Intravenous magnesium versus nimodipine in the treatment of patients with aneurysmal subarachnoid hemorrhage: a randomized study.
OBJECTIVE
The prophylactic use of nimodipine in patients with aneurysmal subarachnoid hemorrhage reduces the risk of ischemic brain damage. However, its efficacy seems to be rather moderate. The question arises whether other types of calcium antagonists offer better protection. Magnesium, nature's physiological calcium antagonist, is neuroprotective in animal models, promotes dilatation of cerebral arteries, and has an established safety profile. The aim of the current pilot study is to evaluate the efficacy of magnesium versus nimodipine to prevent delayed ischemic deficits after aneurysmal subarachnoid hemorrhage.


METHODS
One hundred and thirteen patients with aneurysmal subarachnoid hemorrhage were enrolled in the study and were randomized to receive either magnesium sulfate (loading 10 mg/kg followed by 30 mg/kg daily) or nimodipine (48 mg/d) intravenously until at least postoperative Day 7. Primary outcome parameters were incidence of clinical vasospasm and infarction. Secondary outcome measures were the incidence of transcranial Doppler/angiographic vasospasm, the neuronal markers (neuron-specific enolase, S-100), and the patients' Glasgow Outcome Scale scores at discharge and after 1 year.


RESULTS
One hundred and four patients met the study requirements. In the magnesium group (n = 53), eight patients (15%) experienced clinical vasospasm and 20 (38%) experienced transcranial Doppler/angiographic vasospasm compared with 14 (27%) and 17 (33%) patients in the nimodipine group (n = 51). If clinical vasospasm occurred, 75% of the magnesium-treated versus 50% of the nimodipine-treated patients experienced cerebral infarction resulting in fatal outcome in 37 and 14%, respectively. Overall, the rate of infarction attributable to vasospasm was virtually the same (19 versus 22%). There was no difference in outcome between groups.


CONCLUSIONS
The efficacy of magnesium in preventing delayed ischemic neurological deficits in patients with aneurysmal subarachnoid hemorrhage seems to be comparable with that of nimodipine. The difference in their pharmacological properties makes studies on the combined administration of magnesium and nimodipine seem promising.
Schmid-Elsaesser
Robert
R
Department of Neurosurgery, Ludwig-Maximilians-Universität, Munich, Germany. Schmid-Elsaesser@med.uni-muenchen.de
Kunz
Matthias
M
Zausinger
Stefan
S
Prueckner
Stefan
S
Briegel
Josef
J
Steiger
Hans-Jakob
HJ
D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000627:therapeutic use; D002533:Cerebral Angiography; D002544:Cerebral Infarction / Q000453:epidemiology / Q000209:etiology / Q000401:mortality; D005260:Female; D006801:Humans; D015994:Incidence; D007275:Injections, Intravenous; D002532:Intracranial Aneurysm / Q000150:complications*; D008274:Magnesium / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009553:Nimodipine / Q000008:administration & dosage* / Q000627:therapeutic use; D010865:Pilot Projects; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000209:etiology*; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial; D020301:Vasospasm, Intracranial / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology
D002121:Calcium Channel Blockers; D009553:Nimodipine; D008274:Magnesium