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
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-
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
is large or gross ascites with marked abdominaldistension.
Sodium and Water Restriction
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
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.
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.
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
of ascites removed), and showed that paracentesis wasmore effective than diuretics in eliminating ascites and
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-
, 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.
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, 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.
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
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
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,
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-
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.
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
ϭ .04). However, the risk of severe hepatic en-
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.
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-
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.
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-
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.
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 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
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.
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
there are no studies to date assessing the level of cardiac
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RUSSIA AND THE GLOBAL NATURAL GAS MARKET Russia is the world’s largest reserves-holder, producer and exporter of natural gas and is playing a significant role in development of the European gas market and as an important player in gas deliveries to Former Soviet Union countries. Russia has the world’s largest natural gas reserve base. The estimates for the country’s proved natural ga
Pharmaceutical & Medical Terminology for Pharmacy Technicians Acknowledgements Winnipeg Technical College and the Department of Labour and Immigration of Manitoba wish to express sincere appreciation to all contributors. Special acknowledgments are The Citizenship and Multicultural Division, Funding for this project has been provided by the Manitoba Labour an