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肝硬化腹水处理指南(2006年英国)

肝硬化腹水处理指南(2006年英国)

 

K P Moore, G P Aithal

1.0 INTRODUCTION

 
Ascites is a major complication of cirrhosis,1 occurring in 50% of patients over 10 years of follow up.2 The development of ascites is an important landmark in the natural history of cirrhosis as it is associated with a 50% mortality over two years,25 and signifies the need to consider liver transplantation as a therapeutic option.3 The majority (75%) of patients who present with ascites have underlying cirrhosis, with the remainder being due to malignancy (10%), heart failure (3%), tuberculosis (2%), pancreatitis (1%), and other rare causes.6 The true prevalence and incidence of cirrhosis of the liver and its complications in the UK are unknown. Mortality from cirrhosis has increased from 6 per 100 000 population in 1993 to 12.7 per 100 000 population in 2000.7 Approximately 4% of the general population have abnormal liver function or liver disease8 and approximately 1020% of those with one of the three most common chronic liver diseases (non-alcoholic fatty liver disease, alcoholic liver disease, and chronic hepatitis C) develop cirrhosis over a period of 1020 years. With a rising frequency of alcoholic and non-alcoholic fatty liver disease, a huge increase in the burden of liver disease is expected over the next few years8 with an inevitable increase in the complications of cirrhosis. There have been several changes in the clinical management of cirrhotic ascites over recent years, and the purpose of these guidelines is to promote a consistent clinical practice throughout the UK.
1.0绪论
腹水是肝硬化的一个主要并发症,1随访超过10年的病人中50%发生。2腹水的出现在肝硬化自然史中是一个重要的里程碑,因为其标示着2年间有50%的死亡率,2-5而且意味着需要考虑进行肝移植做为治疗方案。3以腹水为表现的病人大部分(75%)有潜在的肝硬化,其余的可能是恶性肿瘤(10%)、心衰(3%)、结核(2%)、胰腺炎(1%)和其它少见原因。6英国肝硬化真正的流行情况和发生率及其并发症尚不清楚。肝硬化的死亡率已经从1993年的6/10万上升到了2000年的12.7/10万。7普通人群中约4%有肝功能异常或肝病8,患三种最常见的慢性肝病(非酒精性脂肪肝,酒精性脂肪肝和慢性丙型肝炎)之一的病人约10-20%在10-20年间会发展成肝硬化。随着酒精性和非酒精性脂肪肝发生率的上升,在今后的数年间肝病的负担会大幅增加8并且不可避免要伴随着肝硬化并发症增加。在最近的几年间肝硬化腹水的临床处理上已有几个变化,本指南的目的是在全英国倡仪一个一致性的临床实践。
These guidelines are based on a comprehensive literature search, including the results of randomised control trials, systematic reviews, prospective retrospective studies and, in some instances, evidence obtained from expert committee reports. Where possible a judgement is made on the quality of the information used to generate the guidelines, and the specific recommendations have been graded according to the Oxford Centre for Evidence-based Medicine Levels of Evidence (May 2001) (see appendices 1 and 2).9 These guidelines conform to the international guidelines recently published by the International Ascites Club10 and are intended for use by physicians. We hope to revise these guidelines in three years time.
这些指南建立在深入的文献调查基础之上,包括RCT结果,系统综述,前瞻性回顾性研究,在有些情况下,证据是源于专家委员会的报告。如果可能的话,要对产生指南的材料的质量进行判断,并根据剑桥EBM中心的证据水平(2001年5月)(见附录1和2)对详细的建议进行分级。9这些指南符合最近由国际腹水俱乐部10出版的国际指南,也希望为内科医师所用。我们希望在3年的时间内对这些指南进行更新。
2.0 DEFINITIONS
The terms used in this article have been defined by the International Ascites Club.11
 Uncomplicated ascites 
Ascites that is not infected and which is not associated with the development of the hepatorenal syndrome. Ascites can be graded as follows:
● Grade 1 (mild). Ascites is only detectable by ultrasound examination.
● Grade 2 (moderate). Ascites causing moderate symmetrical distension of the abdomen.
● Grade 3 (large). Ascites causing marked abdominal distension.
Refractory ascites
Ascites that cannot be mobilised or early recurrence of which (that is, after therapeutic paracentesis) cannot be satisfactorily prevented by medical therapy. This includes two different subgroups.
● Diuretic resistant ascites—ascites that is refractory to dietary sodium restriction and intensive diuretic treatment (spironolactone 400 mg/day and frusemide 160 mg/day for at least one week, and a salt restricted diet of less than 90 mmol/day (5.2 g of salt)/day).
● Diuretic intractable ascites—ascites that is refractory to therapy due to the development of diuretic induced complications that preclude the use of an effective diuretic dosage.
2.0定义
本文中所用的词汇已为国际腹水俱乐部所定义。11
简单的(无并发症的)腹水
指没有被感染的腹水,其与肝肾综合征的出现无关。腹水分级如下:
●1级(少量):腹水为超声检查所检测到。
●2级(中量):腹水可引起中度对称性的腹部膨胀。
●3级(大量):腹水可引起明显的腹胀。
难治性腹水
药物治疗不能消除腹水或无法满意阻止早期复发(指治疗性腹水穿刺后)。这包括两个不同的亚群。
●利尿剂抵抗性腹水-限盐饮食和增加利尿治疗(安体舒通400mg/d及速尿160mg/d至少一周,饮食中每日盐少于90mmol/d即5.2g盐)腹水仍难以控制。
●利尿剂难治性腹水-由于利尿导致并发症使得有效的利尿剂的量无法应用。
3.0 PATHOGENESIS OF ASCITES FORMATION
A detailed description of the pathogenesis of ascites formation is beyond the scope of this article but more detailed reviews are available.1214 There are two key factors involved in the pathogenesis of ascites formationnamely, sodium and water retention, and portal (sinusoidal) hypertension.
3.0腹水形成的病机
对腹水形成的病机进行详细阐述不在本文的范围,不过有许多详细的综述可以参阅。12-14有两个关键因素涉及到腹水形成的病机,即钠水的潴留和门脉(肝窦)高压。
3.1 Role of portal hypertension
Portal hypertension increases the hydrostatic pressure within the hepatic sinusoids and favours transudation of fluid into the peritoneal cavity. However, patients with presinusoidal portal hypertension without cirrhosis rarely develop ascites. Thus patients do not develop ascites with isolated chronic extrahepatic portal venous occlusion or non-cirrhotic causes of portal hypertension such as congenital hepatic fibrosis, except following an insult to liver function such as gastrointestinal haemorrhage. Conversely, acute hepatic vein thrombosis, causing postsinusoidal portal hypertension, is usually associated with ascites. Portal hypertension occurs as a consequence of structural changes within the liver in cirrhosis and increased splanchnic blood flow. Progressive collagen deposition and formation of nodules alter the normal vascular architecture of the liver and increase resistance to portal flow. Sinusoids may become less distensible with the formation of collagen within the space of Disse. While this may give the impression of a static portal system, recent studies have suggested that activated hepatic stellate cells may dynamically regulate sinusoidal tone and thus portal pressure.
3.1门脉高压的作用
门脉高压增加了肝窦的静水压并促使液体渗透入腹腔。不过,没有肝硬化的窦前性门脉高压病人很少出现腹水。因此,单纯的慢性肝外门脉阻塞或非肝硬化病因的门脉高压如先天性肝纤维化病人是不会出现腹水的,除非是伴随有如胃肠道大出血等引起的肝功能的损害。相反,急性肝静脉血栓形成引起窦后性门脉高压常与腹水有关。门脉高压是硬化肝内结构性变化及内脏血流增加的结果。进行性的胶原沉积以及结节的形成改变了肝内正常的血管系统,使得门脉血流的阻力增加。肝窦的扩张性可能会随着Disse间隙内胶原的形成而更行降低。这给人形成的当然是静态的印象,其实最近的研究已提示肝内星形细胞的激活可能会从动力学上调节肝窦状况进而调节门脉压力。
Sinusoidal endothelial cells form an extremely porous membrane which is almost completely permeable to macromolecules, including plasma proteins. In contrast, splanchnic capillaries have a pore size 50–100 times less than that of hepatic sinusoids. As a consequence, the trans-sinusoidal oncotic pressure gradient in the liver is virtually zero while it is 0.8–0.9 (80%–90% of maximum) in the splanchnic circulation.12 Oncotic pressure gradients at such extreme ends of the spectrum minimise any effect the changes in plasma albumin concentration may have on transmicrovascular fluid exchange. Therefore, the old concept that ascites is formed secondary to decreased oncotic pressure is false, and plasma albumin concentrations have little influence on the rate of ascites formation. Portal hypertension is critical to the development of ascites, and ascites rarely develops in patients with a wedged hepatic venous portal gradient of<12 mm Hg.15 Conversely, insertion of a side to side portacaval shunt to decrease portal pressure often causes resolution of ascites. 
肝窦内皮细胞形成的多孔性膜性结构对大分子物质如血浆蛋白几乎完全通透。相反,内脏毛细血管孔径较肝窦的小50-100倍。结果,肝内跨窦的胶体渗透oncotic压力梯度实际上为零而在内脏循环中则为0.8-0.9(最大值的80-90%)。12 这样一个范围的极端下oncotic压力梯度会使所有可能的血浆白蛋白浓度的变化对跨越微细血管的液体交换效应减低到最小。所以,腹水的形成是继发于胶体渗透oncotic压力降低这一古老的概念是错误的,血浆白蛋白浓度对于腹水形成速率几乎没有影响。门脉高压对于腹水的出现至关重要,腹水很少出现于肝静脉门脉梯度小于12mmHg的病人。15相反,用以降低门脉压力的侧侧式的门体分流常常会使腹水消退。
3.2 Pathophysiology of sodium and water retention
The classical explanations of sodium and water retention occurring due to ‘‘underfill’’ or ‘‘overfill’’ are oversimplified. Patients may exhibit features of either ‘‘underfill’’ or ‘‘overfill’’ depending on posture or severity of liver disease. One of the key events thought to be critical in the pathogenesis of renal dysfunction and sodium retention in cirrhosis is the development of systemic vasodilatation, which causes a decrease in effective arterial blood volume and a hyperdynamic circulation.16 The mechanism responsible for these changes in vascular function is unknown but may involve increased vascular synthesis of nitric oxide, prostacyclin, as well as changes in plasma concentrations of glucagon,substance P, or calcitonin gene related peptide.14
3.2钠水潴留的病理生理学
经典的钠水潴留的发生是由于“充盈不佳”或“过度充盈”的解释显然是过于简单了。患者可能表现为要么是“充盈不佳”要么是“过度充盈”的特征取决于姿势或肝病严重程度。在肝硬化中被认为在肾功能不全和钠水潴留发生机制的至关重要的其中一个关键事件是全身血管舒张的出现,这将会导致有效动脉血流量的降低和低动力循环。16血管功能的这些变化的机制还不清楚,不过可能涉及到血管一氧化氮、前列环素合成的降低以及血浆中胰高糖素、P物质浓度或者降钙基因相关钛的变化。14
However, the haemodynamic changes vary with posture, and studies by Bernardi et al have shown marked changes in secretion of atrial natriuretic peptide with posture, as well as changes in systemic haemodynamics.17 18 In addition, data showing a decreased effective arterial volume in cirrhosis have been disputed.19 It is agreed however that under supine conditions and in experimental animals, there is an increase in cardiac output and vasodilatation.
不过,血流动力学变化会随不同姿势而改变,Bernardi等的研究已经显示心钠素(利钠肽)的分泌会随着不同姿势出现明显的变化。17-18另外,对于显示肝硬化时有效动脉血流量减少的资料现已有所争论。19不过,一致认为在仰卧状态下及实验动物中心输出量和血管舒张有所增加。
The development of renal vasoconstriction in cirrhosis is partly a homeostatic response involving increased renal sympathetic activity and activation of the renin-angiotensin system to maintain blood pressure during systemic vasodilatation. 20 Decreased renal blood flow decreases glomerular filtration rate and thus the delivery and fractional excretion of sodium. Cirrhosis is associated with enhanced reabsorption of sodium both at the proximal tubule and at the distal tubule.20 Increased reabsorption of sodium in the distal tubule is due to increased circulating concentrations of aldosterone. However, some patients with ascites have normal plasma concentrations of aldosterone,21 leading to the suggestion that sodium reabsorption in the distal tubule may be related to enhanced renal sensitivity to aldosterone or to other undefined mechanisms.22
肝硬化时肾血管收缩的出现,部分是由于全身血管舒张期间涉及到肾交感活性的增加和肾血管紧张素系统的激活以维持血压的稳态反应。20肾血流的减少降低了肾小球滤过率并因而降低钠的传输和部分排泄。肝硬化涉及近、远端小管钠的重吸收增加。20钠在远端小管重吸收的增加是因循环中醛固酮浓度增加,21这提示钠在远端小管的重吸收可能与肾脏对醛固酮或其它不明机制敏感性的增加有关。22
In compensated cirrhosis, sodium retention can occur in the absence of vasodilatation and effective hypovolaemia. Sinusoidal portal hypertension can reduce renal blood flow even in the absence of haemodynamic changes in the systemic circulation, suggesting the existence of a hepatorenal reflex.23 24 Similarly, in addition to systemic vasodilation, the severity of liver disease and portal pressure also contribute to the abnormalities of sodium handling in cirrhosis.25 
在代偿期肝硬化中,钠潴留可出现于没有血管舒张和有效血容量降低时。甚至在没有全身循环动力学变化时,肝窦门脉高压可减少肾血流量,提示有肝肾反射的存在。23-24同样,除全身血管舒张外,肝病严重程度和门脉压力也会使肝硬化时钠的处置出现问题。25
4.0 DIAGNOSIS
4.1 Initial investigations
The underlying cause of ascites is frequently obvious from the history and physical examination. However, it is important to exclude other causes of ascites. It should not be assumed that the alcoholic patient has alcoholic liver disease. Therefore, tests must be directed at diagnosing the cause of ascites. The essential investigations on admission include a diagnostic paracentesis with measurement of ascitic fluid albumin or protein, ascitic fluid neutrophil count and culture, and ascitic fluid amylase. Ascitic fluid cytology should be requested when there is a clinical suspicion of underlying malignancy. Other investigations should include abdominal ultrasound scan to evaluate the appearance of the liver, pancreas, and lymph nodes as well as the presence of splenomegaly, which may signify portal hypertension. Blood tests should be taken for measurement of urea and electrolytes, liver function tests, prothrombin time, and full blood count.
4.0诊断
4.1初始检查(调查,研究)
腹水潜在的原因通常可从病史和体检中得到明确。不过排除腹水的其它原因也很重要。不应该去假定嗜酒的病人就有酒精性肝病。所以在腹水原因诊断中必须进行实验室检查。对住院病人必需的检查包括诊断性腹水穿刺以检测腹水白蛋白或蛋白、腹水中性粒细胞计数和培养以及腹水淀粉酶。在临床怀疑有潜在恶性肿瘤时,腹水细胞学检查也应该进行。其它检查还应该包括腹部超声扫描以评估肝表面、胰腺、淋巴结以及脾肿大的存在,这可能标示着有门脉高压。血液检测也应进行以检查尿素氮和电解质、肝功、凝血酶原时间和全血细胞计数。
4.2 Abdominal paracentesis
The commonest site for an ascitic tap is approximately 15 cm lateral to the umbilicus, with care being taken to avoid an enlarged liver or spleen, and is usually done in the left or the right lower abdominal quadrant.12 The inferior and superior epigastric arteries run just lateral to the umbilicus towards the mid-inguinal point and should be avoided. For diagnostic purposes, 1020 ml of ascitic fluid should be withdrawn (ideally using a syringe with a blue or green needle) for inoculation of ascites into two blood culture bottles and an EDTA tube, and the tests outlined below. Complications of ascitic taps occur in up to 1% of patients (abdominal haematomas) but are rarely serious or life threatening.26 27 More serious complications such as haemoperitoneum or bowel perforation are rare (,1/1000 procedures).28 Paracentesis is not contraindicated in patients with an abnormal coagulation profile. The majority of patients with ascites due to cirrhosis have prolongation of the prothrombin time and some degree of thrombocytopenia. There are no data to support the use of fresh frozen plasma before paracentesis although if thrombocytopenia is severe (,40 000) most clinicians would give pooled platelets to reduce the risk of bleeding. 
4.2腹穿
最常选用的腹穿点是脐侧一边约15cm,要注意避开增大的肝脏或脾脏,通常在左或右下腹。12上和下腹主动脉正好于脐到腹股沟中间的一边通过,要注意避开。为诊断目的,要抽10-20ml的腹水(最好用带有兰或绿色针头的注射器)将腹水接种入两个血培养瓶和一个EDTA管,实验会在下边进行描述。腹穿并发症出现于达1%的病人(腹部血肿),不过严重的或有生命危险的很少有。26-27更为严重的并发症诸如腹腔内出血或肠穿孔罕见(1/1000)。28凝血机制不正常的患者进行腹穿并无不当。大多数肝硬化腹水的患者凝血酶原时间延长并有一定程度的血小板减少。虽然如果血小板减少严重(40,000)时大多数临床医生会予以浓缩血小板以降低出血的风险,但没有资料支持在腹穿前需要用新鲜冷冻血浆。
Recommendation
It is recommended that patients give informed consent for a therapeutic or diagnostic paracentesis.(Level of evidence: 5; recommendation: D.)
推荐:
建议征得病人同意进行诊断或治疗性腹穿(证据水平:5;推荐:D)
4.3 Ascitic fluid investigations
4.3.1 Ascitic fluid neutrophil count and culture
All patients should be screened for the development of spontaneous bacterial peritonitis (SBP), which is present in approximately 15% of patients with cirrhosis and ascites admitted to hospital.2931 An ascitic neutrophil count of .250 cells/mm3 (0.25109/l) is diagnostic of SBP in the absence of a known perforated viscus or inflammation of intrabdominal organs. The concentration of red blood cells in cirrhotic ascites is usually ,1000 cells/mm3 and bloody ascitic fluid (.50,000 cells/mm3) occurs in about 2% of cirrhotics.32 In approximately 30% of cirrhotics with bloody ascites, there is an underlying hepatocellular carcinoma.33 However, in 50% of patients with bloody ascites, no cause can be found.33 Grams stain of ascitic fluid is not indicated, as it is rarely helpful.34 The sensitivity of smear for mycobacteria is very poor while fluid culture for mycobacteria has a sensitivity of 50%.35 Several studies have shown that inoculation of ascitic fluid into blood culture bottles will identify an organism in approximately 7290% of cases whereas sending ascitic fluid in a sterile container to the laboratory will only identify an organism in about 40% of cases of SBP.34 3639
4.3腹水检查
4.3.1腹水中性粒细胞计数及培养
全部患者需要筛查有无出现自发性细菌性腹膜炎(SBP),约15%有肝硬化和腹水的住院患者会出现SBP。29-31在没有已知的内脏穿孔或腹内器官炎症情况下,腹水中性粒细胞计数250/mm3(0.25×109/L)对SBP有诊断意义。肝硬化腹水中红细胞通常是1000细胞/mm3,血性腹水(50000细胞/mm3)见于大约2%的肝硬化。32有血性腹水的肝硬化中约30%有潜在的肝细胞癌。33不过50%血性腹水患者找不到原因。33腹水Gram染色没有必要,因为很少有帮助。34涂片找分枝杆菌的敏感性非常差,腹水培养分枝杆菌的敏感性为50%。35有多个研究显示腹水接种入血培养瓶中在近72-90%的病例会识别出一种微生物,而将腹水加入消毒器皿中送到实验室只在大约40%的SBP病例中识别出一种微生物。34,36-39
4.3.2 Ascitic fluid protein and ascitic fluid amylase
Conventionally, the type of ascites is divided into exudates and transudates, in which the ascitic protein concentration is .25 g/l or ,25 g/l, respectively. The purpose of this subdivision is to help identify the cause of ascites. Thus ‘‘malignancy classically causes an exudative ascites and cirrhosis causes a transudate’’. However, there are many misconceptions in clinical practice. For example, it is often presumed that cardiac ascites is a transudate when this is rarely the case, ascitic protein is .25 g/l in up to 30% of patients with otherwise uncomplicated cirrhosis,32 4043 and patients with cirrhosis and tuberculous ascites may have a low ascitic protein.44 The serum ascites-albumin gradient (SA-AG) is far superior in categorising ascites with 97% accuracy (table 1).42 45 46 It is calculated as:
SA-AG = serum albumin concentration - ascitic fluid albumin concentration
As a high ascitic amylase is diagnostic of pancreatic ascites,4749 ascitic fluid amylase should be determined in patients where there is clinical suspicion of pancreatic disease.
4.3.2腹水蛋白和腹水淀粉酶
按照惯例,腹水分为漏出液和渗出液两种,其腹水蛋白浓度分别是<25g/L和>25g/L。这样细分的目的是帮助鉴别腹水原因,因此,才有“经典的恶性肿瘤引起渗出性腹水而肝硬化则为漏出性腹水”之说。不过在临床实践中有很多的误解。如通常假定心源性腹水为漏出液而这其实非常少见,在达30%的没有并发症的肝硬化病人中腹水蛋白>25g/L,32,40-43有肝硬化和结核腹水的病人也可能腹水蛋白很低。44血清腹水-白蛋白梯度(SA-AG)在腹水分类时有更高的优越性,准确率达97%(表1)。42,45-46计算方式如下:
SA-AG =血清白蛋白浓度-腹水白蛋白浓度
因为腹水淀粉酶增高对胰腺性腹水有诊断意义,47-49在临床怀疑有胰腺疾病时应检测患者的腹水淀粉酶。
4.3.3 Ascitic fluid cytology
Only 7% of ascitic fluid cytologies are positive50 yet cytological examination is 6090% accurate in the diagnosis of malignant ascites, especially when several hundred millilitres of fluid is tested and concentration techniques are used.12 Clinicians should liaise with their local cytology department to discuss fluid requirements before paracentesis. But ascites fluid cytology is not the investigation of choice for the diagnosis of primary hepatocellular carcinoma.
4.3.3腹水细胞学
只有7%的腹水细胞学检查阳性50,不过在恶性腹水的诊断中细胞学检查准确率达60-90%,尤其是当腹水检测量达数千ml并且应用浓缩技术时。12在腹穿进行前临床医生应该与本地细胞学实验室保持联络以讨论所需要的腹水量。不过腹水细胞学检查并不是原发性肝癌诊断的有效检查方法。
Recommendations
The initial ascitic fluid analysis should include serum ascites-albumin gradient in preference to ascitic protein. (Level of evidence: 2b; recommendation: B.)
Ascitic amylase should be measured when there is clinical suspicion of pancreatic disease. (Level of evidence: 4; recommendation: C.)
Ascitic fluid should be inoculated into blood culture bottles at the bedside and examined by microscopy for a neutrophil count. (Level of evidence: 2a; recommendation:B.)
推荐:
初始的腹水检查应包括SA-AG并优先于腹水蛋白(证据水平:2b;推荐:B)
当临床怀疑胰腺疾病时应检测腹水淀粉酶(证据水平:4;推荐:C)
腹水应在床边接种入血培养瓶中并需用显微镜检测中性粒细胞计数。(证据水平:2a;推荐:B)
5.0 TREATMENT
5.1 Bed rest
In patients with cirrhosis and ascites, assumption of upright posture is associated with activation of the renin-angiotensin- aldosterone and sympathetic nervous system, a reduction in glomerular filtration rate and sodium excretion, as well as a decreased response to diuretics.14 51 These effects are even more striking in association with moderate physical exercise. 52 53 These data strongly suggest that patients should be treated with diuretics while on bed rest. However, there have been no clinical studies to demonstrate increased efficacy of diuresis with bed rest or decreased duration of hospitalisation. As bed rest may lead to muscle atrophy, and other complications, as well as promoting extended stays in hospital, it is not generally recommended for the management of patients with uncomplicated ascites.
5.0治疗
5.1卧床休息
在肝硬化和腹水的病人,直立位时肾素-血管紧张素醛固酮及交感神经系统激活,肾小球滤过率及钠外排减少,对利尿剂反应降低。14,51这种效应在适度的活动时更为明显。52,53这些资料强烈提示患者在卧床休息时应该用利尿剂进行治疗。不过,还没有临床研究显示卧床增加利尿剂效能或者减少住院时间。因为卧床休息可能引起肌肉萎缩及其它并发症并延长住院时间,一般不推荐用于对没有并发症的腹水病人进行处理。
Recommendation
 Bed rest is NOT recommended for the treatment of ascites. (Level of evidence: 5; recommendation: D.)
推荐
卧床休息不推荐用于腹水的治疗(证据水平:5;推荐:D)
5.2 Dietary salt restriction
Dietary salt restriction alone can create a negative sodium balance in 10% of patients.54 Sodium restriction has been associated with lower diuretic requirement, faster resolution of ascites, and shorter hospitalisation.55 56 In the past, dietary salt was often restricted to 22 or 50 mmol/day. These diets may lead to protein malnutrition and a similar outcome,57 and are no longer recommended. A typical UK diet contains about 150 mmol of sodium per day, of which 15% is from added salt and 70% is from manufactured food.58 59 Dietary salt should be restricted to ,90 mmol/day (5.2 g) salt by adopting a no-added salt diet and avoidance of pre-prepared foodstuffs (for example, pies). Dieticians guidance and information leaflets will assist in educating patient and relatives regarding salt restriction. Certain drugs, especially those in the effervescent tablet form, have high sodium contents. Intravenous antibiotics generally contain 2.1 3.6 mmol of sodium per gram with the exception of ciprofloxacin which contains 30 mmol sodium in 200 ml (400 mg) for intravenous infusion. Although in general it is preferable to avoid infusion of fluids which contain salt in patients with ascites, there are occasions, such as the development of hepatorenal syndrome or renal impairment with severe hyponatraemia, when it may be appropriate and indicated to give volume expansion with a crystalloid or colloid. For patients developing hepatorenal syndrome, the International Ascites Club recommend infusion of normal saline.
5.2饮食限盐
单用饮食限盐在10%病人可以产生钠的负平衡。54限制钠可以减少利尿剂的用量,加快腹水吸收并减少住院时间。55,56以前饮食中盐量常限制到22或50mmol/d。这样的饮食可能会引起蛋白质营养不良或相似的结果,57不再予以推荐使用。传统的英国饮食每天饮食中含钠约150mmol,其中15%源于加入的食盐,70%源于食品加工。58,59应该通过采用不增加食盐并避免使用预处理的食品(如馅饼)将饮食中的盐每天限制到90mmol(5.2g)。营养学家的指导及宣传册会有助于教育患者及亲属注意限盐。某些药物尤其是以泡腾片形式者含钠较高。静脉输注抗生素每克通常含2.1-3.6mmol钠,而每200ml(400mg)环丙沙星含30mmol钠。虽然一般来说腹水病人避免输注含盐液体,但也有例外,如出现肝肾综合征或伴有严重低钠血症的肾功能障碍,这时就有予以晶体或胶体扩容的适应症。对于出现肝肾综合征的病人,国际腹水俱乐部推荐输注生理盐水。
Recommendation
Dietary salt should be restricted to a no-added salt diet of 90 mmol salt/day (5.2 g salt/day). (Level of evidence: 2b; recommendation: B.)
推荐     
饮食中盐应该限制到不再另加食盐的每天90mmol(5.4g)水平(证据水平:2b,推荐:B)
5.3 Role of water restriction
There have been no studies on the benefits or harm of water restriction on the resolution of ascites. Most experts agree that there is no role for water restriction in patients with uncomplicated ascites. However, water restriction for patients with ascites and hyponatraemia has become standard clinical practice in many centres. However, there is real controversy about the best management of these patients, and at present we do not know the best approach. Most hepatologists treat these patients with severe water restriction. However, based on our understanding of the pathogenesis of hyponatraemia, this treatment is probably illogical and may exacerbate the severity of effective central hypovolaemia that drives the non-osmotic secretion of antidiuretic hormone (ADH). This may result in further increases in circulating ADH, and a further decline of renal function. Impaired free water clearance is observed in 25 60% of patients with ascites due to cirrhosis,60 and many develop spontaneous hyponatraemia.61 Therefore, some hepatologists, including the authors, advocate further plasma expansion to normalise and inhibit stimulation of ADH release. Studies are needed to determine the best approach.62 There are data emerging that support the use of specific vasopressin 2 receptor antagonists in the treatment of dilutional hyponatraemia,6365 but whether this improves overall morbidity and mortality is not yet known. It is important to avoid severe hyponatraemia in patients awaiting liver transplantation as it may increase the risk of central pontine myelinolysis during fluid resuscitation in surgery.
5.3限水的作用
还没有有关限水对腹水消退益、害的研究。多数专家同意对于无并发症腹水患者限水没有作用。不过,在许多中心限水对于有腹水和低钠血症的病人已成为标准的临床实践。但是,对于这些患者的最佳处理也确实存在争议,目前我们尚不知道最佳路径。大多数肝病专家用严格的限水来治疗这些患者。但是,基于我们对低钠血症病机的理解,这种治疗可能是不合理的,有可能会加重有效的中心性低血容量的严重度,而这将会促使非渗透性的ADH的分泌。这可能会导致循环中ADH的进一步增加,以及肾功能的进一步下降。肝硬化腹水病人25-60%可能观察到游离水清除受损,60许多出现自发性低钠血症。61所以,有些肝病专家包括本文作者提倡进一步的血浆扩容以使ADH释放的刺激因素正常化和受抑。还需研究来确定最佳路径。62有资料显示在治疗稀释性低钠血症中支持使用特异的抗利尿激素2受体拮抗剂63-65,但是这是否会改善整体的发病率和死亡率还不知道。重要的是在等待进行肝移植的病人要避免出现严重的低钠血症,因为这会增加外科液体复苏过程中出现脑桥中央髓鞘溶解的风险。
5.4 Management of hyponatraemia in patients on diuretic therapy
5.4.1 Serum sodium ≥126 mmol/l
For patients with ascites who have a serum sodium ≥126 mmol/l, there should be no water restriction, and diuretics can be safely continued, providing that renal function is not deteriorating or has not significantly deteriorated during diuretic therapy.
5.4利尿剂治疗病人低钠血症的处理
5.4.1血钠≥126mmol/L
         对于血钠≥126mmol/L的腹水患者,不应该限水。如果在利尿治疗期间肾功能没有损害或者没有明显损害利尿剂可以继续安全使用,
5.4.2 Serum sodium≤125 mmol/l
For patients with moderate hyponatraemia (serum sodium 121125 mmol/l), opinion is divided on what is the next best course of action. The international opinion,10 in which a consensus of international experts was sought and reported, is that diuretics should be continued. However, there are no or few data to support the best course of action, and our personal view is to adopt a more cautious approach. We believe that diuretics should be stopped once serum sodium is (125 mmol/l and the patient observed. All experts in the field recommend stopping diuretics if serum sodium is (120 mmol/l. If there is a significant increase in serum creatinine or serum creatinine is .150 mmol/l, we would recommend volume expansion. Gelofusine, haemaccel, and 4.5% albumin solutions contain sodium concentrations equivalent to normal saline (154 mmol/l). This will worsen their salt retention but we take the view that it is better to have ascites with normal renal function than to develop potentially irreversible renal failure. Water restriction should be reserved for those who are clinically euvolaemic with severe hyponatraemia in which free water clearance is decreased, and who are not currently taking diuretics, and in whom serum creatinine is normal.
5.4.2血钠≤125 mmol/L
对于中度低钠血症(血钠121-125 mmol/L)患者,意见因下一步最佳course of action不同而不同。国际上的意见10(寻找及报告国际专家共识)是继续使用利尿剂,但是,没有或很少有将被支持最佳course of action,我们个人的意见是采用更为谨慎的方法。我们相信一旦血钠≤125 mmol/L利尿剂应该停用并且要对患者进行观察。该领域所有的专家推荐如果血钠≤120 mmol/L,停用利尿剂。如果血肌酐明显增加或血肌酐>150 mmol/L,我们推荐进行扩容。佳乐施(译者注:含琥珀明胶,平均分子量30000,血容量补充药),海脉素(译者注:尿素交联明胶,血浆代用品) 和4.5%的白蛋白溶液包含的钠浓度与生理盐水相当(154mmol/L)。这将会使盐的贮留更加恶化。不过我们相信肾功能正常时有腹水要好于发展为潜在的不可逆性肾衰。对于临床上are euvolaemic with严重低钠血症者,其游离水的清除降低,目前未服用利尿剂,其血肌酐正常,仍然要限水。
5.5 Diuretics
Diuretics have been the mainstay of treatment of ascites since the 1940s when they first became available. Many diuretic agents have been evaluated over the years but in clinical practice in the UK this has been mainly confined to spironolactone, amiloride, frusemide, and bumetanide. These are discussed below.
5.5利尿剂
自20世纪40年代利尿剂首先可用时就一直是腹水治疗的主要用药。在过去的多年间已对许多利尿剂进行了评估,不过英国的临床实践中,还主要限于螺内酯,阿米罗利,速尿和布美他尼。这将在以下进行讨论。
5.5.1 Spironolactone
Spironolactone is an aldosterone antagonist, acting mainly on the distal tubules to increase natriuresis and conserve potassium. Spironolactone is the drug of choice in the initial treatment of ascites due to cirrhosis.66 The initial daily dose of 100 mg may have to be progressively increased up to 400 mg to achieve adequate natriuresis. There is a lag of 35 days between the beginning of spironolactone treatment and the onset of the natriuretic effect.67 Controlled studies have found that spironolactone achieves a better natriuresis and diuresis than a ‘‘loop diuretic’’ such as frusemide.6871 Most frequent side effects of spironolactone in cirrhotics are those related to its antiandrogenic activity, such as decreased libido, impotence, and gynaecomastia in men and menstrual irregularity in women (although most women with ascites do not menstruate anyway). Gynaecomastia can be significantly reduced when the hydrophilic derivative potassium canrenoate is used,72 but this is not readily available in the UK. Tamoxifen at a dose 20 mg twice a day has been shown to be useful in the management of gynaecomastia.73 Hyperkalaemia is a significant complication that frequently limits the use of spironolactone in the treatment of ascites.
5.1.1螺内酯
螺内酯是醛固酮拮抗剂,主要作用于远端小管增加尿钠排泄和保钾。螺内酯是肝硬化腹水初始治疗的首选药物。66初始每天100mg的量可能需要逐步增加到400mg以达到适当的尿液排钠。在应用螺内酯治疗开始和出现尿钠排泄之间会有3-5天的延迟。67对照研究发现螺内酯较绊利尿剂如速尿能取得更好的排钠和利尿效果。68-71螺内酯在肝硬化中大部分常见的副作用与其抗雄激素活性有关,如男性性欲降低,阳萎和男性乳腺发育,而在女性则为月经紊乱(虽然大多数有腹水的女性不来月经)。当使用亲水性衍生物烯睾丙酸钾时男性乳腺发育可以明显的减少,72不过在英国还不会很快就能用。他莫昔芬20mg每日两次在处理男性乳腺发育中已显示有益。73高钾血症常是腹水治疗中限制采用螺内酯的一个重要并发症。
Recommendations
Serum sodium 126135 mmol/l, normal serum creatinine. Continue diuretic therapy but observe serum electrolytes. Do not water restrict. 
Serum sodium 121125 mmol/l, normal serum creatinine. International opinion is to continue diuretic therapy, our opinion is to stop diuretic therapy or adopt a more cautious approach.
 Serum sodium 121–125 mmol/l, serum creatinine elevated (>150 mmol/l or>120 mmol/l and rising). Stop diuretics and give volume expansion. 
Serum sodium ≤120 mmol/l, stop diuretics. Management of these patients is difficult and controversial. We believe that most patients should undergo volume expansion with colloid (haemaccel, gelofusine, or voluven) or saline. However, avoid increasing serum sodium by .12 mmol/l per 24 hours. (Level of evidence: 5; recommendation: D.)
推荐
血清钠126~135 mmol/l,血肌酐正常:继续利尿治疗不过要注意观察血电解质。不用限水。
血钠121~125 mmol/l,血肌酐正常:国际上的意见是继续利尿治疗,我们的意见是停止利尿治疗或采用更加谨慎的方法。
血钠121~125 mmol/l,血肌酐升高(>150 mmol/l 或者是>120 mmol/l并继续升高):停止利尿并予以扩容。
血钠≤120 mmol/l:停止利尿,这些患者的处理很困难且有争议。我们相信大多数患者应该用胶体(海脉素, 佳乐施, 或万汶voluven)或盐水进行扩容。但是,要避免每24小时增加血钠>12 mmol/l。(证据水平:5;推荐:D)
5.5.2 Frusemide
Frusemide is a loop diuretic which causes marked natriuresis and diuresis in normal subjects. It is generally used as an adjunct to spironolactone treatment because of its low efficacy when used alone in cirrhosis.71 The initial dose of frusemide is 40 mg/day and it is generally increased every 2 3 days up to a dose not exceeding 160 mg/day. High doses of frusemide are associated with severe electrolyte disturbance and metabolic alkalosis, and should be used cautiously. Simultaneous administration of frusemide and spironolactone increases the natriuretic effect.12 28
5.5.2速尿(呋塞米)
速尿是绊利尿剂,在正常情况下可引起明显的排钠和利尿作用。一般用做螺内酯治疗时的辅助因为其单独用于肝硬化时效能较低。71速尿的初始剂量是40mg/d,一般每2-3天增加直到不超过160 mg/d的剂量。大剂量的速尿会引起严重电解质紊乱和代谢性碱中毒,应该慎重使用。同时应用螺内酯和速尿会增加排钠效果。12,28
5.5.3 Other diuretics
Amiloride acts on the distal tubule and induces diuresis in 80% of patients at doses of 1530 mg/day.75 It is less effective compared with spironolactone or potassium canrenoate.71 72        Bumetanide is similar to frusemide in its action and efficacy.76
Generally, a ‘‘stepped care’’ approach is used in the management of ascites starting with modest dietary salt restriction, together with an increasing dose of spironolactone. Frusemide is only added when 400 mg of spironolactone alone has proved ineffective.7779 In patients with severe oedema there is no need to slow down the rate of daily weight loss.28 Once the oedema has resolved but ascites persists, then the rate of weight loss should not exceed ,0.5 kg/day.80 Over diuresis is associated with intravascular volume depletion (25%) leading to renal impairment, hepatic encephalopathy (26%), and hyponatraemia (28%).81 Approximately 10% of patients with cirrhosis and ascites have refractory ascites.71 82 In patients who fail to respond to treatment, a careful dietary and drug history should be obtained. It is important to ensure that they are not consuming drugs that are rich in sodium, or drugs that inhibit salt and water excretion such as non-steroidal anti-inflammatory drugs.83 84 Compliance with dietary sodium restriction should be monitored by measurement of urinary sodium excretion. If urinary sodium exceeds the recommended sodium intake, and the patient fails to respond to treatment, then it can be assumed that the patient is non-compliant.85
5.5.3其它利尿剂
阿米洛利作用于远端小管,15-30mg/d的剂量对80%病人可引起利尿。75与螺内酯或烯睾丙酸钾相比其效果稍逊。71,72布美他尼的作用和效果与速尿相似。76一般来讲,阶梯疗法用于开始适度饮食限盐腹水处理的同时,要增加螺内酯的剂量。速尿只有在单独螺内酯400mg无效时才予以加用。77-79在有严重水肿的患者,不需要减慢每天体重下降的速度。28一旦水肿消退而腹水仍然存在,则体重下降速度就不要超过0.5kg/d。80过度利尿会引起血管内血容量不足(25%)导致肾功能障碍、肝性脑病(26%)、低钠血症(28%)。81大约10%的肝硬化腹水病人为难治性腹水。71,82对于那些对于治疗没有反应患者,要认真了解其饮食和用药史。确保他们没使用富含钠的药物或者抑制水盐排泄的药物如NSAIDs。83,84要通过检查尿钠排泄来监测对于饮食限盐的依从性。如果尿钠超过了推荐的钠摄入量,患者对治疗没有反应,那么就可以考虑患者没有依从性。85
Recommendations
Firstline treatment of ascites should be spironolactone alone, increasing from 100 mg/day to a dose of 400 mg/day.
If this fails to resolve ascites, frusemide should be added in a dose of up to 160 mg/day, but this should be done with careful biochemical and clinical monitoring.(Level of evidence: 1a; recommendation: A.)
推荐
腹水的一线治疗是螺内酯单独应用,从100mg/d到400mg/d。
如果没有消退腹水,可增加速尿一直到160mg/d,不过要注意生化和临床监测。(证据水平:1a;推荐:A)
5.6治疗性腹水穿刺
大量或难治性腹水病人的处理通常开始时予以重复的大量放腹水。几个对照临床研究显示大量放腹水并补充胶体是快速、安全有效的。81,86-88第一个研究显示连续大量腹穿(4-6l/d)并输注白蛋白(每移除1升腹水8g)与利尿治疗相比更为有效,并发症少且住院时间缩短。86该研究之后的其它数个研究对有效性、安全性、放腹水的速度及腹穿后的血液动力学变化以及对补充胶体治疗的需求进行了评估。如果腹穿后进行扩容,全腹腔穿刺放腹水一般来说较重复腹穿更为安全。89不进行有效的扩容会导致腹穿后循环功能障碍、肾功能损害和电解质紊乱。90-93
Following paracentesis, ascites recurs in the majority (93%) if diuretic therapy is not reinstituted, but recurs in only 18% of patients treated with spironolactone.94 Reintroduction of diuretics after paracentesis (usually within 12 days) does not appear to increase the risk of postparacentesis circulatory dysfunction.
腹穿后,如果不再进行利尿治疗,大部分(93%)腹水会重现,不过用螺内酯治疗的患者只有18%腹水重现。94腹穿后(通常1-2天内)重新开始利尿剂看起来不会增加腹穿后循环功能障碍的风险。
5.6.1 Haemodynamic changes following paracentesis
Total paracentesis is associated with significant haemodynamic effects.91 It has been assumed wrongly that total paracentesis of large volumes of ascites (.10 litre) leads to circulatory collapse. Large volume paracentesis (average .10 litre over 24 hours) causes a marked reduction in intra-abdominal and inferior vena cava pressure, leading to a decrease in right atrial pressure and an increase in cardiac output. These haemodynamic changes are maximal at three hours. Pulmonary capillary wedge pressure decreases at six hours and continues to fall further in the absence of colloid replacement. On average, blood pressure decreases by ,8 mm Hg.91 The severity of post-paracentesis circulatory dysfunction correlates inversely with patient survival.95 There are anecdotal reports of some patients with advanced liver disease developing quite severe hypotension post-paracentesis, but this rarely occurs.
5.6.1腹穿后血液动力学变化
全腹腔穿刺放腹水可以产生明显的血液动力学效应。91人们曾经错误地认为大量腹水的全腹腔穿刺放腹水(>10L)会导致循环的衰竭。大剂量腹穿(2-4小时平均>10L)会引起腹内和下腔静脉压力的明显降低,导致右心房压的降低和心输出量的增加。这些血液动力学变化在3个小时达高峰。在没有补充胶体时,6小时肺毛细血管楔压降低并会继续下降。平均来说,血压下降~8mmHg。91腹穿后循环功能障碍的严重性与患者的生存负性相关。95也有少数报道有些有严重肝病的患者出现非常严重的腹穿后低血压,不过这相当罕见。
5.6.2 Plasma expansion post paracentesis
One study, which evaluated the haemodynamic and neurohumoral responses in 12 patients following a single ,5 litre total paracentesis concluded that it was safe to omit the use of albumin in these patients.96 However, many experts in the field have reservations on basing such a recommendation on a single small unrandomised study. Thus the International Ascites Club recommends that a synthetic plasma expander is used if less than 5 litre is removed, and this recommendation was based on consensus rather than fact.10 Plasma volume expansion should always be used whenever >5 litre of ascites are removed. Serial paracentesis with and without albumin replacement have been evaluated in patients with tense ascites.90 There was a significantly higher rate of renal impairment, significant fall in serum sodium levels, and a marked activation of the renin-angiotensin-aldosterone system in those patients not treated with albumin.90
5.6.2腹穿后血浆扩容
有一个研究评估了12例患者单次<5L的全腹腔穿刺放腹水后的血液动力学和神经激素反应,结论是在这些患者不应用白蛋白是安全的。96不过,该领域的许多专家对于将这样一个建议建立在一个小样本非随机化研究之上持保留意见。因此,国际腹水俱乐部推荐如果移除腹水少于5L要用合成血浆扩容剂,该建议是建立在共识而非实事基础上。10无论何时移除腹水>5L都要用血浆进行扩容。对有张力性腹水的患者连续腹穿用或不用白蛋白补充进行了评估。90不用白蛋白的患者肾功能损害率明显高、血钠水平明显下降而且肾素-血管紧张素-醛固酮系统激活明显。90
There is still some debate about whether volume expansion should be carried out using albumin or artificial plasma expanders. Analysis of individual, but relatively small and underpowered randomised controlled trials comparing dextran 70 or haemaccel/gelofusine with albumin suggest that these plasma expanders are clinically effective in the prevention of hyponatraemia and renal impairment.9799 However, the use of artificial plasma expanders is associated with a significantly greater activation of renin-angiotensinaldosterone. 97 These data suggest that if enough patients were studied, that albumin would prove to be clinically superior to haemaccel or gelofusine or dextrans. Indeed, analysis of data from all published studies also suggests that albumin is more effective in the prevention of hyponatraemia (8% of 482 patients) compared with 17% of 344 patients for other plasma expanders.100 A recent study by Moreau et al suggested that administration of albumin post-paracentesis decreases the number of liver related complications, and that the median hospital cost for a 30 day period was significantly lower (less than 50%) than the cost of those treated with artificial plasma expanders.101 Until further studies are undertaken to compare the efficacy of albumin versus artificial plasma expanders, wewould recommend that albumin remains the plasma expander of choice when large volume (.5 litre) paracentesis is undertaken. Albumin (as 20% or 25% solution) should be infused after paracentesis of .5 litre is completed at a dose of 8 g albumin/litre of ascites removed.
关于是否要用白蛋白或人造血浆扩容剂来进行扩容仍然有所争议。个别的分析(但样本相对较小且underpowered随机化对照试验)对右旋糖酐70或海脉素/佳乐施与白蛋白进行了比较,提示在预防低钠血症和肾功能损害中,这些血浆扩容剂在临床上是有效的。97-99不过,应用人工血浆扩容剂可能引起明显强烈的肾素血管紧张素醛固酮系统的激活。97这些资料提示如果所研究的患者足够的话,将会证明白蛋白在临床上要比海脉素或佳乐施或右旋糖酐优越。确实,对所有已发表的研究资料的分析也提示白蛋白在预防低钠血症(482例患者中8%)方面,绕渌┤菁粒?44例中17%)更有效。100最近由Moreau et al进行的一个研究提示腹穿后应用白蛋白会降低肝脏相关并发症的数量,30天期间中位住院花费较用人工血浆扩张剂明显低(不超过50%)。101
5.7 Procedure
Paracentesis should be carried out under strict sterile conditions. The cannula should have multiple side perforations, otherwise the end becomes blocked by bowel wall. The needle is usually inserted into the left (preferably) or right lower abdominal quadrant using the ‘‘Z’’ track (skin is penetrated perpendicularly). The needle is advanced obliquely in subcutaneous tissue and then the peritoneal cavity is punctured, with the needle pointing perpendicular to the abdominal wall. This will ensure that the needle track has the puncture site on the skin and the peritoneum that do not overlie each other. All ascitic fluid should be drained to dryness in a single session as rapidly as possible over 14 hours, assisted by gentle mobilisation of the cannula or turning the patient on to their side if necessary. In the authors opinion, the drain should not be left in overnight. After paracentesis, the patient should lie on the opposite side for two hours if there is leakage of any remaining ascitic fluid, and/or a suture (ideally purse string) inserted around the site of drainage. These steps help to minimise the risk of ascitic fluid leakage.
5.7步骤
腹穿应该在严格的消毒情况下进行。插管要有多个侧孔,否则前端会被肠壁堵塞。穿刺针通常以“Z”路径(垂直穿过皮肤)刺入左(较多)或右下腹部。针头在皮下组织迂回前行然后刺入腹腔,将针垂直于腹壁。这样会确保针道在皮肤与腹膜上的穿刺点不会相挨(overlie)。全部腹水要尽可能快的在1-4小时一次(a single session)引流完(dryness),如果需要的活可辅以轻轻活动套管或者让患者转身。就作者的意见来说,引流不要过夜。腹穿后,如果患者有剩余的腹水渗漏的话要让患者另一侧卧2小时,和/或在引流位置插入一个缝合(最好是收缩性的),这些会有助于减少腹水渗漏的危险。
Recommendations
Therapeutic paracentesis is the firstline treatment for patients with large or refractory ascites. (Level of evidence: 1a; recommendation: A.)
Paracentesis of <5 litre of uncomplicated ascites should be followed by plasma expansion with a synthetic plasma expander and does not require volume expansion with albumin (Level of evidence: 2b; recommendation: B.)
Large volume paracentesis should be performed in a single session with volume expansion being given once paracentesis is complete, preferably using 8 g albumin/litre of ascites removed (that is, ,100 ml of 20% albumin/3 l ascites). (Level of evidence: 1b; recommendation:A.)
建议:
治疗性腹穿是大量腹水或难治性腹水的一线治疗方法。(证据水平:1a;推荐:A)
无并发症腹水<5L的腹穿要继以合成血浆扩容剂进行血浆扩容,不需要用白蛋白进行扩容(证据水平:2b;推荐:B)
大量放腹水要一次(in a single session)完成并要于完成后就进行扩容,大多每放腹水1L用8g白蛋白(即3L腹水用100ml20%的白蛋白)。(证据水平:1b;推荐:A)
5.8 Transjugular intrahepatic portosystemic shunt(TIPS)
As elevated portal pressure is one of the main factors contributing to the pathogenesis of ascites, it is not surprising that TIPS is a highly effective treatment for refractory ascites. It functions as a side to side portocaval shunt that is placed under local anaesthesia and intravenous sedation, and has largely replaced the use of surgically placed portocaval or mesocaval shunts. Numerous uncontrolled studies have been published assessing the effectiveness of TIPS in patients with refractory ascites.102105 In most studies technical success was achieved in 93100% of cases,103 106108 with control of ascites achieved in 2792%103 108 109 and complete resolution in up to 75% of cases.103 TIPS results in a secondary decrease in the activation of the renin-angiotensin-aldosterone system, and increases sodium excretion.110
5.8 TIPS
因为门脉压力升高是腹水病机的一个重要因素,毫无疑问TIPS是难治性腹水最有效的治疗方法。其作用相当于一个局麻和静脉镇静剂下进行的侧侧门腔分流,可以很大程度上取代外科术中的门腔分流或肠腔分流。许多对照研究发表了评估TIPS对难治性腹水患者的效果。102-105大部分研究中在93-100%的病例中取得了技术上的成功,103,106-108而对照组腹水为27-92%103,108,109,75%病例达到了完全腹水消退。TIPS可以继发性地使肾素血管紧张素醛固酮系统活性下降,并增加钠的排泄。110
Prospective randomised trials have shown TIPS to be more effective in controlling ascites compared with large volume paracentesis.111–113 However, there is no consensus regarding the impact of TIPS on transplant free survival in patients with refractory ascites. In one study TIPS had no effect on survival112 while others have reported both reduced111 as well as improved survival113 compared with therapeutic paracentesis. Moreover, TIPS also improves the overall nutritional well being of patients, but whether this is simply secondary to control of ascites and improved eating is not clear.110 114 115 Hepatic encephalopathy after TIPS insertion occurs in approximately 25% of patients, and the risk is higher in those over the age of 60 years.116 TIPS is associated with less favourable outcome in advanced Child-Pugh class C patients.111 TIPS increases the cardiac preload, and hence it may precipitate heart failure in those with pre-existing heart disease.117 TIPS insertion should be considered as a treatment option for patients who require frequent paracentesis (generally>3 a month). TIPS has also been shown to resolve hepatic hydrothorax in 60–70% of patients.118–120
前瞻性随机研究显示与大量放腹水相比TIPS在控制腹水方面更有效。111-113不过,还没有有关TIPS对难治性腹水患者移植后自由生存率影响方面的共识。在一个研究中,TIPS对生存没有影响112而其它的则报道与治疗性腹穿相比有降低111也有提高生存的113。此外,TIPS也会改善病人的总体营养状况,不过这是否单纯继发于腹水的控制和进食情况的改善还不清楚。110,114,115TIPS后肝性脑病出现于大约25%的病人,年龄超过60岁患者风险相对高。116在进展期的Child-Pugh C级患者TIPS的效果较不好。111TIPS增加了心脏前负荷,因此有可能使以前有心脏病的患者发生心衰。117对于需要频繁放腹水(一般来说每月超过3次)的患者应该考虑TIPS做为一种治疗选择。TIPS也显示可能消退60-70%患者的肝性胸水。118-120
Model for end stage liver disease score, which was originally developed to predict survival following a TIPS procedure,121 has continued to evolve into a model that predicts prognosis in cirrhosis.122 According to the initial TIPS model, a risk score is calculated as R=0.9576loge (creatinine mg/dl) + 0.3786loge (bilirubin mg/dl) + 1.1206loge (international normalised ratio) + 0.6436(cause of cirrhosis) where cause of cirrhosis is coded as 0 for alcoholic or cholestatic liver diseases and 1 for other causes. Please note that old units are used for both creatinine and bilirubin. Patients with a risk score R>1.8 have a median survival of three months after elective TIPS and are considered unsuitable for the procedure unless it is being performed as a bridge to liver transplantation.121 Patients with a risk score R=1.5 have a median survival of six months and those with R=1.3 have a median survival of 12 months.
晚期肝病分数模型最初出现是用来预测TIPS后生存率的,121现在则继续演变成了预测肝硬化预后的模型。122根据最初的TIPS模型,风险分数的计算如下
R=0.9576×log e(肌酐mg/dl)+0.3786×log e(胆红素mg/dl)+1.1206×log e(国际标准化比)+0.6436×(肝硬化原因)
此处对于肝硬化的原因酒精性或胆汁淤积性肝病计为0,其它原因计为1。请注意肌酐和胆红素用的是旧单位。风险分数R>1.8的患者在选择性TIPS后中位生存率为三个月,被认为不适合采用这项操作,除非是作为肝移植的过渡。121风险分数为1.5的患者中位生存率是6个月,而R为1.3的患者则为12个月。
Recommendation
TIPS can be used for the treatment of refractory ascites requiring frequent therapeutic paracentesis or hepatic hydrothorax with appropriate assessment of risk benefit ratio. (Level of evidence: 1b; recommendation: B.)
推荐
TIPS可用做需要频繁放腹水的难治性腹水或者经评估有合适的风险利益比的肝性胸水的治疗。(证据水平:1b;推荐:B)
7.0 SPONTANEOUS BACTERIAL PERITONITIS
Spontaneous bacterial peritonitis (SBP) is the development of a monomicrobial infection of ascites in the absence of a contiguous source of infection. SBP is a frequent and serious complication of cirrhotic patients with ascites. The prevalence of SBP in cirrhotic hospitalised patients with ascites ranges between 10% and 30%.2931 When first described, its mortality exceeded 90% but inhospital mortality has been reduced to approximately 20% with early diagnosis and prompt treatment. 85
7.0自发性细菌性腹膜炎
自发性细菌性腹膜炎(SBP)是在临近没有感染源情况下腹水出现单一细菌的感染。SBP是肝硬化腹水患者常见且严重的并发症。SBP在住院肝硬化腹水患者中发生率在10%到30%之间。29-31当本病首次描述时,其死亡率超过90%,不过随着早期诊断和及时的治疗住院死亡率已降到约20%。85
7.1 Diagnosis
Patients with SBP are frequently asymptomatic.129 130 However, a significant proportion have some symptoms such as fever, mild abdominal pain, vomiting, or confusion. Diagnosis should also be suspected in those who present with hepatic encephalopathy, impairment of renal function, or peripheral leucocytosis without any obvious precipitating factor. A diagnostic paracentesis is mandatory in all patients with cirrhosis requiring hospital admission.31
7.1诊断
SBP患者常没有症状。129,130不过,有相当大一部分会有某些症状如发热,轻微腹痛,呕吐或意识障碍。在患者出现肝性脑病,肾功能损害或周围血白细胞升高而没有任何明显促发因素时也应该考虑诊断。所有需要住院的肝硬化患者诊断性腹穿是必须的。31
7.1.1 Ascitic fluid analysis
The diagnosis of SBP is confirmed when ascitic neutrophil count is>250 cells/mm3 (0.25×109/l) in the absence of an intra-abdominal and surgically treatable source of sepsis. A cutoff of neutrophils/mm3 has the greatest sensitivity although a cutoff of 500 neutrophils/mm3 has greater specificity.131–134 In patients with haemorrhagic ascites with a fluid red blood cell count of >10 000/mm3 (due to concomitant malignancy or traumatic tap), subtraction of one neutrophil per 250 RBC should be made to adjust for the presence of blood in ascites.31 Historically, neutrophil counts have been carried out by oncall microbiologists, as coulter counter determinations of neutrophil counts were inaccurate at the relatively low but pathological levels of neutrocytosis in ascitic fluid (for example, polymorphonuclear cell (PMN) count of 500 cells/mm3). However, one recent study found excellent correlation between these two techniques, even at low counts, suggesting that automated counting may replace manual counts.135 Gram’s stain of a smear of sediments obtained after centrifugation of ascites fluid is rarely helpful and should not be routinely requested.34
7.1.1腹水分析
当腹水嗜中性粒细胞计数>250个/mm3(0.25×109/l)而没有腹内和外科可治疗的败血症来源时,SBP的诊断可以确立。250个嗜中性粒细胞/mm3的截断值有着最高的敏感性虽然500嗜中性粒细胞/mm3的截断值特异性更高。131-134血性腹水患者腹水中红细胞计数>10 000/mm3 (由于伴发的恶性肿瘤或穿刺性外伤)时,每250个红细胞减去一个嗜中性粒细胞用以调整腹水中出现的血液。31在历史上,嗜中性粒细胞计数是由oncall微生物学家来做的,因为库尔特粒度仪对嗜中性粒细胞计数的测量不准确,除了病理学水平上的腹水白细胞升高(如多形核细胞PMN计数500细胞/mm3)外计数相对较低。不过,最近的一个研究发现,即使在计数较低的情况下,这两项技术之间存在着极好的关系,提示自动计数可能会代替人工计数。135腹水离心后沉淀物涂片的Gram’s染色很少有帮助不应该做为常规进行。34
7.1.2 Ascitic fluid culture
This has been discussed before under ascitic fluid investigations (see above). Patients with ‘‘culture negative neutrocytic ascites’’ (PMN count >250 cells/mm3 (0.25×109/l)) have a similar clinical presentation to those with culture positive SBP.136 137 As both groups of patients are associated with significant morbidity and mortality,136 137 they should be treated in a similar fashion. Some patients have ‘‘monomicrobial bacterascites’’ in which cultures are positive but there is normal ascitic neutrophil count.138 Such infections are thought to occur relatively commonly, and the majority are eradicated by the body’s natural defence mechanisms (for example, opsonic and complement mediated bactericidal activity).138 139 When a positive culture is obtained, a further ascitic tap with a neutrophil count should be obtained. If the neutrophil is normal and patient is asymptomatic, then ignore the positive culture, but re-culture.138–140 If the neutrophil count is .250 cells/mm3, then treat as per SBP.
7.1.2腹水培养
这在腹水调查部分(见上述)已进行了讨论。“培养阴性的白细胞性腹水”(PMN计数>250 个细胞/mm3 (0.25×109/l))患者与培养阳性的SBP患者临床表现相似。136,137因为两组患者均有显著的发病率和死亡率,136,137其治疗应该是相似的。有些患者有着“单一微生物细菌性腹水”,其腹水培养为阳性但腹水白细胞计数正常。138这些感染被认为较为常见,大部分可被机体天然的防御机制(如调理素和补体介导的杀菌活性)所根除。138,139当腹水培养为阳性时,应进一步进行腹穿并行嗜中性粒细胞计数。如嗜中性粒细胞正常且患者没有症状,则不要管培养为阳性,但要重新培养。138-140如果嗜中性粒细胞计数>250个细胞/mm3,则按SBP进行治疗。
Recommendations
A diagnostic paracentesis should be performed in all cirrhotic patients with ascites on hospital admission.(Level of evidence 1a; recommendation A.)
A diagnostic paracentesis should be performed in all cirrhotic patients with ascites in those who have signs and symptoms of peritoneal infection, including the development of encephalopathy, renal impairment, or peripheral leucocytosis without a precipitating factor. (Level of evidence: 2b; recommendation: C.)
Ascitic fluid should be inoculated into blood culture bottles at the bedside. (Level of evidence: 2a;recommendation: B.)
推荐
所有肝硬化腹水入院患者均要进行诊断性腹水穿刺(证据水平:1a;推荐:A)
有腹膜感染症状和体征的所有肝硬化腹水患者均应进行诊断性腹穿,包括没有诱因出现脑病、肾功能损害或周围血白细胞升高时。(证据水平:2b;推荐:C)
腹水应该在床旁接种入血培养瓶。(证据水平:2a;推荐:B)
7.2 Treatment
7.2.1 Antibiotics
The commonest organisms isolated in patients with SBP include Escherichia coli, gram positive cocci (mainly streptococcus species) and enterococci. These organisms account for approximately 70% of all cases of SBP.85 141 Cefotaxime has been the most extensively investigated in patients with SBP because it covers 95% of the flora isolated from ascitic fluid and achieves high ascitic fluid concentrations during therapy.28 142 Five days of treatment with cefotaxime is as effective as 10 day therapy,143 and low dose (2 g twice daily) is similar in efficacy to the higher doses (2 g four times daily).144 Other cephalosporins, such as ceftriaxone and ceftazidime as well as co-amoxiclav (amoxicillin plus clavulanic acid), have been shown to be as effective as cefotaxime in resolving SBP.31 145 In patients who are ‘‘well’’ (asymptomatic), with bowel sounds, SBP can be treated with oral antibiotics.27 Under these circumstances either oral ciprofloxacin (750 mg twice daily) or oral co-amoxiclav (1000/200 mg amoxicillin/clavulanic acid three times daily), subject to renal function, is logical.
7.2治疗
7.2.1抗菌素
在SBP患者分离出的最常见的微生物包括大肠埃希杆菌、革兰(氏)阳性球菌(主要是链球菌)和肠球菌。这些微生物占全部SBP患者的大约70%。85,141头孢噻肟是在SBP患者中研究得最广泛的因为它覆盖了自腹水分离的菌丛的95%,在治疗期间其在腹水有高的浓度。28,142用头孢噻肟治疗5天与10天一样有效,143低剂量(2g,2/d)在效力上与高剂量(2g,4/d)相似。144其它头孢菌素类,如头孢三嗪,头孢他定和co-amoxiclav(阿莫西林加克拉维酸)在消退SBP方面与头孢噻肟同样有效。31,145在“正常”(无症状)伴有肠鸣音的患者,SBP可用口服抗生素治疗。27在这些情况下,口服环丙沙星(750mg,2/d)或co-amoxiclav (1000/200 mg阿莫西林/克拉维酸,3/d)都是合理的(取决于肾功能)。
Resolution of infection in SBP is associated with an improvement in symptoms and signs. However, for those patients who do not improve, treatment failure should be recognised early. A reduction in ascitic fluid neutrophil count of less than 25% of the pretreatment value after two days of antibiotic treatment suggests failure to respond to therapy.31 This should raise the suspicion of ‘‘secondary peritonitis’’ (secondary to perforation or inflammation of intra-abdominal organs) and indicate further evaluation or modification of antibiotic treatment according to in vitro sensitivity or on an empiric basis. The presence of multiple organisms in ascitic fluid is strongly suggestive of perforated bowel, and needs further urgent investigation.31 Although algorithms, including estimation of ascetic fluid protein, glucose, lactate dehydrogenase, carcinoembryonic antigen, and alkaline phosphatase levels have been proposed to distinguish ‘‘secondary peritonitis’’ from SBP,146 147 erect chest x ray and abdominal computed tomography scan are the most useful in practice.
SBP感染的消退与症状和体征的改善相一致。不过,对于那些没有改善的患者,应该尽早考虑到治疗的失败。抗生素治疗2天后,腹水嗜中性粒细胞计数治疗之前的值(pretreatment value)降低少于25%提示对治疗无效。31这应该更加怀疑是“继发性腹膜炎”(继发于腹内器官的穿孔或炎症),提示应该根据体外敏感试验或基于临床经验对抗生素治疗进一步的评估或修改。腹水中多种微生物的出现强烈提示肠穿孔,需要进一步的紧急检查。31虽然algorithms,已经提出包括腹水蛋白、糖、LDH、CEA和AKP水平测定用以鉴别继发性腹膜炎与SBP,146,147直立胸部X线检查和腹部CT扫描在临床上是最有用的。
7.2.2 Albumin infusion in SBP
Development of renal impairment occurs in 30% of patients with SBP and is one of the strongest predictors of mortality in SBP.146 A recent study suggests that cefotaxime plus albumin improves survival and decreases the incidence of renal impairment to 10%.149 This study has since been criticised as the control group were not given an equivalent amount of fluid as crystalloid. A further study has demonstrated that treatment with albumin is associated with significant improvement in circulatory function and lower frequency of endothelial dysfunction compared with equivalent doses of hydroxyethyl starch.150 But the latter study was not powered to compare clinical outcomes such as renal failure and mortality. We believe that further studies are required before making any formal recommendations about the use of albumin in SBP. However, if patients have an increased serum creatinine or a rising serum creatinine, we would support infusing 1.5 g albumin/kg in the first six hours, followed by 1 g/kg on day 3, which is the regimen adopted by the Barcelona group in their study on the use of albumin in SBP.149
7.2.2 SBP的白蛋白输注
肾功能损害会出现于30%的SBP患者,是SBP死亡最强烈的预测指标。146最近的一项研究提示头孢噻肟加白蛋白可以改善生存率并将肾功能损害发生率降低到10%,149 该研究已因为对照组没有给予同等量的液体如类晶体而受到批评。一项进一步的研究提示与同等剂量的706代血浆相比,用白蛋白治疗可以明显改善循环功能并降低内皮功能障碍的发生率。150但是后一个研究没有能够对临床结局如肾衰和死亡率做比较。我们相信在做出有关SBP治疗中白蛋白应用的任何正式的建议前需要进一步的研究。不过,如果患者血肌酐升高或正在升高,我们支持在前六个小时输用1.5g白蛋白/kg,继之在第三天用1g/kg(这是为Barcelona组在他们有关SBP中使用白蛋白的研究中所采用的作法)。149
7.2.3 Total paracentesis for SBP
There are no data on the role of total paracentesis in the management of SBP.
7.2.3 SBP的全腹腔穿刺放腹水
还没有有关SBP处理中全腹腔穿刺放腹水作用的资料。
Recommendations
In patients with an ascitic fluid neutrophil count of .250 cells/mm3, empiric antibiotic therapy should be started. (Level of evidence: 1b; recommendation: A.)
Third generation cephalosporins such as cefotaxime have been most extensively studied in the treatment of SBP and have been shown to be effective. (Level of evidence: 1a; recommendation: A.)
Patients with SBP and signs of developing renal impairment should be given albumin at 1.5 g albumin/ kg in the first six hours followed by 1 g/kg on day 3. (Level of evidence: 2b; recommendation: B.)
建议
对于腹水嗜中性粒细胞计数>250个细胞/mm3的患者,应该开始按经验进行抗生素治疗。(证据水平:1b;推荐:A)
第三代头孢如头孢噻肟在SBP治疗中研究得最广泛,并且已显示有效。(证据水平:1a;推荐:A)
有SBP和出现肾功能损害体征的患者在头六个小时要予以白蛋白1.5g/kg,继之在第三天予以1g/kg。(证据水平:2b;推荐:B)
7.3 Prophylaxis
For patients who have never had SBP and in whom ascitic fluid protein concentration is low (,10 g/l), there is no consensus among experts regarding primary prophylaxis.31 In patients who survive an episode of SBP, the cumulative recurrence rate at one year is approximately 70%.85 Probability of survival at one year after an episode of SBP is 3050% and falls to 2530% at two years.151 152 Therefore, patients recovering from an episode of SBP should always be considered as a potential candidate for liver transplantation. In patients who had one episode of SBP, oral norfloxacin (400 mg/day) reduces the probability of recurrence of SBP from 68% to 20% and the probability of SBP due to gram negative bacilli from 60% to 3%.153 However, studies of antibiotic prophylaxis using norfloxacin or ciprofloxacin in patients with low ascites fluid protein concentration (,15 g/ l) have included a heterogeneous group of patients with and without previous episodes of SBP.154 155 In the UK many centres use once daily ciprofloxacin as prophylaxis against SBP, although many also use norfloxacin. One study reported that patients with cirrhosis on long term quinolone prophylaxis developed more gram positive bacterial infections (79%), including methicillin resistant Staphylococcus aureus, compared with predominantly gram negative infections (67%) in those who were not on prophylaxis.156
7.3预防
对于以前从没有SBP、其腹水蛋白浓度低( <10g/L=的患者,专家内部还没有有关初级预防的共识。31对于曾患过SBP的患者,一年的累积复发率大约为70%。85患SBP后一年的生存率为30-50%,二年降到25-30%。151,152所以,从SBP恢复的患者应该经常被作为肝移植潜在的候选者。对于曾患过(一次)SBP的患者,口服氟哌酸 (400 mg/d)可将SBP复发的概率从68%降到20%,而由于Gram 阴性杆菌引起的SBP的概率则从60%降到3%。150不过在腹水蛋白浓度低(<15g/L=的患者用氟哌酸或环丙沙星来进行抗生素预防的研究包含了不同种类的患者,这些患者以前有或没有SBP。154,155在英国,许多中心用每日一次环丙沙星来预防SBP,虽然许多也用氟哌酸。一个研究报告说长期用喹诺酮预防的肝硬化患者更容易出现Gram阳性细菌感染(79%),包括耐甲氧苯青霉素的金黄色葡萄球菌,,而没有预防的患者则以Gram阴性感染为主(67%)。156
Recommendations
Patients recovering from one episode of SBP should receive prophylaxis with continuous oral norfloxacin 400 mg/day (or ciprofloxacin at 500 mg once daily).(Level of evidence: 1b; recommendation: B.)
All patients with SBP should be considered for referral for liver transplantation. (Level of evidence: 1c;recommendation: B.)
建议
自SBP恢复的患者应该接受用不间断口服氟哌酸 400 mg/d (或环丙沙星 500 mg每日一次).(证据水平:1b;推荐:B)
全部SBP患者均应被考虑安排进行肝移植。(证据水平:1c;推荐:B)
8.0 CONCLUSIONS
The development of ascites is an important landmark in the natural history of cirrhosis. Adequate management of ascites is important, not only because it improves quality of life in patients with cirrhosis, but also prevents serious complication such as SBP. However, treatment of ascites does not significantly improve survival. Therefore, development of ascites should be considered as an indication for transplantation. Liver transplantation is the ultimate treatment of ascites and its complications.
8.0结论
腹水的出现在肝硬化自然史中是一个重要的里程碑。对腹水进行适当处理非常重要,不仅因为可以提高肝硬化患者的生活质量,而且也可以预防严重的并发症如SBP。不过腹水的治疗并没能显著改善生存率。所以,腹水的出现应被考虑为移植的适应症。肝移植是腹水及其并发症的最根本的治疗方法。
Summary of recommendations: management of ascites in cirrhosis
Diagnosis
It is recommended that patients give informed consent for a therapeutic or diagnostic paracentesis.
The initial ascitic fluid analysis should include serum ascites-albumin gradient in preference to ascetic protein.
Ascitic amylase should be measured when there is clinical suspicion of pancreatic disease.
Ascitic fluid should be inoculated into blood culture bottles at the bedside and examined by microscopy for a neutrophil count.
建议摘要:肝硬化腹水处理
诊断
建议征得患者同意进行治疗性或诊断性腹穿。
腹水的初步分析应该包括血清腹水-白蛋白梯度并要优先于腹水蛋白。
当临床怀疑胰腺疾病时应检测腹水淀粉酶。
腹水要在床边接种入血液培养瓶,并要在显微镜下检查嗜中性粒细胞计数。
Treatment
Bed rest is not recommended for the treatment of ascites.
Dietary salt should be restricted to a no added salt diet of 90 mmol salt/day (5.2 g salt/day).
治疗
不推荐卧床休息做为腹水治疗。
饮食中盐应该被限制到不再增加食盐的90mmol盐/d(5.2g盐/d)。
Hyponatraemia
Serum sodium 126135 mmol/l, normal serum creatinine. Continue diuretic therapy, but observe serum electrolytes. Do not water restrict.
Serum sodium 121125 mmol/l, normal serum creatinine.International opinion is to continue diuretic therapy, our opinion is to stop diuretic therapy or adopt a more cautious approach.
Serum sodium 121125 mmol/l, serum creatinine elevated (.150 mmol/l or .120 mmol/l and rising).Stop diuretics and give volume expansion.
Serum sodium (120 mmol/l, stop diuretics. The management of these patients is difficult and controversial.We believe that most patients should undergo volume expansion with colloid (haemaccel, gelofusine, or voluven) or saline. However, avoid increasing serum sodium by >12 mmol/l per 24 hours.
低钠血症
血钠126-135mmol/L,血肌酐正常:继续利尿治疗,不过要注意观察血电解质,不要限水。
血钠121-125mmol/L,血肌酐正常:国际意见是继续利尿治疗,我们的意见是停止利尿治疗或采用一种更为谨慎的方法。
血钠121-125mmol/L,血肌酐升高(>150 mmol/l或>120 mmol/l且继续升高):停止利尿,这种患者的处理困难且有争议。我们相信大多数患者应该接受用胶体 (海脉素, 佳乐施, 或万汶voluven)或盐水扩容。不过,避免增加血钠>12mmol/L/24h。
Diuretics
Firstline treatment of ascites should be spironolactone alone, increasing from 100 mg/day to a dose of 400 mg/day.
If this fails to resolve ascites, frusemide should be added in a dose of up to 160 mg/day but this should be done with careful biochemical and clinical monitoring.
利尿剂
腹水的一线治疗是单独用螺内酯,从100mg/d增加到400mg/d的剂量。
如果不能消除腹水,可增加速尿达160mg/d,不过要注意生化和临床监测。
Therapeutic paracentesis
 Therapeutic paracentesis is the firstline treatment for patients with large or refractory ascites.
 Paracentesis of <5 litre of uncomplicated ascites should be followed by plasma expansion with a synthetic plasma expander (150–200 ml of gelofusine or haemaccel), and does not require volume expansion with albumin.
 Large volume paracentesis should be performed in a single session with volume expansion being given once paracentesis is complete, preferably using 8 g albumin/ l of ascites removed (that is, ~100 ml of 20% albumin/3 l ascites).
治疗性腹穿
治疗性腹穿是大量或难治性腹水患者的一线治疗。
无并发症的<5L的腹穿要继以合成血浆扩容剂进行血浆扩容(150-200ml的佳乐施或海脉素),不需要用白蛋白进行扩容。
大剂量腹穿应该一次完成(in a single session),腹穿一旦完成要进行扩容。最好每移除1L腹水用8g白蛋白(即,~100ml20%白蛋白/3L腹水)。
TIPS procedure
TIPS could be used for the treatment of refractory ascites requiring frequent therapeutic paracentesis or hepatic hydrothorax with appropriate assessment of risk benefit ratio.
TIPS程序
TIPS可用于需要频繁治疗性腹穿的难治性腹水或经评估风险利益比合适的肝性胸水的治疗
Liver transplantation
 Liver transplantation should be considered in patients with cirrhotic ascites.
All patients with SBP should be considered for referral for liver transplantation.
肝移植
有肝硬化腹水的患者应该考虑肝移植。
所有SBP患者应该安排进行肝移植。
Spontaneous bacterial peritonitis (SBP)
Diagnosis
A diagnostic paracentesis should be performed in all cirrhotic patients with ascites on hospital admission.
 A diagnostic paracentesis should be performed in all cirrhotic patients with ascites in those who have signs and symptoms of peritoneal infection including the development of encephalopathy, renal impairment, or peripheral leucocytosis without a precipitating factor.
Ascitic fluid should be inoculated into blood culture bottles at the bedside.
SBP
诊断
n        所有住院的肝硬化腹水患者均应该进行诊断性腹穿。
n        所有有腹膜感染的体征和症状,n         包括出现脑病、肾功能损害或周围血白细胞升高而n     没有诱因的肝硬化腹水均应进行诊断性腹穿。
n        腹水应该在床边接种入血培养瓶中。
Treatment
In patients with ascitic fluid neutrophil count of >250 cells/mm3, empiric antibiotic therapy should be started.
Third generation cephalosporins such as cefotaxime have been most extensively studied in the treatment of SBP and have been shown to be effective.
Patients with SBP and signs of developing renal impairment should be given albumin at 1.5 g albumin/kg in the first six hours followed by 1 g/kg on day 3.
治疗
腹水嗜中性粒细胞计数>250细胞/mm3的患者,应该开始进行经验性的抗生素治疗。
第三代头孢如头孢噻肟在SBP治疗中研究得最为广泛并显示有效。
SBP患者出现肾损害时要在前六个小时予以白蛋白1.5g/kg,并在第三天予以1g/kg。
Prophylaxis
Patients recovering from one episode of SBP should receive prophylaxis with continuous oral norfloxacin 400 mg/day (or ciprofloxacin at 500 mg once daily).
预防
从SBP恢复的患者应该接受用不间断口服氟哌酸400 mg/d (或环丙沙星at 500 mg每日一次)来预防。



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