Fluid-retentive diseases

A diuretic is a drug that increases die secretion of urine (ie, water, electrolytes, and waste products) by die kidneys. Many conditions or diseases, such as heart failure, endocrine disturbances, and kidney and liver diseases can cause retention of excess fluid (edema). When die patient shows signs of excess fluid retention, die primary healdi care provider may order a diuretic. There are various types of diuretic drugs, and the primary healdi care provider selects the one that best suits die patient s needs and effectively reduces the amount of excess fluid in body tissues. 

Inflammatory (or exudative) diarrhea results from changes to the intestinal mucosa that damage absorption processes and lead to an increase in proteins and other products in the intestinal lumen with fluid retention. The presence of blood or fecal leukocytes in the stool is indicative of an inflammatory process. The diarrhea of inflammatory bowel disease (e.g., ulcerative colitis) is inflammatory in nature. 

NSAIDs may accentuate the increased risk of cardiovascular events inherent in patients with RA. Increases in blood pressure and fluid retention may exacerbate existing cardiovascular disease. With the evidence associating COX-2 inhibitors with cardiovascular disease, clinicians must carefully evaluate the potential risks of NSAID therapy against the potential benefits.2 See Chap. 55 for additional discussion of NSAID therapy. 

Compensatory mechanisms in HF stimulate excessive sodium and water retention, often leading to systemic and pulmonary congestion. Consequently, diuretic therapy (in addition to sodium restriction) is recommended in all patients with clinical evidence of fluid retention. However, because they do not alter disease progression or prolong survival, they are not considered mandatory therapy for patients without fluid retention. 

Fluid retention may occur, perhaps as a result of peripheral vasodilation and/or improved insulin sensitization with a resultant increase in renal sodium and water retention. A dilutional anemia may result, which does not require treatment. Edema is reported in 4% to 5% of patients when glitazones are used alone or with other oral agents. When used in combination with insulin, the incidence of edema is about 15%. Glitazones are contraindicated in patients with New York Heart Association Class III and IV heart failure and should be used with great caution in patients with Class I or II heart failure or other underlying cardiac disease. 

Pericardial effusion Pericardial effusion, occasionally with tamponade, has occurred in approximately 3% of treated patients not on dialysis, especially those with inadequate or compromised renal function. Many cases were associated with connective tissue disease, the uremic syndrome, CHF or fluid retention, but were instances in which these potential causes of effusion were not present. Observe patients closely for signs of pericardial disorder. Perform echocardiographic studies if suspicion arises. More vigorous diuretic therapy, dialysis, pericardiocentesis, or surgery may be required. If the effusion persists, consider drug withdrawal. 

Metolazone - Metolazone, rapidly acting Mykrox), has not been evaluated for the treatment of CHF or fluid retention due to renal or hepatic disease, and the correct dosage for these conditions and other edematous states has not been established. 

Patients with renal diseases leading to the nephrotic syndrome often present complex problems in volume management. These patients may exhibit fluid retention in the form of ascites or edema but have reduced plasma volume due to reduced plasma oncotic pressures. This is very often the case in patients with "minimal change" nephropathy. In these patients, diuretic use may cause further reductions in plasma volume that can impair GFR and may lead to orthostatic hypotension. Most other causes of nephrotic syndrome are associated with primary retention of salt and water by the kidney, leading to expanded plasma volume and hypertension despite the low plasma oncotic pressure. In these cases, diuretic therapy may be beneficial in controlling the volume-dependent component of hypertension. 

When given in larger than physiologic amounts, steroids such as cortisone and hydrocortisone, which have mineralocorticoid effects in addition to glucocorticoid effects, cause some sodium and fluid retention and loss of potassium. In patients with normal cardiovascular and renal function, this leads to a hypokalemic, hypochloremic alkalosis and eventually to a rise in blood pressure. In patients with hypoproteinemia, renal disease, or liver disease, edema may also occur. In patients with heart disease, even small degrees of sodium retention may lead to heart failure. These effects can be minimized by using synthetic non-salt-retaining steroids, sodium restriction, and judicious amounts of potassium supplements. 

Congestive heart failure occurred in a 47-year-old woman after she had taken fludrocortisone 100 micro-grams/day for 2 weeks for Addison s disease (2). Ten months later, fludrocortisone 25 micrograms/day was restarted, and the dosage was increased to 100 micrograms/day over 2 months. At follow-up after 4 months she was well, without fluid retention or electrolyte abnormalities. 

Hypogonadism can be accompanied by hot flushes, similar to those seen in postmenopausal women, and gynecomastia. The potential risks of testosterone replacement in adult men are precipitation or worsening of sleep apnea, hastened onset of clinical significant prostate disease, benign prostatic hyperplasia, prostatic carcinoma, gynecomastia, fluid retention, polycythemia, exacerbation of hypertension, edema, and an increased risk of cardiovascular disease. 

The parenteral formulation diethylstilbestrol diphosphate is less commonly used than the oral formulation. In Japan, 24 elderly patients with advanced relapsed prostatic cancer were treated with high doses supplemented with ethi-nylestradiol (doses unclear) there was some slight therapeutic effect, but there were gastrointestinal symptoms and fluid retention (48). Also in Japan, a few patients with advanced disease were treated using intravenous diethylstilbestrol diphosphate 500 mg/day for 20 consecutive days to a total dose of 10 g the authors conclusion was more positive but adverse events were not specified (49). 

Despite the well-known beneficial effects of estrogen therapy on menopausal symptoms (Grady et al., 1992 Greendale and Judd, 1993 Lomax and Schonbaum, 1993) and their role in reducing bone loss and coronary heart disease (Barrett-Connor and Bush, 1991 Field et al., 1993 Harris et al., 1991 Lindsay, 1993 Lobo, 1991 Stampfer et al., 1991), compliance is low. Women decide not to take estrogens or stop treatment early because of the fear of breast and uterine cancer (Grady et al., 1992) and of symptoms associated with their therapy, namely, uterine bleeding, breast tenderness, and fluid retention. 

Compensatory mechanisms in HP stimulate excessive sodium and water retention, often leading to systemic and pulmonary congestion. Consequently, diuretic therapy (in addition to sodium restriction) is recommended in all patients with clinical evidence of fluid retention. However, because they do not alter disease progression or prolong survival, they are not considered mandatory therapy for patients without fluid retention. Thiazide diuretics (e.g., hydrochlorothiazide) are relatively weak diuretics and are used alone infrequently in HE. However, thiazides or the thiazide-hke diuretic metolazone can be used in combination with a loop diuretic to promote effective diuresis. Thiazides may be preferred over loop diuretics in patients with only mild fluid retention and elevated blood pressure because of their more persistent antihypertensive effects. 

Analgesics. Opiates can precipitate hepatic encephalopathy in patients with decompensated liver disease. If required to control postoperative pain, doses should be reduced to 25-50% of normal. Constant intravenous infusions should be avoided if the patient is not to be insidiously overdosed. Codeine can precipitate hepatic encephalopathy by its constipating effect alone. Aspirin and other NSAIDs may exacerbate impaired renal function and fluid retention by inhibiting prostaglandin synthesis and may also precipitate gastrointestinal bleeding. 

Severe fluid retention resistant to furosemide and fluid restriction was observed in 10 patients randomized to receive subcutaneous oprelvekin 50 pg/kg/day to prevent mucositis and acute graft-versus-host disease after allogeneic stem cell transplantation (2). One patient also had a large but reversible increase in serum transaminases. 

Demers, et al [137] described the observation of pretibial edema and sodium retention in lithium treated patients, in the absence of clear evidence of renal, hepatic or cardiac disease. The mechanism for such fluid retention remains unclear, but two plausible mechanisms have been suggested an excessive sodium intake, perhaps related to the manic phase and a lithium-induced reduction in maximum sodium excretory capacity which tends to be negligible when sodium intake is normal. Such patients manifested varying degrees of edema, combined with significantly increased urinary sodium > 200 mEqs/ day. Furthermore, due to increased urinary excretion of lithium, actual serum lithium levels may fall below therapeutic ranges, thereby leading to precipitation of manic crises. As volume expands, there is decreased reabsorption of sodium in the proximal tubules similarly, since hthium is reabsorbed via the same channels and transporters as sodium, lithium reabsorption also decreases [11]. 

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