Phase I trial of tissue plasminogen activator for the prevention of vasospasm in patients with aneurysmal subarachnoid hemorrhage.
Phase I trial of tissue plasminogen activator for the prevention of vasospasm in patients with aneurysmal subarachnoid hemorrhage.
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组织纤溶酶原激活剂预防动脉瘤性蛛网膜下腔出血患者血管痉挛的 I 期试验。
DOI：
10.3171/jns.1991.75.2.0189
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发表时间：
1991
影响因子：
4.1
通讯作者：
Bederson
中科院分区：
文献类型：
--
作者：
J. Zabramski;K. Lee;M. Stephen;Papadopoulos;EOWiN Bovill;Richard S. Zimmerman;B. Joshua;Bederson
最近的实验室研究表明，脑池内施用重组组织纤溶酶原激活剂（rt-PA）可以促进蛛网膜下腔血液的正常清除，并预防或改善迟发性动脉痉挛。报告了 10 名患有动脉瘤性蛛网膜下腔出血 (SAH) 患者的脑池内 rt-PA 初步 I 期试验的结果。所有入组患者均被分类为临床 III 级或 IV 级（根据 Hunt 和 Hess），基底池和主要脑裂处有厚厚的凝块或血层（Fisher 3 级）。出血后 48 小时内进行了脑室造口术和动脉瘤夹闭手术。在一名患者中，在闭合硬脑膜之前将 10 mg rt-PA 滴入蛛网膜下腔。其余 9 名患者在蛛网膜下腔留置小硅胶导管，术后 12 至 24 小时滴注 rt-PA（4 例 5 mg，5 例 1.5 mg（每 8 小时 0.5 mg，输注 3 次））。所有接受 5 或 10 mg rt-PA 的患者均出现轻微局部出血并发症。五名患者中的四名在手术切口部位发现渗血，两名患者在脑室造口部位发现渗血。一名患者出现了小的硬膜外血肿，通过延迟引流治疗。接受较低 rt-PA 方案（每次 0.5 mg 输注 3 次）的患者未发现出血并发症。连续凝血研究表明没有全身纤维蛋白溶解的证据。对脑池脑脊液样本的分析显示，溶栓组织纤溶酶原激活剂 (t-PA) 水平持续 24 至 48 小时。破裂后7至8天的后续脑血管造影显示，9名患者出现轻度至中度痉挛，而一名小脑后下动脉瘤出血患者出现无症状的严重椎动脉局灶性痉挛。这些结果表明，术后使用 rt-PA 治疗可能有效减轻迟发性脑血管痉挛的严重程度。连续 t-PA 水平的结果表明，以 8 小时间隔给药的较低剂量方案具有良好的耐受性，甚至更低的剂量也可能有效。进一步的研究已明确指出。
Recent laboratory studies have demonstrated that intracisternal administration of recombinant tissue plasminogen activator (rt-PA) can facilitate the normal clearing of blood from the subarachnoid space and prevent or ameliorate delayed arterial spasm. The results of a preliminary Phase I trial of intracisternal rt-PA in 10 patients are reported with documented aneurysmal subarachnoid hemorrhage (SAH). All patients enrolled were classified as clinical Grade III or IV (according to Hunt and Hess) with thick clots or layers of blood in the basal cisterns and major cerebral fissures (Fisher Grade 3). Ventriculostomy and surgery for clipping of the aneurysms were performed within 48 hours of hemorrhage. In one patient, 10 mg rt-PA was instilled into the subarachnoid cisterns prior to closing the dura. In the remaining nine patients, a small silicone catheter was left in the subarachnoid space and rt-PA (5 mg in four cases or 1.5 mg (0.5 mg every 8 hours for three infusions) in five cases) was instilled 12 to 24 hours after surgery. Minor local bleeding complications were noted in all patients receiving 5 or 10 mg rt-PA. Oozing was noted at the operative incision site in four of five patients and at the ventriculostomy site in two patients. One patient developed a small epidural hematoma that was treated by delayed drainage. No bleeding complications were noted in the patients receiving the lower regimen of rt-PA (three infusions of 0.5 mg each). Serial coagulation studies demonstrated no evidence of systemic fibrinolysis. Analysis of cisternal cerebrospinal fluid samples revealed thrombolytic tissue plasminogen activator (t-PA) levels for 24 to 48 hours. Follow-up cerebral angiography 7 to 8 days after rupture disclosed mild to moderate spasm in nine patients, while one patient with hemorrhage from a posterior inferior cerebellar artery aneurysm had severe focal spasm of the vertebral arteries that was not symptomatic. These results suggest that postoperative treatment with rt-PA may be effective in reducing the severity of delayed cerebral vasospasm. The results of serial t-PA levels suggest that the lower dosage regimen with divided dosages at 8-hour intervals is well tolerated and that even lower dosages may be effective. Further studies are clearly indicated.
影响因子：
37.8
作者：
Stump,DC;Califf,RM;Topol,EJ;Sigmon,K;Thornton,D;Masek,R;Anderson,L;Collen,D
通讯作者：
Collen,D
鞘内纤溶治疗时机对灵长类蛛网膜下腔出血模型脑血管痉挛的影响。
影响因子：
4.8
作者：
Findlay,JM;Weir,BK;Kanamaru,K;Grace,M;Baughman,R
通讯作者：
Baughman,R