Zabramski J M, Spetzler R F, Lee K S, Papadopoulos S M, Bovill E, Zimmerman R S, Bederson J B
Division of Neurological Surgery, Barrow Neurological Institute, Phoenix, Arizona.
J Neurosurg. 1991 Aug;75(2):189-96. doi: 10.3171/jns.1991.75.2.0189.
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.
近期的实验室研究表明，脑池内注射重组组织型纤溶酶原激活剂（rt-PA）可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。本文报告了10例确诊为动脉瘤性蛛网膜下腔出血（SAH）患者进行脑池内rt-PA治疗的I期初步试验结果。所有入选患者均为临床III级或IV级（根据Hunt和Hess分级），基底池和大脑主要脑沟内有浓稠血块或血液层（Fisher 3级）。在出血后48小时内进行了脑室造瘘术和动脉瘤夹闭手术。1例患者在缝合硬脑膜前将10 mg rt-PA注入蛛网膜下腔。其余9例患者在蛛网膜下腔留置一根小硅胶导管，术后12至24小时注入rt-PA（4例为5 mg，5例为1.5 mg（每8小时0.5 mg，共输注3次））。所有接受5或10 mg rt-PA治疗的患者均出现轻微局部出血并发症。5例患者中有4例手术切口部位渗血，2例患者脑室造瘘部位渗血。1例患者出现小的硬膜外血肿，经延迟引流治疗。接受较低剂量rt-PA方案（每次输注0.5 mg，共3次）的患者未出现出血并发症。连续凝血研究未发现全身纤溶的证据。对脑池脑脊液样本的分析显示，溶栓组织型纤溶酶原激活剂（t-PA）水平持续24至48小时。破裂后7至8天的随访脑血管造影显示，9例患者有轻度至中度痉挛，1例小脑后下动脉动脉瘤出血患者椎动脉有严重局灶性痉挛，但无症状。这些结果表明，rt-PA术后治疗可能有效降低迟发性脑血管痉挛的严重程度。连续t-PA水平结果表明，每8小时分次给药的较低剂量方案耐受性良好，甚至更低剂量可能也有效。显然需要进一步研究。
