托伐普坦治疗难治性腹水患者的疗效观察  

Curative effect observation on tolvaptan in treatment of refractory ascites

作　　者：杨敬貌 陈丽萍[1] 尚礼胤 王亚洁[3] 赵红[2] 黄绍萍[1] 樊贞瑜[1] 李俊[1] 唐荣[1] 陆基华[1] 殷科珊[1] 程计林[1,2] YANG Jing-mao CHEN Li-ping SHANG li-yin WANG Ya-jie ZHAO Hong HUANG Shao-ping FAN Zhen-yu LI Jun TANG Rong LU Ji-hua YIN Ke-shan CHENG Ji-lin(Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China The First Affiliated Hospital of Wenzhou Medical University, Zhefiang Whenzhou 325000, China)

机构地区：[1]上海市公共卫生临床中心,上海201508 [2]温州医科大学第一临床医学院,浙江温州325000 [3]佳木斯大学第一附属医院,黑龙江佳木斯154002

出　　处：《上海预防医学》2017年第7期513-517,共5页Shanghai Journal of Preventive Medicine

摘　　要：目的观察托伐普坦对传统利尿药物治疗无效的肝源性难治性腹水患者的疗效。方法分析41例传统利尿药物治疗无效而加用托伐普坦的肝源性难治性腹水患者的临床资料。所有患者均接受托伐普坦(7.5 mg/d或15 mg/d)联合利尿剂(螺内酯40~120 mg/d和呋塞米20~60 mg/d)治疗至少1周。比较患者加用托伐普坦前后相关生化指标及尿量的变化。同时根据患者前3天的尿量变化情况调整托伐普坦用量。尿量无明显增加者(24 h尿量增加<500 mL),托伐普坦剂量均增至15 mg/d;尿量增加者(24 h尿量增加500~1 500 mL),则维持原剂量不变;尿量明显增加者(24 h尿量增加>1 500 mL),则剂量均调整至7.5 mg/d,继续观察患者疗效至第7天。记录不良事件发生情况。结果 9例起始剂量无效而增加剂量患者,仅2例尿量明显增加,腹水消退,但与剂量调整前相比尿量未见明显增加[(1 960.00±510.59)mL vs.(2 161.11±956.81)mL,P=0.452]。8例起始剂量疗效显著而减少剂量患者,仅1例出现尿量明显回落,与调整前相比尿量相对减少[(4 281.25±445.37)mL vs.(3 048.75±710.88)mL,P=0.001]。托伐普坦治疗7 d后患者尿量较治疗前明显增多[(1 484.05±612.0)mL vs.(2 508.92±887.97)mL,P<0.001]。63.41%患者腹水明显消退,68.29%患者下肢水肿减轻,50%低钠血症患者较治疗前血钠升高[(131.88±4.59)mmol/L vs.(134.68±6.30)mmol/L,P=0.03]。同时伴有肝功能异常的患者加用托伐普坦后并未出现肝损害加重。肝硬化程度Child-Pugh分级影响托伐普坦疗效。主要不良反应为口干、口渴。结论托伐普坦对传统利尿剂治疗无效的难治性腹水肝病患者有一定促排水利尿作用,同时可改善患者低钠血症。托伐普坦起始剂量无效者,即使增加药物剂量也未见疗效增加;而起始剂量显著有效者减少药物剂量后,疗效相对将降低,但尿量仍明显增加。Objective To observe and evaluate the efficacy of tolvaptan for the hepatogenic refractory ascites, when treatment is ineffective with traditional diuretic drugs. Methods A series of 41 patients with liver cirrhosis refractory ascites were enrolled. Traditional diuretic drugs were invalid for them. All patients were treated with tolvaptan （ 7.5 or 15 mg/d ） and diuretic drugs （ spironolaetone 40- 120 mg/d and furosemide 20-60 mg/d） for at least one week. Then the biochemical indices and urine volume were compared between preand post-treatment with tolvaptan. The doses of tolvaptan were based on the urine volume of the first three days ： for patients with no obvious increasing urine （ urine volume increase less than 500 mL） , the tolvaptan doses increased to 15 mg/d; for patients with increasing urine urine volume increase between 500 mL to 1 500 mL） , the tolvaptan doses were maintained; for patients with obvious increasing urine（urine volume increase more than 1 500 mL） , the tolvaptan dose changed to 7.5 mg/d. During the seven days, the efficacy and the adverse events were observed. Results There were nine patients taking increasing dosage of tolvaptan instead of the invalid starting dose. Among them, two patients＇ urine increased obviously and their asctes subsided. However, there was no statistic signifi- cant improvement on the urine volume before and after increasing tolvaptan dosage [ （ 1 960.00 ± 510.59） mL vs. （2 161.11 ±956.81 ）mL,P =0. 452]. Among the eight patients who had a good response to start- ing dose and subsequently decreased the dose, only one patient＇ s urine decreased greatly. The urine volume decreased after changing the tolvaptan dose [ （ 4 281.25± 445.37 ） mL vs. （ 3048.75± 710.88 ） mL, P =0.001 ]. After treating with tolvaptan for seven days, patients＇ urine increased [（1 484.05± 612.0） mL vs. （2 508.92± 887.97 ） mL, P 〈 0. 001 ]. The percentage of patients showed improvement in their aseites was 63.41% , while the alleviate edem

关 键 词：托伐普坦 难治性腹水 药物剂量 低钠血症 肝病 肝硬化 

分 类 号：R575[医药卫生—消化系统]