Previous studies of intra-arterial

Previous studies of intra-arterial thrombolysis for acute ischemic stroke
To date, three randomized studies evaluating the effect of intra-arterial thrombolysis on recanalization and outcome after ischemic stroke have been conducted. Patients with acute ischemic stroke and onset of symptoms within ± hours were evaluated in the PROACT I and II trials. In PROACT I, patients with TIMI Grade 0 or 1 occlusion of the M1 or M2segments of the MCA were randomized 2:1 to receive prourokinase (6 mg) or placebo over the course of 120 minutes into the thrombus (4). Of 105 patients who underwent angiography, 36 patients were randomized. All patients received intravenously administered heparin for 4 hours. The first 16patients received a 100-U/kg bolus, then a 100-U/h infusion during 4 hours. The remaining patients received a 4000-Ubolus intravenously, then a 500-U/h infusion. Partial or complete recanalization was observed in 15 of 36 patients treated with prourokinase and in 2 of 14 placebo-treated patients. Intracerebral hemorrhage was observed in 11 of the prourokinase-treated patients and 1 placebo-treated patient. In the PROACT II trial, 180 patients with documented angiographic occlusion of the MCA were randomized to receive either 9 mg of intra-arterial prourokinase and heparin or heparin alone (5). All patients received a 2000-U bolus, then a500-U/h infusion of heparin for 4 hours. A total of 121 patients received 9 mg of prourokinase during 2 hours. The recanalization rate was 66% in the prourokinase group and18% in the group treated with heparin alone. The rate of intracerebral hemorrhage associated with neurological deterioration was 10% in the prourokinase group and 2% in the heparin-only group. Forty percent of the patients treated with prourokinase had a modified Rankin score of 2 or less, compared with 25% in the control group. The Emergency Management of Stroke Bridging Trial evaluated the use of intravenous and intra-arterial alteplase in patients with acute ischemic stroke (9). According to the study protocol, patients received a 0.6-mg/kg dose of intravenously administered alteplase or placebo. After a catheter was placed intra-arterially in the proximity of the thrombus, 2 mg of alteplase was infused, then a 10-mg/h infusion. The maximum intra-arterial dose administered was 20 mg. Hemorrhagic infarction was observed on CT scan in 8 of the 35 patients (3 were symptomatic). A higher rate of recanalization was observed in patients who received higher doses of alteplase. The mean overall(intravenous and intra-arterial) dose of alteplase was 35.6mg in patients with final TIMI Grade 1 and 56.7 mg of dose with final TIMI Grade 3.A direct comparison of the results from our study with those from previous studies is not possible because of important differences in patient selection. An indirect comparison with PROACT II (5) suggests a higher rate of recanalization associated with the use of intra-arterially administered reteplase with or without angioplasty (TIMI Grade $2 in 94%)than with intra-arterial prourokinase without angioplasty(TIMI Grade $2 in 66%). This difference was observed despite the fact that PROACT II included only patients with either TIMI Grade 0 or 1 occlusion of the M1 or M2 division of the MCA. In our series, a large proportion (eight patients) displayed TIMI Grade 0 occlusion of the ICA, which is associated with a lower rate of recanalization than MCA occlusion (16).The overall rate of intracranial hemorrhage in our series was 25%. In PROACT II, the rate of any type of intracranial hemorrhage within the first 10 days was 68%. Intracranial hemorrhages with neurological deterioration (four-point or more increase in NIHSS score) occurred in 10% of 108 patients treated with prourokinase. We observed neurological deterioration (one-point or more increase in NIHSS score) associated with intracranial hemorrhage in 1 (6%) of the 16 patients treated. Overall, the rates of symptomatic intracranial hemorrhages were comparable, despite the more sensitive definition of deterioration in our study. The mortality rate was high (56%) in our study but does not seem to be directly related to intra-arterial treatment because most deaths (seven of nine) in our series were attributable to massive cerebral edema associated with infarction. In one patient (Patient 5), intracerebral hemorrhage contributed to the mass effect, in addition to infarction-related cerebraledema. In PROACT II, the 90-day mortality rate for prourokinase-treated patients was 25%. The higher mortality rate in our series may be related to the severity of initial deficits and other associated comorbid conditions. The median initial NIHSS score in our patients was 20 (range, 10–26),compared with 17 (range, 5–27) in the prourokinase-treated patients. Patients undergoing any surgical procedures within30 days of stroke onset were excluded in PROACT II but included in our series. Our study focused on determining immediate outcome after the use of intra-arterially administered reteplase. Therefore, no definite conclusions can be drawn with respect to long-term functional outcome.

結果 (中文) 1:

以前对动脉内溶栓治疗急性缺血性脑卒中的研究到目前为止，已进行了三项随机的研究缺血性脑卒中后评价动脉内溶栓治疗对血管再通与结果的影响。急性缺血性卒中和 ± 小时内的出现症状的患者进行评定在 PROACT 第一和第二试验。在 PROACT，TIMI 等级 0 或 1 的 M1 或 M2segments 的 MCA 闭塞患者被随机的 2:1 接受尿激酶原 (6 毫克) 或安慰剂，当然 120 分钟到血栓 (4)。105 术血管造影的患者 36 例患者被随机分配。所有患者接受静脉内都管理，肝素为 4 小时。第一 16patients 收到 100-U/公斤丸，然后在 4 个小时 100-U/h 输液。其余患者接受了 4000 Ubolus 静脉注射，然后 500-U/h 输液。部分或完全再通与会者在 15 36 患者尿激酶原和 2 14 安慰剂治疗的患者。11 的尿激酶原治疗的患者和 1 安慰剂治疗的患者中观察脑出血。在 PROACT II 试验中，马华记录造影闭塞 180 患者随机接受 9 毫克的动脉内尿激酶原和肝素或肝素单独 (5)。所有患者都接受 2000年-U 丸，然后 a500-U/h 输液的肝素为 4 小时。121 例共收到 9 毫克的尿激酶原在 2 个小时。再通率是 66%与肝素单独治疗组尿激酶原组 18 个 %。脑出血伴神经功能恶化率尿激酶原组为 10%和 2%只肝素组中。40%的患者尿激酶原已改良的 Rankin 比分的 2 或更少，相比对照组的 25%。应急管理的中风弥合试验评估静脉和动脉内阿替普酶 (9) 急性缺血性脑卒中患者的使用。按照试验方案、 患者收到 0.6-毫克/千克剂量静脉注射阿替普酶或安慰剂。一根导管动脉被放置在附近的血栓后，2 毫克的阿替普酶静脉滴注，然后 10-毫克/h 输液。最大的动脉内剂量药物是 20 毫克.出血性脑梗死观察 CT 扫描在 8 35 例患者 (3 例)。较高的再通率被观察患者接受高剂量的纤溶酶。总体均值 (静脉和动脉) 剂量的阿替普酶是 35.6 mg 患者最后 TIMI 等级 1 和 56.7 毫克的剂量与期末 TIMI 成绩重要的差异，在病人的选择 3.A 从我们的研究结果与那些从以往的研究直接比较是不可能。与 PROACT II (5) 间接比较建议使用所引起的动脉内少量管理瑞替普酶有或没有比与动脉成形术 (TIMI 级 $2 94%) 无血管成形术 (TIMI 美元 2 级 66%) 尿激酶原的再通的率高。这个差异尽管 PROACT II 包括唯一患者，要么 TIMI 等级 0 或 1 M1 或 M2 分工的 MCA 闭塞。在我们的系列，很大比例 (8 例) 显示 TIMI 0 级闭塞颈内动脉，这是与大脑中动脉闭塞 (16) 再通率低于相关联。在我们的系列颅内出血总体率为 25%。在 PROACT II，任何类型的颅内出血的头 10 天之内率为 68%。10%的 108 例尿激酶原发生颅出血与神经功能恶化 (四个点或更多增加 NIHSS 评分)。我们观察到神经功能恶化 (单点或更多增加 NIHSS 评分) 治疗 16 例伴颅内出血 1 (6%)。总体来看的症状性颅出血率可比性，尽管在我们的研究恶化更敏感定义。死亡率高 (56%) 在我们的研究却似乎并不直接与动脉内治疗，因为大多数死亡 (七个九) 在我们的系列被归因于大量脑水肿与梗死相关联。一个病人 (病人 5)，脑出血贡献占位效应，除了梗死相关的 cerebraledema。在 PROACT II，尿激酶原治疗的患者的 90 天死亡率约为 25%。在我们的系列中的病死率高可能与初始赤字的严重程度和其他相关的共病状况相关。在我们的病人中位数初始 NIHSS 评分中尿激酶原治疗的患者是 20 (范围，10-26)，相比 17 (范围，5-27)。患者的中风发病任何外科手术的 30 天之内被排除在 PROACT II，但列入我们的系列。我们的研究集中在动脉管理瑞替普酶在使用后确定直接成果。因此，没有明确的结论可以得出有关长期功能结局。

結果 (中文) 3:

对急性缺血性脑卒中动脉溶栓
日期之前的研究，三项随机研究评估缺血性脑卒中后溶栓再通和结局的影响进行了。急性缺血性脑卒中发病的症状在±小时评估患者在PROACT I和II期临床试验。我在PROACT，TIMI 0级或1的MCA M1或m2segments闭塞患者按2:1比例随机分配接受尿激酶原（6毫克）或安慰剂，在120分钟的课程为血栓（4）。105例患者行血管造影，36例患者随机分组。所有患者均接受静脉注射肝素4小时。第一例接受100-u /公斤丸，然后100-u／h输注期间4小时。其余的患者接受了4000 ubolus静脉，然后500-u／h输注。在15部分或全部36例尿激酶原和2 14安慰剂治疗的患者观察到血管再通治疗。在11的尿激酶原治疗的患者和1的安慰剂治疗的病人中观察到脑出血。在PROACT II试验，180例患者记录的MCA闭塞病变患者随机接受9毫克的动脉内尿激酶和肝素或肝素治疗（5）。所有的患者都接受了2000-u丸，然后a500-u／h输注肝素4小时。共有121例患者在2小时内收到9毫克的尿激酶原。血管再通率为66%与肝素单独治疗组的尿激酶原组18%。与神经功能恶化相关的脑出血率为10%，在对照组的尿激酶原组和2%。尿激酶治疗百分之四十患者改良Rankin评分2或更少，较对照组的25%。脑卒中的桥接试验应急管理评估的静脉和动脉内溶栓治疗的患者使用急性缺血性中风（9）。根据研究方案，患者0.6-mg/kg剂量静脉注射阿替普酶或安慰剂。经导管在动脉内的血栓附近放置，阿替普酶2毫克静脉滴注，然后一个10毫克/小时输液。最大剂量为20毫克的动脉。35例患者8例（3），出血性脑梗死的临床观察。较高的再通观察患者接受高剂量的阿替普酶。总平均（静脉和动脉）剂量的阿替普酶是35.6mg患者最终TIMI 1级和56。与最终TIMI 3级剂量7毫克。从我们的研究结果与以往研究直接比较是不可能的因为患者选择的重要差异。与PROACT II间接比较（5）提出了一个更高的无血管成形术再通动脉内给予瑞替普酶或使用相关率（TIMI 2美元94%）比动脉内尿激酶原无血管成形术（TIMI 2美元66%）。观察尽管PROACT II只包括与TIMI 0级或1的MCA M1或M2分闭塞患者的差异。在我们的系列，一个大的比例（八例）显示TIMI 0级闭塞ICA，这是比MCA闭塞的血管再通率较低相关（16）。本组颅内出血的总发生率为25%。在PROACT II，在最初的10天中任何类型的颅内出血率为68%。与神经功能恶化的颅内出血（四点或更多的NIHSS评分增加）在108例尿激酶原10%发生。我们观察到神经功能恶化（一点或更多的NIHSS评分增加）在1导致的颅内出血（6%）治疗的16例患者。总的来说，症状性颅内出血率相当，尽管在我们的研究中，恶化的更敏感的定义。病死率高（56%）在我们的研究中，但似乎并不直接相关，因为大多数动脉治疗死亡（七九）在我们的系列是由大量脑水肿合并脑梗死。在一个病人（5例），脑出血导致的质量效应，除了梗死相关脑水肿。在PROACT II，尿激酶原治疗的患者90天的死亡率为25%。在我们的系列中的死亡率较高，可能与初始赤字和其他相关的共病条件的严重程度。平均初始NIHSS评分在我们的患者为20（范围，10–26），与17（范围，5–27）患者尿激酶原。接受任何外科手术之日起30天内发病的患者被排除在PROACT II但包含在我们的系列。我们的研究主要集中在确定动脉内给予瑞替普酶使用后的直接后果。因此，没有明确的结论可以得出相对于长期的功能结果。