Normal Range for Ionized Calcium
The normal range for ionized calcium is 1.1–1.3 mmol/L (or 4.6–5.4 mg/dL), and this value is pH-dependent. 1
Standard Reference Range
- Ionized calcium concentration normally ranges from 1.1 to 1.3 mmol/L in adults, as established by multiple European trauma guidelines 1
- When expressed in conventional units, this corresponds to 4.6 to 5.4 mg/dL 1
- Ionized calcium represents approximately 45-48% of total calcium in extracellular plasma, with the remainder bound to proteins (40%) or complexed with anions like phosphate and citrate (12-15%) 1
Critical pH Dependency
- Each 0.1 unit increase in pH decreases ionized calcium concentration by approximately 0.05 mmol/L 1
- This pH effect occurs because hydrogen ions displace calcium from albumin binding sites, while alkalosis enhances calcium binding to albumin 1
- You must account for pH changes when interpreting ionized calcium levels, as laboratory tests using citrated samples that are subsequently recalcified do not accurately reflect the detrimental effects of hypocalcemia on coagulation 1
Clinical Thresholds
Hypocalcemia Definitions
- Ionized calcium <0.9 mmol/L requires immediate treatment, particularly in massive transfusion or post-surgical settings 1
- Symptomatic hypocalcemia typically occurs when ionized calcium falls near or below 2.50 mg/dL (approximately 0.625 mmol/L) 2
- Critical low limits used by US medical centers average 0.82 ± 0.14 mmol/L (3.29 ± 0.56 mg/dL) 3
Hypercalcemia Definitions
- Mild hypercalcemia is defined as ionized calcium of 5.6 to 8.0 mg/dL (1.4-2.0 mmol/L) 4
- Severe hypercalcemia is defined as ionized calcium ≥10 mg/dL (≥2.5 mmol/L) 4
- Critical high limits used by US medical centers average 1.55 ± 0.19 mmol/L (6.21 ± 0.76 mg/dL) 3
Important Clinical Context
Why Ionized Calcium Matters
- Ionized calcium is essential for fibrin polymerization, platelet function, cardiac contractility, and systemic vascular resistance 1
- It serves as a cofactor for activation of coagulation factors II, VII, IX, and X, as well as proteins C and S 1
- Hypocalcemia within the first 24 hours can predict mortality and transfusion needs better than fibrinogen, acidosis, or platelet counts in critically bleeding patients 1
Common Pitfalls
- Do not rely solely on total calcium measurements when protein levels are abnormal, as correction formulas have significant limitations 1
- Direct measurement of ionized calcium discriminates better than albumin-corrected total calcium, particularly in borderline cases 5
- Venous serum collected in vacuum tubes may show falsely elevated ionized calcium compared to capillary blood unless separated at 4°C 6
- Samples can be stored at 4°C for up to 4 hours without significant change in ionized calcium and pH 6