http://stroke.ahajournals.org/content/46/11/3190.abstract?sid=91e31b88-1bd1-4122-8871-1b3d3f007f8c
Individual Patient Data Meta-Analysis
- Sanne M. Dorhout Mees, MD, PhD;
- Ale Algra, MD, PhD;
- George K.C. Wong, MD;
- Wai S. Poon, MBChB;
- Celia M. Bradford, MD;
- Jeffrey L. Saver, MD;
- Sidney Starkman, MD;
- Gabriel J.E. Rinkel, MD;
- Walter M. van den Bergh, MD, PhD;
- on behalf of the writing groups of MASH-I, IMASH, MASH-II, MASH and FAST-MAG
+ Author Affiliations
- Correspondence to Walter M. van den Bergh, MD, PhD, Department of Critical Care, University Medical Center Groningen, University of Groningen, Room BA.49, PO Box 30001, 9700 RB Groningen, The Netherlands. E-mail w.m.van.den.bergh@umcg.nl
Abstract
Background and Purpose—Delayed
cerebral ischemia (DCI) is an important cause of poor outcome after
aneurysmal subarachnoid hemorrhage (SAH). Trials
of magnesium treatment starting <4 days
after symptom onset found no effect on poor outcome or DCI in SAH.
Earlier installment
of treatment might be more effective, but
individual trials had not enough power for such a subanalysis. We
performed an individual
patient data meta-analysis to study whether
magnesium is effective when given within different time frames within 24
hours
after the SAH.
Methods—Patients
were divided into categories according to the delay between symptom
onset and start of the study medication: <6,
6 to 12, 12 to 24, and >24 hours. We
calculated adjusted risk ratios with corresponding 95% confidence
intervals for magnesium
versus placebo treatment for poor outcome and
DCI.
Results—We included
5 trials totaling 1981 patients; 83 patients started treatment <6
hours. For poor outcome, the adjusted risk ratios
of magnesium treatment for start <6 hours
were 1.44 (95% confidence interval, 0.83–2.51); for 6 to 12 hours 1.03
(0.65–1.63),
for 12 to 24 hours 0.84 (0.65–1.09), and for
>24 hours 1.06 (0.87–1.31), and for DCI, <6 hours 1.76
(0.68–4.58), for 6 to
12 hours 2.09 (0.99–4.39), for 12 to 24 hours
0.80 (0.56–1.16), and for >24 hours 1.08 (0.88–1.32).
The
primary endpoint was poor clinical outcome (mrs 4-5) or death at 3-6
months, with a secondary endpoint of delayed cerebral ischemia (which
was determined differently by each trial).
Conclusions—This
meta-analysis suggests no beneficial effect of magnesium treatment on
poor outcome or DCI when started early after SAH
onset. Although the number of patients was
small and a beneficial effect cannot be definitively excluded, we found
no justification
for a new trial with early magnesium
treatment after SAH.
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