Sandbox hypocalcemia

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

Main article: Hypocalcemia

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. 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).
• The normal range of ionized Ca⁺⁺ concentration in adults is 4.65–5.28 mg/dL (1.16–1.32 mmol/L).
• 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).
• Adjustment of total serum calcium concentration for changes in plasma albumin level:

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

• Hypoparathyroidism following parathyroidectomy or irradiation
• Vitamin D deficiency due to malabsorption, low dietary intake, or insufficient exposure to ultraviolet light
• Autoimmune disorders (e.g., activating antibodies against calcium-sensing receptors, autoimmune polyendocrine syndrome type 1)

Rare

• Parathyroid hormone resistance
• Vitamin D resistance
• Hypomagnesemia
• Osteoblastic metastasis
• Autosomal dominant hypocalcemia

Miscellaneous

• Excess phosphate absorption caused by enemas
• Massive phosphate release caused by tumor lysis syndrome, rhabdomyolysis, or crush injury
• Foscarnet
• Bisphosphonates
• Massive transfusion of large volumes of citrate-containing blood
• Acute pancreatitis
• Gadolinium salts in contrast media
• Critical illness
• Hungry bone syndrome
• Fanconi syndrome

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

NO Proceed to Complete Diagnostic Approach

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: ❑ 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: ❑ 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: 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: ❑ 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.

↓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

• Calcitriol is the optimal modality in hypocalcemic patients associated with hypoparathyroidism, pseudohypoparathyroidism, and chronic kidney disease, as these states are characterized by a deficiency of 1,25(OH)₂D.

• Dose: 0.25–0.50 mcg (capsule) or 1 mcg/mL (oral solution)

• 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.
• After treating vitamin D deficiency, recheck 25(OH)D in 12–14 weeks.

Dos

• Serum concentration of total calcium should be adjusted for changes in plasma albumin level:

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

• Do not administer intravenous calcium gluconate in mild, chronic hypocalcemic state. IV therapy should be reserved for severe, symptomatic hypocalcemia.
• Calcium ions from the intravenous solutions may precipitate phosphate or bicarbonate and form insoluble salts. If phosphate or bicarbonate administration is necessary, a separate IV line in another limb should be established.
• Hypocalcemia associated with hyperphosphatemia (as in tumor lysis syndrome or massive trauma) should not be treated with calcium until hyperphosphatemia is corrected. Hemodialysis may be considered in this setting.

References