Workup and Management of Hypokalemia and Hypercalcemia
Hypokalemia Workup
Begin by measuring serum potassium and obtaining an ECG immediately to assess for life-threatening cardiac manifestations. 1
Classification and Risk Stratification
- Classify severity: mild (3.0-3.5 mEq/L), moderate (2.5-2.9 mEq/L), or severe (≤2.5 mEq/L) 1
- ECG changes indicating urgent treatment include ST depression, T wave flattening, prominent U waves, and ventricular arrhythmias 1
- Severe hypokalemia (≤2.5 mEq/L) carries life-threatening risk of ventricular arrhythmias, particularly in patients with cardiac disease 1
Essential Laboratory Workup
- Check serum magnesium first—this is the most common reason for treatment failure 1
- Measure serum creatinine and blood urea nitrogen to assess renal function 2
- Obtain arterial blood gas if metabolic alkalosis is suspected 3
- Review medication list for diuretics, laxatives, insulin, beta-agonists, and other potassium-depleting drugs 2
Identify the Underlying Cause
- Gastrointestinal losses: vomiting, diarrhea, nasogastric suction 2
- Renal losses: diuretic use (most common), hyperaldosteronism, renal tubular acidosis 2
- Transcellular shifts: insulin therapy, beta-agonist use, alkalosis 2
- Inadequate intake: rarely the sole cause unless combined with increased losses 2
Hypokalemia Management
Severe Hypokalemia (≤2.5 mEq/L) with Symptoms or ECG Changes
- Administer IV potassium in a monitored setting with continuous cardiac monitoring 1
- Standard IV replacement: 10-20 mEq/hour through peripheral line (maximum 40 mEq/L concentration) 2
- Rates exceeding 20 mEq/hour require central venous access and intensive care monitoring 1
- Never administer digoxin before correcting hypokalemia—this significantly increases risk of life-threatening arrhythmias 1
Moderate Hypokalemia (2.5-2.9 mEq/L)
- Oral potassium chloride 40-100 mEq daily in divided doses is preferred if patient can tolerate oral intake 3
- IV potassium 10 mEq/hour if oral route unavailable or inadequate 2
- Monitor serum potassium every 2-4 hours initially 1
Mild Hypokalemia (3.0-3.5 mEq/L)
- Oral potassium chloride 20-40 mEq daily in divided doses 3
- For diuretic-induced hypokalemia, add potassium-sparing diuretics (spironolactone 25-100 mg daily) rather than relying solely on oral supplements 1
- Dietary advice to increase potassium-rich foods (bananas, oranges, potatoes, spinach) may suffice if patient not on diuretics and has no cardiac disease 1
Critical Management Principles
- Correct hypomagnesemia first—hypokalemia is resistant to treatment without adequate magnesium 1
- Each 10 mEq of potassium chloride raises serum potassium by approximately 0.1 mEq/L 2
- Avoid potassium chloride controlled-release preparations if liquid or effervescent forms tolerated, due to risk of intestinal ulceration 3
- Monitor serum potassium and renal function within 3 days, again at 1 week, then every 1-2 weeks until stable 1
Hypercalcemia Workup
Measure serum calcium, albumin (to calculate corrected calcium), and intact PTH to differentiate primary hyperparathyroidism from malignancy—these two conditions account for >90% of hypercalcemia cases. 4
Initial Laboratory Assessment
- Serum calcium (corrected for albumin): Corrected Ca = measured Ca + 0.8 × (4.0 - albumin) 4
- Intact parathyroid hormone (PTH): elevated in hyperparathyroidism, suppressed in malignancy and other causes 5, 4
- Serum phosphate: low in hyperparathyroidism, variable in malignancy 4
- Serum creatinine and BUN to assess renal function 4
- 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D if PTH suppressed 5
Distinguish Primary Hyperparathyroidism from Malignancy
- Primary hyperparathyroidism: calcium typically <12 mg/dL, duration >6 months, elevated PTH, kidney stones common, hyperchloremic metabolic acidosis, no anemia 4
- Malignancy-associated hypercalcemia: calcium typically >12 mg/dL, rapid onset, suppressed PTH, marked anemia, no kidney stones or metabolic acidosis 4
Additional Workup Based on PTH Level
If PTH elevated (hyperparathyroidism):
- Parathyroid imaging (sestamibi scan or ultrasound) for surgical planning 5
- Bone density scan to assess for osteoporosis 5
- 24-hour urine calcium to rule out familial hypocalciuric hypercalcemia 5
If PTH suppressed (non-parathyroid causes):
- PTH-related peptide (PTHrP) if malignancy suspected 4
- Chest X-ray and CT chest/abdomen/pelvis to evaluate for malignancy or granulomatous disease 4
- Serum and urine protein electrophoresis if multiple myeloma suspected 4
- Vitamin D levels (25-OH and 1,25-OH) to assess for vitamin D intoxication or granulomatous disease 5, 4
Special Populations
- Williams syndrome: check serum calcium every 4-6 months until age 2 years, then every 2 years thereafter 5
- Williams syndrome with hypercalcemia: measure serum BUN, creatinine, vitamin D (25-OH and 1,25-OH), intact PTH, and urine calcium/creatinine ratio 5
- Tumor lysis syndrome: hypercalcemia is NOT a feature—expect hypocalcemia instead 5
Hypercalcemia Management
Severe Symptomatic Hypercalcemia (>14 mg/dL or symptomatic)
Initiate aggressive IV hydration with normal saline 200-300 mL/hour to restore intravascular volume and promote calciuresis. 4
- IV normal saline 2-4 liters over first 24 hours (adjust based on cardiac and renal function) 4
- Loop diuretics (furosemide 40-80 mg IV) only after volume repletion, and only if renal insufficiency or heart failure present to prevent fluid overload 4
- Calcitonin 4 IU/kg subcutaneously or IM every 12 hours for immediate short-term management—lowers calcium within 4-6 hours but tachyphylaxis develops after 48 hours 4
- Bisphosphonates for long-term control: zoledronic acid 4 mg IV over 15 minutes or pamidronate 60-90 mg IV over 2-4 hours—effect begins in 2-4 days, peaks at 7 days 4
Moderate Hypercalcemia (12-14 mg/dL)
- IV hydration with normal saline 100-150 mL/hour 4
- Bisphosphonates (zoledronic acid or pamidronate) for sustained control 4
- Avoid thiazide diuretics, calcium supplements, and vitamin D 5, 4
Mild Hypercalcemia (<12 mg/dL)
- Increase oral fluid intake to maintain urine output >2 liters/day 4
- Discontinue calcium supplements, vitamin D, and thiazide diuretics 5, 4
- Treat underlying cause (e.g., parathyroidectomy for primary hyperparathyroidism) 4
Cause-Specific Management
Malignancy-associated hypercalcemia:
- Bisphosphonates are first-line: zoledronic acid preferred over pamidronate 4
- Denosumab 120 mg subcutaneously if bisphosphonates contraindicated or ineffective 4
Granulomatous disease or lymphoma:
- Glucocorticoids (prednisone 40-60 mg daily) are highly effective 4
Vitamin D intoxication:
- Discontinue vitamin D, glucocorticoids, and bisphosphonates 4
Williams syndrome with hypercalcemia:
- Low-calcium diet and increased water intake under medical supervision 5
- Avoid multivitamin preparations containing vitamin D 5
- Refer to pediatric nephrologist and/or endocrinologist for persistent hypercalcemia, hypercalciuria, or nephrocalcinosis 5
Refractory Hypercalcemia
- Hemodialysis with low-calcium or calcium-free dialysate for severe hypercalcemia with renal failure 4
- Consider cinacalcet for refractory hyperparathyroidism 5
Critical Pitfall: Concurrent Hypokalemia and Hypercalcemia
Hypokalemia occurs in 32% of patients with hypercalcemia, with higher prevalence (52%) in malignancy-associated hypercalcemia versus primary hyperparathyroidism (17%). 6
- Check serum potassium before initiating aggressive diuresis for hypercalcemia—vigorous loop diuretic use can cause profound hypokalemia and tachyarrhythmias 6
- Hypokalemia frequency and severity increase at higher serum calcium levels 6
- Correct hypokalemia concurrently with hypercalcemia treatment 6
- Avoid calcium polystyrene sulfonate for hyperkalemia in patients at risk for hypercalcemia—it can cause severe hypercalcemia (>3.25 mmol/L) 7