What is the utility of ionized calcium levels in critical care?

From the Guidelines

Ionized calcium level is a crucial parameter in critical care, particularly in patients with major bleeding and coagulopathy, as it plays a pivotal role in the coagulation cascade and cardiac contractility, with hypocalcaemia being associated with increased mortality and morbidity. The normal range of ionised calcium is 1.1–1.3 mmol/L, and it is essential to monitor its levels, especially in patients receiving massive transfusions, as citrate-mediated chelation of serum Ca2+ can lead to hypocalcaemia 1. Hypocalcaemia is associated with platelet activation, aggregation, decreased clot strength, blood transfusions, and increased mortality, and its correction is crucial to prevent cardiac dysrhythmias and other complications 1.

Key Points to Consider

• Ionised calcium levels are easily monitored as part of a blood gas analysis, and transfusion-induced hypocalcaemia should be corrected promptly 1.
• The preferred agent to correct hypocalcaemia is calcium chloride, which contains more elemental calcium than calcium gluconate and may be preferable in patients with abnormal liver function 1.
• Hypocalcaemia within the first 24 h of critical bleeding can predict mortality and the need for multiple transfusions with greater accuracy than other parameters, highlighting the importance of monitoring ionized calcium levels in critical care 1.
• While an association between admission ionised hypocalcaemia and mortality has been identified, no data demonstrate that the prevention or treatment of ionised hypocalcaemia reduces mortality in patients with critical bleeding requiring massive transfusions, emphasizing the need for further research in this area 1.

Clinical Implications

• Prompt correction of hypocalcaemia is essential to prevent complications and improve patient outcomes, and calcium chloride is the preferred agent for this purpose 1.
• Regular monitoring of ionized calcium levels, particularly during massive transfusions, continuous renal replacement therapy, or after parathyroid surgery, allows for timely interventions that can significantly impact patient outcomes in critical care.
• The importance of ionized calcium measurement in critical care settings cannot be overstated, as it provides the most accurate assessment of physiologically active calcium in the bloodstream, which is essential for various bodily functions, including coagulation and cardiac contractility 1.

From the FDA Drug Label

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action Intravenous administration of calcium gluconate increases serum ionized calcium level. Calcium gluconate dissociates into ionized calcium in plasma. Ionized calcium and gluconate are normal constituents of body fluids.

1. 3 Pharmacokinetics Absorption Calcium Gluconate Injection is 100% bioavailable following intravenous injection. Metabolism Calcium itself does not undergo direct metabolism. The release of ionized calcium from intravenous administration of calcium gluconate is direct and does not seem to be affected by the first pass through the liver Distribution Calcium in the body is distributed mainly in skeleton (99%). Only 1% of the total body calcium is distributed within the extracellular fluids and soft tissues. About 50% of total serum calcium is in the ionized form and represents the biologically active part. 8% to 10% serum calcium is bound to organic and inorganic acid and approximately 40% is protein-bound (primarily to albumin) Elimination Studies have shown a relationship between urinary calcium excretion and the intravenous administration of calcium gluconate, with a significant increase in urinary calcium excretion observed after the intravenous administration of calcium gluconate.

The ionized calcium level is a crucial parameter in critical care as it represents the biologically active part of serum calcium, with about 50% of total serum calcium being in the ionized form. Monitoring ionized calcium levels can help guide the administration of calcium gluconate, as intravenous administration increases serum ionized calcium levels [ 2 ]. Key points to consider include:

• Ionized calcium is essential for various physiological processes
• Calcium gluconate administration can increase ionized calcium levels
• Monitoring ionized calcium levels is important in critical care settings to ensure proper calcium homeostasis [ 2 ]

From the Research

Utility of Ionized Calcium Level in Critical Care

• Ionized calcium levels are crucial in critical care settings, as hypocalcemia is a common derangement in critically ill patients 3.
• The measurement of ionized calcium can be critical in determining an individual's true serum calcium status, especially in the presence of hypoalbuminemia and disorders of acid-base balance 4.
• Hypocalcemia is associated with high mortality and disease severity in critically ill patients, and its correction is a routine procedure in intensive care units 3.

Diagnosis and Treatment of Hypocalcemia

• The diagnosis of hypocalcemia is complicated by limitations in the interpretation of total plasma calcium concentration, making ionized calcium measurement essential 4.
• Treatment of moderate to severe acute hypocalcemia with calcium gluconate infusion can be effective in increasing serum ionized calcium levels 5, 6.
• However, the scientific evidence concerning the correction of hypocalcemia remains conflicting, and multicenter clinical trials are needed to assess the efficacy and safety of hypocalcemia treatment in critically ill patients 3.

Availability and Critical Limits of Ionized Calcium Testing

• The availability of ionized calcium testing has increased dramatically over the years, with most hospitals now providing in-house testing 7.
• Critical limits for ionized calcium levels vary among medical centers and children's hospitals, with mean critical limits ranging from 0.82 to 1.55 mmol/L 7.
• Aggressive monitoring of ionized calcium can prevent cardiac and neurologic catastrophes, and appropriate levels can optimize cardiac function 7.