目的 探讨超早期应用阿加曲班治疗急性缺血性脑卒中静脉溶栓后早期神经功能恶化（END）的疗效及安全性。方法 回顾性选取2018年1月—2021年7月在涿州市医院神经内科诊治的发病6 h内急性缺血性脑卒中行尿激酶静脉溶栓治疗后神经功能恶化患者90例，根据患者神经功能恶化时是否使用阿加曲班治疗分为对照组（n＝45）及试验组（n＝45），对照组在常规治疗基础上应用注射用尿激酶1.50×10⁶ U溶于100 mL 0.9%氯化钠注射液中，静脉滴注30 min，进行静脉溶栓治疗，溶栓24 h后复查头颅CT排除脑出血后启动口服阿司匹林肠溶片，每次100 mg，每日1次，持续服用14 d。试验组在对照组基础上加用阿加曲班治疗，溶栓24 h内发现脑血管病进展，即启动阿加曲班注射液抗凝治疗。具体用法：阿加曲班注射液治疗前2 d用120 mg原液以2.5 mg·h⁻¹持续静脉泵入48 h；治疗第3天开始改为阿加曲班注射液每次10 mg加入至0.9%氯化钠注射液250 mL中，持续静脉滴注3 h，每日2次，连用5 d，阿加曲班注射液共用药7 d；静脉溶栓24 h后启动阿司匹林肠溶片治疗，用法用量及疗程同对照组。应用美国国立卫生研究院卒中量表（NIHSS）评分比较两组不同时间点（尿激酶静脉溶栓前、溶栓治疗后神经功能恢复最好时、神经功能恶化时和应用阿加曲班干预治疗第7、14天）神经功能缺损情况，出院后第90天应用改良Rankin量表（mRS）对所有患者的日常生活能力恢复情况进行评估，以mRS评分＞2分为预后不良，mRS评分≤2分为预后良好，评估住院期间所有患者是否存在脑出血及死亡等并发症。结果 应用阿加曲班干预治疗的试验组患者的治疗总有效率为97.78%，显著高于对照组的82.22%，两组总有效率比较，差异显著（P＜0.05）。静脉溶栓前、溶栓后神经功能恢复最好时、溶栓后神经功能恶化时，两组NIHSS评分差异无统计学意义（P＞0.05）；在阿加曲班干预治疗第7、14天，对照组NIHSS评分较神经功能恶化时有降低趋势，在阿加曲班干预治疗第14天时对照组NIHSS评分较神经功能恶化时比较显著降低（P＜0.05）；在阿加曲班干预治疗第7、14天，试验组NIHSS评分较神经功能恶化时显著降低（P＜0.05），且较同一时间点的对照组显著降低（P＜0.05）。出院后90 d进行mRS评分，试验组显著低于对照组（P＜0.05），试验组神经功能远期预后良好者有31例（占比68.89%），显著高于对照组的11例（占比24.44%），两组比较差异显著（P＜0.05）。住院治疗期间，两组均未发现脑出血等并发症，两组患者出院后随访90 d，均未发现死亡病例。结论 对于尿激酶静脉溶栓后发生END的急性缺血性脑卒中患者，超早期应用阿加曲班能有效改善患者的神经功能缺损症状及生活能力，患者远期预后良好，未发现脑出血等并发症。

Objective To investigate the clinical efficacy and safety of ultra-early application of argatroban in the treatment of early neurological deterioration (END) after urokinase intravenous thrombolysis in acute ischemic stroke. Methods A total of 90 patients with early neurological deterioration after intravenous thrombolytic therapy with urokinase in acute ischemic stroke treated in the Department of Neurology of Zhuozhou hospital from January 2018 to July 2021 were selected retrospectively. According to whether the patients were treated with argatroban or not, they were divided into control group (n = 45) and experimental group (n = 45). Patients in the control group were treated with Urokinase for Injection on the basis of routine treatment, Urokinase for Injection 1.50 × 10⁶ U was dissolved in 100 mL of 0.9% Sodium Chloride Injection, intravenous drip for 30 min, intravenous thrombolysis treatment, 24 h after thrombolysis, recheck the head CT, and start oral Aspirin Enteric Coated Tablets after excluding intracerebral hemorrhage, 100 mg each time, once a day, for 14 d. Patients in the experimental group were treated with argatroban on the basis of the control group. If the progress of cerebrovascular disease was found within 24 h of thrombolysis, the anticoagulant treatment of Argatroban Injection was started. Specific usage: Argatroban Injection was continuously pumped intravenously with 120 mg stock solution at 2.5 mg·h⁻¹ for 48 h two days before treatment. Starting from the third day of treatment, it was changed to add 10 mg of Argatroban Injection to 250 mL of 0.9% Sodium Chloride Injection. It was continuously injected intravenously for three hours, twice a day, for five days. Argatroban Injection shared the drug for seven days. Aspirin Enteric Coated Tablets were started 24 h after intravenous thrombolysis. The usage, dosage and course of treatment were the same as those in the control group. The National Institutes of Health Stroke Scale (NIHSS) score was used to compare the neurological deficit of the two groups at different time points (before intravenous thrombolysis with urokinase, when the neurological function recovered best after thrombolysis, when the neurological function deteriorated, and on the 7th and 14th days after argatroban intervention). The recovery of daily living ability of all patients were evaluated by modified Rankin Scale (mRS) on the 90th day after discharge. The prognosis was poor if the mRS score was > 2, and good if the mRS score was ≤ 2. Whether all patients had complications such as intracerebral hemorrhage and death during hospitalization was evaluated. Results The total effective rate of the experimental group treated with argatroban was 97.78%, which was significantly higher than 82.22% of the control group. There was significant difference between the two groups (P < 0.05).There was no significant difference in NIHSS score between the two groups before intravenous thrombolysis, when the neurological function recovered best after thrombolysis, and when the neurological function deteriorated after thrombolysis (P > 0.05). On the 7th and 14th day of argatroban intervention, the NIHSS score in the control group decreased compared with that in the deterioration of neurological function, and on the 14th day of argatroban intervention, the NIHSS score in the control group decreased significantly compared with that in the deterioration of neurological function (P < 0.05). On the 7th and 14th days of argatroban intervention, NIHSS score in the control group decreased compared with the NIHSS score when the neurological function deteriorated.The NIHSS score of the experimental group was significantly lower than that when the neurological function deteriorated and that of the control group at the same time point (P < 0.05). The mRS score of the experimental group was significantly lower than that of the control group 90 days after discharge (P < 0.05). There were 31 cases with good long-term prognosis of neurological function in the experimental group (68.89%), which was significantly higher than that of 11 cases in the control group (24.44%). There was significant difference between the two groups (P < 0.05). During hospitalization, no complications such as intracerebral hemorrhage were found in the two groups. The patients in the two groups were followed up for 90 days after discharge, and no death was found. Conclusion For acute ischemic stroke patients with END after intravenous thrombolysis with urokinase, the ultra early application of argatroban can effectively improve the symptoms of neurological deficit and living ability. The long-term prognosis of the patients is good, and no complications such as intracerebral hemorrhage are found.

R971

2021年保定市科技局自筹项目课题（2141ZF176）