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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 the curative effect of tolvaptan on refractory ascites due to traditional diuretic drugs. Methods The clinical data of 41 cases of refractory ascites due to traditional treatment of diuretic drugs combined with tolvaptan were analyzed. All patients received tolvaptan (7.5 mg / day or 15 mg / day) in combination with diuretics (40-120 mg / day for spironolactone and 20-60 mg / day for furosemide) for at least 1 week. The changes of biochemical parameters and urine volume before and after treatment with tolvaptan were compared between the two groups. At the same time according to the patient’s urine volume changes in the first 3 days to adjust the amount of tolvaptan. No significant increase in urine output (24 h increased urine output <500 mL), tolvaptan dose increased to 15 mg / d; increased urine output (24 h urine output increased 500 ~ 1 500 mL), the maintenance of the original Dosage unchanged; urine output increased significantly (24 h urine output> 1 500 mL), the dose was adjusted to 7.5 mg / d, continue to observe the efficacy of the patients until the 7th day. Record the occurrence of adverse events. Results In 9 patients with initial dose ineffective and increasing doses, only 2 patients had a significant increase in urine output and ascites, but no significant increase in urine output compared with that before dose adjustment [(1 960.00 ± 510.59) mL vs. (2 161.11 ± 956.81) mL, P = 0.452]. In 8 patients with a significant initial dose reduction and a decrease in the dose, only 1 patient experienced a significant decrease in urine output with a corresponding decrease in urine output compared with that before adjustment (4 281.25 ± 445.37 mL vs. 3 048.75 ± 710.88 mL, P = 0.001]. The urinary volume of patients treated with tolvaptan was significantly increased after 7 days of treatment ([(1 484.05 ± 612.0) mL vs. (508.92 ± 887.97) mL, P <0.001]. The ascites of 63.41% patients subsided obviously, the edema of lower extremities in 68.29% patients was alleviated, and the serum sodium level in 50% hyponatremia patients was higher than that before treatment [(131.88 ± 4.59) mmol / L vs. (134.68 ± 6.30) mmol / L, P = 0.03]. At the same time patients with liver dysfunction plus tolvaptan did not appear after liver damage worse. The degree of cirrhosis Child-Pugh classification affect the efficacy of tolvaptan. The main adverse reactions were dry mouth and thirst. Conclusions Tolvaptan can promote drainage and diuresis in patients with refractory ascites hepatopathy which is not effective in traditional diuretic therapy, and can improve hyponatremia in patients. No effective dose of tolvaptan at the initial dose, even if the increase in the dose of the drug also did not see an increase in efficacy; and the initial dose of a significant reduction in the dose of the drug, the effect will be reduced, but the urine output was significantly increased.