Predicting ionized hypocalcemia: External validation of an ionized calcium prediction model in patients with COVID-19...

Ionized hypocalcemia is common in critically ill patients with COVID-19 and is associated with adverse outcomes. We previously developed a linear model that estimates ionized calcium (I_Ca) by adjusting total calcium (T_Ca) for the three components of the anion gap and albumin. On internal validation, it outperformed the popular method that corrects T_Ca for albumin alone (cT_Ca) in diagnosing low I_Ca. In this study, we sought to externally validate our I_Ca model in hospitalized COVID-19 positive patients.

We retrospectively studied all 200 patients with COVID-19 who were admitted to the State University of New York Downstate Medical Center between March 11^th and April 30^th 2020 and referred to the nephrology service for renal failure, and who had I_Ca measured on a venous blood gas within 25 min of a comprehensive metabolic panel. We compared the performance of the I_Ca model and cT_Ca in diagnosing low I_Ca by ROC analysis, and also examined the accuracy of the absolute values predicted by the two methods relative to measured I_Ca.

On ROC analysis, the I_Ca model was better than cT_Ca (area under ROC curve: 0.872 [0.025] vs. 0.835 [0.028]; p = 0.045). The I_Ca model estimated I_Ca accurately, but the cT_Ca method seemed to overcorrect T_Ca, as a substantial number of patients with clearly normal cT_Ca values had low I_Ca.

In an external validation cohort, the I_Ca model estimated I_Ca accurately and was better than cT_Ca in the diagnosis of low I_Ca. This finding can be useful in guiding direct I_Ca testing.