• Jessica R Ansari, Daniel J Conti, Guillermina Michel, Alla Yarmosh, Naida M Cole, and Steven L Shafer.
• Clinical Assistant Professor, Division of Obstetric Anesthesia and Maternal Health, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA. jansari@stanford.edu.
• Anesthesiology. 2024 Oct 3.

BackgroundFew studies have assessed the dose ratio of calcium gluconate to calcium chloride or defined the time course of change in serum ionized calcium concentration after intravenous injection.MethodsIn a bioequivalence (dose ratio) trial, parturients undergoing cesarean delivery were randomly assigned to receive calcium chloride 0.5 grams or calcium gluconate 1.5 or 2 grams by 10-minute intravenous infusion. Venous serum ionized calcium concentration was measured prior to calcium infusion and approximately 5, 10, 15, 30, and 60 minutes after infusion start. We combined these data with serum ionized calcium concentration measurements in parturients who received 1 gram calcium chloride or saline placebo in two recent clinical trials to define the pharmacokinetics of intravenous calcium over the first hour during and after drug administration.ResultsThe bioequivalence study enrolled 34 participants, from whom we collected 181 serum ionized calcium concentration measurements. The dose ratio of calcium gluconate to calcium chloride was 3.11 (95% CI: 2.77-3.48). Population pharmacokinetics of calcium were determined using 311 serum ionized calcium concentration measurements from 70 parturients. The pharmacokinetics of intravenous calcium were described by a two-compartment model with systemic clearance of 0.18 (95% CI: 0.07-0.27) L/min, distributional clearance of 1.25 (95%CI: 1.03-1.56) L/min, central volume of 10.9 (95% CI: 9.3-12.6) L, and peripheral volume of 16.5 (95% CI: 12.5-24.7) L. After adjusting for the dose ratio, calcium gluconate and calcium chloride had identical time courses. A one-gram infusion of calcium chloride results in a peak increase in serum ionized calcium concentration of 0.39 (0.38-0.42 mmol/L), which decreases by half 29 (23-40) minutes after initiation of the 10-minute infusion.ConclusionsWe confirmed a 3:1 dose ratio of calcium gluconate to calcium chloride and estimated the pharmacokinetics over the first hour following intravenous delivery. These data inform clinical care and may guide future trials assessing calcium efficacy to reduce bleeding in obstetric patients.Clinicaltrials.Gov RegistrationNCT05973747 (bioequivalence), NCT05027048, and NCT03867383 (trials included in pharmacokinetic assessment).Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.

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