General Introduction:
Therapeutic paracentesis is the first line of treatment for patients with symptomatic
malignant ascites. The practice of intravenous albumin infusion during abdominal paracentesis
comes from evidence in patients with liver cirrhosis. A meta-analysis of seventeen randomised
trials evaluating patients receiving albumin versus alternative treatment during large volume
paracentesis found that albumin reduced the incidence of post-paracentesis circulatory
dysfunction, hyponatraemia and mortality (Bernardi M, 2012). The mechanisms of ascites in
patients with cirrhosis are driven by portal hypertension. Portal hypertension brings about
systemic vasodilation and hyperdynamic circulation that eventually contribute to functional
and biochemical changes leading to ascites (Gines. P, 1997).
In contrast, cause of ascites in patients with malignancies is usually multi-factorial. It
occurs commonly in several tumours including malignancies of ovary, breast, colon, lung,
pancreas and liver. In each of these cancer types, the mechanisms leading to
malignancy-related ascites may be different. Peritoneal carcinomatosis is a major cause of
malignancy-related ascites. Other causes include massive liver metastasis causing portal
hypertension, chronic hypoalbuminaemia, hepatocellular carcinoma, chylous ascites from
lymphoma and Budd-Chiari syndrome due to occlusion of hepatic veins (Runyon BA, 1988).
In patients with cancer, aside from those who develop ascites as a result of portal
hypertension, the benefit of intravenous albumin infusion with large volume paracentesis is
uncertain, if at all present. Locally, the current clinical practice is for infusion of
intravenous albumin during abdominal paracentesis in patients with malignancy-related ascites
regardless of cause. The drawbacks of such an approach include exposing patients to risk of
anaphylaxis and increased financial costs (50 ml of 20% Albumin costs $42).
Granted that the potential harms of albumin infusion are rare, the burden of proof to show
that an intervention works is held by those who introduce it. To date, there have been no
studies specifically examining the role of intravenous albumin infusion in this population.
In the setting of advanced cancer where life expectancy is limited, the most clinically
relevant benefit of albumin infusion would be to reduce the rates of post-paracentesis
circulatory dysfunction. Through a pilot study, we hope to evaluate the effectiveness of IV
albumin in reducing rates of hypotension, thereby guiding clinical practice in this area.
Rationale and justification for the Study:
Hypothesis: Intravenous albumin infusion during abdominal paracentesis does not prevent
hypotension in patients with malignancy-related ascites without portal hypertension.
Rationale for the Study Purpose:
Three significant outcomes have been proven for the use of intravenous albumin in large
volume paracentesis in patients with cirrhosis. These are prevention of hypotension,
prevention of hyponatraemia and survival benefit. Ascites in the setting of patients with
malignancy usually occurs in advanced stage, of which the most meaningful outcome would be
that of prevention of hypotension. At present, the current clinical practice locally is
extrapolated from studies in patients with cirrhosis, and some physicians would opt to
administer IV albumin with every litre of ascitic fluid drained. We propose a study to
compare the rates of hypotension in patients who received IV albumin and those who do not. In
this study, we will randomise patients with a known history of cancer who are admitted for
symptomatic ascites to two groups. Both groups of patients will undergo insertion of
abdominal drain for symptomatic relief. Group 1 will receive intravenous albumin and Group 2
will not.
Rationale for Doses Selected:
In Group 1, 50 ml of 20% intravenous albumin will be given for every litre of ascitic fluid
drained as this is the current local preparation and practice.
Rationale for Study Population:
Replacement of intravenous albumin has been established in patients with ascites drainage for
patients with liver cirrhosis. It has not been shown to benefit patients with malignancy.
Rationale for Study Design:
There have been no previous studies in patients of this population. This is a prospective
pilot randomised study in order to compare the rates of hypotension between the two groups.
