From the Guidelines
Elevated ionized calcium with normal total calcium levels is a significant finding that requires attention, as ionized calcium is the physiologically active form responsible for cellular functions throughout the body. The most recent and highest quality study, 1, highlights the importance of maintaining ionized calcium levels within the normal range, especially in patients with major trauma and during massive transfusion. According to this study, the normal range of ionized calcium is 1.1–1.3 mmol/L, and it is essential to monitor and maintain these levels to prevent complications such as cardiac dysrhythmias and impaired coagulation. The study also recommends the administration of calcium chloride to correct hypocalcaemia, which is a common finding in trauma patients and can complicate massive transfusion. However, in the case of elevated ionized calcium with normal total calcium levels, the management approach may differ. It is crucial to identify and treat the underlying cause of the elevated ionized calcium, which may involve further testing, including parathyroid hormone levels, vitamin D status, and assessment for malignancy. Treatment might involve addressing the primary condition, maintaining hydration, possibly using bisphosphonates for severe cases, and monitoring both ionized and total calcium levels. Some key points to consider in the management of elevated ionized calcium include:
- Assessing for symptoms of hypercalcemia, such as fatigue, weakness, kidney stones, bone pain, or neurological symptoms
- Identifying and treating the underlying cause of the elevated ionized calcium
- Monitoring both ionized and total calcium levels
- Maintaining hydration and considering the use of bisphosphonates for severe cases
- Avoiding the use of calcium supplements, as they may exacerbate the condition. Overall, the management of elevated ionized calcium with normal total calcium levels requires a comprehensive approach that takes into account the underlying cause and the patient's overall clinical condition, as highlighted in the study 1.
From the Research
Normal Calcium but Elevated Ionized Calcium
- The condition of having normal calcium levels but elevated ionized calcium can be observed in certain cases, such as in patients with IgA paraproteinemia 2.
- In one study, a 70-year-old woman with IgA paraproteinemia had persistently elevated total calcium levels but normal ionized calcium levels, and extensive clinical investigations did not reveal hyperparathyroidism or cancer-mediated hypercalcemia 2.
- The study found that the high-molecular-weight IgA paraprotein in the patient had an increased capacity to reduce the amount of free calcium in solution, providing a direct mechanistic explanation for the clinical findings 2.
Measurement of Ionized Calcium
- Ionized calcium is the biologically active form of calcium, and its measurement is important in assessing calcium status, especially in patients with suspected calcium metabolic diseases 3, 4.
- The use of albumin-corrected calcium may not accurately reflect the ionized calcium levels, and the measurement of ionized calcium is recommended in clinical practice 3, 4.
- A study found that 31.0% of patients were misclassified when serum total calcium was measured instead of serum ionized calcium, and the diagnostic discrepancy decreased with the calculation of albumin-corrected total calcium or calculated ionized calcium 4.
Clinical Implications
- The measurement of ionized calcium is important in the diagnosis and management of hypercalcemia, and it can help identify the underlying cause of the condition 5, 2.
- In patients with hypercalcemia, an elevated or normal parathyroid hormone (PTH) concentration is consistent with primary hyperparathyroidism, while a suppressed PTH level indicates another cause 5.
- The treatment of hypercalcemia depends on the underlying cause, and it may include hydration, intravenous bisphosphonates, and other medications 5.