title: Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage: Individual Patient Data Meta-Analysis.
abstract: OBJECTIVE
  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).
  
  
  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.
authors.affiliation: 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.).
authors.forename: Sanne M
authors.initials: SM
authors.lastname: Dorhout Mees
authors.affiliation: 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.).
authors.forename: Ale
authors.initials: A
authors.lastname: Algra
authors.affiliation: 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.).
authors.forename: George K C
authors.initials: GK
authors.lastname: Wong
authors.affiliation: 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.).
authors.forename: Wai S
authors.initials: WS
authors.lastname: Poon
authors.affiliation: 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.).
authors.forename: Celia M
authors.initials: CM
authors.lastname: Bradford
authors.affiliation: 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.).
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Saver
authors.affiliation: 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.).
authors.forename: Sidney
authors.initials: S
authors.lastname: Starkman
authors.affiliation: 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.).
authors.forename: Gabriel J E
authors.initials: GJ
authors.lastname: Rinkel
authors.affiliation: 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.). w.m.van.den.bergh@umcg.nl.
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authors.initials: WM
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mesh_terms: D017542:Aneurysm, Ruptured / Q000150:complications; D002545:Brain Ischemia / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000627:therapeutic use; D061345:Early Medical Intervention; D006801:Humans; D002532:Intracranial Aneurysm; D008278:Magnesium Sulfate / Q000008:administration & dosage* / Q000627:therapeutic use; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D061665:Time-to-Treatment / Q000706:statistics & numerical data*; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000517:prevention & control*
chemical_list: D002121:Calcium Channel Blockers; D008278:Magnesium Sulfate
keywords: brain ischemia; magnesium; meta-analysis; stroke; subarachnoid hemorrhage