Prophylactic intravenous magnesium sulfate for treatment of aneurysmal subarachnoid hemorrhage: a randomized, placebo-controlled, clinical study.
OBJECTIVE
To examine whether the maintenance of elevated magnesium serum concentrations by intravenous administration of magnesium sulfate can reduce the occurrence of cerebral ischemic events after aneurysmal subarachnoid hemorrhage.


METHODS
Prospective, randomized, placebo-controlled study.


METHODS
Neurosurgical intensive care unit of a University hospital.


METHODS
One hundred ten patients were randomized to receive intravenous magnesium sulfate or to serve as controls. Magnesium treatment was started with a bolus of 16 mmol, followed by continuous infusion of 8 mmol/hr. Serum concentrations were measured every 8 hrs, and infusion rates were adjusted to maintain target levels of 2.0-2.5 mmol/L. Intravenous administration was continued for 10 days or until signs of vasospasm had resolved. Thereafter, magnesium was administered orally and tapered over 12 days.


RESULTS
Delayed ischemic infarction (primary end point) was assessed by analyzing serial computed tomography scans. Transcranial Doppler sonography and digital subtraction angiography were used to detect vasospasm. Delayed ischemic neurologic deficit was determined by continuous detailed neurologic examinations; clinical outcome after 6 months was assessed using the Glasgow outcome scale. Good outcome was defined as Glasgow outcome scale score 4 and 5.The incidence of delayed ischemic infarction was significantly lower in magnesium-treated patients (22% vs. 51%; p = .002); 34 of 54 magnesium patients and 27 of 53 control patients reached good outcome (p = .209). Delayed ischemic neurologic deficit was nonsignificantly reduced (9 of 54 vs. 15 of 53 patients; p = .149) and transcranial Doppler-detected/angiographic vasospasm was significantly reduced in the magnesium group (36 of 54 vs. 45 of 53 patients; p = .028). Fewer patients with signs of vasospasm had delayed cerebral infarction.


CONCLUSIONS
These data indicate that high-dose intravenous magnesium can reduce cerebral ischemic events after aneurysmal subarachnoid hemorrhage by attenuating vasospasm and increasing the ischemic tolerance during critical hypoperfusion.
Department of Neurosurgery, University of Wuerzburg, Wuerzburg, Germany. Westermaier.T@nch.uni-wuerzburg.de
Thomas
T
Westermaier
Christian
C
Stetter
Giles H
GH
Vince
Mirko
M
Pham
Jose Perez
JP
Tejon
Jörg
J
Eriskat
Ekkehard
E
Kunze
Cordula
C
Matthies
Ralf-Ingo
RI
Ernestus
Laszlo
L
Solymosi
Klaus
K
Roosen
D000328:Adult; D000368:Aged; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006785:Hospitals, University; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000209:etiology / Q000517:prevention & control; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D002532:Intracranial Aneurysm / Q000150:complications*; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000517:prevention & control*
D002121:Calcium Channel Blockers; D008278:Magnesium Sulfate