Hypo (Ca)

Also See Other bone disorder (Labs)Hyperparathyroidism

THE CALL

Overview

  • Serum calcium concentration that is below the normal physiologic range
    • Normal range
      • Total serum calcium: 8.4-10.2 mg/dL [2.10-2.60 mmol/L]
      • Ionized serum calcium: 4.65 to 5.25 mg/dL [1.16-1.31 mmol/L]
         
  • Can present as asymptomatic lab finding or life threatening metabolic disturbance
    • Acute hypocalcemia can result in severe Sx
      • Requires rapid admission to hospital & correction
    • When hypocalcemia develops slowly pts are often asymptomatic
       
  • Classic Sx of acute hypocalcemia:
    • Neuromuscular excitability: muscle twitches (Chvostek's sign)
    • Severe cases can progress to tetany, seizures, carpopedal spasms, dysrhythmias
       
  • Longstanding hypocalcemia assoc with:
    • Neuropsych Sx (eg, depression)
    • Cataracts
    • Incr ICP (rare)
    • May not necessarily present with neuromuscular Sx.

Mechanism

  • Serum calcium concentration is regulated by parathyroid hormone (PTH) & vitamin D on kidneys, bones, GI tract
  • Extracellular Ca concentrations important for normal fxn of muscles, nerves
  • Development of neuromuscular excitability depends on both
    • Absolute Ca concentration
    • Rate of descent (acute vs chronic)
      • Rapid falls in Ca often assoc w/ Sx (eg, after parathyroid adenoma removal)
  • Gradual descent of serum calcium concentration
    • Can be asymptomatic
    • Often diagnosis made from incidental finding

Etiology

  • Most common cause is vitamin D deficiency
    • Usually secondary to hypoparathyroidism
    • Chronic renal failure
  • Lab artifact (interaction of albumin protein chain and calcium assay)
    • Normal ionized Ca with decreased total Ca
    • Must correct for hypoalbuminemia
    • Ionized Ca still accurate despite hypoalbuminemia (ionized calcium independent of albumin levels)
  • Hypoparathyroidism secondary to
    • Post-Op
    • Autoimmune
    • Polyglandular autoimmune syndrome type I
  • Critically ill & postsurgical pts
    • Incidence approaches 80%
  • Sepsis & severe burns
    • Also assoc w/ clinically important hypocalcemia
    • D/t impaired secretion of PTH coupled w/ reduced calcitriol production
  • Acid-Base disturbance
    • Acidosis reducing binding of albumin to Ca
    • Alkalosis enhances binding of albumin to Ca
    • In setting of marked acidosis or alkalosis clinical decision making should be based on ionized Ca levels
  • Renal tubular acidosis
  • Renal failure
    • Impairment of calcitriol synthesis: decr intestinal Ca absorption & hypocalcemia
  • Vitamin D deficiency secondary to
    • Hypoparathyroidism
    • Chronic renal failure
  • Hypomagnesemia induced hypocalcemia
    • Mg depletion can cause hypocalcemia by producing PTH resistance
    • Mg & Ca must both be repleted before hypocalcemia resolves
  • Hyperphosphatemia
    • Secondary to incr phosphate intake in setting of acute renal failure
    • Secondary to incr phosphate production in setting of tumor lysis syndrome
  • Pancreatitis
    • Hypocalcemia can complicate severe pancreatitis (Ca soaps precipitation in abd cavity)
  • Massive blood transfusions
    • Symptomatic hypocalcemia during transfusion of citrated blood or plasma rare
    • Normally, citrate rapidly metabolized in liver & kidney
    • Significant fall in ionized Ca occurs when
      • Citrate metabolism impaired d/t hepatic or renal failure OR
      • Large quantities of citrate given rapidly (ie, during massive blood transfusion)
  • Medication Induced
    • Bisphophonate: causes important hypocalcemia, esp if renal dysfxn or hypoparathyroidism present
    • Chelation therapy: citrate (used to inhibit coagulation in banked blood or plasma, lactate, sodium EDTA) chelate Ca in serum, which reduces ionized Ca levels but not serum total Ca concentrations
    • Cinacalcet: control secondary hyperparathyroidism of renal failure; can induce hypocalcemia from inhibition of PTH release
    • Cisplatin induced: causes hypomagnesemia; induces hypoparathyroidism & hypocalcemia
    • Foscarnet induced: complexes ionized Ca resulting in hypocalcemia

History/Symptoms

  • Muscle twitching, spasms
  • Tingling, paresthesias, numbness
  • Carpopedal spasms
  • Can progress to tetany, seizures, dysrhythmias
  • Neuropsychiatric
    • Depression
    • Anxiety
  • Poor eye sight (not specific)

Physical Exam/Signs

  • Neurologic
    • Trousseau's sign: 94% specificity
    • Chvostek's sign: unreliable bedside discriminator (29% false-neg rate)
    • Incr ICP (rare)
  • HEENT
    • Longstanding leads to cataracts
  • Musculoskeletal
    • Tetany, spasms, hyperactive reflexes
    • Severe, long-standing can have bone deformation
  • Cardiovascular
    • Dysrhythmias

Diagnosis

  • Labs/Tests
    • Measure total & ionized Ca (w/ serum albumin)
      • 50% bound to albumin
      • Only ionized is biologically important
      • Serum Ca "corrected" to a reference albumin concentration of 40 g/L
        • For every 1 g/L of albumin above or below this value, Ca adjusted by decr or incr by 0.02 mmol/L
    • Magnesium and phosphourous levels
    • PTH levels
      • True hypocalcemia: high PTH (normal parathyroid response)
      • Hypoparathyroidism: PTH low to normal with hypocalcemia
      • Vitamin D deficiency or Ca malabsorption: high PTH in presence of normal renal function
  • Imaging
    • Usually imaging is not indicated unless other etiologies (eg, tumor) is suspected
       
  • Other Tests/Criteria
    • ECG
      • QT interval prolongation by incr of ST segment duration
      • T-wave inversion
      • Sinus bradycardia, heart block
      • Dysrhythmias can occur secondary to hypocalcemia or if Ca correction is too rapid

Differential Diagnosis

  • Acute renal failure
  • Electrolyte abnormalities
    • Hyperphosphatemia
    • Hypomagnesemia
  • Metabolic alkalosis
  • Hyperparathyroidism
  • Acute pancreatitis

Management

  1. Initial/Prep/Goals
    • ABCs, treat underlying condition if feasible
    • Hypocalcemia can usually be managed when underlying etiology is diagnosed and treated
  2. Correct hypomagnesemia
  3. Tx underlying cause
  • Mild (< 6 mg/dL), asymptomatic
    • Oral supplement
      • Calcium carbonate 1250 mg PO tid or qid is a good starting point (= 500 mg elemental calcium/tab)
      • Calcium lactogluconate (Liquid Calcium┬«) 20 mg/mL elemental calcium, 500 mg PO/NG/J-tube tid or qid
      • Consider starting vitamin D (400 units PO daily) or an active metabolite like calcitriol, depending on the suspected etiology.
      • PO calcium is best given between meals (otherwise binds phosphate).
    • If NPO: calcium gluconate 1 - 2 g IV over 2h
       
  • Moderate (< 6 mg/dL),+/- symptomatic
    • If phosphate < 2 mmol/L:
      • Calcium gluconate 3 - 4 g IV 50 mL D5W IV over 10 min, repeat PRN; decrease dose if phosphate > 2 mmol/L.
    • Usual MAX daily dose is 15 g calcium gluconate, max infusion rate of 4 g/h.
       
    • Avoid concurrent phosphate administration
    • Caution w/ concurrent digoxin use
       
  • Severe (< 6 mg/dL) + symptomatic (neuromuscular, cardiovascular)
    • Correct phosphate PRN, be +++ cautious with digoxin.
    • Calcium gluconate 10%, 10 mL (1 amp) IV over 10 - 20 min, repeat x 2 - 3. Consider starting a continuous infusion of calcium gluconate 5.6 mg calcium gluconate/kg/h (= 0.5 mg Ca/kg/h).
    • Repeat ionized calcium 4h post-infusion and PRN.
       
    • Avoid concurrent phosphate administration
    • Caution w/ concurrent digoxin use

Disposition

  1. Admit all symptomatic pts
    • Those w/ acute pancreatitis
    • Severe underlying dz
    • Moderate-severe CHF on Digoxin
       
  2. Asymptomatic pts w/ corrected serum calcium < 7.5 mg/dL [< 1.9 mmol/L] may develop serious complications
    • Admission should be considered
    • Oral replacement may be sufficient
       
  3. Admit pts if
    • Ionized Ca level < 3.5 mg/dL [0.88 mmol/L]
    • Unable to increase Ca level w/ IV boluses
 

Admission Order Set

1. Admit to:
2. Diagnosis: Hypocalcemia
3. Condition:
4. Vital Signs: q4h. Call physician if BP >160/90, <90/60; P >120, <50; R>25, <10; T >38.5┬░C.
5. Activity: Up ad lib
6. Nursing: Inputs and outputs.
7. Diet: No added salt diet.
8. Special Medications:

Symptomatic Hypocalcemia:
-Calcium chloride, 10% (270 mg calcium/10 mL vial), give 5-10 mL slowly over 10 min or dilute in 50-100 mL of D5W and infuse over 20 min, repeat q20-30 min if symptomatic, or hourly if asymptomatic. Correct hyperphosphatemia before hypocalcemia OR
-Calcium gluconate, 20 mL of 10% solution IV (2 vials)(90 mg calcium/10 mL vial) infused over 10-15 min, followed by 60 mL of calcium gluconate in 500 cc of D5W (1 mg/mL) at 0.5-2.0 mg/kg/h.

Chronic Hypocalcemia:
-Calcium carbonate with vitamin D (Oscal-D) 1-2 tab PO tid OR
-Calcium carbonate (Oscal) 1-2 tab PO tid OR
-Calcium citrate (Citracal) 1 tab PO q8h or Tums 1-2 tabs PO with meals.
-Vitamin D2 (Ergocalciferol) 1 tab PO qdOR
-Calcitriol (Rocaltrol) 0.25 mcg PO qd, titrate up to 0.5-2.0 mcg qid.
-Docusate sodium (Colace) 1 tab PO bid.

9. Extras: CXR, ECG.
10. Labs: chem 7&12, phosphate, Mg. 24h urine calcium, potassium, phosphate, magnesium.