TY - JOUR
T1 - Magnesium sulfate for neuroprotection after traumatic brain injury
T2 - a randomised controlled trial
AU - Temkin, Nancy R.
AU - Anderson, Gail D.
AU - Winn, H. Richard
AU - Ellenbogen, Richard G.
AU - Britz, Gavin W.
AU - Schuster, James
AU - Lucas, Timothy
AU - Newell, David W.
AU - Mansfield, Pamela Nelson
AU - Machamer, Joan E.
AU - Barber, Jason
AU - Dikmen, Sureyya S.
N1 - Funding Information:
This study was supported by a grant (R01 NS19643, PIs: H R Winn and N RTemkin) from the NINDS/NIH. We thank the patients and families who participated in the study and the data and safety monitoring boards (Joseph F Collins, Thomas R McCormick, Steven Roper, Nina Graves, Richard G Ellenbogen, Jacqueline K Benedetti).
PY - 2007/1
Y1 - 2007/1
N2 - 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 Clinicaltrials.gov, number NCT00004730. Findings: 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. Interpretation: 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.
AB - 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 Clinicaltrials.gov, number NCT00004730. Findings: 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. Interpretation: 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.
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U2 - 10.1016/S1474-4422(06)70630-5
DO - 10.1016/S1474-4422(06)70630-5
M3 - Article
C2 - 17166799
AN - SCOPUS:33845309465
SN - 1474-4422
VL - 6
SP - 29
EP - 38
JO - Lancet Neurology
JF - Lancet Neurology
IS - 1
ER -