Volume 39, Issue 2 , Pages e7-e9, February 2010
Targeting Diuretic Use for Malignant Ascites—Two Case Reports Highlighting the Value of the Serum-Ascites Albumin Gradient in a Palliative Setting
Article Outline
To the Editor:
Malignant ascites is a distressing, debilitating, and common complication occurring in up to half of all malignancies.1, 2 Repeated paracentesis is widely recognized as the mainstay of treatment but benefits tend to be short-lived and the procedure can be associated with fatigue and hypotension.2 Studies have shown that patients with ascites formed because of liver metastases, termed central ascites, tend to respond to diuretics and that identification of such patients can allow targeted diuretic use.2 The serum-ascites albumin gradient (SAAG) is a simple test that can accurately distinguish the mechanism of formation of malignant ascites.3 Two cases are described where the SAAG was successfully used to guide the use of diuretics in the control of ascites.
Case 1
An 84-year-old woman with pancreatic cancer was referred with progressive symptomatic ascites. She also had marked peripheral edema with lymphorrhea. The patient had been on spironolactone 50
mg for four weeks, increased from the 25mg that she had been taking for three weeks. This had not been further increased as she had experienced transient dizziness when it was originally started. She wanted paracentesis and it was performed without complication. Five liters of fluid was drained over the course of six hours and a further six liters in the four days after removal of the drain before the site healed. The patient was well throughout and her symptoms improved.
A sample of the fluid was sent for albumin level and her SAAG was calculated to be 17 (serum albumin 24g/L−ascitic albumin 7g/L). This was suggestive of a central cause for the ascites, and, therefore, her spironolactone was increased to 100mg and furosemide 20mg was added, in the hope of reducing the rate of reaccumulation. The patient tolerated these adjustments and has remained on these doses for four months with no significant reaccumulation of her ascites and resolution of her peripheral edema.
Case 2
A 77-year-old woman, with a clinical diagnosis of cholangiocarcinoma, underwent paracentesis of 17L of fluid over 48 hours in the local hospital, with significant symptomatic benefit. She was discharged on spironolactone 100mg daily, but after discharge, deteriorated and was seen by the specialist palliative community team nine days after paracentesis. At this point, her ascites had reaccumulated and was large but not tense. She still had a stoma bag over the drain site, which had continued to collect a few milliliters daily. This fluid was sent for albumin level. Her SAAG was calculated to be 18 (serum albumin 22g/L−ascitic albumin 4g/L). Her diuretics were increased to spironolactone 200mg, and furosemide 20mg daily was added. The ascites reduced clinically and remained stable until her death nine weeks later.
Comment
Maintenance of patients with ascites due to liver cirrhosis on high doses of diuretics is well established and generally well tolerated.4 Combination diuretics are generally used to minimize the interval between starting treatment and natriuresis, with starting daily doses of spironolactone 100mg and furosemide 40mg.4, 5 These are adjusted according to clinical response and electrolyte balance up to “ceiling” doses of spironolactone 400mg and furosemide 160mg.4, 5 Studies demonstrate that 90% of cirrhotics have a successful diuresis in combination with a restricted sodium diet of 2000mg/day.5
The morbidity associated with cirrhosis can be likened to patients with advanced malignancy, and yet, use of diuretics by physicians treating malignant ascites is extremely varied. The risk of their burden is often felt to outweigh their unpredictable benefit.6 It is of note that in both cases described, clinicians involved were wary of increasing diuretic doses for this reason, yet both patients tolerated the higher doses well and had clinical benefit.
Malignant ascites is thought to be formed in four ways. Approximately half of all cases seen are thought to have developed because of peritoneal seeding and are termed peripheral ascites. Chylous ascites is reported to account for around one-fifth of cases, being formed as a result of tumor infiltrating the retroperitoneal space and obstructing lymphatic flow. Central ascites, accounting for 15% of cases, is the most physiologically similar to primary hepatic failure, as it is caused by extensive hepatic metastases.2 The remaining cases are because of a combination of these causes. Because malignant central ascites formation can be likened to ascites formation in hepatic failure, it is postulated that such ascites should be responsive to diuretics. Pockros et al.7 undertook a prospective study that confirmed that patients with ascites because of massive hepatic metastases responded to diuretics but those with peripheral or chylous ascites failed to respond. The study also demonstrated that the mechanism of ascites formation could be accurately predicted by measurement of the SAAG.
The SAAG is a well-established measurement in ascites and has been shown to have a differential diagnostic accuracy of 97%.3 In central ascites, the SAAG is usually greater than 11g/L and this type is the most likely to respond to diuretic therapy. Peripheral ascites and chylous ascites have a SAAG of less than 11g/L, and there is no evidence to suggest that diuretic therapy is helpful in controlling the ascites. In fact, Pockros et al.7 demonstrated a higher frequency of diuretic-related complications within the lower gradient group.
The cases described demonstrate the potential benefit of using the SAAG as a guide for diuretic trial or titration. The measurement is a simple one and may allow diuretic use to be targeted, both reducing potentially burdensome trials in patients unlikely to respond and allowing confident titration in those with central ascites where the benefits may be significant. Further formal work within the malignant ascites population would allow the development of protocol guidance.
Acknowledgments
Where possible, informed consent was obtained from the patients involved in the cases described, and I am grateful to them and also to Drs. Sally Johnson and Nicola Wilderspin for their support.
References
- . Controlling malignant ascites. Eur J Palliat Care. 2001;8(5):187–189
- In: Doyle D, Hank G, Cherny N, Calman K editor. The Oxford textbook of palliative medicine. 3rd ed.. Oxford, UK: Oxford University Press; 2005;
- The serum-ascites albumin gradient is superior to the exudates-transudate concept in the differential diagnosis of ascites. Ann Intern Med. 1992;117:215–220
- . Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009;49:2087–2107
- In: Yamada T, Alpers DH, Laine C, Owyang C, Powell DW editor. Textbook of gastroenterology. 3rd ed.. Philadelphia, PA: Lippincott Williams & Wilkins; 1999;
- . A survey of practice in management of malignant ascites. J Pain Symptom Manage. 1998;16:96–101
- . Mobilization of malignant ascites with diuretics is dependant on ascitic fluid characteristics. Gastroenterology. 1992;103:1302–1306
PII: S0885-3924(09)01142-7
doi:10.1016/j.jpainsymman.2009.10.002
© 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
Volume 39, Issue 2 , Pages e7-e9, February 2010
