背景:普萘洛尔,一种非选择性β受体阻滞剂,常用于预防静脉曲张出血,但可能导致严重腹水的循环功能障碍。米多君,α-1肾上腺素能激动剂可改善肾脏灌注和全身血流动力学.添加米多君可能有助于提高普萘洛尔的最大耐受剂量(MTD),从而降低肝硬化严重腹水患者静脉曲张出血的风险。
方法:140例肝硬化和重度/难治性腹水患者随机-普萘洛尔和米多君(Gr。A,n=70)或单独使用普萘洛尔(Gr。B,n=70)。主要结果是1年时出血的发生率。次要结果包括腹水控制,实现目标心率(THR),HVPG反应和不良反应。
结果:两组的基线特征相当。Gr中1年出血的累积发生率较低。A比B(8.5%vs.27.1%,p-0.043)。普萘洛尔在Gr中的MTD较高。A(96.67±36.6mgvs.76.52±24.4mg;p-0.01),更多患者达到THR(84.2%vs.55.7%,p-0.034)。Gr患者比例显著增高。A的腹水完全消退[17.1%vs.11.4%,p-0.014),利尿剂耐受性(80%vs.60%,p-0.047)在较高剂量(p-0.02)和较少需要穿刺。Gr患者。A还降低了静脉曲张等级(75.7%对55.7%;p-0.01),血浆肾素活性(基线54.4%)(p=0.02)。Gr中的平均HVPG降低更大。A比B[4.38±2.81mmHg(23.5%)2.61±2.87mmHg(14.5%),p-0.045].在随访中,诸如穿刺后循环功能障碍和自发性细菌性腹膜炎等并发症在Gr中较高。B比A(22.8%vs.51.4%,p=0.013和10%vs.15.7%,分别为p=0.03)。
结论:添加米多君有助于普萘洛尔在较高剂量下的有效使用和更大的HVPG降低,从而防止第一次静脉曲张出血,肝硬化严重/难治性腹水患者的腹水穿刺需求减少,腹水相关并发症减少。
BACKGROUND: Propranolol, a non-selective beta-blocker, commonly used to prevent variceal bleed, but might precipitate circulatory dysfunction in severe ascites. Midodrine, an alpha-1 adrenergic agonist improves renal perfusion and systemic hemodynamics. Addition of midodrine might facilitate higher maximum tolerated dose (MTD) of propranolol, thereby less risk of variceal bleed in cirrhosis patients with severe ascites.
METHODS: 140 patients with cirrhosis and severe/refractory ascites were randomized- propranolol and midodrine (Gr.A,n = 70) or propranolol alone (Gr.B,n = 70). Primary outcome was incidence of bleed at 1 year. Secondary outcomes included ascites control, achievement of target heart rate (THR), HVPG response and adverse effects.
RESULTS: Baseline characteristics were comparable between two groups. Cumulative incidence of bleed at 1 year was lower in Gr.A than B (8.5%vs.27.1%,p-0.043). The MTD of propranolol was higher in Gr.A (96.67 ± 36.6 mg vs. 76.52 ± 24.4 mg; p-0.01) and more patients achieved THR (84.2%vs.55.7%,p-0.034). Significantly higher proportion of patients in Gr.A had complete resolution of ascites [17.1%vs.11.4%,p-0.014), diuretic tolerance (80%vs.60%,p-0.047) at higher doses(p-0.02) and lesser need for paracentesis. Patients in Gr.A also had greater reduction in variceal grade (75.7%vs.55.7%;p-0.01), plasma renin activity (54.4% from baseline) (p = 0.02). Mean HVPG reduction was greater in Gr.A than B [4.38 ± 2.81 mmHg(23.5%) vs. 2.61 ± 2.87 mmHg(14.5%),p-0.045]. Complications like post-paracentesis circulatory dysfunction and spontaneous bacterial peritonitis on follow-up were higher in Gr.B than A (22.8%vs.51.4%,p = 0.013 and 10%vs.15.7%, p = 0.03, respectively).
CONCLUSIONS: Addition of midodrine facilitates effective use of propranolol in higher doses and greater HVPG reduction, thereby preventing first variceal bleed, reduced paracentesis requirements with fewer ascites- related complications in patients with cirrhosis with severe/refractory ascites.