Department of Gastroenterology, The Brooklyn Hospital Center, Brooklyn, NY, USA.
Am J Ther. 2012 Mar;19(2):121-32. doi: 10.1097/MJT.0b013e3181ff7a8b.
Ascites that does not respond or recurs after high-dose diuresis and sodium restriction should be considered refractory ascites. As cirrhosis advances, the escaping fluid overwhelms the lymphatic return. Decrease in renal plasma flow leads to increased sodium reabsorption at the proximal tubule leading to decreased responsiveness to loop diuretics and mineralocorticoid antagonists, which work distally. These complex hemodynamic alterations lead to refractory ascites. In refractory ascites, high-dose diuresis (400 mg of spironolactone and 160 mg of furosemide) and sodium restriction (<90 mmol/d) result in inadequate weight loss and sub optimal sodium excretion (<78 mmol/d). Further use of diuretics is limited by complications such as encephalopathy, azotemia, renal insufficiency, hyponatremia, and hyperkalemia. Therapy for refractory ascites is limited. The available therapies are repeated large volume paracentesis (LVP), transjugular intrahepatic portosystemic shunts, peritoneovenous shunts, investigational medical therapies, and liver transplantation. LVP with concomitant volume expanders is the initial treatment of choice. Transjugular intrahepatic portosystemic seems to be superior to LVP in reducing the need for repeated paracentesis and improves the quality of life. Several treatments that act at different steps in the pathogenesis of ascites are investigational, and some show promising results. Splanchnic and peripheral vasoconstrictors (Octreotide, Midodrine, and Terlipressin) increase effective arterial volume and decrease activation of the renin-angiotensin system with resultant increase in renal sodium excretion. Clonidine when given with spironolactone has been shown to cause rapid mobilization of ascites by significantly decreasing the sympathetic activity and renin-aldosterone levels. Natural aquaretics and synthetic V2 receptor antagonists (satavaptan) are being evaluated for mobilization of ascites by increasing the excretion of solute-free water. Liver transplantation remains the only definitive therapy for refractory ascites. Because refractory ascites is a poor prognostic sign, liver transplantation should be considered and incorporated early in the treatment plan.
对于大量利尿剂和钠限制治疗后仍未缓解或复发的腹水，应考虑为难治性腹水。随着肝硬化的进展，漏出液超过了淋巴回流。肾血浆流量减少导致近端小管钠重吸收增加，从而降低了对袢利尿剂和盐皮质激素拮抗剂的反应性，这些药物在远端起作用。这些复杂的血流动力学改变导致难治性腹水。在难治性腹水中，大剂量利尿剂（螺内酯 400mg 和呋塞米 160mg）和钠限制（<90mmol/d）导致体重减轻不足和钠排泄不理想（<78mmol/d）。进一步使用利尿剂会受到并发症的限制，如脑病、氮质血症、肾功能不全、低钠血症和高钾血症。难治性腹水的治疗有限。现有的治疗方法包括反复大量腹腔穿刺术（LVP）、经颈静脉肝内门体分流术、腹膜静脉分流术、试验性医学治疗和肝移植。LVP 联合容量扩张剂是首选的初始治疗方法。经颈静脉肝内门体分流术似乎优于 LVP，可减少反复穿刺的需要，并提高生活质量。一些作用于腹水发病机制不同阶段的治疗方法正在进行研究，其中一些显示出有希望的结果。内脏和外周血管收缩剂（奥曲肽、米多君和特利加压素）增加有效动脉血量，减少肾素-血管紧张素系统的激活，从而增加肾脏钠排泄。可乐定与螺内酯联合使用可通过显著降低交感神经活性和肾素-醛固酮水平，迅速动员腹水。天然水通道蛋白和合成 V2 受体拮抗剂（沙他伐坦）正在被评估用于通过增加无溶质水的排泄来动员腹水。肝移植仍然是难治性腹水的唯一确定性治疗方法。因为难治性腹水是预后不良的标志，所以应考虑肝移植，并在治疗计划早期纳入。
