Haley E C, Kassell N F, Torner J C
Department of Neurology, University of Virginia Health Sciences Center, Charlottesville.
J Neurosurg. 1993 Apr;78(4):537-47. doi: 10.3171/jns.1993.78.4.0537.
Because of their action as cerebral vasodilators, dihydropyridine calcium antagonists have received intense scrutiny for their potential benefit in ameliorating the devastating consequences of delayed cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH). From October, 1987, to September, 1989, 41 North American neurosurgical centers in the Cooperative Aneurysm Study accrued 906 patients with recent (Days 0 to 7) aneurysmal SAH into a prospective randomized double-blind placebo-controlled trial of high-dose intravenous nicardipine to test whether treatment with this agent improved overall outcome. Eligible patients received 0.15 mg/kg/hr of either nicardipine or placebo by continuous infusion for up to 14 days following hemorrhage. The 449 patients randomly assigned to the nicardipine-treated group and the 457 patients assigned to the placebo-treated group were balanced with regard to prognostic factors for ischemic deficits from vasospasm and for overall outcome. Other medical and surgical interventions were used with similar frequency in both groups, except that antihypertensive agents were used less frequently in the nicardipine-treated patients (26% of the nicardipine-treated group vs. 43% of the placebo-treated group, p < 0.001), and more patients in the placebo-treated group had intentional hypervolemia, induced hypertension, and/or hemodilution administered therapeutically for symptomatic vasospasm (38% of the placebo-treated group vs. 25% of the nicardipine-treated group, p < 0.001). The incidence of symptomatic vasospasm during the treatment period was higher in the placebo-treated group (46%) than in the nicardipine-treated group (32%) (p < 0.001). Despite the reduction in symptomatic vasospasm in the nicardipine-treated group, overall outcome at 3 months was similar between the two groups. Fifty-five percent of nicardipine-treated patients were rated as having a good recovery according to the Glasgow Outcome Scale at follow-up review and 17% were dead, compared to 56% and 18%, respectively, in the placebo-treated group (not statistically significant). These data suggest that high-dose intravenous nicardipine treatment is associated with a reduced incidence of symptomatic vasospasm in patients with recent aneurysmal SAH, but not with an improvement in overall outcome at 3 months when compared to standard management in North America. It is postulated that, while nicardipine prevents vasospasm, hypertensive/hypervolemic therapy may be effective in reversing ischemic deficits from vasospasm once they occur.
由于二氢吡啶类钙拮抗剂具有脑血管扩张作用，其在改善动脉瘤性蛛网膜下腔出血（SAH）后迟发性脑血管痉挛的灾难性后果方面的潜在益处受到了密切关注。1987年10月至1989年9月，北美41个神经外科中心参与了合作动脉瘤研究，将906例近期（0至7天）发生动脉瘤性SAH的患者纳入一项前瞻性随机双盲安慰剂对照试验，以测试高剂量静脉注射尼卡地平治疗是否能改善总体预后。符合条件的患者在出血后连续输注尼卡地平或安慰剂，剂量为0.15mg/kg/hr，持续14天。随机分配到尼卡地平治疗组的449例患者和分配到安慰剂治疗组的457例患者在血管痉挛导致缺血性缺陷的预后因素和总体预后方面是平衡的。两组使用其他药物和手术干预的频率相似，但尼卡地平治疗的患者使用抗高血压药物的频率较低（尼卡地平治疗组为26%，安慰剂治疗组为43%，p<0.001），安慰剂治疗组更多患者因症状性血管痉挛接受了治疗性的故意高血容量、诱导性高血压和/或血液稀释（安慰剂治疗组为38%，尼卡地平治疗组为25%，p<0.001）。治疗期间，安慰剂治疗组症状性血管痉挛的发生率高于尼卡地平治疗组（46%对32%）（p<0.001）。尽管尼卡地平治疗组症状性血管痉挛有所减少，但两组3个月时的总体预后相似。随访复查时，根据格拉斯哥预后量表，尼卡地平治疗组55%的患者被评为恢复良好，17%死亡，而安慰剂治疗组分别为56%和18%（无统计学意义）。这些数据表明，高剂量静脉注射尼卡地平治疗与近期动脉瘤性SAH患者症状性血管痉挛的发生率降低有关，但与北美标准治疗相比，3个月时总体预后并无改善。据推测，虽然尼卡地平可预防血管痉挛，但一旦血管痉挛导致缺血性缺陷发生，高血压/高血容量治疗可能有效逆转这些缺陷。
