Effect of fasudil hydrochloride, a protein kinase inhibitor, on cerebral vasospasm and delayed cerebral ischemic symptoms after aneurysmal subarachnoid hemorrhage.
The efficacy and safety of fasudil hydrochloride, a novel protein kinase inhibitor, were evaluated for the treatment of cerebral vasospasm and associated cerebral ischemic symptoms in patients with ruptured cerebral aneurysm. This randomized open trial with nimodipine as the control included 72 patients who underwent subarachnoid hemorrhage surgery for ruptured cerebral aneurysm of Hunt and Hess grades I to IV. For 14 days following surgery, patients were administered either 30 mg of fasudil hydrochloride by intravenous injection over a period of 30 minutes three times a day or 1 mg/hr of nimodipine by continuous intravenous infusion. Fasudil hydrochloride and nimodipine both showed inhibitory effects on cerebral vasospasm. The incidence of symptomatic vasospasm was five of 33 patients in the fasudil group and nine of 32 patients in the nimodipine group. Good recovery evaluated by the Glasgow Outcome Scale was achieved by 23 of 33 patients in the fasudil group and 19 of 34 patients in the nimodipine group. Both drugs significantly improved consciousness levels and neurological deficits such as aphasia. However, fasudil hydrochloride improved motor disturbance more than nimodipine. Adverse reactions occurred in 13 of 37 patients receiving fasudil hydrochloride and 15 of 35 patients receiving nimodipine. There were no serious adverse events in the fasudil group. The results of this clinical trial indicate that fasudil hydrochloride is a safe and efficient agent for suppressing cerebral vasospasm after subarachnoid hemorrhage surgery for ruptured cerebral aneurysm.
Zhao
Jizong
J
Department of Neurosurgery, Capital Medical University Affiliated Beijing Tiantan Hospital, Beijing PRC. zhaojz@public.bta.net.cn
Zhou
Dingbiao
D
Guo
Jing
J
Ren
Zyuan
Z
Zhou
Liangfu
L
Wang
Shuo
S
Xu
Bainan
B
Wang
Renzhi
R
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009553:Nimodipine / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000601:surgery; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000517:prevention & control*
D047428:Protein Kinase Inhibitors; D014665:Vasodilator Agents; D009553:Nimodipine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049347:fasudil