Traumatic brain injuries represent an important health problem; they occur with high frequency, the population affected contains many previously healthy young people, and they are associated with high mortality and morbidity. The proposed study continues on our 16 years of experience in conducting clinical trials evaluating treatments for preventing seizures following head injury (Dilantin Prophylaxis of Post-traumatic Seizures, Valproate for Prophylaxis of Post-traumatic Seizures) and in examining neurobehavioral outcome after head injury. Our previous trials showed that Dilantin prevents early seizures but is ineffective in preventing epilepsy following head trauma and that Valproate is possibly associated with higher mortality that short-term Dilantin. The trials and outcome studies found that epileptic seizures, serious cognitive difficulties, high unemployment, and inability to live independently are common among survivors of moderate or severe head injury. Using a randomized, double-blind design, the present study will evaluate magnesium sulfate as a neuroprotectant and anti-epileptogenic agent following head injury. Magnesium sulfate is a widely used, well-tolerated compound that has been shown in the laboratory to be effective in reducing seizures and also in limiting neuronal damage and in improving functional outcome following experimental head injury. Specifically, the study will test the hypothesis that magnesium sulfate, when given within 8 hours of a moderate or severe head injury, a) increases survival, b) decreases seizures, and c) improves neurobehavioral functioning. Additionally, the study will: assess the effects of timing of dosage (e.g. <4 hours vs. 4-8 hours), gender, and race; determine the rate of adverse events: and evaluate the time course and correlates of total and ionized magnesium concentrations. Patients with moderate or severe head injury (post-resuscitation Glasgow Coma Scale 3-12) will be randomized to receive high doses of magnesium sulfate or placebo. Treatment will be started as soon as possible, and definitely within 8 hours of injury. The initial bolus of magnesium sulfate will be followed by a 7 day infusion to keep magnesium levels high during the period when secondary damage from the head injury is most likely. Patients will be closely monitored for survival and seizures over the first six months after injury and will have a comprehensive neurobehavioral assessment at six months after injury. In summary, this placebo-controlled, randomized clinical trial will determine the effects of magnesium sulfate on survival, post-traumatic seizures, and the patients behavioral functioning following head injury.
Showing the most recent 10 out of 37 publications
