低剂量重组组织型纤溶酶原激活剂与尿激酶联合溶栓治疗急性脑梗死

Combined thrombolytic therapy with low-dose recombinant tissue plasminogen activator and urokinase for patients with acute cerebral infarction

目的观察联合应用重组组织型纤溶酶原激活剂（rt—PA）和尿激酶治疗急性脑梗死的有效性和安全性。方法选择发病〈6h的急性脑梗死患者81例，分为联合溶栓组（20例）、单用rt—PA组（22例）、单用尿激酶组（18例）及对照组（21例）。联合溶栓组静脉给予rt—PA20mg，尿激酶30万-50万IU；单用rt—PA组静脉给予rt—PA0．9mg／kg；单用尿激酶组静脉给予尿激酶1万～2万IU／kg（体质量超过75kg者按75kg给药），最大剂量150万IU；未溶栓病例为对照组。主要疗效指标是观察治疗前与发病后4周的神经功能缺损评分（NIHSS）变化，以溶栓后出血转化、24h内再梗死及死亡等作为安全指标。结果联合溶栓组、单用rt—PA组、单用尿激酶组及对照组的观察结果为：①NIHSS评分治疗前分别为18．1±3．6、17．9±3．6、18．0±3．4、17．3±4．0，治疗后分别为9．1±5．6、8．8±5．5、9．6±5．2、14．1±4．6，符组治疗前、后比较，差异均有统计学意义（P〈0．01），3个溶栓组与对照组比较差异均有统计学意义（P〈0．01）；3个溶栓组比较，差异无统计学意义。②4组治疗后总有效率分别为85．0％（17／20）、86．4％（19／22）、83．3％（15／18）和42．9％（9／21），与对照组比较差异有统计学意义（P〈0．05）；各溶栓组间比较，差异无统计学意义（P〉0．05）。③联合溶栓组溶栓后24h内再发脑梗死1例，出血转化1例；单用rt—PA组出血转化3例；单用尿激酶组再梗死1例，出血转化有2例，其中死亡1例。对照组再梗死1例，死亡1例。结论与单用rt—PA和单用尿激酶比较，联合低剂量rt-PA和尿激酶溶栓治疗急性脑梗死同样安全、有效，相对rt—PA价格便宜，值得推广应用。

Objective To observe the efficacy and safety of combined thrombolytic therapy with recombinant tissue plasminogen activator （rt-PA） and urokinase （UK） on patients with acute cerebral infarction. Method Eighty-one patients with acute cerebral infarction （ 〈 6 hours from onset） were recruited and randomly allocated into four groups ： combined thrombolysis group （ n = 20 ） , rt-PA group （ n =22）, UK group （ n = 18） , and control group （ n =21 ）. The patients in combined thrombolysis group received rt-PA 20 mg and UK 300 000 - 500 000 IU ; the patients in rt-PA group received rt-PA 0.9 mg/kg intravenously; the patients in UK group received UK 10 000 -20 000 IU/kg （patients with body weight 〉 75 kg received the same dose of medication as 75 kg） , and the maximum dose of UK was 1 500 000 IU ; the patients in the control group received to no thrombolytic drugs. The outcome score were evaluated according to the National Institute of Health Stroke Scale （NIHSS） before treatment and four weeks after symptom onset, and to evaluate hemorrhagic transformation, recurrent infarction, and death as the safety indicators. Results （1）Before treatment the NIHSS scores in the combined thrombolysis, rt-PA, UK,and control groups were 18.1 ± 3.6, 17.9 ± 3.6, 18.0 ± 3.4, and 17.3 ± 4.0, respectively, and after treatment they were 9.1 ± 5.6, 8.8 ±5.5, 9.6 ± 5.2, and 14.1 ± 4.6, respectively. There were significant differences in each group before and after treatment （ P 〈 0.01 ） , and also between the 3 thrombolysis groups and the control group （ P 〈 0.01 ） ; but there were no significant differences between each other of the 3 thrombolysis groups. （2）The total effective rates in the 4 groups but were 85.0% （ 17/20）, 86.4% （ 19/ 22）, 83.3% （ 15/18）, and 42.9% （9/21）, respectively. As compared between the 3 thrombolysis groups with the control group, there were significant differences （P 〈 0. 05） ; and there were no significant differences among the 3 thrombolysis groups （P 〉 0.05 ）. （3）ne patient had new attack of cerebral infarction, and 1 patient had hemorrhagic transformation within 24 hours after thrombolytic therapy in the combined thrombolytic group; 3 patients had hemorrhagic transformation in the rt-PA group; 1 patient had new attack of cerebral infarction in the UK group; 2 patients had hemorrhagic transformation, and 1 of them died. One patient had new attack of cerebral infarction, and 1 patient was died in the control group. Conclusion The combined thrombolytic therapy with low-dose rt-PA and UK for the treatment of acute cerebral infarction is safe and effective.