title: Prehospital use of magnesium sulfate as neuroprotection in acute stroke.
abstract: BACKGROUND
  Magnesium sulfate is neuroprotective in preclinical models of stroke and has shown signals of potential efficacy with an acceptable safety profile when delivered early after stroke onset in humans. Delayed initiation of neuroprotective agents has hindered earlier phase 3 trials of neuroprotective agents.
  
  
  METHODS
  We randomly assigned patients with suspected stroke to receive either intravenous magnesium sulfate or placebo, beginning within 2 hours after symptom onset. A loading dose was initiated by paramedics before the patient arrived at the hospital, and a 24-hour maintenance infusion was started on the patient's arrival at the hospital. The primary outcome was the degree of disability at 90 days, as measured by scores on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability).
  
  
  RESULTS
  Among the 1700 enrolled patients (857 in the magnesium group and 843 in the placebo group), the mean (±SD) age was 69±13 years, 42.6% were women, and the mean pretreatment score on the Los Angeles Motor Scale of stroke severity (range, 0 to 10, with higher scores indicating greater motor deficits) was 3.7±1.3. The final diagnosis of the qualifying event was cerebral ischemia in 73.3% of patients, intracranial hemorrhage in 22.8%, and a stroke-mimicking condition in 3.9%. The median interval between the time the patient was last known to be free of stroke symptoms and the start of the study-drug infusion was 45 minutes (interquartile range, 35 to 62), and 74.3% of patients received the study-drug infusion within the first hour after symptom onset. There was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the magnesium group and those in the placebo group (P=0.28 by the Cochran-Mantel-Haenszel test); mean scores at 90 days did not differ between the magnesium group and the placebo group (2.7 in each group, P=1.00). No significant between-group differences were noted with respect to mortality (15.4% in the magnesium group and 15.5% in the placebo group, P=0.95) or all serious adverse events.
  
  
  CONCLUSIONS
  Prehospital initiation of magnesium sulfate therapy was safe and allowed the start of therapy within 2 hours after the onset of stroke symptoms, but it did not improve disability outcomes at 90 days. (Funded by the National Institute of Neurological Disorders and Stroke; FAST-MAG ClinicalTrials.gov number, NCT00059332.).
authors: From the Comprehensive Stroke Center (J.L.S., S.S., D.S.L.) and the Departments of Neurology (J.L.S., S.S., D.S.L.) and Emergency Medicine (S.S., F.P.), David Geffen School of Medicine at the University of California, Los Angeles (UCLA), the Departments of Emergency Medicine (M.E.) and Neurology (G.S., N.S.), Keck School of Medicine of the University of Southern California, the Los Angeles Fire Department (M.E.), the Los Angeles County Fire Department (F.P.), the Department of Emergency Medicine, Presbyterian Intercommunity Hospital (I.K.), the Department of Emergency Medicine, Long Beach Memorial Medical Center (G.M.), and the Department of Emergency Medicine, Huntington Memorial Hospital (R.G.), Los Angeles, the Los Angeles County Emergency Medical Services (EMS) Agency, the Orange County EMS Agency, and the Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance (S.J.S.), and Stanford University, Palo Alto (S.H.) - all in California; and the National Institute of Neurological Disorders and Stroke, Bethesda, MD (R.C.).
authors: Jeffrey L
authors: JL
authors: Saver
authors: Sidney
authors: S
authors: Starkman
authors: Marc
authors: M
authors: Eckstein
authors: Samuel J
authors: SJ
authors: Stratton
authors: Franklin D
authors: FD
authors: Pratt
authors: Scott
authors: S
authors: Hamilton
authors: Robin
authors: R
authors: Conwit
authors: David S
authors: DS
authors: Liebeskind
authors: Gene
authors: G
authors: Sung
authors: Ian
authors: I
authors: Kramer
authors: Gary
authors: G
authors: Moreau
authors: Robert
authors: R
authors: Goldweber
authors: Nerses
authors: N
authors: Sanossian
mesh_terms: D000208:Acute Disease; D000368:Aged; D002545:Brain Ischemia / Q000150:complications; D004311:Double-Blind Method; D004632:Emergency Medical Services; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D007262:Infusions, Intravenous; D020300:Intracranial Hemorrhages / Q000150:complications; D008278:Magnesium Sulfate / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D061665:Time-to-Treatment
chemical_list: D018696:Neuroprotective Agents; D008278:Magnesium Sulfate
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