title: Pilot study to determine the hemodynamic safety and feasibility of magnesium sulfate infusion in children with severe traumatic brain injury.
abstract: OBJECTIVE
  Magnesium sulfate is neuroprotective in preclinical models, but there are limited safety data regarding its clinical use for pediatric traumatic brain injury. We conducted a pilot study in children with severe traumatic brain injury to a) examine if magnesium sulfate decreases mean arterial pressure, decreases cerebral perfusion pressure, increases intracranial pressure, or adversely effects cardiac conduction; and b) determine the feasibility of a multiple-center trial of magnesium sulfate.
  
  
  METHODS
  Double-blinded, placebo-controlled, randomized pilot trial with repeated measurement of hemodynamic variables.
  
  
  METHODS
  Two pediatric trauma centers.
  
  
  METHODS
  Six children (3 months to 18 yrs) with severe traumatic brain injury.
  
  
  METHODS
  : Magnesium sulfate (50 mg/kg) bolus followed by (8.3 mg/kg/hr) infusion for 24 hr vs. equivolume placebo.
  
  
  RESULTS
  We screened 96 patients with severe traumatic brain injury during 24 months; 20 were eligible for enrollment, six provided informed consent, four received magnesium sulfate, and two received placebo. Before and after study drug infusion, we repeatedly measured blood ionized magnesium concentration, mean arterial pressure, cerebral perfusion pressure, intracranial pressure, heart rate, and corrected QT interval. Mean age (7.9 yrs), mean highest Glasgow Coma Scale score (6), gender (33% boys), inflicted injury rate (17%), and case mortality rate (17%) did not differ between those enrolled and those not enrolled. Compared with baseline, magnesium sulfate did not change cerebral perfusion pressure, intracranial pressure, heart rate, or corrected QT interval. Mean arterial pressure was unchanged until the late phase of magnesium sulfate infusion, when mean arterial pressure rose (82 +/- 5 vs. 93 +/- 6 mm Hg, p < .05). Sixty-four percent of corrected QT interval determinations obtained in the first 6 days after injury exceeded 440 msecs; 12% were >600 msecs.
  
  
  CONCLUSIONS
  In children with severe traumatic brain injury, magnesium sulfate administration did not decrease mean arterial pressure or cerebral perfusion pressure or adversely effect cardiac conduction. Our data suggest that enrollment of brain-injured children in a therapeutic trial remains challenging. These results provide information important for clinical trials of magnesium sulfate in children with severe traumatic brain injury.
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA. jnatale@cnmcresearch.org
authors.forename: JoAnne E
authors.initials: JE
authors.lastname: Natale
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Guerguerian
authors.forename: Jill G
authors.initials: JG
authors.lastname: Joseph
authors.forename: Robert
authors.initials: R
authors.lastname: McCarter
authors.forename: Cheng
authors.initials: C
authors.lastname: Shao
authors.forename: Beth
authors.initials: B
authors.lastname: Slomine
authors.forename: James
authors.initials: J
authors.lastname: Christensen
authors.forename: Michael V
authors.initials: MV
authors.lastname: Johnston
authors.forename: Donald H
authors.initials: DH
authors.lastname: Shaffner
mesh_terms: D000293:Adolescent; D001794:Blood Pressure / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D004562:Electrocardiography; D005240:Feasibility Studies; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007427:Intracranial Pressure / Q000187:drug effects; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018579:Patient Selection; D010865:Pilot Projects; D010919:Placebos; D012449:Safety; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D010919:Placebos; D008278:Magnesium Sulfate