Concomitant Ceftriaxone and High-Concentration Intravenous Calcium Therapy in Adult Critical Care Patients: A Matched Cohort Study

BACKGROUND: Based on case reports in infants, the safety of concomitant use of ceftriaxone and intravenous calcium in all ages has recently come under challenge. Systematic population-based data to guide clinicians with respect to this risk are, however, lacking. OBJECTIVE: To determine whether concomitant administration of ceftriaxone and intravenous calcium was associated with the occurrence of severe cardiorespiratory events or death in critically ill adults. METHODS: We performed a matched-cohort study from retrospective data of adults admitted to intensive care units (ICUs) in Calgary, Canada, who were provided continuous high-dose intravenous calcium. Those who received ceftriaxone while on continuous renal replacement therapy were considered exposed. Up to 3 unexposed patients were selected by matching on a number of prognostic factors from the remaining subjects not concurrently exposed to ceftriaxone and calcium. Univariate methods and multivariate conditional logistic regression were used for statistical analysis. RESULTS: We identified 142 patients exposed to the implicated combination who could be matched to at least one unexposed patient. Hospital mortality was 66% in the exposed versus 63% in unexposed patients (p = 0.442). ICU length of stay, ICU mortality, hospital length of stay, and the frequency of acute oxygenation events were all similar by univariate analysis. Multivariate conditional logistic regression modeling failed to find a significant association between exposure and hospital mortality (adjusted OR 1.15, 95% CI 0.65 to 2.04) or other relevant outcomes. CONCLUSIONS: In this high-risk group, administration of high concentrations of calcium and concurrent ceftriaxone was not significantly associated with greater mortality or adverse outcomes compared to matched unexposed patients. Although this was an underpowered study and rare adverse effects from the interaction of these 2 compounds cannot be completely excluded, these data provide overall reassurance of the safety of this combination in the majority of critically ill adults.