How do I diagnose and treat hypocalcemia and hypercalcemia?

Correcting Calcium: Diagnosis and Management of Hypocalcemia and Hypercalcemia

Hypocalcemia Correction

Acute Symptomatic Hypocalcemia

For symptomatic hypocalcemia (tetany, seizures, laryngospasm, cardiac arrhythmias), administer calcium chloride 10 mL of 10% solution (270 mg elemental calcium) intravenously over 2-5 minutes with continuous ECG monitoring. 1

• Calcium chloride is strongly preferred over calcium gluconate because it delivers 3 times more elemental calcium per volume (270 mg vs 90 mg per 10 mL of 10% solution). 1
• Administer via central line when possible to avoid severe tissue necrosis if extravasation occurs. 1
• Monitor ECG continuously during administration for arrhythmias and QT interval changes. 1
• Never administer calcium through the same IV line as sodium bicarbonate due to precipitation risk. 1

Critical First Step: Correct Magnesium

Before calcium replacement can be effective, you must check and correct hypomagnesemia—present in 28% of hypocalcemic patients—because hypocalcemia cannot be adequately treated without adequate magnesium levels. 1

• Administer magnesium sulfate 1-2 g IV bolus immediately for symptomatic patients with concurrent hypomagnesemia. 1
• Hypomagnesemia causes hypocalcemia through two mechanisms: impaired PTH secretion and end-organ PTH resistance. 1
• Calcium supplementation alone will fail without magnesium correction. 1

Special Clinical Scenarios

In massive transfusion, monitor ionized calcium continuously because each unit of blood products contains approximately 3 g of citrate that binds calcium. 1

• Citrate metabolism may be impaired by hypoperfusion, hypothermia, and hepatic insufficiency, requiring more aggressive calcium replacement. 1
• Hypocalcemia within the first 24 hours of critical bleeding predicts mortality with greater accuracy than fibrinogen, acidosis, or platelet count. 1

In tumor lysis syndrome with elevated phosphate, use extreme caution with calcium replacement due to risk of calcium-phosphate precipitation in tissues and kidneys. 1

• Administer calcium gluconate 50-100 mg/kg IV slowly with ECG monitoring only when symptomatic. 1

Chronic Hypocalcemia Management

Daily calcium carbonate 1-2 g three times daily plus vitamin D3 400-800 IU/day forms the foundation of chronic hypocalcemia treatment. 1

• Limit individual calcium doses to 500 mg elemental calcium to optimize absorption. 1
• Total elemental calcium intake (including dietary sources) should not exceed 2,000 mg/day. 1
• Calcium carbonate is preferred due to 40% elemental calcium content, low cost, and wide availability. 1

For patients with hypoparathyroidism or refractory cases, active vitamin D metabolites (calcitriol or alfacalcidol) are required and should be managed by an endocrinologist. 1

• Target serum calcium in the low-normal range (8.4-9.5 mg/dL) to avoid overcorrection. 1
• Avoid overcorrection, which can cause iatrogenic hypercalcemia, renal calculi, nephrocalcinosis, and renal failure. 1

Monitoring Requirements

• Measure pH-corrected ionized calcium, magnesium, PTH, and creatinine regularly during chronic treatment. 1
• In CKD patients, measure corrected total calcium and phosphorus at least every 3 months. 1
• Monitor urinary calcium excretion to detect hypercalciuria and prevent nephrocalcinosis. 1

CKD-Specific Considerations

In dialysis patients with hypocalcemia, adjust dialysate calcium concentration based on patient needs. 1

• Standard dialysate calcium of 2.5 mEq/L (1.25 mmol/L) permits use of calcium-based binders with minimal calcium loading. 1
• When calcium supply is needed, dialysate levels up to 3.5 mEq/L can be used safely. 1
• Do not use calcium-based phosphate binders when corrected serum calcium >10.2 mg/dL or plasma PTH <150 pg/mL on two consecutive measurements. 1
• Maintain calcium-phosphorus product <55 mg²/dL² to prevent vascular calcification. 1

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Hypercalcemia Correction

Immediate Management of Severe Hypercalcemia

Initiate aggressive IV normal saline hydration immediately, targeting urine output of 100-150 mL/hour, followed by IV zoledronic acid 4 mg infused over at least 15 minutes. 2

• Administer boluses of 250-500 mL crystalloids every 15 minutes until rehydration is achieved. 2
• Continue hydration to maintain diuresis >2.5 L/day in adults. 2
• Loop diuretics (furosemide) should only be added after complete volume repletion and only in patients with cardiac or renal insufficiency to prevent fluid overload. 2

Definitive Pharmacologic Treatment

Zoledronic acid 4 mg IV is the preferred bisphosphonate due to superior efficacy compared to pamidronate, normalizing calcium in 50% of patients by day 4. 2

• Infusion time is 15 minutes (vs 2 hours for pamidronate), offering significant practical advantages. 2
• Check serum creatinine before each dose; withhold if renal function deteriorates. 2
• For creatinine clearance <60 mL/min, dose adjustment is required. 2

For patients with impaired renal function (CrCl <60 mL/min), denosumab 120 mg subcutaneously is preferred due to lower rates of renal toxicity, though it carries higher risk of hypocalcemia. 2

• Provide calcium and vitamin D supplementation concurrently with denosumab. 2
• Baseline dental examination is mandatory before initiating either bisphosphonates or denosumab to prevent osteonecrosis of the jaw. 2

Etiology-Specific Treatment

For hypercalcemia due to granulomatous disease (sarcoidosis), vitamin D intoxication, or lymphoma, corticosteroids are the primary treatment. 2

• Prednisone 20-40 mg/day orally or methylprednisolone IV equivalent. 2
• Allow 3-6 months to demonstrate responsiveness before considering escalation. 2
• Target the lowest effective dose ≤10 mg/day to minimize toxicity. 2

Calcitonin 100 IU subcutaneously or intramuscularly provides rapid onset within hours but has limited efficacy and should be used only as a bridge until bisphosphonates take effect. 2

• Tachyphylaxis develops within 48 hours, limiting long-term utility. 2

Medication Management

Immediately discontinue all calcium-based phosphate binders, vitamin D analogs (calcitriol, paricalcitol), and calcium/vitamin D supplements. 2

• Stop thiazide diuretics, lithium, and any other medications that can elevate calcium. 2
• Review medication list for drugs that affect calcium metabolism. 2

Severe Refractory Hypercalcemia

For severe hypercalcemia complicated by renal insufficiency or oliguria, hemodialysis with calcium-free or low-calcium dialysate (1.25-1.50 mmol/L) is necessary. 2

• Hemodialysis effectively removes calcium through diffusive therapy. 2
• This is reserved for patients who do not respond to standard measures. 2

Monitoring During Acute Treatment

• Measure ionized calcium every 4-6 hours during the first 48-72 hours, then twice daily until stable. 2
• Monitor serum calcium, creatinine, and electrolytes (potassium, magnesium) every 6-12 hours during the acute phase. 2
• Obtain repeat complete blood count after 24-48 hours of adequate rehydration to confirm normalization of hemoconcentration. 2

Target Calcium Levels

Aim for corrected calcium of 8.4-9.5 mg/dL, preferably at the lower end of this range to reduce risk of complications while avoiding overcorrection. 2

• Maintain calcium-phosphorus product <55 mg²/dL² to prevent soft tissue calcification. 2

Critical Pitfalls to Avoid

• Do not rely on corrected calcium instead of ionized calcium, as it can lead to inaccurate diagnosis. 3
• Avoid NSAIDs and intravenous contrast media in patients with renal impairment. 2
• Do not restrict calcium intake excessively without medical supervision, as this can worsen bone disease. 2
• Measure BOTH 25-hydroxyvitamin D AND 1,25-dihydroxyvitamin D together for diagnostic accuracy in PTH-independent hypercalcemia. 3