enhances intestinal absorption Initiate with calcium supplementationalone not sufficient to restore calcium levels. 200 IU for ages 1950 yr 400 IU for ages 5170 yr 600800 for ages >70 yr Multivitamins contain 400 IU of vitamin D o Vitamin D preparations: Ergocalciferol: 125 g/d Dihydrotachysterol: 100400 g/d Calcifediol: 50200 g/d Calcitriol: 0.250.2 g/d: 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: o Calcium chloride: 1 g in 10 mL (1 g = 360 mg [13.6 mEq] elemental calcium) o Calcium gluceptate (IV/IM): 1 g in 5 mL (1 g = 90 mg [4.5 mEq] elemental calcium) o Calcium gluconate: 1 g in 10 mL (1 g = 90 mg [4.5 mEq] elemental calcium) Oral calcium: o Calcium carbonate: 350- to 1,500-mg tablets (1 g = 400 mg) o Calcium citrate: 950-mg tablets (1 g = 211 mg elemental calcium) o Calcium glubionate: 18 g/5 mL of syrup (1 g = 65 mg elemental calcium) o Calcium gluconate: 500- to 1,000-mg tablets (1 g = 90 mg elemental calcium) o Calcium lactate: 350- to 1,000-mg tablets (1 g = 130 mg elemental calcium)

Pediatric Considerations

Initial calcium bolus with 10% calcium gluconate should be 918 mg of elemental calcium/kg or 12 mL/kg not to exceed 5 mL in premature infants or 10 mL in term infants. Calcitriol dose in children ranges from 0.13 g/d. MISCELLANEOUS: o 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 co-morbid illness

Follow-up 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 that 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

Horak HA, Poumand R. Endocrine myopathies. Neurol Clin. 2000;18(1):203213. Kapoor M, Chan Z. Fluid and electrolyte abnormalities. Crit Care Clin. 2001;17(3):503 529. Riggs JE. Neurologic manifestations of electrolyte disturbances. Neurol Clin. 2002;20(1):227239, vii. Thakker R. Hypocalcemia: Pathogenesis, differential diagnosis, and management. In Favus M, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, American Society of Bone and Mineral Research; 2006:6:213. Thomas MK, Demay MB. Vitamin D deficiency and disorders of vitamin D metabolism. Endocrinol Metab Clin North Am. 2000;29(3):611627, viii.

See Also (Topic, Algorithm, Electronic Media Element)

Hypercalcemia Hyperparathyroidism Hypoparathyroidism

Hypocalcemia
Michelle Sergel

Basics
Description

Hypocalcemia is defined as a total plasma calcium level <8.7 mg/dL: o Ionized calcium may be normal and, therefore, have no clinical manifestations occurring. Normal total serum calcium concentrations are 8.710.5 mg/dL.

Etiology

Incidence in the general population is 0.6%. Mechanism: o From either increased loss of calcium from the circulation or decreased entry into the circulation o Intravascular calcium circulates in 3 forms: Bound to proteins (mainly albumin): 4550% Bound to complexing ions (citrate, phosphate, carbonate): 510% Ionized (free) calcium (physiologically active form): 4550% o 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). o Vitamin D (1,25-dihydroxyvitamin D): Decrease in calcium level activates vitamin D (increasing bone resorption and intestinal absorption). o Calcitonin: Causes a direct inhibition of bone resorption with increased calcium levels Hypoalbuminemiathe most common cause: o Each g/dL decrease in serum albumin decreases protein-bound serum calcium by 0.8 mg/dL. o Will not change ionized (free) calcium

Pediatric Considerations

Children have higher values of normal calcium (9.211 mg/dL). Neonatal hypocalcemia: Total serum calcium concentrations <7.0 mg/dL or serumionized calcium levels <4.4 mg/dL Symptoms of hypocalcemia in infancy: o Hyperactivity, jitteriness o Tachypnea o Apneic spells with cyanosis o Vomiting

Diagnosis
Signs and Symptoms

Occur when ionized calcium <3.2 mg/dL Depends on both the absolute and the rate of fall in calcium concentration Neuromuscular: o Paresthesias o Hyperreflexia o Muscle spasm o Tetany: Neuromuscular irritability Uncommon unless ionized calcium <4.3 mg/dL o Latent tetany (Chvostek and Trousseau signs) o Laryngeal stridor o Seizures o Choreoathetosis Cardiovascular: o Dysrhythmias:

Torsades de pointes Heart block o Hypotension o Impaired contractility (CHF) o ECG changes: Bradycardia QT and ST prolongation T-wave abnormalities Psychiatric: o Irritability/anxiety o Psychosis o Depression o Confusion o Delusions o Chorea o Parkinsonisms Ocular: o Papilledema o Cataracts o May occur in patients with acute onset hypocalcemia

Essential Workup
Serum-ionized calcium level confirms the diagnosis

Diagnostic Tests & Interpretation

Lab

Arterial blood gas: o Change from normal pH of 0.1 units equals a reciprocal change in ionized calcium of approximately 1.7 mg/dL. Serum albumin Electrolytes, BUN/creatinine, glucose Magnesium Phosphate: o Increase in phosphate associated with hypoparathyroidism o Decrease in phosphate associated with vitamin D deficiency PTH: o Very high levels of PTH associated with pseudohypoparathyroidism o High levels of PTH associated with vitamin D deficiency o 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: o Parathyroid or thyroid surgery or radical neck surgery and/or irradiation for head and neck cancer o Autoimmune disease (typically presents in childhood) o Congenital hypoparathyroidism o Neonatal secondary to maternal hyperparathyroidism o Pseudohypoparathyroidism (resistance to PTH) o Infiltrative (amyloidosis, sarcoidosis, metastases, iron overload) o HIV infection Impaired vitamin D synthesis or action: o Nutritional malabsorption or poor intake o Renal disease o Pronounced hypophosphatemia Sepsis or severe burns: o Impaired secretion of PTH and calcitriol o End-organ resistance to the action of PTH Calcium complex formation or sequestration: o Hyperphosphatemia o Ethylene glycol, ethylenediaminetetraacetic acid (EDTA), citrate (from transfusion) o Pancreatitis, rhabdomyolysis o Alkalosis (ie, hyperventilation) Hypomagnesemia: o Causes end-organ PTH resistance o Decreased PTH secretion o Seen in chronic and/or critical illness o Must give magnesium to correct hypocalcemia Medications: o Mithramycin, plicamycin, phosphate, calcitonin, bisphosphonates o Phenobarbital, phenytoin o Cisplatin o Cadmium, colchicine o Fluoride, citrate Malignancies: o Prostate cancer o Breast cancer o Lung cancer o Chondrosarcoma Hungry bone syndrome:

o o

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: o Treat symptomatic hypocalcemia as a medical emergency with parenteral calcium administration. o Calcium IV bolus: Calcium gluconate 12 g in 50 mL of 5% dextrose Infuse over 1020 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 12 hr, therefore, must be followed by an infusion o Calcium infusion: Calcium infusion rate: 0.51.5 mg/kg/h Do not mix with bicarbonate or phosphate or precipitation of salts may form. Administer cautiously in patients taking digitalismay initiate and exacerbate digitalis toxicity o Response to therapy: Individual responses vary. Monitor calcium concentrations q14h during therapy. Titrate treatment to symptoms or ECG changes. Consider hypomagnesemia if the patient fails to respond to calcium therapycorrect 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: o Oral calcium supplementation

o o

14 g/d of elemental calcium in divided doses Vitamin D: Enhances intestinal absorption Initiate with calcium supplementationalone not sufficient to restore calcium levels. 200 IU for ages 1950 yr 400 IU for ages 5170 yr 600800 for ages >70 yr Multivitamins contain 400 IU of vitamin D Vitamin D preparations: Ergocalciferol: 125 g/d Dihydrotachysterol: 100400 g/d Calcifediol: 50200 g/d Calcitriol: 0.250.2 g/d: 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: o Calcium chloride: 1 g in 10 mL (1 g = 360 mg [13.6 mEq] elemental calcium) o Calcium gluceptate (IV/IM): 1 g in 5 mL (1 g = 90 mg [4.5 mEq] elemental calcium) o Calcium gluconate: 1 g in 10 mL (1 g = 90 mg [4.5 mEq] elemental calcium) Oral calcium: o Calcium carbonate: 350- to 1,500-mg tablets (1 g = 400 mg) o Calcium citrate: 950-mg tablets (1 g = 211 mg elemental calcium) o Calcium glubionate: 18 g/5 mL of syrup (1 g = 65 mg elemental calcium) o Calcium gluconate: 500- to 1,000-mg tablets (1 g = 90 mg elemental calcium) o Calcium lactate: 350- to 1,000-mg tablets (1 g = 130 mg elemental calcium)

Pediatric Considerations

Initial calcium bolus with 10% calcium gluconate should be 918 mg of elemental calcium/kg or 12 mL/kg not to exceed 5 mL in premature infants or 10 mL in term infants. Calcitriol dose in children ranges from 0.13 g/d. MISCELLANEOUS: o 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 co-morbid illness

Follow-up 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 that 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

Horak HA, Poumand R. Endocrine myopathies. Neurol Clin. 2000;18(1):203213. Kapoor M, Chan Z. Fluid and electrolyte abnormalities. Crit Care Clin. 2001;17(3):503 529. Riggs JE. Neurologic manifestations of electrolyte disturbances. Neurol Clin. 2002;20(1):227239, vii. Thakker R. Hypocalcemia: Pathogenesis, differential diagnosis, and management. In Favus M, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, American Society of Bone and Mineral Research; 2006:6:213.

Thomas MK, Demay MB. Vitamin D deficiency and disorders of vitamin D metabolism. Endocrinol Metab Clin North Am. 2000;29(3):611627, viii.

See Also (Topic, Algorithm, Electronic Media Element)

Hypercalcemia Hyperparathyroidism Hypoparathyroidism