Magnesium sulfate for neuroprotection after traumatic brain injury: a randomised controlled trial.
BACKGROUND
Traumatic brain injuries represent an important and costly health problem. Supplemental magnesium positively affects many of the processes involved in secondary injury after traumatic brain injury and consistently improves outcome in animal models. We aimed to test whether treatment with magnesium favourably affects outcome in head-injured patients.


METHODS
In a double-blind trial, 499 patients aged 14 years or older admitted to a level 1 regional trauma centre between August, 1998, and October, 2004, with moderate or severe traumatic brain injury were randomly assigned one of two doses of magnesium or placebo within 8 h of injury and continuing for 5 days. Magnesium doses were targeted to achieve serum magnesium ranges of 1.0-1.85 mmol/L or 1.25-2.5 mmol/L. The primary outcome was a composite of mortality, seizures, functional measures, and neuropsychological tests assessed up to 6 months after injury. Analyses were done according to the intention-to-treat principle. This trial is registered with , number .


RESULTS
Magnesium showed no significant positive effect on the composite primary outcome measure at the higher dose (mean=55 average percentile ranking on magnesium vs 52 on placebo, 95% CI for difference -7 to 14; p=0.70). Those randomly assigned magnesium at the lower dose did significantly worse than those assigned placebo (48 vs 54, 95% CI -10.5 to -2; p=0.007). Furthermore, there was higher mortality with the higher magnesium dose than with placebo. Other major medical complications were similar between groups, except for a slight excess of pulmonary oedema and respiratory failure in the lower magnesium target group. No subgroups were identified in which magnesium had a significantly positive effect.


CONCLUSIONS
Continuous infusions of magnesium for 5 days given to patients within 8 h of moderate or severe traumatic brain injury were not neuroprotective and might even have a negative effect in the treatment of significant head injury.
Temkin
Nancy R
NR
Department of Neurological Surgery, University of Washington, Seattle, USA. temkin@u.washington.edu
Anderson
Gail D
GD
Winn
H Richard
HR
Ellenbogen
Richard G
RG
Britz
Gavin W
GW
Schuster
James
J
Lucas
Timothy
T
Newell
David W
DW
Mansfield
Pamela Nelson
PN
Machamer
Joan E
JE
Barber
Jason
J
Dikmen
Sureyya S
SS
D000293:Adolescent; D000328:Adult; D000368:Aged; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D008274:Magnesium / Q000097:blood; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D011654:Pulmonary Edema / Q000453:epidemiology / Q000209:etiology; D012131:Respiratory Insufficiency / Q000453:epidemiology / Q000209:etiology; D012640:Seizures / Q000453:epidemiology / Q000209:etiology; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D008278:Magnesium Sulfate; D008274:Magnesium