不同剂量替罗非班在支架辅助栓塞颅内破裂动脉瘤中的应用比较

Application comparison of different doses of tirofiban in stent-assisted coil embolization of ruptured intracranial aneurysms

目的比较不同剂量替罗非班作为支架辅助栓塞治疗颅内破裂动脉瘤术中抗血小板聚集替代方案的安全性和有效性。方法回顾性连续纳入2014年1月至2018年6月第二军医大学附属长海医院神经外科行支架辅助栓塞治疗的破裂动脉瘤患者309例,根据所接受的术中替罗非班药物剂量,分为标准组[211例,10μg/kg静脉注射3 min,0.15μg/(kg·min)微泵维持]和半量组[98例,5μg/kg静脉注射3 min,0.075μg/(kg·min)微泵维持],对两组的人口学资料、动脉瘤形态数据、围术期并发症情况、术后即刻栓塞程度及出院状况进行统计学分析并比较。结果 (1)标准组与半量组患者年龄、性别、高血压病史、入院Hunt-Hess分级以及动脉瘤瘤颈、最大径、动脉瘤部位、是否多发动脉瘤组间差异均无统计学意义(均P>0.05)。(2)缺血并发症共15例(4.9%),其中标准组11例(5.2%),半量组4例(4.1%),组间差异无统计学意义(P>0.05),剔除1例标准组中操作相关缺血并发症后,组间差异仍无统计学意义[4.7%(10/211)比4.1%(4/98),P=1.000]。出血并发症共13例(4.2%),均出现于标准组,组间差异有统计学意义(6.2%比0,P=0.011),剔除2例操作相关出血后,组间差异仍有统计学意义[5.2%(11/211)比0(0/98),P=0.019]。术后早期再出血(10例)并发症发生率两组间差异有统计学意义(4.7%比0,P=0.034)。10例术后早期再出血中,8例于术后10 h内微泵维持替罗非班期间发生,均为致死(5例)、致残(3例)性出血。(3)标准组与半量组术后即刻致密栓塞率、瘤颈残余率及瘤体残余率分别为39.8%(84/211)、18.5%(39/211)、41.7%(88/211)和55.1%(54/98)、9.2%(9/98)、35.7%(35/98),差异有统计学意义(P=0.020)。(4)与半量组比较,标准组预后良好(改良Rankin量表评分0～2分)率[78.7%(166/211)比87.8%(86/98)]和死亡率[5.7%(12/211)比1.0%(1/98)]差异均无统计学意义(均P>0.05)。结论对于破裂动脉瘤行支架辅助栓塞治疗的患者,术中经静脉给予替罗非班抗血小板聚集安全有效,是术前双联抗血小板聚集方案的可行替代方案;标准剂量替罗非班可能与术后严重出血事件相关,剂量减半后可降低出血风险。

Objective To compare the safety and efficacy of different doses of tirofiban as an antiplatelet aggregation alternative for stent-assisted coil embolization in the treatment of ruptured intracranial aneurysms. Methods From January 2014 to June 2018,309 patients with ruptured intracranial aneurysm treated with stent-assisted coil embolization at the Department of Neurosurgery,Changhai Hospital,the Second Military Medical University were enrolled retrospectively. They were divided into either a standard group（ n = 211,intravenous injection of 10 μg/kg for 3 min,0. 15 μg/[kg·min]micro-pump maintenance） or a half-dose group（ n = 98,intravenous injection of 5 μg/kg for 3 min,0. 075 μg [kg·min] micro-pump maintenance） according to the doses of tirofiban administered during the operation. The demographic information,morphologic data of aneurysms,perioperative complications,immediate embolization degree,and discharge status after surgery were statistically analyzed and compared between the two groups. Results（ 1） There were no significant differences in age,gender,history of hypertension,HuntHess grade on admission,as well as aneurysm neck,maximal diameter,aneurysm site,whether having multiple aneurysms between the standard group and the half-dose group（ all P 0. 05）.（ 2） A total of 15 patients（ 4. 9%） had ischemic complications,including 11（ 5. 2%） in the standard group and 4（ 4. 1%） in the half-dose group. There was no significant difference between the groups（ P 0. 05）. After excluding the ischemic complications associated with operation in one case in the standard group,there was no statistically significant difference between the groups（ 4. 7 % [10/211] vs. 4. 1 % [4/98 ],P =1. 000）. A total of 13 patients（ 4. 2%） had bleeding complications in the standard group,and the difference was statistically significant between the groups（ 6. 2 % vs. 0,P = 0. 0 1 1）. After excluding 2 cases of operation-related rebleeding complications,the differences between the groups were still statistically significant（ 5. 2%[11/211]vs. 0 [0/98],P = 0. 019）. There was significant difference in the incidence of early rebleeding（ n = 10） complications between the two groups（ 4. 7% vs. 0,P = 0. 034）. In 10 patients with early postoperative rebleeding,8 cases occurred during the maintenance period of tirofiban within 10 h after procedure,all were fatal（ n = 5） and disabling（ n = 3） bleeding.（ 3） The immediate dense embolization rate,aneurysm neck residual rate,and aneurysm residual rate in the standard group and the half-dose group were 39. 8%（ 84/211）,18. 5%（ 39/211）,41. 7%（ 88/211）,and 55. 1%（ 54/98）,9. 2%（ 9/98）,35. 7%（ 35/98）,respectively. The differences were statistically significant（ P = 0. 020）.（ 4） Compared with the half-dose group,there were no significant differences in good prognosis（ modified Rankin Scale score 0-2） rate（ 78. 7% [166/211] vs. 87. 8% [86/98 ]） and mortality rate（ 5. 7% [12/211]vs. 1. 0% [1/98] in the the standard group（ all P〉 0. 05）. Conclusions For patients with ruptured aneurysm undergoing stent-assisted coil embolization,intravenous administration of tirofiban during the operation is a safe and effective. It is a feasible alternative of preoperative dual antiplatelet aggregation protocol. Standard dose of tirofiban may be associated with postoperative severe bleeding events. After halving the dose,it may reduce the risk of bleeding.