CHAPTER 18. ASCITES
Debra E. Heidrich
DEFINITION AND INCIDENCE
Ascites is the abnormal accumulation of fluid in the peritoneal cavity. The majority of patients with ascites have advanced liver disease—usually cirrhosis (Runyon, Montano, Akriviadis et al., 1992). Other nonmalignant diseases associated with ascites include right-sided heart failure, tuberculous peritonitis, nephrotic syndrome, complications of pancreatitis, and chylous ascites from trauma or surgery (Hostetter, Marincola, & Schwartzentruber, 2005; Runyon, 2004). Approximately 10% of patients with ascites have a malignancy as the primary cause (Runyon et al., 1992). Cancer diagnoses most often associated with ascites are ovarian, endometrium, breast, large bowel, stomach, and pancreas (Kichian & Bain, 2004). About 6% of patients entering hospices have ascites (Waller & Caroline, 2000).
Common symptoms associated with ascites include abdominal bloating, abdominal pain, nausea, decreased appetite, and constipation. Large-volume ascites leads to dyspnea and orthopnea. Patients with cirrhosis and ascites have higher variceal pressure than those without ascites and thus are at greater risk for variceal bleeding, which is associated with a high mortality rate (Kravetz, Bildozola, Argonz et al., 2000). The presence of malignancy-associated ascites is a poor prognostic sign, with a 1-year survival rate of 40% (Kichian & Bain, 2004). The median length of survival in a patient with symptomatic malignant ascites is reported to be 1 to 4 months. However, there is some variability in survival based on cancer type; women with breast or ovarian cancer may have a longer survival (Adam & Adam, 2004; Hostetter et al., 2005). Prolongation of survival has been documented in response to aggressive and more-targeted treatment approaches, but few randomized clinical trials exist in these patient populations (Hostetter et al., 2005).
ETIOLOGY AND PATHOPHYSIOLOGY
Ascites with Liver Disease
Common aspects of all postulated mechanisms for the development of ascites in liver disease involve a combination of sodium retention and portal hypertension (Lingappa, 2003). Portal hypertension can arise from hepatic venous outflow blockage caused by nodules and fibrosis in the liver (Wongcharatrawee & Garcia-Tsao, 2001). Three possible effects of portal hypertension are (1) diversion of the vascular volume to the lymphatics, resulting in overloading of the lymphatic drainage and weeping of fluid into the peritoneum; (2) portal-to-systemic shunting causing irritants that are normally cleared by the liver to be released into circulation where they initiate activities that decrease renal perfusion and increase renal tubular sodium resorption; or (3) endothelin-1 secretion, causing renal vasoconstriction, decreased glomerular filtration rate, and sodium retention. Regardless of the causal mechanism involved, depletion of the intravascular volume activates the renin-angiotensin-aldosterone system and vasopressin, causing sodium and water retention, which further contributes to fluid accumulation (Lingappa, 2003).
Ascites with Malignancy
Several mechanisms have been proposed for the development of malignancy-associated ascites. Patients with liver cancer may develop portal hypertension, resulting in ascites formation in much the same way as those with cirrhosis (Kichian & Bain, 2004). In addition, tumors that have seeded the peritoneum may release high levels of vascular endothelial growth factor (VEGF) that increase capillary permeability. Zebrowski, Liu, Ramirez et al. (1999) showed that VEGF protein levels were markedly increased in malignant ascites compared to levels in ascites associated with cirrhosis and that inhibiting VEGF activity decreased endothelial cell permeability in vitro. Further, animal studies show that ascites recurrence can be blocked by inhibiting VEGF expression (Stoelcker, Echtenacher, Weich et al., 2000). When the vascular permeability increases, proteins enter the peritoneal cavity. In mice, proteins in the peritoneal cavity make ascites worse by functionally impairing lymphatic drainage (Nagy, Herzberg, Masse et al., 1989). These proteins also increase the oncotic pressure pulling in more fluids via osmosis. In addition, obstruction or invasion of lymphatic channels by tumors may lead to chylous ascites (Kichian & Bain, 2004).
Effects of Ascites
The accumulation of abnormal amounts of fluid in the peritoneal cavity causes many uncomfortable symptoms. Pain occurs due to stretching or compression of tissues. Also, inflammation from a peritoneal infection may cause severe pain. Increased pressure on the stomach causes early satiety and nausea. Constipation, due to pressure on the bowel, is also a common complication of ascites. Dyspnea may result from pressure on the diaphragm and leakage of ascitic fluid into the pleural space (Kichian & Bain, 2004).
ASSESSMENT AND MEASUREMENT
An observable enlargement of a patient’s abdomen is a somewhat late sign of ascites. It has been estimated that 1.5 liters of ascitic fluid must be present before flank dullness is detected and 2 liters must be present before bulging is appreciated on physical examination (Cattau, Benjamin, Knuff et al., 1982; Tabbarah & Casciato, 1990). Patients of short stature may show these physical signs with less fluid accumulation. The earliest signs of ascites are often patient complaints of bloating, abdominal discomfort or pain, and increasing weight or waist size (e.g., clothes do not fit). Patients may also complain of fatigue, inability to sit upright, heartburn, nausea, early satiety, and constipation. As ascites becomes more pronounced, dyspnea and orthopnea may occur. Edema of the legs is also possible with progressive ascites (Kichian & Bain, 2004). Abdominal girth measurement provides a baseline that can be used to monitor worsening ascites, effectiveness of interventions, or recurrence of ascites after treatment.
HISTORY AND PHYSICAL EXAMINATION
Review the Patient’s History
Determine the underlying pathophysiology of the ascites (e.g., liver disease, heart disease, renal disease, or cancer).
Assess for Symptoms Associated with Ascites
Ask about onset and severity:
▪ Weight gain
▪ Increasing abdominal girth or a change in the way clothes fit
▪ Indigestion, nausea, and early satiety
▪ Sensation of fullness or bloating
▪ Ankle swelling
▪ Dyspnea
▪ Constipation
▪ Urinary frequency
Perform a Physical Examination
▪ Compare weight to baseline, taking weight loss due to anorexia and cachexia into account.
▪ Measure abdominal girth.
▪ Assess abdomen:
Note distension with bulging flanks when the patient is supine. This may be difficult to discern if the patient is obese or if less than 2 liters of fluid is present.
Percuss abdomen. (Note: percussion may not be sensitive or specific in diagnosing ascites [Cattau et al., 1982].)
Note any shifting dullness on percussion with position changes. In the supine patient with ascites, tympany is heard near the umbilicus but dullness is noted when the clinician percusses away from the umbilicus and reaches the level of fluid. When the patient turns to one side, the dullness shifts to the dependent areas.
Feel for evidence of a fluid wave (i.e., when flank is tapped on one side, an impulse is felt on the opposite side). Be sure to block transmission of a wave through subcutaneous fat by having an assistant place the medial edges of both hands firmly down the midline of the abdomen.
Observe skin across abdomen for signs of tightness or stretch marks.
Look for abdominal venous engorgement.
Identify changes in umbilicus; may be flattened or everted.
Assess for scrotal and/or lower-extremity edema.
Assess for associated complications:
Note any respiratory changes due to pressure on diaphragm or pleural effusion:
Assess rate and depth of respiration.
Listen for diminished or absent breath sounds.
Assess for dehydration or malnutrition due to nausea and early satiety:
Assess hydration of mucous membranes.
Assess general nutritional status.
DIAGNOSTICS
Abdominal radiographic studies, ultrasound, and computed tomography scans do verify the presence of free fluid in the abdomen, but these tests are generally not required after a thorough history and physical examination. On radiography, ascites appears with hazy or ground-glass features, distended and separated loops of bowel, and poor definition of abdominal organs (Hostetter et al., 2005; Kichian & Bain, 2004).
Cytology and examination of the protein concentration of the peritoneal fluid are tests that assist in determining the cause of ascites. However, in end-of-life care, the cause is often evident, so a diagnostic paracentesis is rarely required. More commonly, the peritoneal fluid is examined for cell count, Gram stain, and culture to select the appropriate antibiotic intervention when infection is suspected.
INTERVENTION AND TREATMENT
Sodium Restriction and Diuretics
Sodium restriction and diuretics may be effective for ascites caused by increased portal hypertension (e.g., cirrhosis or cancer in the liver) but are rarely effective for other types of malignant ascites (Adam & Adam, 2004). When portal hypertension is contributing to ascites, restrict sodium to 2000 mg/day or less; fluid restriction is not necessary for any cause of ascites unless serum sodium is less than 120 to 125 mmol/L (Runyon, 2004). In end-of-life care, it is important to balance the potential therapeutic effects of sodium and fluid restriction with the quality of living benefits of allowing patients to eat whatever foods taste good to them. As the appetite decreases, the appropriateness of a sodium-restricted diet also decreases.
When diuretic therapy is appropriate, that is, when portal hypertension is contributing to the ascites, spironolactone is more effective than loop diuretics (Kichian & Bain, 2004). However, a combination of spironolactone and loop diuretics (e.g., furosemide) may be even more effective. It may be reasonable to begin with an oral regiment of 100 mg of spironolactone and 40 mg of furosemide. Doses of both diuretics can be increased every 3 to 5 days, maintaining the 100:40 mg ratio, if weight loss and sodium excretion are inadequate (Runyon, 2004). The recommended maximum oral dose of spironolactone is 400 mg/day and of furosemide is 160 mg/day (Sandhu & Sanyal, 2005). Potential complications of diuretics, especially overuse of diuretics, include fluid and electrolyte imbalances, postural hypotension, hepatic encephalopathy, and pre–renal failure (Kichian & Bain, 2004; Sandhu & Sanyal, 2005).
In addition to monitoring for potential complications of diuretic therapy, assess other burdens of these medications. Patients with fatigue and limited mobility may find that diuretic therapy leads to expenditure of energy (e.g., ambulating to the bathroom, getting out of bed to the bedside commode) that might be better used for other activities that contribute to quality of life. Patients experiencing early satiety may find that taking so many medications leaves little room for the intake of more-satisfying food or fluids.
Paracentesis
Paracentesis may be helpful to achieve short-term relief of uncomfortable symptoms, such as abdominal discomfort and dyspnea. Large-volume paracentesis (i.e., up to 5 liters) can be safely performed without replacement of albumin in patients with diuretic-resistant tense ascites (Peltekian, Wong, Lie et al., 1997; Runyon, 2004; Stephenson & Gilbert, 2002). When ascites is related to portal hypertension, this procedure should be followed by diuretic therapy to attempt to prevent reaccumulation. Albumin replacement is recommended if more than 5 liters of ascitic fluid is removed from a patient with ascites caused by portal hypertension to prevent postparacentesis circulatory dysfunction. The dose of albumin is 8 to 10 g/L of fluid removed (Runyon, 2004; Wongcharatrawee & Garcia-Tsao, 2001). The role of albumin replacement after large-volume paracenteses for malignancy-associated ascites is not clear.
Complications of paracentesis include visceral and vascular injury, infection, hypotension, and ascitic fluid leak (Adam & Adam, 2004). Strict sterile technique should be used for the procedure. As with all invasive procedures, paracentesis is contraindicated in patients with low platelet counts.
Ascitic fluid almost always reaccumulates following paracentesis in patients with malignant ascites and in those with diuretic-resistant portal hypertension–related ascites. Repeated removal of fluid can lead to protein deficiencies and electrolyte abnormalities as well as increasing the potential for visceral and vascular injury. To avoid reaccumulation and the need for repeated paracentesis, attempt to control the disease with medications, when appropriate. Consider a long-term drainage device (discussed later) when other measures do not control the ascites.
Medications
In patients with cancer, intracavitary chemotherapy may control ascites and decrease the frequency of paracenteses. However, there are no good prospective studies of this intervention. It appears that this approach is more effective when a tumor has responded to earlier systemic therapy, especially in patients with ascites related to ovarian or breast cancer (Adam & Adam, 2004). A variety of agents have been used in the limited trials that have been done to date, including nitrogen mustard, thiotepa, cisplatin, 5-fluorouracil, doxorubicin, mitomycin C, etoposide, and bleomycin. Although the goal is to decrease the activity of tumor cells, these agents may work by causing sclerosis and adhesions that obliterate the peritoneal cavity, so that there is no space for fluid accumulation (Adam & Adam, 2004). Acute side effects of intracavitary chemotherapy include fever and abdominal tenderness (Waller & Caroline, 2000). In addition, some drug does cross over to systemic circulation, so systemic side effects, such as nausea, vomiting, hair loss, and bone marrow depression, are possible. There is also a high incidence of mechanical bowel obstruction with peritoneal sclerosing associated with intracavitary chemotherapy (Adam & Adam, 2004).
Intraperitoneal triamcinolone hexacetanide, a slowly metabolized corticosteroid, was used in one phase II study of 15 patients with recurrent malignant ascites (Mackey, Wood, Nabholtz et al., 2000). Although 13 of the 15 patients required repeat paracentesis, the interval between paracenteses was extended. Complications included transient abdominal pain, one case of bacterial peritonitis, and a localized herpes zoster infection. Intraperitoneal immunotherapy showed good results in a study of eight patients with malignant ascites due to carcinomatosis (Heiss, Strohlein, Jager et al., 2005). Further investigation is needed to truly evaluate the benefits and burdens of all of these intraperitoneal therapies.
With the new understanding of some of the molecular pathophysiology of ascites, new treatments may be on the horizon. Phase I and II clinical trials of angioinhibitory therapy (anti-VEGF antibodies, anti-VEGF receptor antibodies, tumor necrosis factor, and metalloproteinase inhibitors) and immunomodulators (OK-432, interleukin 2, and beta-interferon) have shown promise (Adam & Adam, 2004).
The administration of octreotide has been cited in case reports to be effective in controlling malignant ascites (Cairns & Malone, 1999; Mincher, Evans, Jenner et al., 2005). A dose of 200 to 400 mcg/day subcutaneously is reported to be effective in some cases of intractable ascites (Waller & Caroline, 2000). There are no studies that compare the benefits and burdens of octreotide versus other therapies, such as implanted peritoneal drainage catheters (discussed below).
Shunts and Drainage Catheters
When repeated paracenteses are required, consider placement of a shunt or a drainage catheter. A transjugular intrahepatic portasystemic stent-shunt (TIPS) allows blood from the portal circulation to flow into the systemic circulation, relieving portal hypertension (Lake, 2000). This intervention may convert a diuretic-resistant ascites into one that is diuretic sensitive (Runyon, 2004). However, the role of TIPS in the treatment of patients with cirrhosis who have ascites is still not clear. It is recommended that it be reserved for patients for whom large-volume paracentesis repeatedly fails and who have relatively good liver function (Sandu & Sanyal, 2005). Peritoneovenous shunts that empty ascitic fluid from the abdomen through a one-way, pressure-sensitive valve to a catheter in the superior vena cava have also been used to relieve ascites. Because of poor long-term patency, excessive complications, and no survival advantage compared to medical therapy in patients with cirrhosis, this intervention is rarely used today (Runyon, 2004).
In the past, peritoneovenous shunts have not been recommended for malignant ascites because of concerns about dumping malignant cells into the circulation and the tendency for the shunts to fail because of occlusion (Hostetter et al., 2005). However, studies support this procedure as being an effective approach to achieve control of ascites and relief of its associated symptoms (Tueche & Pector, 2000; Zanon, Grosso, Apra et al., 2002). Be aware that peritoneovenous shunting has a complication rate of 25% to 40% and the perioperative mortality rate is between 10% and 20% (Adam & Adam, 2004).
Indwelling peritoneal catheters may be used for continuous or intermittent drainage. Tenckhoff and Groshong catheters were the first catheters used for this purpose. This intervention relieves the discomforts of ascites, avoids the complications of repeated paracenteses, and allows the patient or family to drain ascitic fluid at home (Barnett & Rubins, 2002; Lee, Lau, & Yeong, 2000). Over the past few years, small studies and case reports have shown good outcomes using a tunneled, flexible catheter (Pleurx) originally designed for the treatment of recurrent pleural effusions (Iyengar & Herzog, 2002; Richard, Coldwell, Boyd-Kranis et al., 2001; Rosenberg, Courtney, Nemcek et al., 2004).
General Symptom Management
The symptoms associated with ascites, such as abdominal discomfort, anorexia, nausea, constipation, and dyspnea, must be managed while interventions for ascites are implemented. When ascites is controlled, the interventions initiated to manage the associated symptoms may no longer be required and can be discontinued. In the presence of refractory ascites, the clinician must assess for and treat these associated symptoms on an ongoing basis.
PATIENT AND FAMILY EDUCATION
▪ Teach signs and symptoms to report.
Signs of fluid accumulation (e.g., abdominal discomfort or bloating, dyspnea)
Signs of infection
▪ Prepare for paracentesis or indwelling catheter placement, as appropriate.
Explain the purpose of the paracentesis.
Explain the procedure, potential complications, and follow-up care.
Explain that reaccumulation of fluid is likely with paracentesis alone.
▪ Provide information about diuretic therapy, as appropriate.
▪ If ascites is caused by liver disease, discuss the “pros and cons” of a low-sodium diet.
▪ Teach appropriate use of medications and other interventions initiated to treat the symptoms associated with ascites, such as analgesics, antiemetics, and laxatives.
EVALUATION AND PLAN FOR FOLLOW-UP
▪ Assess abdominal girth after treatment as a measurement of effectiveness.
▪ Monitor for signs of reaccumulation of fluid.
Measure abdominal girth regularly to identify changes.
Assess for symptoms associated with fluid accumulation.
Monitor weight.
▪ Following paracentesis or placement of an indwelling catheter
Monitor for postural hypotension.
Monitor the puncture site for leakage.
Monitor vital signs for evidence of infection.
Provide site care.
Mrs. S. is 58 years old and has advanced ovarian cancer. Over the past month, she has noticed an increasing difficulty in fastening the waist closures of pants and skirts. The only pants she can wear now are sweat pants with a drawstring waist. She complains of a poor appetite but has gained about 25 pounds. She states she is always tired and has difficulty lying flat in bed because of shortness of breath, but she is able to sleep if she keeps the head of her bed elevated.
With the diagnosis of ovarian cancer, the cause of ascites is evident and no diagnostic tests are ordered at this time. Because sodium and fluid restrictions and diuretics are of little value with malignant ascites, paracentesis is performed at the outpatient clinic. About 4 liters of yellow, turbid fluid is removed. Mrs. S. tolerates the procedure well with no signs of postural hypotension. She experiences immediate relief of dyspnea and the generalized abdominal discomfort. Her abdominal girth after the procedure is 105 centimeters. Markings are placed on her abdomen so that her caregiver can monitor the abdominal girth at home. A bowel regimen of two tablets of sennosides 8.6 mg/docusate sodium 50 mg (Peri-Colace/Senokot-S) oral at bedtime is initiated.
Over the next 4 weeks, Mrs. S.’s abdominal girth gradually increases to 124 centimeters and the uncomfortable symptoms return. As repeat paracenteses are anticipated, a Pleurx catheter is placed and 3 liters of yellow, turbid ascitic fluid are removed. The clinician teaches the caregiver how to attach a drainage container to the catheter and to drain up to 2 liters of fluid every 3 days or whenever Mrs. S. reports abdominal fullness. The clinician also explains how to document the amount of drainage on a flow chart and instructs the caregiver to call if there is a change in the color of the drainage; if there is any redness, swelling, or drainage from the catheter insertion site; or if Mrs. S. develops a fever. The caregiver is also shown how to clean the insertion site and change the dressing each time the catheter is connected to drainage.
After 3 weeks of draining 1.5 to 2 liters of ascites fluid every 3 days, the amount of drainage has decreased to an average of 800 ml every 3 days. The clinician instructs the caregiver to try a weekly schedule for draining the catheter unless Mrs. S. reports abdominal fullness. The weekly drainage continues at 1.5 liters. Mrs. S. is eating and drinking very little and is now completely bedbound. Mrs. S. dies at home 2 months after placement of the abdominal drainage catheter with no abdominal distention, no abdominal discomfort, and no dyspnea.
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