Approach Considerations
The treatment of hypocalcemia depends on the cause, the severity, the presence of symptoms, and how rapidly the hypocalcemia developed. [39] Hypocalcemia generally results from another disease process. Awareness of the diseases that cause hypocalcemia is important so that the cause can be identified and managed early.
Most hypocalcemia cases are mild, and patients require only supportive treatment and further laboratory evaluation. On occasion, severe hypocalcemia may result in seizures, tetany, refractory hypotension, or arrhythmias that require a more aggressive approach. To effectively treat hypocalcemia in patients with concurrent magnesium deficiency, hypomagnesemia should be corrected first.
In the emergency department, magnesium and calcium (in their many different forms) are the only medications necessary to treat hypocalcemic emergencies. The consulting endocrinologist may choose to prescribe any of the various vitamin D supplements depending on laboratory workup findings, and oral calcium supplementation for outpatient therapy.
Hypocalcemia is found in over half the patients admitted to intensive care units (ICUs). [47, 35] Studies in critically ill patients have yielded conflicting results, with some suggesting that hypocalcemia is likely a marker of disease severity, and that calcium values usually normalize spontaneously with resolution of the primary disease process. [48, 35] Indeed, it has been posited that low levels in critical illness may be protective and attempted correction may be harmful. [48]
Crespi and Alcock cite evidence that the hypocalcemia seen in severe viral infections, including COVID-19, may represent a beneficial host defense rather than a pathology. According to this hypothesis, viruses increase the intracellular level of calcium in order to enhance their replication, so the body's reduction in calcium levels interferes with viral calcium needs in infected cells. Nevertheless, while mild hypocalcemia may be protective, severe hypocalcemia imposes undue stresses and calcium supplementation should be beneficial in such cases. [49]
In contrast, other studies have concluded that both moderate and mild hypocalcemia are associated with increased mortality, whereas mild hypercalcemia is associated with lower mortality. [47] One large retrospective study found that calcium supplementation during the ICU stay improved 28-day survival in critically ill adult patients. [50] In hospitalized patients with COVID-19 who have hypocalcemia, di Filippo et al suggest that replacing calcium may be reasonable. In addition, for COVID-19 patients with high-risk vitamin D deficiency, vitamin D replacement may be considered, as it might protect against the development of hypocalcemia, among other possible benefits. [51]
Mild Hypocalcemia
In patients whose symptoms are not life-threatening, confirm ionized hypocalcemia and check other pertinent laboratory tests. If the cause is not obvious, send a blood sample for a parathyroid hormone (PTH) level. Depending on the PTH level, the endocrinologist may do further laboratory workup, particularly an evaluation of vitamin D levels.
Oral repletion may be indicated for outpatient treatment; patients requiring intravenous (IV) repletion should be admitted. The recommended dose of elemental calcium in healthy adults is 1-3 g/d.)
Severe Hypocalcemia
Supportive treatment (ie, IV fluid replacement, oxygen, monitoring) often is required prior to directed treatment of hypocalcemia. Be aware that severe hypocalcemia often is associated with other life-threatening conditions. Check ionized calcium and other pertinent screening laboratory tests.
IV replacement is recommended in symptomatic or severe hypocalcemia with cardiac arrhythmias or tetany. Doses of 100-300 mg of elemental calcium (10 mL of calcium gluconate contains 90 mg elemental calcium; 10 mL of calcium chloride contains 272 mg elemental calcium) in 50-100 mL of 5% dextrose in water (D5W) should be given over 5-10 minutes. This dosage raises the ionized level to 0.5-1.5 mmol and should last 1-2 hours. Caution should be used when giving calcium chloride intravenously.
Calcium chloride 10% solution delivers higher amounts of calcium and is advantageous when rapid correction is needed, but it should be administered via central venous access. Calcium infusion drips should be started at 0.5 mg/kg/hr and increased to 2 mg/kg/hr as needed, with an arterial line placed for frequent measurement of ionized calcium.
Measure serum calcium every 4-6 hours to maintain serum calcium levels at 8-9 mg/dL. If low albumin is also present, ionized calcium should be monitored. Admit the patient for further evaluation and observation.
Patients with cardiac arrhythmias or patients on digoxin therapy need continuous electrocardiographic (ECG) monitoring during calcium replacement because calcium potentiates digitalis toxicity. Identify and treat the cause of hypocalcemia and taper the infusion.
Start oral calcium and vitamin D treatment early. Patients with postparathyroidectomy hungry bone disease, especially those with osteitis fibrosa cystica, can present with a dramatic picture of hypocalcemia. Treatment with calcium and vitamin D for 1-2 days prior to parathyroid surgery may help prevent the development of severe hypocalcemia.
Chronic Hypocalcemia
Treatment of chronic hypocalcemia depends on the cause of the disorder. Patients with hypoparathyroidism and pseudohypoparathyroidism can be managed initially with oral calcium supplements. The hypercalcemic effects of thiazide diuretics may offer some additional benefits.
In patients with severe hypoparathyroidism, vitamin D treatment may be required; however, remember that PTH deficiency impairs the conversion of vitamin D to calcitriol. Therefore, the most efficient treatment is the addition of 0.5-2 mcg of calcitriol or 1-alpha-hydroxyvitamin D3. For patients with permanent hypoparathyroidism, the goals of therapy are to relieve symptoms, raise and maintain the serum calcium concentration in the low- normal range ( 8.0- 8.5 mg/dL), and avoid hypercalciuria.
Recombinant human parathyroid hormone (rhPTH, Natpara) is commercially available in the United States and could be used as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism. Its approval was based on the REPLACE trial, in which 48 of 90 patients (53%) receiving rhPTH, but only one of 44 patients in the placebo group (2%), achieved > 50% reduction of daily PO calcium and vitamin D supplementation from baseline while maintaining serum calcium above baseline concentrations and less than upper limits of normal at week 24 (P< 0.0001). [52]
Although most patients on hemodialysis will be hypercalcemic, those who have undergone parathyroidectomy may have considerable difficulty in maintaining appropriate calcium levels. These levels can be managed several ways. First, oral calcium supplements should be provided. They must be given between meals; otherwise, they will primarily act as phosphate binders. Active vitamin D (calcitriol) enhances the absorption of calcium. Finally, the calcium in the dialysate bath can be increased.
Nutritional vitamin D deficiency from lack of sunlight exposure or poor oral intake of vitamin D responds to treatment with ultraviolet light or sunlight exposure. [53] Treat nutritional rickets with vitamin D2. Oral calcium preparations containing 1-2 g of elemental calcium per day can treat patients with a calcium deficiency. For infants who are breastfed, adjust the dose to 30 mg/kg/day. Calcitriol may be used, but it has the disadvantages of a higher price and the possibility of producing hypervitaminosis D with hypercalcemia.
Diet
An increase in dietary calcium to greater than 1 g/day is an important part of the treatment of chronic hypocalcemia, particularly in cases of vitamin D deficiency. In patients with hypocalcemia and chronic kidney disease, the dietary intake of phosphate should be lowered to 400-800 mg/day to prevent hyperphosphatemia.
Patients with chronic hypocalcemia should be educated about the early symptoms of hypocalcemia, such as paresthesias and muscle weakness, so that they can obtain care before more severe symptoms develop.
Consultations and Long-Term Monitoring
Given the variety of causes that hypocalcemia may have, multiple consultations may be necessary. Depending on the clinical situation, consultations may include one or more of the following:
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Internist
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Endocrinologist
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Intensivist
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Surgeon
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Oncologist
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Nephrologist
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Dietitian
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Toxicologist
After determining the cause of hypocalcemia, direct the treatment at preventing further episodes of hypocalcemia and avoiding the complications of chronic hypocalcemia. Although uncommon, outpatient evaluation by an endocrinologist or an internist is appropriate in some patients who present to the ED with hypocalcemia. Patients with diseases that predispose them to the development of hypocalcemia should have scheduled appointments with an outpatient provider.
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Electrocardiogram (ECG) findings in severe hypocalcemia.
