In Response

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We would like to thank Freundlich et al1 for their informed comments regarding our study.2 The concerns regarding the lack of adjusting the analysis to reflect serum pH, serum lactate, and the cationic difference between calcium gluconate and calcium chloride are points well taken. Serum pH does impact free calcium levels through ionic coupling with bicarbonate. In vivo, this equilibration occurs quickly. Thus, measured ionized calcium (iCa2+) levels reliably reflect available calcium stores unless the pH is changing rapidly. Error can be introduced into iCa2+ measurements if samples are stored for a long period of time before being analyzed. In refrigerated samples, the pH generally drops and the measured iCa2+ will be falsely elevated, whereas the opposite occurs in frozen samples. All of the lab results we report were derived from fresh samples. Lactate is known to bind calcium similar to albumin, so this would only alter total calcium levels, not iCa2+. Regarding calcium repletion, calcium chloride contains 27 mg/mL elemental calcium, whereas calcium gluconate contains 9.3 mg/mL. In our pilot study, only 2 patients received a single dose of calcium gluconate, and in both cases, patients received calcium chloride for all subsequent doses. Given the limited sample size, we chose not to exclude these cases. In future studies with larger patient numbers, we will be careful to evaluate and report elemental calcium. Thank you again for these insightful comments.
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