目的 探討超早期應(yīng)用阿加曲班治療急性缺血性腦卒中靜脈溶栓后早期神經(jīng)功能惡化（END）的療效及安全性。方法 回顧性選取2018年1月—2021年7月在涿州市醫(yī)院神經(jīng)內(nèi)科診治的發(fā)病6 h內(nèi)急性缺血性腦卒中行尿激酶靜脈溶栓治療后神經(jīng)功能惡化患者90例，根據(jù)患者神經(jīng)功能惡化時是否使用阿加曲班治療分為對照組（n＝45）及試驗組（n＝45），對照組在常規(guī)治療基礎(chǔ)上應(yīng)用注射用尿激酶1.50×10⁶ U溶于100 mL 0.9%氯化鈉注射液中，靜脈滴注30 min，進(jìn)行靜脈溶栓治療，溶栓24 h后復(fù)查頭顱CT排除腦出血后啟動口服阿司匹林腸溶片，每次100 mg，每日1次，持續(xù)服用14 d。試驗組在對照組基礎(chǔ)上加用阿加曲班治療，溶栓24 h內(nèi)發(fā)現(xiàn)腦血管病進(jìn)展，即啟動阿加曲班注射液抗凝治療。具體用法：阿加曲班注射液治療前2 d用120 mg原液以2.5 mg·h⁻¹持續(xù)靜脈泵入48 h；治療第3天開始改為阿加曲班注射液每次10 mg加入至0.9%氯化鈉注射液250 mL中，持續(xù)靜脈滴注3 h，每日2次，連用5 d，阿加曲班注射液共用藥7 d；靜脈溶栓24 h后啟動阿司匹林腸溶片治療，用法用量及療程同對照組。應(yīng)用美國國立衛(wèi)生研究院卒中量表（NIHSS）評分比較兩組不同時間點（尿激酶靜脈溶栓前、溶栓治療后神經(jīng)功能恢復(fù)最好時、神經(jīng)功能惡化時和應(yīng)用阿加曲班干預(yù)治療第7、14天）神經(jīng)功能缺損情況，出院后第90天應(yīng)用改良Rankin量表（mRS）對所有患者的日常生活能力恢復(fù)情況進(jìn)行評估，以mRS評分＞2分為預(yù)后不良，mRS評分≤2分為預(yù)后良好，評估住院期間所有患者是否存在腦出血及死亡等并發(fā)癥。結(jié)果 應(yīng)用阿加曲班干預(yù)治療的試驗組患者的治療總有效率為97.78%，顯著高于對照組的82.22%，兩組總有效率比較，差異顯著（P＜0.05）。靜脈溶栓前、溶栓后神經(jīng)功能恢復(fù)最好時、溶栓后神經(jīng)功能惡化時，兩組NIHSS評分差異無統(tǒng)計學(xué)意義（P＞0.05）；在阿加曲班干預(yù)治療第7、14天，對照組NIHSS評分較神經(jīng)功能惡化時有降低趨勢，在阿加曲班干預(yù)治療第14天時對照組NIHSS評分較神經(jīng)功能惡化時比較顯著降低（P＜0.05）；在阿加曲班干預(yù)治療第7、14天，試驗組NIHSS評分較神經(jīng)功能惡化時顯著降低（P＜0.05），且較同一時間點的對照組顯著降低（P＜0.05）。出院后90 d進(jìn)行mRS評分，試驗組顯著低于對照組（P＜0.05），試驗組神經(jīng)功能遠(yuǎn)期預(yù)后良好者有31例（占比68.89%），顯著高于對照組的11例（占比24.44%），兩組比較差異顯著（P＜0.05）。住院治療期間，兩組均未發(fā)現(xiàn)腦出血等并發(fā)癥，兩組患者出院后隨訪90 d，均未發(fā)現(xiàn)死亡病例。結(jié)論 對于尿激酶靜脈溶栓后發(fā)生END的急性缺血性腦卒中患者，超早期應(yīng)用阿加曲班能有效改善患者的神經(jīng)功能缺損癥狀及生活能力，患者遠(yuǎn)期預(yù)后良好，未發(fā)現(xiàn)腦出血等并發(fā)癥。

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年保定市科技局自籌項目課題（2141ZF176）