Sandbox hypocalcemia

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Hypocalcemia
Resident Survival Guide
Diagnostic Criteria
Causes
Focused Initial Rapid Evaluation
Complete Diagnostic Approach
Dos
Don'ts

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]; Vidit Bhargava, M.B.B.S [3]; Ammu Susheela, M.D. [4]

Overview

Hypocalcemia, defined as a total serum calcium level (adjusted for albumin) of < 8.4 mg/dL (2.1 mmol/L) or an ionized Ca++ level of < 4.6 mg/dL (1.15 mmol/L), may manifest as an asymptomatic laboratory abnormality or a life-threatening condition requiring emergent correction.[1] Common causes of hypocalcemia include hypoalbuminemia, advanced chronic kidney disease, hypoparathyroidism, and vitamin D deficiency. Patients with acute hypocalcemia usually experience symptoms of neuromuscular excitability (e.g., circumoral tingling and muscle cramping) and should receive intravenous calcium gluconate. Chronic hypocalcemia may present as fatigue, weakness, neuropsychiatric disturbances, papilledema, and cataracts. In conjunction with oral calcium supplementation, treatment of longstanding hypocalcemia should be directed toward the underlying cause.

Diagnostic Criteria

  • The normal range of serum total calcium concentration in adults is 8.6–10.3 mg/dL (2.15–2.57 mmol/L).[2][3]
  • The normal range of ionized Ca++ concentration in adults is 4.65–5.28 mg/dL (1.16–1.32 mmol/L).[4][5]
  • Hypocalcemia is defined as a total serum calcium level (adjusted for albumin) of < 8.4 mg/dL (2.1 mmol/L) or an ionized Ca++ level of < 4.6 mg/dL (1.15 mmol/L).[6]
  • Adjustment of total serum calcium concentration for changes in plasma albumin level:[7]
Adjusted total calcium in mg/dL = Total calcium in mg/dL + 0.8 * (4 - Albumin in g/dL)
Adjusted total calcium in mmol/L = Total calcium in mmol/L + 0.02 * (40 - Albumin in g/L)

Causes

Common

Rare

Miscellaneous

FIRE: Focused Initial Rapid Evaluation

Focused Initial Rapid Evaluation (FIRE) should be undertaken to identify patients requiring urgent intervention.

Abbreviations: amp, ampule; D5W, 5% dextrose in water; ECG, electrocardiography; IV, intravenous; QTc, corrected QT interval.

 
 
 
 

Symptomatic or Severe Hypocalcemia (< 7.6 mg/dL)?


Clinical features of acute hypocalcemia

  • Altered mental status
  • Bronchospasm or laryngeal spasm (laryngismus stridulus)
  • Carpopedal spasm
  • Chvostek sign
  • Circumoral and extremity paresthesia or tingling
  • Hyperreflexia
  • Hypotension
  • Irritability, depression, or psychosis
  • Muscle twitching and cramping
  • Papilledema
  • QTc prolongation
  • Trousseau sign of latent tetany
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
YES

  • Establish IV line and ECG monitoring
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Emergent Therapy


Intravenous calcium gluconate

  • Loading dose
  • Preparation: 1–2 amps of 10% calcium gluconate in 50–100 ml of D5W
  • Administration: slow IV infusion over 10–20 minutes
  • Maintenance dose
  • Preparation: 10 amps of 10% calcium gluconate in 1000 ml of D5W or NS
  • Administration: 50 ml/hour (0.3–1.0 g/kg/hr)
  • Goal: titrate to lower end of the calcium reference range
  • 10 ml/kg infusion over 4–6 hours raises calcium by 1.2–2.0 mg/dL

Additional considerations

  • ± Correct hypomagnesemia
  • ± Dialysis if hyperphosphatemia is present
  • Initiate oral calcium supplementation
  • Proceed to Complete Diagnostic Approach

Complete Diagnostic Approach

Characterize the symptoms:[8]

❑ Neuromuscular excitability

Muscle twitching.
Tingling.
Numbness.
Muscle spasms.
Tetany.
Carpopedal spam.
Seizures.
Paresthesia.
❑ Perioral numbness.
Laryngospasm.

❑ Neuropsychiatric symptoms.
Cataract formation.
❑ Raised intracranial pressure.
Prolonged QT intervals.
Cardiac dyasarhythmia.

Heart failure.
 
 
 
 
 
 
Obtain a detailed history: [8]


❑ Age.
Congenital defects of growth, mental retardation or hearing loss.
❑ Previous surgical history of neck surgery.
❑ List of medications.

❑ Family history of hypocalcemia.
 
 
 
 
 
 
 
Examine the patient:[10]

Vital signs
Blood pressure
Heart rate

Tachycardia (suggestive of heart failure)
Bradycardia (suggestive of heart block or bradyarrhythmias)

Pulses

❑ Strength
Bruits

Skin
❑ Surgical marks on neck.
Heart
Heart sounds

S3 (suggestive of heart failure)
S4 (associated with conditions that increase the stiffness of the ventricle)

Musculoskeletal system
Chvostek sign

❑ Tapping on the cheek 2cm anterior to the earlobe, below the zygomatic process, overlying the facial nerve produces twitching of the upper lip.

Trousseau sign

❑ Application of the inflated blood pressure cuff over the systolic pressure for 3 minutes produces carpopedal spasm
 
 
 
 
 
 
Order labs and tests:[10]

❑ Basic Investigations

❑ Serum calcium (Corrected for albumin)
Magnesium.
Phosphate.
Electrolytes.
Alkaline phosphatase.
Creatinine.
Parathyroid hormone.
25-hydroxy vitamin D.
Complete blood count.
❑ Serum pH.

❑ Further Investigations.

❑ 24-hour urinary phosphate, calcium, Magnesium and creatinine.
❑ Ionized calcium.
❑ Renal ultrasonography to asses for nephrolithiasis.
❑ 1,25-dihydroxyvitamin D.
DNA sequencing to exclude genetic mutations.
Biochemistry in first degree family members.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low calcium, high phosphate and low parathyroid hormone indicate hypoparathyroidism. Goal of treatment is raise calcium levels and remove the symptoms. 1 to 1.5 g of elemental calcium is given orally as calcium carbonate or calcium citrate. 0.25 mcg of calcitriol is also given as twice daily with weekly increments to achieve low- normal serum calcium.
 
Family history of hypocalcemia can indicate the autosomal dominant hypocalcemia. Asymptomatic patients require no treatment.
 
Low calcium, low phosphate and low vitamin D levels may be due to vitamin D deficiency. 50,000 international units of vitamin D2 or D3 is given weekly for 6-8 weeks.
 
Symptomatic hypocalcemia with high blood urea nitrogen and serum creatinine indicates chronic kidney disease. Treatment includes oral calcium and active form of vitamin D
 
Hypercatabollic state(trauma, tumor lysis syndrome) requires the correction of phosphate levels before you correct the calcium level. Symptomatic hypocalcemia requires hemodialysis.
 
Pseudohypoparathyroidism requires 0.25 mcg of calcitriol for twice daily.
 
 
 
 
 

Laboratory Differential Diagnosis of Hypocalcemia

Abbreviations: ADHP, autosomal dominant hypoparathyroidism; CKD, chronic kidney disease; Cr, creatinine; Def, deficiency; HP, hyperphosphatemia; HPTH, hypoparathyroidism; PHP, pseudohypoparathyroidism; VDDR, vitamin D-dependent rickets.[11]

 
 
 
 
 
 
 
 
 
 
 
 
 
↓Ca
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
↑PTH
 
 
 
 
 
 
 
 
 
 
 
 
 
 
↔↓PTH
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
↑PO4
 
 
 
 
 
 
 
↔↓PO4
 
 
 
 
 
 
↔Mg
 
 
 
↓Mg
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
↑Cr
 
 
 
↔Cr
 
↓25(OH)D
 
 
 
↔↑25(OH)D
 
 
 
HPTH
 
 
 
ADHP or Mg def
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CKD
 
 
 
PHP or HP
 
Vitamin D def↓1,25(OH)2D
 
 
 
↑1,25(OH)2D
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Type I VDDR
 
 
 
Type II VDDR
 
 
 
 
 
 
 
 
 

Treatment of Chronic Hypocalcemia

  • In conjunction with oral calcium supplementation, treatment of longstanding hypocalcemia should be directed toward the underlying cause.

Oral Calcium Supplementation

  • Dose: 500–1000 mg of elemental calcium per day (maximum: 2000 mg QD)
  • Goal: correction of serum calcium concentration to the low-normal range
  • Check calcium levels once or twice per week
  • Urinary calcium excretion should be monitored after the initiation of therapy. Frank hypercalciuria (> 300 mg/day) is associated with impaired kidney function and development of nephrocalcinosis.

Vitamin D Supplementation

  • Dose: 0.25–0.50 mcg (capsule) or 1 mcg/mL (oral solution)[12]
  • Ergocalciferol is the preferred form in hypocalcemic patients associated with vitamin D malabsorption.
  • Dose: 50,000 to 200,000 IU daily concomitantly with calcium 4g, six times per day.[13]
  • After treating vitamin D deficiency, recheck 25(OH)D in 12–14 weeks.[14]

Dos

  • Serum concentration of total calcium should be adjusted for changes in plasma albumin level:[15]
Adjusted total calcium in mg/dL = Total calcium in mg/dL + 0.8 * (4 - Albumin in g/dL)
Adjusted total calcium in mmol/L = Total calcium in mmol/L + 0.02 * (40 - Albumin in g/L)
  • For hypoparathyroidism, urinary and serum calcium and serum phosphate are measured weekly until stable levels are achieved.
  • Intravenous calcium should be administered with caution in hypocalcemic patients receiving digoxin due to its membrane-sensitizing effects on excitable tissues.

Don'ts

References

  1. Taal, Maarten (2012). Brenner & Rector's the kidney. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1416061939.
  2. Nordin, B. E. C. (1976). Calcium, phosphate, and magnesium metabolism : clinical physiology and diagnostic procedures. Edinburgh New York New York: Churchill Livingstone Distributed in the United States of America by Longman. ISBN 978-0443011887.
  3. Goldman, Lee (2016). Goldman-Cecil medicine. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455750177.
  4. Burtis, Carl (2015). Tietz fundamentals of clinical chemistry and molecular diagnostics. St. Louis: Elsevier/Saunders. ISBN 978-1455741656.
  5. Rosen, Clifford (2013). Diseases and disorders of mineral metabolism. Iowa, U.S.A: Wiley-Blackwell. ISBN 978-1118453889.
  6. Taal, Maarten (2012). Brenner & Rector's the kidney. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1416061939.
  7. "Correcting the calcium". British Medical Journal. 1 (6061): 598. 1977-03-05. ISSN 0007-1447. PMC 1605322. PMID 843828.
  8. 8.0 8.1 8.2 Cooper MS, Gittoes NJ (2008). "Diagnosis and management of hypocalcaemia". BMJ. 336 (7656): 1298–302. doi:10.1136/bmj.39582.589433.BE. PMC 2413335. PMID 18535072 PMID: 18535072 Check |pmid= value (help).
  9. Fong J, Khan A (2012). "Hypocalcemia: updates in diagnosis and management for primary care". Can Fam Physician. 58 (2): 158–62. PMC 3279267. PMID 22439169.
  10. 10.0 10.1 "Uptodate diagnosis of hypocalcemia".
  11. Ferri, Fred (2015). Ferri's clinical advisor 2015 : 5 books in 1. Philadelphia, PA: Elsevier/Mosby. ISBN 978-0323083751.
  12. "DailyMed - ROCALTROL- calcitriol capsule, gelatin coated". Retrieved 2015-03-31.
  13. "DailyMed - VITAMIN D - ergocalciferol capsule". Retrieved 2015-03-31.
  14. Ferri, Fred (2015). Ferri's clinical advisor 2015 : 5 books in 1. Philadelphia, PA: Elsevier/Mosby. ISBN 978-0323083751.
  15. "Correcting the calcium". British Medical Journal. 1 (6061): 598. 1977-03-05. ISSN 0007-1447. PMC 1605322. PMID 843828.