Treatment of hypocalcaemia

Treatment depends on the primary disease and severity of symptoms:

• treatment usually commences with administration of calcium
  • form of calcium and the need for additional agents such as vitamin D depends on the acuity and severity of the hypocalcaemia as well as the underlying cause
    
    
• patients with symptomatic hypocalcaemia or those with corrected serum levels of 1·875 mmol/L (7·5 mg/dL) or less
  • treated with parenteral calcium until the symptoms cease or the calcium concentration rises above this point
  • in acute symptomatic hypocalcaemia there is a rapid decrease in serum calcium associated with signs and symptoms of hypocalcaemia
    • generally occurs at concentrations of 1·875 mmol/L (7·5 mg/dL) or less
    • infusion of 15 mg/kg (3·75 mmol/kg) of elemental calcium over 4-6 h will increase the total serum calcium by 0·5-0·75 mmol/L (2-3 mg/dL)
      
      
• chronic, asymptomatic mild hypocalcaemia is usually treated with oral calcium supplements
  • note that calcium binds with dietary phosphate and oxalate to form insoluble and unabsorbable salts - therefore calcium is better absorbed when taken between meals
  • patients with little or no PTH are usually treated with calcium and vitamin D
    • treatment of chronic hypocalcaemia requires oral calcium to increase availability for intestinal absorption and, often, vitamin D to enhance absorption
      • teatment usually begins at a daily dose of 1000-2600 mg (250-650 mmol) divided into two, three, or four doses and taken between meals, the dose of oral calcium is adjusted according to follow-up calcium levels
      • calcium carbonate is widely available in tablets containing 500-750 mg calcium
        • calcium citrate is well absorbed - however it enhances aluminium absorption and may predispose to aluminium toxicity in patients with renal insufficiency
        • calcium phosphate should be avoided because it may exacerbate hyperphosphataemia and metastatic calcification
      • when the hypocalcaemia is associated with insufficient vitamin D, replacement of the vitamin D is usually required
        • oral 1,25(OH)2D3 acts rapidly since it requires no further metabolism to function
          • 0·5-1·0 µg daily is generally sufficient - however in extreme cases (e.g. immediately post-parathyroidectomy) larger doses may be required
          • vitamins D2 or D3 are adequate to avoid nutritional deficiency at doses of 400 units a day or for malabsorption at higher doses (50 000-100 000 units)
            • vitamins D2 and D3 require conversion to 1,25(OH)2D3 for maximal biological action
              • therefore they are not suitable if the 25- or 1a-hydroxylation are impaired
                • causes of impairement of 25- or 1a-hydroxylation include liver and renal failure, hypoparathyroidism, and vitamin-D-dependent rickets type 1
            • in contrast to the rapid elimination of 1,25(OH)2D3, vitamins D2 and D3 may continue to function for several weeks, potentially resulting in hypervitaminosis D

Notes:

• general principles apply to the management of a hypocalcaemic patient
  • magnesium level should be checked and, if low, corrected
  • in a setting of sepsis or renal failure, metabolic acidosis may accompany hypocalcaemia and calcium must be replaced before the acidosis is corrected
    • calcium and hydrogen ions compete for protein-binding sites
      • therefore an increase in pH with alkali therapy will increase the binding sites for calcium
        • leads to a rapid fall in ionised calcium, potentially resulting in cardiac arrest - therefore calcium levels should be corrected first
    • sodium bicarbonate and calcium salts must be infused in separate lines to avoid precipitation of calcium carbonate
  • patients on digoxin should be monitored carefully because administration of calcium may potentiate digitalis toxicity and cause death
  • patients with hypoparathyroidism have decreased renal calcium reabsorption
    • oral calcium supplementation, especially with concomitant vitamin D administration, increases the filtered load of calcium and results in hypercalciuria with possible nephrocalcinosis or nephrolithiasis
    • in this situation serum calcium levels should be maintained at the lower limit of normal with 24 h urinary calcium excretion kept below 1 mmol/kg (4 mg/kg)
      • thiazide diuretics increase renal calcium reabsorption and may be useful in patients with hypoparathyroidism
  • hyperphosphataemia may accompany hypocalcaemia in patients with hypoparathyroidism, renal disease, rhabdomyolysis, and tumour lysis
    • in this situationm, to avoid soft-tissue calcium phosphate precipitation, calcium supplementation should be accompanied by oral phosphorus binders
      • also, if possible, calcium supplementation should be delayed until the serum phosphate has fallen below 1·5 mmol/L (6 mg/dL)

Reference:

• (1) Bushinksy DA, Monk RD. Calcium. Lancet 1998; 352 (9124): 306-311.