What is the normal value for ionized calcium (Ca2+) in a healthy adult?

Normal Ionized Calcium Values

The normal ionized calcium range in healthy adults is 4.65 to 5.28 mg/dL (1.16 to 1.32 mmol/L), representing the physiologically active form of calcium that is essential for neuromuscular, cardiac, and coagulation functions. 1

Reference Range Details

• Ionized calcium constitutes approximately 45-50% of total serum calcium, with the remainder being protein-bound (40%) or complexed with anions (12%). 1, 2

• The standard reference range established by the American Society for Clinical Pathology is 4.65 to 5.28 mg/dL or 1.16 to 1.32 mmol/L. 1

• An alternative commonly cited range is 1.1 to 1.3 mmol/L (equivalent to approximately 4.4 to 5.2 mg/dL). 2

Clinical Context and pH Effects

• Ionized calcium levels are pH-dependent: a 0.1 unit increase in pH decreases ionized calcium by approximately 0.05 mmol/L (or 0.1 mEq/L for a 0.1 unit pH decrease raises ionized calcium by 0.1 mEq/L). 3, 2

• Alkalosis decreases free calcium by enhancing albumin binding, while acidosis increases ionized calcium levels. 3

• This pH sensitivity makes ionized calcium the preferred measurement in critically ill patients with acid-base disturbances. 3

When to Measure Ionized Calcium Directly

Direct measurement of ionized calcium is superior to calculated values and should be obtained in specific clinical scenarios:

• Critically ill patients requiring intensive care monitoring 3
• Patients with abnormal albumin levels (hypoalbuminemia or hyperalbuminemia) 3
• Acid-base disturbances where pH affects calcium distribution 3
• Massive transfusion protocols where citrate binding affects calcium availability 3
• Major trauma with ongoing bleeding (ionized calcium <0.8 mmol/L predicts mortality better than other coagulation parameters) 3

Clinical Significance of Abnormal Values

Hypocalcemia thresholds:

• Symptomatic hypocalcemia or ionized calcium below 0.8-0.9 mmol/L requires treatment. 1
• In massive transfusion, maintain ionized calcium >0.9 mmol/L to prevent coagulopathy and cardiovascular dysfunction. 3
• Ionized calcium <0.8 mmol/L is associated with cardiac dysrhythmias and independently predicts mortality in critical illness. 3, 4

Hypercalcemia thresholds:

• Mild hypercalcemia is defined as ionized calcium of 5.6 to 8.0 mg/dL (1.4-2 mmol/L). 5
• Severe hypercalcemia is defined as ionized calcium ≥10 mg/dL (≥2.5 mmol/L). 5
• Ionized calcium >1.4 mmol/L is independently associated with increased intensive care unit and hospital mortality. 4

Important Caveats

• Correction formulas for total calcium have significant limitations and may not accurately reflect ionized calcium, particularly outside normal albumin ranges or in patients with chronic kidney disease. 3, 6, 7

• Direct measurement of ionized calcium discriminates better than corrected total calcium in borderline cases, though it has worse reproducibility and higher cost. 3, 6

• In the broad middle range of values (approximately 0.9-1.35 mmol/L), ionized calcium concentration has no independent association with mortality—only extreme abnormalities (<0.8 or >1.4 mmol/L) are independent predictors. 4