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Purpose: Results of a study to determine potential cost benefits of substituting an alternative electrolyte solution for 0.9% sodium chloride injection for the initial fluid resuscitation of trauma patients are presented., Methods: Using data from a randomized clinical trial that compared 24-hour fluid resuscitation outcomes in critically injured trauma patients treated with 0.9% sodium chloride injection and those who received a balanced electrolyte solution (Plasma-Lyte A, Baxter Healthcare), a cost-minimization analysis was performed at a large medical center. The outcomes evaluated included fluid and drug acquisition costs, materials and nurse labor costs, and costs associated with electrolyte replacement., Results: The use of Plasma-Lyte A was associated with a relatively higher fluid acquisition cost but a reduced need for magnesium replacement. During the first 24 hours of hospitalization, 4 of 24 patients (17%) treated with 0.9% sodium chloride injection and none of the patients who received the comparator product (n = 22) required supplemental magnesium. Patients treated with 0.9% sodium chloride injection received a median of 4 g of magnesium (interquartile range [IQR], 2.5-4.0 g), compared with a median of 0 g (IQR 0-2 g) in the comparator group. Taking into account the costs of consumable supplies and nursing labor, the cost-minimization analysis indicated a 24-hour cost differential of $12.35 in favor of Plasma-Lyte A., Conclusion: Substitution of Plasma-Lyte A for 0.9% sodium chloride injection for fluid resuscitation during the first 24 hours after traumatic injury was associated with decreased magnesium replacement requirements and a net cost benefit to the institution.