From the Guidelines
Measuring ionized calcium is clinically superior to total calcium for accurately assessing calcium status in patients, as it represents the physiologically active form that regulates critical bodily functions. Ionized calcium represents about 50% of total calcium and is essential for neuromuscular activity, cardiac function, and blood clotting. While total calcium measurement is more widely available and less expensive, it can be misleading in many clinical scenarios because it's affected by albumin levels, acid-base disturbances, and other protein abnormalities. Ionized calcium should be prioritized in critically ill patients, those with abnormal protein levels (especially hypoalbuminemia), acid-base disorders, patients receiving blood transfusions, those with hypercalcemia or hypocalcemia, pregnant women, and patients undergoing parathyroid surgery 1. Although formulas exist to "correct" total calcium for albumin, these adjustments are often inaccurate. When ionized calcium testing isn't available, clinicians should interpret total calcium results cautiously, particularly in patients with conditions affecting serum proteins or acid-base status. The physiological basis for this distinction is that only unbound calcium ions can participate in cellular processes, making ionized calcium the true reflection of calcium homeostasis and the measurement of choice when accurate calcium assessment is crucial for clinical decision-making. Some key points to consider include:
- Ionized calcium levels should be monitored and maintained within the normal range following major trauma and during massive transfusion 1.
- Calcium chloride should be administered to correct hypocalcaemia 1.
- The normal range for ionized calcium is approximately 4.65 to 5.28 mg/dL (1.16 and 1.32 mmol/L) for adults 1.
- Free calcium can be measured using ion-selective electrodes in most hospitals 1.
- A fall in pH of 0.1 unit will cause approximately a 0.1 mEq/L rise in the concentration of ionized calcium since hydrogen ion displaces calcium from albumin, whereas alkalosis decreases free calcium by enhancing binding of calcium to albumin 1.
From the Research
Clinical Significance of Measuring Ionized Calcium versus Total Calcium
The clinical significance of measuring ionized calcium versus total calcium in patients is a crucial aspect of understanding calcium homeostasis in various clinical settings.
- Ionized calcium is the biologically active form of calcium, and its measurement is essential in critically ill patients, as it reflects the true calcium status more accurately than total calcium levels 2, 3.
- Total calcium levels, on the other hand, include both bound and free fractions of calcium, and can be influenced by various factors such as albumin levels, pH, and other ions 4, 5.
- The differentiation between primary or tertiary hyperparathyroidism and secondary hyperparathyroidism requires the identification of hypercalcemia, which can be accurately diagnosed using fasting ionized calcium levels 4.
- In critically ill patients, the use of formulas to estimate ionized or "corrected" serum calcium concentrations is not recommended, as they lack sensitivity and specificity, and can introduce errors based on inaccuracies in the measurement of other metabolites 5, 3.
- Direct measurement of serum ionized calcium concentration is indicated for assessing calcium status in critically ill patients, as it provides a more accurate reflection of the patient's calcium status 5, 3, 6.
Diagnostic Pitfalls and Recommendations
- The McLean-Hastings nomogram, a commonly used method for estimating serum ionized calcium levels, has been shown to underestimate the protein-induced changes in serum calcium in critically ill patients, and its use is not recommended 3.
- Ultrafilterable calcium concentrations offer an alternative to ionized calcium measurements when an ion-selective electrode is not available, and can provide a more accurate reflection of the patient's calcium status 6.
- Fasting total and ionized calcium measurements are recommended for diagnostic purposes, as they can help identify hypercalcemia and other calcium disorders more accurately 4.