【摘要】 目的肝硬化顽固性腹水常并发低钠血症,若继续应用常规利尿剂不但影响利尿效果,且不利于血钠改善。本研究观察新一代高度选择性血管加压素受体拮抗剂托伐普坦对肝硬化顽固性腹水合并低钠血症的疗效和安全性。方法选取2014-08-01-2017-10-31大连大学附属中山医院住院治疗的肝硬化顽固性腹水合并低钠血症患者42例,按治疗方法不同分为托伐普坦组22例和常规利尿剂组20例,托伐普坦组给予常规治疗(保肝、支持治疗)和托伐普坦15mg/d治疗;常规利尿剂组给予常规治疗,螺内酯50～150mg/d和呋塞米20～60mg/d,治疗>1周。比较观察治疗前1d、治疗后第4天及治疗后第7天变化,主要观察项目包括血钠、氯、钾浓度、肝功能、肾功能、腹围下降及下肢水肿改善,并记录不良事件发生情况。结果两组的血Na+、血Cl-、血K+基础值差异均无统计学意义,均P>0.05。治疗第4天,血Na+浓度托伐普坦组为(133.1±6.2)mol/mL,高于常规利尿剂组的(128.9±5.9)mol/mL;治疗第7天托伐普坦组为(133.9±6.9)mol/mL,高于常规利尿剂组的(129.6±6.5)mol/mL,F=5.76,P=0.01。治疗第4天,血Cl-浓度托伐普坦组为(92.1±9.5)mol/mL,高于常规利尿组的(89.4±8.6)mol/mL;治疗第7天,托伐普坦组为(92.7±10.5)mol/mL,高于常规利尿组的(90.1±8.7)mol/mL,F=5.08,P=0.02。治疗第4和第7天血K+浓度两组差异均无统计学意义,P>0.05。治疗第4天,托伐普坦组血Na+浓度达标率为63.6%(14/22),高于常规利尿剂组的20.0%(4/20),χ2=6.46,P=0.01。治疗第7天,托伐普坦组血Na+浓度达标率为68.2%(15/22),高于常规利尿剂组的25.0%(5/20),χ2=6.20,P=0.01。托伐普坦组24h尿量均高于常规利尿剂组,差异有统计学意义,t=4.15,P<0.01。托伐普坦组治疗第7天腹围下降16例(72.7%),高于常规利尿剂组的7例(35.0%),χ2=4.59,P=0.032;下肢水肿改善两组差异无统计学意义,χ2=0.06,P=0.808。两组治疗前后谷丙转氨酶(glutamic pyruvic transaminase,ALT)、总胆红素(total bilirubin,TBIL)、肌酐(creatinine,Cr)和尿素(blood urea nitrogen,BUN)的变化比较,差异无统计学意义,均P>0.05。结论托伐普坦对肝硬化顽固性腹水患者有较强排水利尿作用,同时能够纠正低钠血症;短期应用对肝肾功能无明显影响。更多还原

【Abstract】 OBJECTIVE Refractory ascites of cirrhosis is often associated with hyponatremia.Continued use of conventional diuretics not only affects the diuretic effect,but also is detrimental to the improvement of blood sodium.This study is to investigate the efficacy and safety of a new generation of selective vasopressin receptor antagonist tolvaptan in treatment of refractory ascites in cirrhosis with hyponatremia.METHODS A total of 42 patients of cirrhosis with refractory ascites and hyponatremia were randomly divided into tolvaptan group(22 patients)and routine diuretic group(20 patients).The tolvaptan group were given routine treatment and 15 mg/d tolvaptan tablets.The conventional diuretic group were given routine treatment including 50-150 mg/d of spironolactone and 20-60 mg/d of furosemidum at least for 1 week.The observation points were 1-day before treatment(baseline),day 4 and day 7 during the treatment.Serum sodium,chloride,potassium,hepatic function,renal function,abdominal circumference,lower limb edema and adverse events were recorded and compared.RESULTS There was no statistically significant difference in serum sodium,chlorine and potassium between the two groups in the base value.On the fourth day of treatment,the blood Na+concentration in the tolvaptan group was(133.1±6.2)mol/ml,which was higher than that in the conventional diuretic group(128.9±5.9)mol/ml.On the 7 th day of treatment,it was(133.9±6.9)mol/ml of the tolvaptan group,which was higher than that of the conventional diuretic group(129.6±6.5)mol/ml,F=5.76,P=0.01.On the fourth day of treatment,the blood Cl-concentration in the tolvaptan group was(92.1±9.5)mol/ml,which was higher than that in the conventional diuretic group(89.4±8.6)mol/ml.On the 7 th day of treatment,it was(92.7±10.5)mol/ml of the tolvaptan group,which was higher than that of the conventional diuretic group(90.1±8.7)mol/ml,F=5.08,P=0.02.On the fourth and seventh day of treatment,the difference of blood K+was not statistically significant,P>0.05.On the fourth day of treatment,the blood Na+concentration compliance rate in the tolvaptan group was 63.6%(14/22),higher than that in the conventional diuretic group 20.0%(4/20),χ2=6.46,P=0.01.On the 7 th day of treatment,the blood Na+concentration compliance rate in the tolvaptan group was 68.2%(15/22),higher than that in the conventional diuretic group 25.0%(5/20),χ2=6.20,P=0.01.The 24 hurine volume of the tolvaptan group was higher than that of the conventional diuretic group,and the difference was statistically significant,t=4.15,P<0.01.On the 7 th day,the ascites of 16 cases(72.7%)decreased in the tolvaptan group,which was more than that in the conventional diuretic group(75.0%),χ2=4.59,P=0.032.There was no significant difference in the changes of glutamic pyruvic transaminase,total bilirubin,creatinine and blood urea nitrogen between the two groups before and after treatment.CONCLUSIONS Tolvaptan exerts a strong diuretic effect in cirrhosis patients with refractory ascites,and can correct hyponatremia.Short-term application has no significant effect on liver and kidney function.更多还原