A. Disorders of mineral metabolism (calcium, magnesium, phosphorus) occur frequently in patients admitted to ICUs. They are rarely the primary cause for admission, but they may exacerbate existing medical situations.

B. Calcium, magnesium, and phosphorus metabolisms are controlled by interaction of parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25 D), and calcitonin.

A. Pathophysiology.

1. In extracellular fluids, calcium is free (40%) and bound to albumin or other anions (60%). The free (ionized) form is biologically active. Measurements of total serum calcium should be corrected for the albumin level with the following equation: Corrected calcium = Measured calcium + (0.8 × [4 − Measured albumin].).

2. Changes in acid-base balance affect binding of calcium to albumin.

a. Acidosis decreases binding and increases the free form.

b. Alkalosis increases binding and decreases the free form.

3. Calcium balance depends on bone resorption and formation, intestinal absorption, and renal excretion.

a. Persistent PTH exposure increases bone resorption and renal calcium reabsorption.

b. 1,25 D enhances intestinal calcium absorption.

c. Calcitonin inhibits bone resorption and increases renal calcium excretion.

B. Diagnosis of hypercalcemia.

1. Signs and symptoms.

a. Mental manifestations vary from stupor to coma.

b. Neurologic effects include reduced muscle tone and reflexes.

c. Intestinal and urologic signs include vomiting, polyuria, polydipsia, and constipation.

d. Cardiovascular effects include shortening of the QT interval and increasing the potential for arrhythmias.

2. Differential diagnoses can be divided into PTH independent and PTH dependent.

a. PTH independent (PTH level will be suppressed) is more common in ICU patients.

i. Malignancy—especially lung, head and neck, breast, hematologic (myeloma and lymphoma), and renal cell carcinoma.

ii. Granulomatous disease.

iii. Immobilization.

iv. Milk-alkali syndrome.

v. Thyrotoxicosis.

vi. Vitamin D or A intoxication.

vii. Addison’s disease.

viii. If PTH is suppressed (PTH independent), then thyroid-stimulating hormone, PTH-rP, 1,25 D levels, and urine/serum protein electrophoreses can help establish the diagnosis.

b. PTH dependent (PTH level will be high or normal) is more common in outpatients.

i. Hyperparathyroidism from adenoma, hyperplasia, or carcinoma (rare).

ii. Familial hypocalciuric hypercalcemia (FHH).

C. Treatment of hypercalcemia.

1. Isotonic saline hydration.

a. Pivotal because response is rapid. Aim is to achieve a urine output of 3 to 5 L/24 hours, usually requiring 200 to 500 mL/hour of normal saline.

b. Furosemide (Lasix) 20 to 40 mg intravenously (IV) once rehydration has been achieved—prevents fluid overload and inhibits renal calcium reabsorption. Electrolyte measurement is mandatory.

2. Calcitonin.

a. Inhibits bone resorption when a rapid decrease is required.

b. Dose is 4 to 8 international units/kg body weight subcutaneously or intramuscularly every 12 hours with hydration.

c. Decrease in serum calcium 2 hours after dose and lasts 6 to 8 hours. Average decrease is 9% and lasts 4 to 7 days (tachyphylaxis occurs).

3. Bisphosphonates.

a. Inhibit bone resorption and provide a more prolonged calcium decrease.

b. Pamidronate (Aredia) 60 to 90 mg IV over 2 hours, with hydration.

c. Zoledronate (Zometa) 4 mg IV over not <15 minutes, with hydration.

i. Calcium normalizes in 60% to 90% of patients with significant decreases within 4 days and duration of response between 1 and 3 weeks.

ii. Renal function needs to be monitored.

iii. Retreatment after a minimum of 7 days to allow full response to initial dose. Dose and manner of retreatment identical to initial treatment.

D. Diagnosis of hypocalcemia.

1. Signs and symptoms.

a. Neurologic manifestations include hyperreflexia and tetany.

b. Chvostek sign—facial muscle spasm by tapping the facial nerve.

c. Trousseau sign—carpal spasm elicited with a blood pressure cuff inflated above systolic pressure for 3 minutes.