Total Calcium Versus Ionized Calcium

Calcium is traditionally reported as a total serum concentration (ie, complete metabolic profiles) and ionized calcium concentration (ie, blood gases). In order to interpret these labs, one must understand what they represent. Under normal physiologic conditions, roughly 50% of calcium is bound (primarily to albumin) and 50% is ionized (the biologically active component). Therefore, total calcium = bound + ionized.

Based on this relationship, it’s possible to see an increase/decrease in total calcium WITHOUT a change in ionized. This is the premise behind “pseudo-hyper/hypo-calcemia” which is largely driven by changes in albumin concentration. More recent literature has shown that the “albumin correction formula” (corrected [Ca] = 0.8 * (4 – [albumin]) + measured [Ca]) provides poor estimates in the critically ill/renally compromised patient populations, so use it mindfully!

Ionized fractions can also change without affecting the total calcium concentration! In the OR and ICU, I see this in the context of acid-base derangements. Albumin is a negatively charged protein which attracts positively charged calcium ions AND H+ ions (which determine pH). In acidotic states, [H+] increases and competes with calcium to bind albumin. Now, less calcium has a home on albumin and more is left ionized in its biologically active state. Since this just represents a shift between bound and unbound states, the TOTAL remains relatively UNCHANGED.

As a cardiac anesthesiologist and intensivist, I’m almost invariably looking for an ionized calcium to guide therapy, electrolyte repletion, etc. Why? Because this tells me what I need to know – the biologically active fraction! In lower risk patients… well… please don’t send extra labs unless you’re going to DO something with them!

Drop me a comment below with questions!

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  1. What level of ionized calcium do you treat? Iā€™m a CICU RN and I push to treat under 1.05 ionized calcium. Usually I meet resistance from doctors to treat those levels and I never have a good enough argument to tell them why they should lol.

    1. Cardiac anesthesiologists LOVE calcium! In the context of a large surgery (especially if I’m struggling with coagulopathy, low systemic vascular resistance, or contractility issues), I have a very low threshold to give calcium for ionized < 1.1.

  2. Why then is the lab reported as ionized calcium and then below it is listed the normalized calcium, I do not know what to do with this and can’t remember when it started be reported this way. Sometimes the ionized is slightly high but then the normalized calcium is normal. For example 1.53 (high ionized) vs 1.31 ( normal normalized).

    1. Hmmm, I’m not sure what a “normalized” calcium is in this context! Our labs/ABGs give calcium as either ionized or total, so that’s what I referenced in my post.

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