Abstracts

RATIONALE: To demonstrate safety and ability to attain desired levels and maintain blinding in preparation for a clinical trial of MgSO4 as a neuroprotectant and antiepileptogenic agent following traumatic brain injury. METHODS: Within 24 hours of their injury, 20 patients were treated to maintain levels of about 2.8 mEq/L and groups of 5 each were targeted for levels of 3.8, 4.3, and 4.8. Dosing was by bolus load and 7-day infusion. RESULTS: Serum concentrations were easily kept in the desired range. No clinical side effects were observed. Blood pressure changes were comparable to untreated subjects. Calcium levels decreased with increasing Mg levels. To avoid unblinding, Mg levels need to be kept under 4.0 mEq/L. Steady state magnesium concentrations were obtained within 12 hours. Clearance was significantly related to body weight, age, baseline Mg level. Clearance did not depend on gender, ethanol, or extent of injury. CONCLUSIONS: MgSO4 can be given safely to patients following traumatic brain injury. Dose-limiting effect for a blinded study is decreasing calcium levels. Clearance is influenced by a number of factors, but levels could readily be kept in the desired ranges.