Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage

The failure could easily been because they were using invalid endpoints like the Rankin scale.
http://stroke.ahajournals.org/content/46/11/3190.abstract?sid=91e31b88-1bd1-4122-8871-1b3d3f007f8c

Individual Patient Data Meta-Analysis

1. Sanne M. Dorhout Mees, MD, PhD;
2. Ale Algra, MD, PhD;
3. George K.C. Wong, MD;
4. Wai S. Poon, MBChB;
5. Celia M. Bradford, MD;
6. Jeffrey L. Saver, MD;
7. Sidney Starkman, MD;
8. Gabriel J.E. Rinkel, MD;
9. Walter M. van den Bergh, MD, PhD;
10. on behalf of the writing groups of MASH-I, IMASH, MASH-II, MASH and FAST-MAG

+ Author Affiliations

1. From the Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience (S.M.D.M., A.A., G.J.E.R.) and Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht, Utrecht, The Netherlands; Division of Neurosurgery, Department of Critical Care, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China (G.K.C.W., W.S.P.); Department of Critical Care, Royal North Shore Hospital, Sydney, Australia (C.M.B.); Department of Neurology (J.L.S.) and Departments of Emergency Medicine and Neurology (S.S.), Comprehensive Stroke Center, David Geffen School of Medicine at the University of California, Los Angeles; and Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands (W.M.v.d.B.).

1. 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.