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Report on the Consensus Conference of the Kevin P. Moore,1 Florence Wong,2 Pere Gines,3 Mauro Bernardi,4 Andreas Ochs,5 Francesco Salerno,6 Paolo Angeli,7 Michael Porayko,8 Richard Moreau,9 Guadelupe Garcia-Tsao,10 Wladimiro Jimenez,11 Ascites is a common complication of cirrhosis, and heralds a new phase of hepatic decompensation in
the progression of the cirrhotic process. The development of ascites carries a significant worsening of
the prognosis. It is important to diagnose noncirrhotic causes of ascites such as malignancy, tubercu-
losis, and pancreatic ascites since these occur with increased frequency in patients with liver disease.
The International Ascites Club, representing the spectrum of clinical practice from North America to
Europe, have developed guidelines by consensus in the management of cirrhotic ascites from the early
ascitic stage to the stage of refractory ascites. Mild to moderate ascites should be managed by modest
salt restriction and diuretic therapy with spironolactone or an equivalent in the first instance. Diuretics
should be added in a stepwise fashion while maintaining sodium restriction. Gross ascites should be
treated with therapeutic paracentesis followed by colloid volume expansion, and diuretic therapy.
Refractory ascites is managed by repeated large volume paracentesis or insertion of a transjugular
intrahepatic portosystemic stent shunt (TIPS). Successful placement of TIPS results in improved renal
function, sodium excretion, and general well-being of the patient but without proven survival benefits.
Clinicians caring for these patients should be aware of the potential complications of each treatment
modality and be prepared to discontinue diuretics or not proceed with TIPS placement should
complications or contraindications develop. Liver transplantation should be considered for all ascitic
patients, and this should preferably be performed prior to the development of renal dysfunction to
prevent further compromise of their prognosis. (HEPATOLOGY 2003;38:258-266.)
Ascitesoccursinmorethan50%ofpatientswithin malignancy (10%), cardiac failure (3%), pancreatitis 10 years of the diagnosis of cirrhosis. Cirrhotic (1%), tuberculosis (2%), or other rarer causes.1 There ascites accounts for over 75% of patients who have been several changes in the clinical management of present with ascites, with the remaining 25% being due to ascites over recent years. The recommendations put for-ward in this document were agreed on by an InternationalAscites Club Consensus Meeting on the management of Abbreviations: SBP, spontaneous bacterial peritonitis; HRS, hepatorenal syn- drome; PPH, postparacentesis effective hypovolemia; TIPS, transjugular intrahe- ascites. This meeting was supported by an unconditional educational grant from Searle, Spain. These recommen- From the 1Centre for Hepatology, Royal Free and University College Medical School, dations have been updated in line with subsequent recent UCL, London, United Kingdom; 2Division of Gastroenterology, Toronto General Hos-pital, University of Toronto, Toronto, Canada; 3Liver Unit, Hospital Clinic, Barcelona publications of controlled clinical studies.
and the University of Barcelona School of Medicine, Barcelona, Spain; 4DepartmentMedicina Interna, Cardioangiologia, Epatologia, Alma Mater Studiorum–Universita`di Bologna, Italy; 5Department of Internal Medicine, University of Freiburg, Freiberg, Diagnosis and Investigation of Ascites
Germany; 6Department of Internal Medicine, IRCCS Policlinico, University of Milan,Milan, Italy; 7Department of Clinical and Experimental Medicine, University of All patients need investigation of the causes of ascites, Padua, Padova, Italy; 8Department of Liver Transplantation, Thomas Jefferson Uni- even when cirrhosis is suspected. Ascitic fluid should be versity, Philadelphia, PA; 9INSERM U-481 et Service d’Hepatologie, Hopital Beaujon, sent for the determination of albumin or protein concen- Clichy, France; 10Digestive Diseases Section, Yale University School of Medicine, New tration. To diagnose spontaneous bacterial peritonitis Haven, CT; 11Hormal Laboratory, Hospital Clinic, Barcelona and the University ofBarcelona School of Medicine, Barcelona, Spain; and 12Department of Gastroenterol- (SBP), ascitic fluid should be examined by microscopy ogy, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. and inoculated directly into blood culture bottles. An as- Received October 31, 2002; accepted May 7, 2003. Address reprint requests to: Kevin Moore, M.D., Centre for Hepatology, Royal Free and University College Medical School, UCL, Rowland Hill St., London cells/mm3 is diagnostic of SBP, but a Gram stain of the NW3 2PF, England. E-mail: [email protected]; fax: (44) 207-433-2877. ascitic fluid is usually uninformative.2 Ascitic fluid from Copyright 2003 by the American Association for the Study of Liver Diseases. patients with suspected malignant or pancreatic ascites should be sent for cytology or measurement of amylase.
The use of ascitic fluid protein in the differential diag- Table 1. Revised Diagnostic Criteria of Refractory Ascites
nosis of the causes of ascites is overrated and misinter- 1. Treatment duration: Patients must be on intensive diuretic therapy preted. Conventionally, the type of ascites is divided into (spironolactone 400 mg/d and furosemide 160 mg/d) for at least 1 week exudates and transudates in which the ascitic fluid protein and on a salt-restricted diet of less than 90 mmoles or 5.2 g of salt/d.
2. Lack of response: Mean weight loss of Ͻ0.8 kg over 4 days and urinary concentration is Ն25 g/L or Ͻ25 g/L, respectively, to sodium output less than the sodium intake.
help in the differential diagnosis of the causes of ascites.
3. Early ascites recurrence: Reappearance of grade 2 or 3 ascites within 4 However, many physicians assume that cardiac ascites will 4. Diuretic-induced complications: Diuretic-induced hepatic encephalopathy is have a low ascitic protein, but this is rarely the case.3 the development of encephalopathy in the absence of any other Moreover, ϳ15% of cases of cirrhotic ascites have an precipitating factor. Diuretic-induced renal impairment is an increase of ascitic protein Ͼ25 g/L, and 20% of patients with malig- serum creatinine by Ͼ100% to a value Ͼ2 mg/dL in patients with ascites responding to treatment. Diuretic-induced hyponatremia is defined as a decrease of serum sodium by Ͼ10 mmol/L to a serum sodium of Ͻ125 min gradient (i.e., serum albumin Ϫ ascitic fluid albumin mmol/L. Diuretic induced hypo- or hyperkalemia is defined as a change in concentration) is more specific and sensitive at distin- serum potassium to Ͻ3 mmol/L or Ͼ6 mmol/L despite appropriate guishing ascites due to portal (sinusoidal) hypertension (gradient Ն11 g/L) from that occurring as a result ofdifferent pathogenetic mechanisms, such as inflammationor peritoneal malignancy (gradient Յ11 g/L).5,6 Thus, the disease runs its natural course. Patients with alcohol- ascitic fluid protein classified the causes of ascites correctly induced cirrhosis who stop drinking may have a consid- in 55% of cases, whereas serum-ascitic albumin gradient erable improvement of liver function with resolution of assigns the causes correctly 97% of the time.5 Definitions
Bed Rest
Uncomplicated Ascites. Uncomplicated ascites is as-
In patients with cirrhosis and ascites, upright posture cites that is not infected and that is not associated with the activates sodium-retaining systems and impairs renal per- development of the hepatorenal syndrome (HRS). Grade fusion and sodium excretion. In one study, bed rest im- 1 ascites is mild ascites only detectable by ultrasound ex- proved the response to diuretics.9 However, no clinical amination. Grade 2 ascites or moderate ascites is manifest trials have shown that bed rest actually improves the effi- by moderate symmetrical distension of abdomen. Grade 3 ascites is large or gross ascites with marked abdominaldistension.
Sodium and Water Restriction
Refractory Ascites. In 1996 the International Ascites
A negative sodium balance can be achieved by dietary Club defined “refractory ascites” as ascites that cannot be salt restriction or by increasing renal sodium excretion.
mobilized or the early recurrence of which cannot be sat- With dietary salt restriction, loss of ascites occurs in 10% isfactorily prevented by medical therapy.7 It occurs in ap- to 15% of patients.1 The use of low salt diets is almost proximately 5% to 10% of all cases of ascites.8 Two universally recommended. However, this approach is not subgroups were identified as diuretic-resistant ascites and backed by the results of controlled clinical trials.
diuretic-intractable ascites.7 Additional findings fre- Trials on Sodium Restriction. Severe sodium re-
quently include type II HRS, dilutional hyponatremia, stricted diets are unpalatable, leading to poor patient and wasting. The diagnostic criteria for refractory ascites compliance and poor nutrition. Five studies have com- have been slightly revised and are shown in Table 1.
pared the efficacy of different dietary regimes.10-14 Somesocieties readily adapt to a lower salt intake, whereas oth- Prognosis of Cirrhosis With Ascites
ers are less compliant because of cultural differences.
The development of ascites in patients with cirrhosis When severe dietary salt restriction (22 mmol/d) was indicates a poor prognosis. The probability of death in compared with a less restricted diet, dietary salt restriction cirrhotic patients hospitalized with ascites is ϳ40% at 2 was associated with a shorter time for resolution of ascites years.8 The prognosis is worse for those with refractory but was associated with a higher incidence of diuretic- induced renal impairment and hyponatremia.10-13 In onecontrolled study, a slightly reduced salt diet (120 Treatment of Ascites: An Evidenced Based
mmoles/d) was equally effective in patients with ascites Approach
when compared with a low-salt diet (50 mmol/d).14 The aim of treatment is to improve sodium balance or There are no significant differences in survival between circulatory function until liver transplantation or until patients receiving salt-restricted or -unrestricted diets, al- though the survival of patients with previous gastrointes- a response rate in up to 90% of patients without renal tinal bleeding was better in the low-salt group.13 A failure in controlled clinical trials.14,18,20 limitation of all such studies is patient compliance andbeing able to verify compliance.
Paracentesis
Water Restriction. Dilutional hyponatremia occurs
Paracentesis is used to treat ascites that has not re- in patients with decreased free water clearance, which is sponded to medical therapy, to resolve large-volume as- driven by nonosmotic baroceptor secretion of antidiuretic cites rapidly, to enable easier ultrasound examination in hormone secondary to effective central hypovolemia.15 patients with massive ascites, and to periodically treat re- Treatment of dilutional hyponatremia classically consists of water restriction. However, there have been no clinical Trials of Paracentesis Versus Diuretics. There have
trials to assess the effects of water restriction in patients been 5 randomized controlled trials comparing therapeu- with cirrhosis and dilutional hyponatremia, and indeed tic paracentesis with diuretics in cirrhotic patients with this treatment may exacerbate the central hypovolemia.
ascites.25-29 These studies compared repeated large vol-ume paracentesis (5 L/d) with albumin infusion (6-8 g/L Diuretics
of ascites removed), and showed that paracentesis wasmore effective than diuretics in eliminating ascites and Anti-Mineralocorticoids. Secondary
shortened the duration of hospitalization. Moreover, ronism is a major factor promoting renal sodium reten- there were significantly fewer complications in the para- tion16 in the distal tubules and collecting ducts of the centesis-treated group compared with those treated with nephron. Both controlled and uncontrolled clinical trials diuretics alone. These data have been confirmed by other have shown that spironolactone is the drug of choice for studies.30 The issue of whether paracentesis should be the initial treatment.11-14,17,18 Spironolactone or canreno- repeated daily with 5-liter paracentesis or a single total ate (not available in North America) achieves a better paracentesis has been resolved.31,32 Tito` et al.31 showed natriuresis more often than “loop” diuretics such as furo- that total paracentesis was as effective and as safe as re- semide.18,19 The recommended initial dose of spironolac- peated partial paracentesis. Paracentesis causes an acute tone is 100 to 200 mg once daily. When severe increase of cardiac output and a lowering of systemic vas- hyperaldosteronism (i.e., severe sodium retention) is cular resistance, leading to a modest reduction of blood present, the dosage may be increased to 400 mg/d.18,20,21 pressure.32 Pulmonary capillary wedge pressure decreases A therapeutic response is observed in ϳ75% of patients.
at ϳ6 hours postparacentesis, whereas the right atrial Gynecomastia is the main side effect of spironolactone, pressure falls acutely following the onset of paracentesis, but metabolic acidosis with or without hyperkalemia may secondary to a reduction of intrathoracic pressure.32 Since postparacentesis effective hypovolemia (PPH) can occur Other Potassium-Sparing Diuretics. Amiloride and
hours or days after the procedure (see below), volume triamterene also act in the distal tubule. No controlled expansion should commence once the paracentesis has clinical trials on triamterene are available. Amiloride been completed. Total paracentesis shortens the period of (20-60 mg/d) has been shown to be less effective than hospitalization and can be done as an outpatient proce- dure. However, paracentesis does not obviate the need for Loop Diuretics. Loop diuretics, such as furosemide,
diuretics. In one study, ascites recurred within 4 weeks are frequently used as an adjunct to spironolactone ther- postparacentesis in 18% of patients receiving diuretics apy. The initial oral dose of furosemide is usually 20 to 40 immediately postparacentesis, compared with 93% in pa- mg/d, and is generally adjusted upward every few days up to a maximum of 160 mg/d. Furosemide may cause po- Controversy of Volume Expansion. There is only
tassium depletion, metabolic hypochloremic alkalosis, one controlled trial comparing therapeutic paracentesis and hyponatremia, as well as hypovolemia, leading to re- with and without volume expansion with follow-up over a few weeks. In this study, Gines et al. randomized pa- Assessing the Response to Diuretics. The mobiliza-
tients to receive repeated paracentesis (ϳ5 L/d) plus albu- tion of ascites is best assessed by daily weighing of the min or to repeated paracentesis alone.30 Side effects patient using accurate standardized weighing protocols.
occurred in 30% of patients treated with paracentesis The rate of weight loss should not exceed Ͼ0.5 kg/d in without albumin compared with 16% in those treated the absence of edema, or Ͼ1 kg/d when edema is with albumin. Complications included a high incidence present.24 Medical treatment based on sodium-restricted of renal impairment and hyponatremia and a marked el- diets, anti-mineralocorticoids, and loop diuretics achieves evation of plasma renin and aldosterone concentrations.
If volume expansion is not given following paracentesis, In the longer term it can also improve nitrogen balance patients may develop postparacentesis hypovolemia, lead- and patient well being.42-44 It has largely replaced the use ing to hyponatremia and renal impairment. Postparacen- of surgically placed shunts. Insertion of a TIPS shunt tesis volume expansion is recommended in patients with leads to a marked increase of cardiac output, right atrial cirrhosis and ascites. The choice of fluid is, however, con- pressure, and pulmonary artery pressure,45 with a second- troversial. Human albumin solution is expensive and car- ary decrease of systemic vascular resistance and an increase ries the risk of infection with noneradicated viruses or in pulmonary vascular resistance and effective arterial prion-related diseases. The use of albumin has been con- blood volume. Sodium excretion and renal function im- tested by the Practice Guidelines Committee of the Amer- prove over 4 weeks.46 Thus, serum creatinine decreased ican Association for the Study of Liver Diseases.34 There from 1.5 to 0.9 mg/dL in patients with refractory ascites have been 5 randomized controlled trials comparing vol- ume expansion with albumin with other forms of plasma Complications. Immediate complications include
expanders, including dextrans, collagen-based colloids, capsule puncture and intra-abdominal bleeding. Late but and hydroxyethyl starch.35-39 All studies have shown that common complications include shunt thrombosis and synthetic plasma expanders are as effective as albumin at stenosis. The development of hepatic encephalopathy oc- preventing the clinical complications of paracentesis, curs in ϳ30% of patients post-TIPS, but the incidence is namely hyponatremia or renal impairment. However, higher in those patients with pre-TIPS encephalopathy Gines et al. showed that PPH, as defined by an increase in and in those greater than 60 years old.48 TIPS increases plasma renin activity or aldosterone concentrations, was the cardiac preload45 and may precipitate cardiac failure prevented more effectively by albumin than synthetic in patients with cardiac disease. Liver function can also deteriorate significantly in the post-TIPS period, possibly Contraindications and Complications of Paracen-
secondary to shunting of blood away from the liver. The tesis. Depite the fact that all published studies on para-
efficacy of TIPS to improve sodium excretion is depen- centesis have excluded patients with SBP, renal failure, dent on the pre-TIPS renal function and age being less severe hepatic encephalopathy, thrombocytopenia, low effective in those greater than 60 years old or those with blood pressure, or severe jaundice, there is no evidence that these complications should be considered as contra- Controlled Trials Comparing TIPS With Paracen-
indications for paracentesis in clinical practice. Thus, tesis. There have been 4 randomized controlled trials
some physicians carry out a total paracentesis in patients comparing TIPS versus large-volume paracentesis as a with SBP to remove the infected fluid. However, there are treatment for refractory ascites.50-53 In the first study, no data to support this approach, and controlled studies none of the Child-Pugh class C patients eliminated their are needed. There are no data to support the correction of ascites, and their overall survival was significantly worse in mild coagulopathy with blood products prior to thera- the TIPS group.50 Thus, TIPS is generally considered to peutic paracentesis,40 but caution is needed when severe be contraindicated in Child-Pugh class C patients. In a thrombocytopenia is present. Acute complications fol- larger study involving 60 patients with refractory or re- lowing paracentesis are sporadic. Bleeding occasionally current ascites, patients were randomized to repeated occurs and may be fatal. Leakage of ascitic fluid should be paracentesis or TIPS.51 However, albumin was not sys- managed by placing a purse-string suture around the tematically given postparacentesis. In the TIPS group opening and instructing the patient to lie with the punc- there were 15 patient deaths and 1 underwent liver trans- ture site uppermost. The most common complication is plantation during follow-up compared with 23 deaths PPH and renal impairment. To date, there are no studies and 2 patients undergoing liver transplantation in the identifying factors that predict the development of post- paracentesis group over ϳ4 years. The probability of sur- paracentesis hypovolemia and renal impairment.
vival without liver transplantation was 69% at 1 year and58% at 2 years in the shunt group, as compared with 52% Transjugular Intrahepatic Portosystemic Shunt
and 32% in the paracentesis group (P ϭ .11). In a mul- (TIPS)
tivariate analysis, treatment with TIPS was independently Short-Term and Long-Term Effects of TIPS on
associated with survival without the need for transplanta- Circulatory Function and Renal Function. TIPS, in
tion (P ϭ .02). At 3 months, 61% of the patients in the which a self-expanding shunt is inserted to create a shunt shunt group and 18% of those in the paracentesis group between the hepatic vein (low pressure) and portal vein had no ascites (P ϭ .006). The frequency of hepatic en- (high pressure), can lead to an improvement of renal func- cephalopathy was similar in the two groups.51 In the third tion and sodium excretion and the resolution of ascites.41 study, 49% of patients who received TIPS had recurrent ascites compared with 83% of those treated by repeated Table 2. The Effects of TIPS on the Management of Ascites,
large-volume paracentesis (P ϭ .003).52 Furthermore, the Summary of Published Randomized Controlled Trials
TIPS patients had a significantly lower risk of developing Child-Pugh
Control of
HRS (P ϭ .04). However, the risk of severe hepatic en- Survival
cephalopathy and the cost of therapy were higher in the TIPS group, while the survival rate was no different.52 Finally, in the North American multicenter randomized controlled trial involving 109 patients, TIPS was clearly superior to large-volume paracentesis in the control of ascites. The mean survival was identical in both groups.
There was no difference in the frequency of adverse events, apart from a trend towards more severe encepha- lopathy in the TIPS arm (P ϭ .058). There was no dif- ference in the quality of life between the 2 treatment Abbreviations: LVP, large-volume paracentesis; C-P, Child-Pugh class.
Peritoneovenous Shunts
There is little role for the use of peritoneovenous shunting in the treatment of refractory ascites. Peritone-ovenous shunting may be useful in patients who are not good initial response to diuretics. However, there are data candidates for liver transplantation, TIPS placement, or to suggest that it may be beneficial in those with a poor response to diuretics, but further studies are required.
Dietary sodium restriction. Dietary salt should be mod- Liver Transplantation
erately restricted to 5.2 g/d (90 mmol) and should be Any patient with cirrhosis who develops ascites should continued unless there is normalization of the renal ability be considered as a potential candidate for liver transplan- to excrete sodium. In selected cases, it may be necessary to tation, because the long-term prognosis of patients with restrict sodium intake further. There is no role for the ascites is poor. The success of liver transplantation has prophylactic use of sodium restriction in patients who resulted in a rapid growth in numbers of patients waiting for the procedure, out of proportion to the number of Use of diuretics. Treatment of grade 2 ascites should available donors. The mean waiting time for liver trans- initially include both salt restriction (5.2 g or 90 mmol plantation in the United States is estimated to be about salt/d) and administration of diuretics. A positive re- 500 days, but this is considerably shortened in Europe sponse to diet alone is slow and rare. The aim of diuretic with an average wait in the United Kingdom of 120 days treatment is to achieve a negative sodium balance and in Spain of 180 days. The long waiting time in the such that ascites resolves completely. The core diuretic United States limits the options for timing the work-up should be spironolactone (or canrenoate, not available in and listing for liver transplantation. Given these limita- North America), which should initially be given alone tions, some liver centers adopt the philosophy of placing once per day with food (e.g., 100-200 mg spironolactone/ every patient on the active waiting list as soon as ascites d). The clinical response to diuretics should be monitored develops in order to successfully compete for an organ by daily weighing of the patient, and the rate of weight loss should not exceed 0.5 kg/d in those without periph-eral edema and 1 kg/d in those with edema. Daily weights Consensus Proposals for the Treatment of
can be recorded by patients who are at home. The devel- opment of electrolyte or renal abnormalities should be Treatment of Uncomplicated Ascites
monitored by measurement of serum electrolytes, urea, Grade 1 Ascites. Grade 1 ascites does not require
and creatinine. The initial response to diuretics is slow, specific treatment, but the patient should be followed up and therefore diuretic dosage should be increased stepwise carefully and advised to reduce their sodium intake, since if there is insufficient diuretic response as defined by a these patients usually progress to the development of weight loss of less than 1 kg in the first 7 days, and 2 kg every 7 days thereafter until ascites is adequately mobi- Grade 2 Ascites. Bed rest. Bed rest is probably of no
lized. A loop diuretic (furosemide 20-40 mg/d) may be benefit in patients with preserved renal function and a added if a patient fails to respond to the equivalent of 200 mg spironolactone per day after the first 2 to 3 weeks. The be withheld from patients in whom the renal impairment dose of spironolactone or furosemide should be doubled is secondary to their liver disease or hypovolemia. There to a maximum of 400 or 160 mg/d, respectively, for those are no data on the level of serum sodium at which diuret- that fail to respond. Urinary sodium excretion should be ics should be stopped. It was agreed that diuretics should determined in nonresponders to identify noncompliance be stopped temporarily when the serum sodium is less with sodium restriction. Patients who excrete greater than than 120 mmoles/L. Patients with type 2 HRS usually 90 mmol of sodium per day, and who fail to lose ascites are not compliant with their diet. Amiloride (5-30 mg/d) Grade 3 Ascites. Paracentesis. Paracentesis is the
or canrenoate may be used as an alternative diuretic in treatment of choice in grade 3 ascites and should be fol- those patients who develop gynecomastia on spironolo- lowed by diuretic therapy and sodium restriction. Total actone. Amiloride is particularly effective in those patients paracentesis should be carried out as a single procedure, with a nonactivated renin-angiotensin-aldosterone sys- and it is safe to remove all of the ascitic fluid in a single tem. Loop diuretics other than furosemide may be equally session, even when a large amount of ascites is present.
Plasma volume expansion is recommended in all patients, Complications of diuretic therapy. The common com- including those with peripheral edema, to prevent renal plications of diuretic therapy are hyponatremia, renal im- complications. Following total paracentesis, a synthetic pairment, hepatic encephalopathy, and muscle cramps.
plasma substitute may be used if the volume of ascites Patients on diuretic therapy should be monitored for the removed is less than 5 L.58 For those in whom greater than development of renal impairment, which is usually revers- 5 L ascites is removed, it is generally recommended that ible after discontinuation of treatment and correction of albumin is used at a dose of 8 g/L of ascites removed.
hypovolemia. Specific complications include the develop- There are no data on whether smaller or larger amounts of ment of hyperkalemia, metabolic acidosis, or gynecomas- albumin have differing degrees of efficacy. Further large tia with spironolactone, and hypokalemia when randomized controlled trials are needed to determine furosemide is used alone. Hyperkalemia usually occurs in whether giving smaller amounts of albumin or whether those patients with refractory ascites and impaired renal synthetic plasma expanders are equally safe in terms of function requiring high doses of diuretics. In patients de- veloping hyperkalemia, the dose of spironolactone should Complications and contraindications to paracentesis. It be decreased or stopped when the serum potassium is is generally agreed that there are no contraindications to Ͼ5.5 mmol/L or 6 mmol/L, respectively. For those that paracentesis. Some clinicians have concerns about carry- develop hypokalemia secondary to the use of loop diuret- ing out paracentesis in patients with severe coagulopathy ics, furosemide should be stopped or decreased if serum or marked thrombocytopenia in case of localized bleeding potassium is less than 3.5 mmol/L. Diuretics may cause complications, but there are no published data to support hepatic encephalopathy. In cases of mild hepatic enceph- this. Many clinicians correct severe thrombocytopenia alopathy (grade 1), diuretics may be continued and he- (platelet count Ͻ50 000/mm3) to minimize the risk of patic encephalopathy treated conventionally. For those bleeding, since this is logical and there are no data to with more severe hepatic encephalopathy, diuretics support or refute this approach. Second, patients who should be stopped temporarily and their use reassessed.
have undergone previous surgery and who have peritoneal Diuretic therapy is often associated with the development adhesions have an increased risk of bowel perforation, and of muscle cramps.54 Muscle cramps in patients with as- paracentesis should be carried out with care or avoided cites are frequently due to effective hypovolemia. For altogether. These, and other patients may also have locu- those with severe incapacitating muscle cramps, diuretics lated ascites, which is not amenable to total or effective should be decreased or stopped. Therapies that have been shown to be effective in muscle cramps include albu-min,54 quinidine,55 quinine,56 and possibly zinc sulfate.57 Contraindications of diuretic therapy. Diuretics are rel- Treatment of Refractory Ascites
atively contraindicated in patients with severe hyponatre- Paracentesis. The first-line treatment of refractory as-
mia, renal dysfunction (serum creatinine Ͼ150 ␮moles/L cites is repeated total paracentesis. To reduce the fre- or 1.75 mg/dL), or active bacterial infection. With respect quency of repeated paracentesis, patients may continue to to the use of diuretics in patients with renal impairment, receive diuretics as tolerated. Diuretics should be stopped there are no data to support the withholding of diuretics if there are significant complications or if urine sodium is in patients with a primary renal abnormality, e.g., diabetic less than 30 mmoles/d. Some patients may require very nephropathy, although it is agreed that diuretics should frequent paracenteses, which becomes intolerable to the patient. In this instance, the use of TIPS should be con- this improves overall morbidity and mortality is not yet TIPS. TIPS is an effective treatment for refractory as-
cites. The main indication for insertion of a TIPS for the The Role of Liver Transplantation in Patients With
treatment of refractory ascites is the frequency of repeated Ascites
paracentesis. It is generally agreed on that when the fre- The prognosis of patients with ascites is poor, and es- quency of paracentesis is greater than 3 times per month, pecially so in those with complicated ascites. Since the TIPS insertion should be considered, but this decision overall 1-year survival rate is 85% in patients undergoing will depend on practical and patient issues and informed liver transplantation, all patients with ascites should be discussion about the risks of encephalopathy and consent considered as potential candidates for liver transplanta- with the patient. TIPS may be indicated in any patient tion. The policy for deciding the point at which a patient that does not tolerate paracentesis or in whom paracente- should be listed for liver transplantation largely depends on sis is contraindicated or ineffective, such as multiple ad- local factors such as organ availability and waiting time.
hesions or loculated ascites. Although there are norandomized studies available, TIPS should be considered for the treatment of recurrent massive hepatic hydrotho- The development of ascites is a major event in the rax, because it results in resolution of hepatic hydro- natural history of cirrhosis and is associated with a signif- icant deterioration in prognosis. With better understand- Complications and contraindications of TIPS. TIPS is ing of the pathophysiology of ascites formation, the associated with a 30% incidence of hepatic encephalopa- management of ascites has improved significantly in re- thy. Shunt stenosis or obstruction occurs in 70% by 1 cent years. The mainstay of treatment of responsive ascites year,53 although recent studies have suggested that poly- remains sodium restriction and judicious use of diuretic tetrafluoroethylene-coated TIPS stents may have a lower therapy together with paracentesis for gross ascites. As- rate of occlusion.60 Other important complications in- cites that is refractory to diuretic therapy requires either clude cardiopulmonary disease or hemolytic anemia.
repeated large-volume or total paracentesis. In selected There are data to suggest that TIPS-associated mortality patients, TIPS insertion has provided satisfactory control in Child class C patients may be increased. The main of ascites. Liver transplantation should be considered for contraindications are pre-existing hepatic encephalopathy, all cirrhotic patients with ascites.
age greater than 70 years, pre-existing cardiac dysfunc-tion, and Child-Pugh Score greater than 12. Although References
there are no studies to date assessing the level of cardiac 1. Reynolds TB. Ascites. Clin Liver Dis 2000;4:151-168.
function that contraindicates TIPS placement, it is gen- 2. Rimola A, Garcia-Tsao G, Navasa M, Piddock LJ, Planas R, Bernard B, erally accepted that patients need to have a normal ejec- Inadomi JM. Diagnosis, treatment and prophylaxis of spontaneous bacte- tion fraction of greater than 55% in order to cope with the rial peritonitis: a consensus document. International Ascites Club. J Hepa-tol 2000;32:142-153.
volume returned from the splanchnic circulation imme- 3. Runyon BA. Cardiac ascites: a characterization. J Clin Gastroenterol 1988; 4. Alexandrakis MG, Moschandrea JA, Koulocheri SA, Kouroumalis E, Elio- poulos GD. Discrimination between malignant and nonmalignant ascites Treatment of Dilutional Hyponatremia
using serum and ascitic fluid proteins in a multivariate analysis model. Dig Dilutional hyponatremia is a problem in terms of man- agement, since there are no published controlled trials.
5. Runyon BA, Montano AA, Akriviadis EA, Antillon MR, Irving MA, McHutchison JG. The serum-ascites albumin gradient is superior to the There is general agreement that water restriction is inef- exudate-transudate concept in the differential diagnosis of ascites. Ann fective at increasing serum sodium concentration in pa- tients with dilutional hyponatremia in liver disease. Water 6. Pare P, Talbot J, Hoefs JC. Serum-ascites albumin concentration gradient: restriction may cause a further decline of renal function.
a physiologic approach to the differential diagnosis of ascites. Gastroenter-ology 1983;85:240-244.
Since the nonosmotic secretion of antidiuretic hormone 7. Arroyo V, Gines P, Gerbes AL, Dudley FJ, Gentilini P, Laffi G, Reynolds due to a decreased effective arterial blood volume is a TB, et al. Definition and diagnostic criteria of refractory ascites and hepa- prime mover in the development of dilutional hyponatre- torenal syndrome in cirrhosis. International Ascites Club. HEPATOLOGY1996;23:164-176.
mia, many experts in the field use volume expansion with 8. Salerno F, Borroni G, Moser P, Badalamenti S, Cassara L, Maggi A, Fusini colloids (which are usually saline based) to try to improve M, et al. Survival and prognostic factors of cirrhotic patients with ascites: a renal function. There are data emerging that support the study of 134 outpatients. Am J Gastroenterol 1993;88:514-519.
9. Ring-Larsen H, Henriksen JH, Wilken C, Clausen J, Pals H, Christensen use of specific vasopressin-2 receptor antagonists in the NJ. Diuretic treatment in decompensated cirrhosis and congestive heart treatment of dilutional hyponatremia,61,62 but whether failure: effect of posture. Br Med J 1986;292:1351-1353 10. Reynolds TB, Lieberman FL, Goldman AR. Advantages of treatment of diuretics and punctures compensated by albumin]. Gastroenterol Clin Biol ascites without sodium restriction and without complete removal of excess 30. Gines P, Tito L, Arroyo V, Planas R, Panes J, Viver J, Torres M, et al.
11. Descos L, Gauthier A, Levy VG, Michel H, Quinton A, Rueff B, Ferma- Randomized comparative study of therapeutic paracentesis with and with- nian J, et al. Comparison of six treatments of ascites in patients with liver out intravenous albumin in cirrhosis. Gastroenterology 1988;94:1493- cirrhosis. A clinical trial. Hepatogastroenterology 1983;30:15-20.
12. Strauss E, De Sa MF, Lacet CM, Cartapattida da Silva E, Dos Santos RW.
31. Tito` L, Gine`s P, Arroyo V, Planas R, Panes J, Rimola A, Llach J, et al. Total Padronizac¸ao de conduta terapeutica das ascites do hepatopata cronico.
paracentesis associated with intravenous albumin management of patients Estudo prospectivo de 100 casos. GED 1985;4:79-86.
with cirrhosis and ascites. Gastroenterology 1990;98:146-151.
13. Gauthier A, Levy VG, Quinton A, Michel H, Rueff B, Descos L, Durbec 32. Panos MZ, Moore K, Vlavianos P, Chambers JB, Anderson JV, Gimson JP, et al. Salt or no salt in the treatment of cirrhotic ascites: a randomised AES, Slater JDH, et al. Single, total paracentesis for tense ascites: sequential hemodynamic changes and right atrial size. HEPATOLOGY 1990;11:662- 14. Bernardi M, Laffi G, Salvagnini M, Azzena G, Bonato S, Marra F, Tre- visani F, et al. Efficacy and safety of the stepped care medical treatment of 33. Fernandez-Esparrach G, Guevara M, Sort P, Pardo A, Jimenez W, Gines P, ascites in liver cirrhosis: a randomized controlled clinical trial comparing Planas R, Lebrec D, et al. Diuretic requirements after therapeutic paracen- two diets with different sodium content. Liver 1993;13:156-162.
tesis in non-azotemic patients with cirrhosis. A randomized double-blind 15. Porcel A, Diaz F, Rendon P, Macias M, Martin-Herrera L, Giron-Gonza- trial of spironolactone versus placebo. J Hepatol 1997;26:614-620.
lez JA. Dilutional hyponatremia in patients with cirrhosis and ascites. Arch 34. Runyon BA. Management of adult patients with ascites caused by cirrhosis.
16. Wilkinson SP, Jowett TP, Slater JD, Arroyo V, Moodie H, Williams R.
35. Gine`s A, Fernandez-Esparrach G, Monescillo A, Villa C, Domenech E, Renal sodium retention in cirrhosis: relation to aldosterone and nephron Abecasis R, Angeli P, et al. Randomized trial comparing albumin, dextran 70, and polygeline in cirrhotic patients with ascites treated by paracentesis.
17. Fogel MR, Sawhney VK, Neal EA, Miller RG, Knauer CM, Gregory PB.
Gastroenterology 1996;111:1002-1010.
Diuresis in the ascitic patient: a randomized controlled trial of three regi- 36. Altman C, Bernard B, Roulot D, Vitte RL, Ink O. Randomized compar- mens. J Clin Gastroenterol 1981;3(Suppl 1):73-80.
ative multicenter study of hydroxyethyl starch versus albumin as a plasma 18. Pe´rez-Ayuso RM, Arroyo V, Planas R, Gaya J, Bory F, Rimola A, Rivera F, expander in cirrhotic patients with tense ascites treated with paracentesis.
et al. Randomized comparative study of efficacy of furosemide versus spi- Eur J Gastroenterol Hepatol 1998;10:5-10.
ronolactone in patients with liver cirrhosis and ascites. Gastroenterology 37. Planas R, Gine`s P, Arroyo V, Llach J, Panes J, Vargas V, Salmeron JM, et al. Dextran-70 versus albumin as plasma expanders in cirrhotic patients 19. Angeli P, Dalla Pria M, De Bei E, Albino G, Caregaro L, Merkel C, with ascites treated with total paracentesis. Results of a randomized study.
Ceolotto G, et al. Randomized clinical study of the efficacy of amiloride and potassium canrenoate in nonazotemic cirrhotic patients with ascites.
38. Salerno F, Badalamenti S, Lorenzano E, Moser P, Incerti P. Randomized comparative study of hemaccel vs albumin infusion after total paracentesis 20. Gatta A, Angeli P, Caregaro L, Menon F, Sacerdoti D, Merkel C. A in cirrhotic patients with refractory ascites. HEPATOLOGY 1991;13:707- pathophysiological interpretation of unresponsiveness to spironolactone in a stepped care approach to the diuretic treatment of ascites in nonazotemic 39. Fassio E, Terg R, Landeira G, Abecasis R, Salemne M, Podesta A, Rodri- cirrhotic patients with ascites. HEPATOLOGY 1991;14:231-236.
guez P, et al. Paracentesis with dextran 70 vs paracentesis with albumin in 21. Bernardi M, Servadei D, Trevisani F, Rusticali AG, Gasbarrini G. Impor- cirrhosis with tense ascites. Results of a randomized study. J Hepatol 1992; tance of plasma aldosterone concentration on the natriuretic effect of spi- ronolactone in patients with liver cirrhosis and ascites. Digestion 1985;31: 40. McVay PA, Toy PT. Lack of increased bleeding after paracentesis and thoracentesis in patients with mild coagulation abnormalities. Transfusion 22. Gabow PA, Moore S, Schrier RW. Spironolactone-induced hyperchlor- emic acidosis in cirrhosis. Ann Intern Med 1979;90:338-340.
41. Wong F, Sniderman K, Liu P, Allidina Y, Sherman M, Blendis LM. The 23. Bernardi M, De Palma R, Trevisani F, Santini C, Patrono D, Motta R, effects of transjugular intrahepatic portosystemic shunt on systemic and Servadei D, et al. Effects of a new loop diuretic (muzolimine) in cirrhosis renal hemodynamics and sodium homeostasis in cirrhotic patients with with ascites: comparison with furosemide. HEPATOLOGY 1986;6:400-405.
refractory ascites. Ann Intern Med 1995;122:816-822.
24. Pockros PJ, Reynolds TB. Rapid diuresis in patients with ascites from 42. Nazarian GK, Ferral H, Bjarnason H, Castaneda-Zuniga WR, Rank JM, chronic liver disease: the importance of peripheral edema. Gastroenterol- Bemadas CA, Hunter DW. Effect of transjugular intrahepatic portosys- temic shunt on quality of life. AJR 1996;167:963-969.
25. Gine`s P, Arroyo V, Quintero E, Planas R, Bory F, Cabrera J, Rimola A, et 43. Trotter JF, Suhocki PV, Rockey DC. Transjugular intrahepatic portosys- al. Comparison of paracentesis and diuretics in the treatment of cirrhotics temic shunt (TIPS) in patients with refractory ascites: effect on body with tense ascites. Results of a randomized study. Gastroenterology 1987; weight and Child-Pugh score. Am J Gastroenterol 1998;93:1891-1894.
44. Allard JP, J Chau, Sandokji AM, Blendis L, Wong F. Effects of transjugular 26. Salerno F, Badalamenti S, Incerti P, Tempini S, Restelli B, Bruno S, Bellati intrahepatic portosystemic shunt (TIPS) on the nutritional status of cir- G, et al. Repeated paracentesis and iv albumin infusion to treat tense ascites rhotic patients with refractory ascites. Am J Gastroenterol 2001;96:2442- in cirrhotic patients. A safe alternative therapy. J Hepatol 1987;5:102-108.
27. Sola R, Vila MC, Andreu M, Oliver MI, Coll S, Gana J, Ledesma S, et al.
45. Huonker M, Schumacher YO, Ochs A, Sorichter S, Keul J, Rossle M.
Total paracentesis with dextran 40 vs diuretics in the treatment of ascites in Cardiac function and haemodynamics in alcoholic cirrhosis and effects of cirrhosis: a randomized controlled study. J Hepatol 1994;20:282-288.
the transjugular intrahepatic portosystemic stent shunt. Gut 1999;44:743- 28. Cotrim HP, Garrido V, Parana R, Santana G, Dultra D, Pinto M, Lyra L.
Paracentesis associated to dextran-70 in the treatment of ascites in patients 46. Wong F, Sniderman K, Liu P, Blendis LM. The mechanism of the initial with chronic liver diseases: a randomized therapeutic study. Arq Gastroen- natriuresis after transjugular intrahepatic portosystemic shunt. Gastroen- 29. Hagengue H, Ink O, Ducreux M, Pelletier G, Buffet C, Etienne JP [Treat- 47. Ochs A, Rossle M, Haag K, Hauenstein KH, Deibert P, Siegerstetter V, ment of ascites in patients with liver cirrhosis without neither hyponatre- Huonker M, et al. Transjugular intrahepatic portosystemic stent shunt mia nor renal insufficiency. Results of a randomized study comparing procedure for refractory ascites. N Engl J Med 1995;332:1192-1197.
48. Sanyal AJ, Freedman AM, Shiffman ML, Purdum PP 3rd, Luketic VA, 55. Lee FY, Lee SD, Tsai YT, Lai KH, Chao Y, Lin HC, Wang SS, Lo KJ. A Cheatham AK. Portosystemic encephalopathy after transjugular intrahe- randomized controlled trial of quinidine in the treatment of cirrhotic pa- patic portosystemic shunt; results of a prospective controlled study. HEPA- tients with muscle cramps. J Hepatol 1991:12:236-240.
56. Diener HC, Dethlefsen U, Dethlefsen-Gruber S, Verbeek P. Effectiveness 49. Deschenes M, Dufresne MP, Bui B, Fenyves D, Spahr L, Roy L, Lafortune of quinine in treating muscle cramps: a double-blind, placebo-controlled, M, et al. Predictors of clinical response to transjugular intrahepatic porto- parallel-group, multicentre trial. Int J Clin Pract 2002;56:243.
systemic shunt (TIPS) in cirrhotic patients with refractory ascites. Am J 57. Kugelmas M. Preliminary observation: oral zinc sulfate replacement is effective in treating muscle cramps in cirrhotic patients. J Am Coll Nutr 50. Lebrec D, Giuily N, Hadenque A, Vilgrain V, Moreau R, Poynard T, Gadano A, et al. Transjugular intrahepatic portosystemic shunt: compar- 58. Peltekian K, Wong F, Liu P, Allidina Y, Sherman M, Blendis LM. The ison with paracentesis in patients with cirrhosis and refractory ascites: a effect of large volume paracentesis on total central blood volume, systemicand renal hemodynamics and renal sodium handling in cirrhosis. Am J randomized trial. J Hepatol 1996;25:135-144.
51. Rossle M, Ochs A, Gulberg V, Siegerstetter V, Holl J, Deibert P, Ol- 59. Siegerstetter V, Deibert P, Ochs A, Olschewski M, Blum HE, Rossle M.
schewski M, et al. A comparison of paracentesis and transjugular intrahe- Treatment of refractory hepatic hydrothorax with transjugular intrahepatic patic portosystemic shunting in patients with ascites. N Engl J Med 2000; portosystemic shunt: longterm results in 40 patients. Eur J Gastroenterol 52. Gines P, Uriz J, Calahorra B, Garcia-Tsao G, Kamath P, Ruiz del Arbol L, 60. Saxon RR, Timmermans HA, Uchida BT, Petersen BD, Benner KG, Planas R, et al. Transjugular intrahepatic portosystemic shunt versus para- Rabkin J, Keller FS. Stent-grafts for revision of TIPS stenoses and occlu- centesis plus albumin for refractory ascites in cirrhosis. A multicenter ran- sions: a clinical pilot study. J Vasc Interv Radiol 1997;8:539-548.
domized comparative study. Gastroenterology 2002;123:1839-1847.
61. Gerbes AL, Gulberg V, Gines P, Decaux G, Gross P, Gandjini H, Djian J.
53. Sanyal A, Gennings C, Reddy KR, Wong F, Kowdley K, Benner K, Mc- Therapy of hyponatremia in cirrhosis with a vasopressin receptor antago- Cashland T, et al and the North American Study for Treatment of Refrac- nist: a randomized double-blind multicenter trial. Gastroenterology 2003; tory Ascites. A randomized controlled study of TIPS versus large volume paracentesis in the treatment of refractory ascites Gastroenterology 2003; 62. Wong F, Blei A, Blendis LM, Thuluvath PJ, and the North American VPA-985 Study Group. The effects of VPA-985, a vasopressin receptor 54. Angeli P, Albino G, Carrarro P, Dalla Pria M, Merkel C, Caregaro L, De antagonist, on water metabolism in patients with hyponatremia: a multi- Bei E, et al. Cirrhosis and muscle cramps: evidence of a causal relationship.
center randomized placebo controlled trial. HEPATOLOGY 2003;37:182-

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