OBJECTIVE:We sought to compare resuscitation with 0.9% NaCl versus Plasma-Lyte A, a calcium-free balanced crystalloid solution, hypothesizing that Plasma-Lyte A would better correct the base deficit 24 hours after injury. BACKGROUND:Sodium chloride (0.9%) (0.9% NaCl), though often used for resuscitation of trauma patients, may exacerbate the metabolic acidosis that occurs with injury, and this acidosis may have detrimental clinical effects. METHODS:We conducted a randomized, double-blind, parallel-group trial (NCT01270854) of adult trauma patients requiring blood transfusion, intubation, or operation within 60 minutes of arrival at the University of California Davis Medical Center. Based on a computer-generated, blocked sequence, subjects received either 0.9% NaCl or Plasma-Lyte A for resuscitation during the first 24 hours after injury. The primary outcome was mean change in base excess from 0 to 24 hours. Secondary outcomes included 24-hour arterial pH, serum electrolytes, fluid balance, resource utilization, and in-hospital mortality. RESULTS:Of 46 evaluable subjects (among 65 randomized), 43% had penetrating injuries, injury severity score was 23 ± 16, 20% had admission systolic blood pressure less than 90 mm Hg, and 78% required an operation within 60 minutes of arrival. The baseline pH was 7.27 ± 0.11 and base excess −5.9 ± 5.0 mmol/L. The mean improvement in base excess from 0 to 24 hours was significantly greater with Plasma-Lyte A than with 0.9% NaCl {7.5 ± 4.7 vs 4.4 ± 3.9 mmol/L; difference3.1 95% confidence interval (CI)0.5–5.6}. At 24 hours, arterial pH was greater 7.41 ± 0.06 vs 7.37 ± 0.07; difference0.05 (95% CI0.01–0.09) and serum chloride was lower 104 ± 4 vs 111 ± 8 mEq/L; difference−7 (95% CI−10 to −3) with Plasma-Lyte A than with 0.9% NaCl. Volumes of study fluid administered, 24-hour urine output, measures of resource utilization, and mortality did not significantly differ between the 2 arms. CONCLUSIONS:Compared with 0.9% NaCl, resuscitation of trauma patients with Plasma-Lyte A resulted in improved acid-base status and less hyperchloremia at 24 hours postinjury. Further studies are warranted to evaluate whether resuscitation with Plasma-Lyte A improves clinical outcomes. Randomized controlled trial, level I. (ClinicalTrials.gov Record UCDIRB-200917793.)