Ca++拮抗薬 Diltiazem による遅発性脳血管攣縮の予防と治療

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The clinical effects of diltiazem on cerebral vasospasm were evaluated in 38 patients with ruptured intracranial aneurysm. The drug was administered for therapeutic purpose of cerebral vasospasm to 21 cases (Group 1: 10 with associated cerebral vasospasm due to subarachnoid hemorrhage (SAH) and 11 with vasospasm after radical operation). The drug was also given for preventive purpose of postoperative development of vasospasm to 17 cases without arterial spasm in preoperative angiogram (Group 2). In general, 20 mg of diltiazem was initially administered by intravenous bolus injection, followed by continuous drip infusion of 60 mg per day for 7 days. Relief of vasospasm was evaluated by angiogram taken at suitable intervals under observation of clinical symptoms. The following results were obtained. 1) Following administration of diltiazem, clinical symptoms such as disturbance of consciousness, hemiplegia, and aphasia were improved in 12 (57.1%) of the 21 cases of group 1. 2) Improvement of clinical symptoms appeared between 24 and 72 hours after administration of diltiazem, which preceded complete relief of cerebral vasospasm. 3) Diltiazem was more effective on postoperative vasospasm than on vasospasm occurring after SAH in group 1. The drug was ineffective in most of the patients with such SAH acute complication as primary brain damage, brain swelling or acute hydrocephalus, and in whom intracranial pressure was severely elevated. A trend was seen for diltiazem to be less effective in patients over 65 years of age than younger patients. 4) Many cases responded to diltiazem satisfactorily when the medication was initiated within 5 or 6 days after the onset of vasospasm, while the drug was practically ineffective when it was started a week or more after the onset of vasospasm. 5) The efficacy of diltiazem was correlated closely with timing of medication rather than with severity of cerebral vasospasm; the correlation was detected in cases with more than 40 ng/ml of the blood drug level. 6) Cerebral vasospasm manifested in 4 of the 17 cases of preventive group (group 2). Of these 4 cases, 1 suffered from transient hemiparesis while 3 progressed asymtomatically. 7) Protective effect of diltiazem on the formation of ischemic lesion was evaluated in 103 control cases without diltiazem administration and 21 cases that received diltiazem treatment. There was no great difference in the incidence of infarction between the control and therapeutic group. As for extent of infarction, the lesion in the therapeutic group tended to be small in comparison with the control group. From this study, we can suggest that administration of diltiazem for the treatment of vasospasm should be instituted in the early stage after the onset of vasospasm or the drug should be prescribed for prevention of the onset of vasospasm.
The Japanese Society on Surgery for Cerebral Strokeの論文

Ca<SUP>++</SUP>拮抗薬 Diltiazem による遅発性脳血管攣縮の予防と治療

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