Feline-feline Idiopathic Lower Urinary Tract Disease.part Iv.

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Vol. 21, No. 6 June 1999

CE

Refereed Peer Review

FOCAL POINT ★ Consistently effective treatment of feline idiopathic lower urinary tract disease (iLUTD) remains undetermined.

KEY FACTS ■ Randomized, double-blind, placebo-controlled clinical trials are needed to prove the efficacy and safety of therapies used for symptomatic treatment of iLUTDs, p. 497. ■ Antibiotics were reportedly of no benefit in reducing the severity or duration of clinical signs in cats with iLUTD. ■ Results of one controlled clinical trial indicated that antiinflammatory doses of glucocorticoids (prednisolone) were of no benefit in reducing the severity or duration of clinical signs in cats with iLUTD. ■ Clients should be sufficiently educated about the biologic behavior of iLUTD and lack of credible evidence about treatment safety and efficacy to make informed decisions about therapeutic options.

Feline Idiopathic Lower Urinary Tract Disease. Part IV. Therapeutic Options* Michigan State University

University of Minnesota

Tina S. Kalkstein, DVM, MA John M. Kruger, DVM, PhD

Carl A. Osborne, DVM, PhD

ABSTRACT: Many therapeutic agents have been advocated for use in cats with idiopathic lower urinary tract disease (iLUTD); however, few have been subject to controlled clinical trials proving their efficacy and safety. The problem is compounded by the fact that clinical signs associated with iLUTD are frequently of short duration and self-limiting. Consequently, any form of therapy may appear beneficial as long as it is not harmful. This article explores various options for managing clinical signs and potential sequelae associated with iLUTD.

E

ffective treatment of male and female cats with idiopathic lower urinary tract disease (iLUTD) remains an enigma. Because clinical signs associated with this form of the disease are frequently of short duration and selflimiting, any form of therapy might appear to be beneficial if it is not harmful. The self-limiting nature of clinical signs in many cats with iLUTD underscores the need for controlled, prospective, double-blind clinical studies to prove the efficacy of various forms of therapy. Therapies discussed in this article, among others, are summarized in Table I. Selection of therapy for cats with nonobstructive iLUTD should be based on (1) thorough diagnostic evaluation to exclude other causes of lower urinary tract disease (LUTD), (2) client education emphasizing the lack of definitive studies demonstrating efficacy of proposed therapies, (3) strategies to minimize risk factors associated with urethral obstruction, (4) strategies to prevent iatrogenically induced disease, and (5) consideration of pharmacologic agents for symptomatic management of persistent or recurrent clinical signs. The treatment methods for nonobstructive feline iLUTD discussed in this article have not all been substantiated by experimental and/or clinical investigations and should therefore be considered with appropriate caution. This is the fourth article in a four-part presentation reviewing current concepts regarding

*Parts I, II, and III of this four-part presentation appeared in the January (Vol. 21, No. 1), February (Vol. 21, No. 2), and May (Vol. 21, No. 5) 1999 issues, respectively, of Compendium.

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TABLE I Therapy of Undetermineda Efficacy for Managing Nonobstructive Idiopathic Lower Urinary Tract Disease Therapy

Properties

Route

Predicted Efficacy b

Acepromazine

Antispasmodic

PO, IV, IM, SC

Unlikely

Amitriptyline

Anticholinergic, antiinflammatory, analgesic

PO

Probable in some cases

Ammonium chloride

Acidifier

PO

Effective for MAP

Butorphanol

Analgesic

PO, IV, IM, SC

Unlikely

Copper coils

Unknown

Intravesicular

Contraindicated

Glucosamine, chondroitin sulfate, and magnesium ascorbate Dantrolene

Glycosaminoglycan

PO

Probable in some cases

Antispasmodic

PO, IV

Unlikely

Debridement

Unknown

Intravesicular

Contraindicated

Diazepam

Antispasmodic

PO, IV

Unlikely

Diet Acidifying Low magnesium Moist

Acidifier Reduces urine magnesium Reduces USG

PO PO PO

Effective for MAP Effective for MAP Possible

Dimethyl sulfoxide

Antiinflammatory, analgesic

Intravesicular

Unlikely

Feline calicivirus vaccine

Immunogenic

SC

Unlikely

Furosemide

Diuretic

PO, IV, IM, SC

Unlikely

Hydrodistention

Analgesic

Intravesicular

Unlikely

Hydroxyzine

Antihistamine, anticholinergic, antispasmodic, analgesic, anxiolytic, sedative

PO

Unlikely

Hyaluronidase

Enzymatic

SC

Unlikely

Interferon α-2a

Immunomodulator, antifibrotic, antiviral

PO, intravesicular

Possible

Lugol’s solution

Cautery

Intravesicular

Contraindicated

Megesterol acetate

Hormone

PO

Unlikely

Methenamine

Antiseptic

PO

Unlikely

Methionine

Acidifier

PO

Effective for MAP

Methylene blue

Antiseptic

PO

Contraindicated

Oxybutynin

Antispasmodic

PO

May reduce pollakiuria

Pentosan polysulfate

Glycosaminoglycan

PO, intravesicular

Probable in some cases

Phenazopyridine

Analgesic

PO

Contraindicated

Phenol

Cautery

Intravesicular

Contraindicated

Phenoxybenzamine

Antispasmodic

PO

Unlikely

Piroxicam

Antiinflammatory

PO

Unknown

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TABLE I (continued) Therapy

Properties

Route

Predicted Efficacy b

Potassium chloride

Reduces USG

PO

Unlikely

Prazosin

Antispasmodic

PO

Unlikely

Propantheline

Antispasmodic

PO

May reduce pollakiuria

Prostaglandin E1

Cytoprotective

Intravesicular

Unlikely

Sodium chloride

Reduces USG

PO

Unlikely

Testosterone

Hormone

IM

Unlikely

0.085% Tetrasodium ethylenediamine tetraacetic acid and 0.06% sodium tripolyphosphate

Chelator

PO

Very unlikely

Vitamin A

Vitamin

PO

Unlikely

a No controlled studies comparing the degree of reduction in severity or duration of clinical signs in affected cats treated with the listed therapeutic agents compared with placebo-treated or untreated controls have been conducted to evaluate the efficacy of these treatments. b Our prediction of efficacy against nonobstructive idiopathic lower urinary tract disease if treatment was evaluated by a controlled clinical trial. IM = intramuscular; IV = intravenous; MAP = magnesium ammonium phosphate; PO = oral; SC = subcutaneous; USG = urine specific gravity.

feline iLUTD. Parts I, II, and III reviewed the clinical features, potential causes, and diagnostic evaluation, respectively, of the condition.

ANTIBACTERIAL AGENTS Antibiotics have commonly been prescribed to empirically treat iLUTD. However, bacterial urinary tract infections (UTIs) are rare in young to middle-aged cats with signs of LUTD.1–5 In one pilot study, antibiotic therapy was neither beneficial nor harmful in abacteriuric cats with LUTD.6 If antibiotics are not harmful, one may question why concern is warranted; however, indiscriminate use of antibiotics is believed to play an important role in the development of bacterial resistance. URINARY TRACT ANTISEPTICS Urinary tract antiseptics are sometimes used as adjunctive agents in the treatment, control, and prevention of bacterial UTIs in humans. Although their use is frequently acknowledged in the treatment of bacterial UTIs in dogs and occasionally mentioned for the treatment of feline LUTDs, studies substantiating the effectiveness of urinary tract antiseptics in these species have not been reported. In an acidic environment (pH below 6.0), methenamine hydrolyzes to form formaldehyde, an essential component of its antimicrobial activity. Because acidic

urine is needed to form formaldehyde, methenamine is usually given in combination with acidifiers, such as mandelic acid (methenamine mandelate) or hippuric acid (methenamine hippurate). Methenamine must remain in the urinary tract for a sufficient period to allow the generation of effective concentrations of formaldehyde. Once generated in sufficient concentration, formaldehyde is capable of killing bacteria, mycoplasma, and viruses in urine at any pH. Methenamine does not attain high intracellular concentrations and therefore would not be expected to eradicate intracellular viruses. Because the efficacy of methenamine has not been evaluated by controlled studies, we cannot recommend its use. Methylene blue (tetramethylthionine chloride) is a weak antiseptic agent that was once commonly used in combination with products designed to treat symptoms of lower urinary tract disorders, especially uroliths. Its effectiveness, however, is highly questionable. In addition, because methylene blue has the potential to cause Heinz bodies and severe anemia, medications containing the agent are contraindicated in cats.7

URINARY TRACT ANALGESICS Phenazopyridine, an azo dye commonly used as a urinary tract analgesic in humans, has recently become available as an over-the-counter preparation. The use of phenazopyridine, alone or in combination with sulfa

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drugs, is contraindicated in cats because they are very susceptible to dose-related methemoglobinemia and irreversible oxidative changes in hemoglobin that result in the formation of Heinz bodies and anemia.8 The use of analgesics other than phenazopyridine for the management of lower urinary tract pain has been infrequently reported in humans with interstitial cystitis (IC).9 It has been hypothesized that the analgesic properties of amitriptyline are at least partly responsible for relieving bladder pain when used to treat IC in humans.10 Butorphanol has been recommended for symptomatic management of clinical signs associated with feline iLUTD.11 However, controlled studies evaluating the efficacy of analgesics in reducing the severity or duration of clinical signs of iLUTD have not been reported.

URINE ACIDIFIERS Urine acidifiers have been commonly used to treat cats with nonobstructive and obstructive LUTDs. Their use was apparently based on the assumption that most, if not all, cases of feline hematuria, dysuria, and urethral obstruction resulted from struvite crystalluria and the formation of struvite uroliths and struvite-containing urethral plugs.12–18 Although little doubt exists that struvite uroliths and struvite-containing urethral plugs are important causes of feline LUTD, crystalluria per se and struvite crystalluria in particular are not significant factors in the etiopathogenesis of all nonobstructive feline iLUTDs. In one prospective study of 62 cats with nonobstructive iLUTD, the detection of crystalluria in affected cats was not different from that of unaffected controls.19 In a more recent study, crystalluria was uncommonly observed in cats with nonobstructive iLUTD.20 Acidification of urine is valuable in helping to dissolve or prevent sterile struvite uroliths or struvite-containing urethral plugs (see Management and Prevention of Sequelae section) but is unlikely to be of value in treating nonobstructive iLUTD. Many commercially manufactured diets are designed to acidify urine. Overacidification with acidifiers resulting in metabolic acidosis is most likely to occur in cats with concomitant renal failure, cats consuming acidifying diets, and immature cats.21 Long-term overacidification may contribute to hypokalemia, renal dysfunction, demineralization of bones, and calcium oxalate urolithiasis.22–25 In addition, high doses of methionine may result in Heinzbody anemia and methemoglobinemia.26 SKELETAL AND SMOOTH MUSCLE ANTISPASMODICS Pollakiuria commonly occurs in cats with LUTDs. Inappropriate voiding of small volumes of urine that

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are contained in undistended urinary bladders may be associated with sensations of pain, bladder fullness, and urgency. Pollakiuria is presumably the result of inflammation-induced stimulation of urinary bladder sacral sensory afferent nerves. Sensations of pain, fullness, and urgency induce a premature micturition reflex and subsequent inappropriate or involuntary voiding of small quantities of urine. Because cholinergic parasympathetic efferents are normally responsible for detrusor contraction, anticholinergic drugs may logically be considered a form of symptomatic treatment of pollakiuria and urge incontinence. 27 However, dosage and efficacy of these agents in cats with nonobstructive iLUTD have not been established by controlled clinical trials. The anticholinergic agent propantheline minimizes the force and frequency of uncontrolled detrusor contractions28 and has been recommended for the management of pollakiuria associated with iLUTD.6,29 In a controlled clinical study of the efficacy of one oral dose of propantheline (7.5 mg) for treating naturally occurring hematuria and dysuria in nonobstructed male and female cats, no difference in duration of clinical signs was observed between treated and untreated cats. 6 Treatment of longer duration would possibly have reduced the severity and duration of dysuria. Propantheline has a rapid onset of action. Care must therefore be taken to prevent urinary retention as a result of excessive doses. Other potential adverse effects include tachycardia, vomiting, and constipation. An empiric dose of 0.25 to 0.5 mg/kg orally every 12 to 24 hours has been suggested. Further studies are needed to establish appropriate doses and substantiate a beneficial symptomatic effect of propantheline in cats with severe pollakiuria. Other smooth (e.g., oxybutynin, phenoxybenzamine, acepromazine, prazosin) and skeletal (e.g., dantrolene, diazepam) muscle antispasmodics have been recommended for the symptomatic management of urethrospasm associated with LUTDs.29–35 Although some of these pharmacologic agents produced significant decreases in intraurethral pressure in normal male cats and cats with naturally occurring urethral obstruction,29,31–34 the role of urethral smooth or skeletal muscle spasm in producing clinical signs associated with feline iLUTD has not been determined. In a pilot study of six male cats with urethral obstruction due to unspecified causes, intraurethral pressures before administration of antispasmodics were not significantly different from those of normal, nonobstructed male cats.33 Similar studies in cats with idiopathic forms of nonobstructive LUTD have not been performed. On the basis of available data, we do not routinely recommend

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smooth or skeletal muscle antispasmodics to treat cats with iLUTD.

ANTIINFLAMMATORY AGENTS Mucosal ulceration and submucosal edema, hemorrhage, fibrosis, and mononuclear inflammatory cell infiltration are common light microscopic features observed in the urinary bladders of cats with iLUTD. These abnormalities are consistent with inflammation; however, the specific causes of inflammation in many cats with iLUTD are unknown. The unavailability of specific therapy for cats with iLUTD has resulted in widespread use of antiinflammatory agents in an attempt to reduce the severity of inflammation-associated clinical signs. However, there have been few controlled clinical trials to study the short- and long-term efficacy of antiinflammatory agents in the symptomatic treatment of dysuria and hematuria in cats. In addition, recall that hematuria and dysuria in cats with iLUTD are often self-limiting. Glucocorticoids By virtue of their potent antiinflammatory properties, glucocorticoids are a logical therapeutic choice to minimize dysuria and hematuria in cats with iLUTD. However, results of a pilot double-blind, placebo-controlled study of untreated male and female cats with iLUTD indicated that antiinflammatory doses of prednisolone (1 mg/kg orally every 12 hours for 10 days) were of no benefit in reducing the severity or duration of clinical signs in affected cats.36 Clinical signs subsided within 1 to 2 days in cats treated with prednisolone (n = 6) and in those treated with placebo (n = 6); urinalysis abnormalities of hematuria and pyuria subsided in approximately 2 to 5 days in both groups. Because of the inconsistency of favorable clinical responses and potential adverse effects associated with glucocorticoids, we suggest that they not be used to treat iLUTD. Dimethyl Sulfoxide Dimethyl sulfoxide (DMSO) is an analgesic and antiinflammatory agent with weak antibacterial, antifungal, and antiviral activity.37 It is apparently effective in treating some genitourinary disorders in humans, including IC, radiation cystitis, chronic prostatitis, and female chronic trigonitis. 38 Results of uncontrolled studies suggest that retrograde infusion of 50% solutions of pyrogen-free DMSO into the bladder lumina of humans with IC minimized associated clinical signs in 50% to 90% of patients.39,40 Dimethyl sulfoxide has been used to treat feline LUTD, presumably on the basis of its reported efficacy in humans with IC. Dosages and frequency of adminis-

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tration of DMSO have been entirely empiric. Intravesicular instillation of 10 to 20 ml of 10% DMSO was associated with amelioration of clinical signs in three cats with chronic LUTD, although a causative relationship was not established.29 Appropriately controlled clinical trials designed to evaluate the effectiveness of local instillation of DMSO into the urinary bladder of cats with idiopathic disease apparently have not been reported. In one controlled study of cats with induced chemical cystitis, intravesicular administration of 45% DMSO for 3 days was of no detectable benefit in minimizing bacterial infection or inflammation.6 Adverse effects of intravesicular DMSO administration in normal cats and cats with iLUTD have apparently not been evaluated. Pending further studies, we do not recommend DMSO to treat iLUTD.

Piroxicam Piroxicam, a nonsteroidal antiinflammatory drug, may be a potential therapy to reduce dysuria and pollakiuria in cats with iLUTD. The empiric dosage is 0.3 mg/kg orally every 24 hours. Pending double-blind, controlled clinical trials, it is not possible to make recommendations about the safety and efficacy of piroxicam for treating cats with iLUTD. GLYCOSAMINOGLYCANS Transitional epithelium of the urinary bladder is covered by a thin coating of hydrated extracellular macromolecules called glycosaminoglycans (GAGs). Major classes of biologically important GAGs include hyaluronic acid, heparan sulfate, heparin, chondroitin 4sulfate, chondroitin 6-sulfate, dermatan sulfate, and keratan sulfate.41 Urothelial GAGs minimize adherence of microorganisms and crystals to the bladder urothelium and also limit movement of urine proteins and other ionic and nonionic solutes from the bladder lumen into surrounding tissue.42 Quantitative or qualitative defects in surface GAGs and subsequent increased urothelial permeability have been hypothesized to be causative factors in the pathogenesis of feline iLUTD and human IC.42,43 Oral or intravesicular administration of GAGs is commonly used to manage IC in humans. Pentosan polysulfate sodium is a semisynthetic, low-molecularweight heparin analogue that reinforces urothelial GAGs and reduces transitional cell injury. 44 Symptomatic remission was observed in 28% to 40% of human patients with IC treated with oral or intravesicular pentosan polysulfate sodium compared with 13% to 20% of patients treated with placebo.45–48 Prolonged prothrombin time, epistaxis, gingival bleeding, alopecia, abdominal pain, diarrhea, and nausea have been

PREDNISOLONE ■ UROTHELIAL GAGs ■ PENTOSAN POLYSULFATE SODIUM

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Answering Owner Questions What is idiopathic lower urinary tract disease (iLUTD)? ■ Idiopathic lower urinary tract disease is a common disorder of the urinary bladder and urethra of cats that is characterized by nonspecific signs of bloody urine (hematuria), difficult and painful urination (dysuria), frequent urination (pollakiuria), and urinating outside of the litter box (periuria). What causes iLUTD? ■ Despite extensive study, the specific cause or causes are unknown. However, bacteria and crystals do not appear to be causative agents of the disease. How is iLUTD diagnosed? ■ Not all cats with hematuria, dysuria, and periuria have idiopathic disease. ■ There is no one specific diagnostic test or procedure that definitively establishes a diagnosis of idiopathic disease. ■ Idiopathic lower urinary tract disease is an exclusionary diagnosis; other causes of hematuria, dysuria, and periuria must be excluded by urinalysis, urine culture, and examination of the urinary bladder and urethra by radiographic studies or cystoscopy.

uncommonly observed in humans treated with pentosan polysulfate sodium.49 Despite encouraging studies in humans, the safety and efficacy of pentosan polysulfate sodium or other GAG preparations for treating feline iLUTD have not been evaluated by controlled clinical trials. Pending further safety and efficacy studies, we urge caution in the use of GAGs to treat feline iLUTD.

AMITRIPTYLINE Amitriptyline has been advocated for symptomatic therapy of feline iLUTD.11,50 Amitriptyline is a tricyclic antidepressant and anxiolytic drug with anticholinergic, antihistaminic, anti–α-adrenergic, antiinflammatory, and analgesic properties. Amitriptyline is used extensively for treatment of IC in humans. Despite amitriptyline’s popularity, its exact mechanism of action and therapeutic value in managing patients with IC are unknown. In an uncontrolled study of 28 human patients

Is effective specific treatment available? ■ Because the exact cause is unknown, specific treatment for iLUTD is unavailable. Is effective symptomatic treatment available? ■ Consistently effective treatments for the symptomatic management of cats with iLUTD are currently unavailable. However, very few welldesigned and controlled studies evaluating the value of various therapies have been conducted. What is the prognosis? ■ In general, the prognosis for cats with iLUTD is good. In many untreated male and female cats, clinical signs of hematuria, dysuria, pollakiuria, and periuria are frequently self-limiting in approximately 1 week. Signs may recur after variable periods of time and again subside without therapy. Recurrent episodes of iLUTD tend to decrease in frequency and severity over time.75 ■ Clinical signs may be frequently recurrent or persist for weeks to months in a small percentage of cats with iLUTD. ■ Male cats with iLUTD are at increased risk for urethral obstruction because of the formation of urethral plugs.

with refractory IC, remission of clinical signs occurred in 18 (64%) patients, whereas 5 (18%) developed unacceptable side effects. No improvement occurred in 5 (18%) patients.51 Anecdotal reports and limited data have been interpreted to suggest that treatment of chronic iLUTD was associated with amelioration of clinical signs.52 Consequently, amitriptyline has gained popularity as an agent for symptomatic therapy of feline iLUTD.50 As is the case in humans, however, appropriately controlled clinical studies designed to evaluate the effectiveness of amitriptyline in cats with idiopathic forms of LUTD have not been reported. Dose, frequency, and duration of amitriptyline therapy have been empiric. A dosage of 2.5 to 12.5 mg/cat orally every 24 hours (given at night) has been suggested; the dosage may be adjusted to produce a slight calming effect on the cat.43 Adverse reactions reported in humans, who were treated with antidepressant doses

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of amitriptyline include urinary retention, dry mucous membranes, blurred vision, hypotension, tachycardia, arrhythmias, sedation, weakness, lethargy, thrombocytopenia, agranulocytosis, elevations in liver enzyme activities, and hypersensitivity reactions. 53 Sedation, weight gain, unkempt haircoat, urine retention, neutropenia, and thrombocytopenia54,a have been observed in cats treated with amitriptyline. Pending further studies of the safety and efficacy of amitriptyline in cats, we urge caution with its use.

ANTIHISTAMINES AND MAST-CELL INHIBITORS Hydroxyzine is a heterocyclic piperazine H1-receptor antagonist drug with antihistaminic, anticholinergic, antispasmodic, analgesic, anxiolytic, and sedative properties. It also appears to inhibit mast-cell secretion and neuropeptide-induced urinary bladder mast-cell activation.55–57 Results of preliminary uncontrolled studies indicate that substantial improvement in symptoms occurred in 40% to 55% of humans with IC treated with hydroxyzine.58 Anecdotal observations also indicate that some cats with chronic forms of iLUTD improved after hydroxyzine administration.59 However, the safety and efficacy of hydroxyzine for managing cats with iLUTD has not been investigated. Sedation, weakness, hypotension, urine retention, hyperexcitability, tremors, and seizures have been associated with hydroxyzine administration in other species.55,60,61 UROHYDRODISTENTION Controlled distention of the urinary bladder under anesthesia (i.e., therapeutic urohydrodistention) is of recognized value in alleviating signs of IC in humans.62 Approximately 30% of human IC patients experience substantial but temporary relief of symptoms after urohydrodistention.38,40 Although the exact mechanism of action is unknown, urohydrodistention may induce (1) increased urothelial GAG production, (2) depletion of bladder sensory nerve neuropeptides, and/or (3) mechanic or ischemic degeneration of sensory nerve endings within the bladder wall.38,40 Controlled distention of the urinary bladder during cystoscopy reportedly has been associated with a reduction in the severity of clinical signs in some cats with iLUTD. 63 As with nearly all forms of symptomatic therapy, however, the efficacy of urohydrodistention has not been evaluated by appropriately controlled clinical trials. Establishing a diagnosis of iLUTD currently requires retrograde contrast radiography and/or cystoscopy (both of which distend the urinary bladder). Until other, more specific markers of iLUTD are idena Personal communication: Murphy C, Broomfield, CO, 1997.

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tified, it will be difficult to differentiate the beneficial effects of bladder distention for diagnostic purposes versus those induced by other forms of therapy.

UROTHELIAL DEBRIDEMENT Several decades ago, cystotomy to lavage and debride the bladder mucosa was a popular method of treating cats with cystitis, urethritis, and/or urethral obstruction. Although this procedure is still occasionally used, efficacy has not been proven by controlled clinical or experimental studies. Furthermore, reports of clinical experiences suggest that the technique is of little benefit.64 Current knowledge and understanding about the behavior of LUTDs suggest that bladder mucosal debridement may actually increase, rather than decrease, morbidity associated with the disorder.64 In light of current knowledge, we view this procedure as unethical. STRESS REDUCTION Stress has been implicated in precipitating or exacerbating clinical signs associated with iLUTD. 43 Although it is unlikely that stress is a primary cause of iLUTD, cat owners can attempt to reduce environmental stress by minimizing changes in the home, maintaining a constant diet, and providing toys and hiding places.43 OTHER AGENTS A variety of other agents have been advocated by various authors to treat and prevent feline LUTDs, but none have been evaluated by appropriate selection of patients for study or controlled clinical trials. Recommendations for testosterone, castor oil, garlic, megestrol acetate, feline calicivirus/feline herpesvirus type 1 vaccines, Lugol’s solution, tetrasodium ethylenediamine tetraacetic acid and sodium tripolyphosphate, vitamin A, hyaluronidase, and various homeopathic preparations appear to be based on supposition rather than fact. We do not recommend them. MANAGEMENT AND PREVENTION OF SEQUELAE Vesicourachal Diverticula In the past, therapeutic recommendations for any feline macroscopic vesicourachal diverticulum associated with hematuria, dysuria, pollakiuria, and/or periuria consisted of partial cystectomy and diverticulectomy.65 However, our observations suggest that macroscopic diverticula may develop at the bladder vertex of cats with microscopic urachal remnants as a sequela to concurrent but unrelated acquired diseases of the lower urinary tract (e.g., idiopathic disease, urolithiasis, bacterial cystitis, urethral obstruction).66 Many of these macroscopic diverticula heal within 2 to 3 weeks after amelio-

HYDROXYZINE ■ CYSTOTOMY ■ MACROSCOPIC DIVERTICULA

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ration of clinical signs of LUTD as demonstrated by repeated double-contrast cystography.66 Consequently, rather than perform needless diverticulectomy, therapeutic efforts should be directed toward eliminating underlying causes of LUTD. If a macroscopic diverticulum persists because the underlying cause remains and the patient has a persistent or recurrent UTI, diverticulectomy is a rational therapeutic option.

Urethral Plugs Because insoluble crystals appear to be an integral component of many matrix–crystalline urethral plugs, using medical protocols to prevent crystal formation in affected patients is logical. Struvite is the primary mineral component of most naturally occurring urethral plugs, although other mineral types may also be found. Successful prevention of recurrent urethral obstruction using diets designed to reduce urine pH and urine magnesium and phosphorous concentration has been reported.67 Attempts to dissolve struvite crystals with urine acidifiers or diets designed to promote acidic urine should not be initiated in cats with postrenal azotemia. The metabolic sequelae of urethral obstruction, particularly severe metabolic acidosis, must be corrected before diets designed to acidify urine are used. Perineal urethrostomy is an effective method of minimizing recurrent obstruction of the penile urethra in patients unresponsive to medical management. Contrast urethrography should first be performed to confirm that the site(s) of urethral obstruction is (are) only within the penile urethra. We emphasize that perineal urethrostomies may be associated with significant short- and long-term complications, including postoperative hemorrhage; wound dehiscence; urine scald dermatitis; urethral stricture; bacterial UTI; and, rarely, subcutaneous extravasation of urine, perineal hernia, and urethrorectal fistula.67–74 Bacterial UTIs were identified postoperatively in 22% to 45% of patients managed with perineal urethrostomy for urethral obstruction.67,73 UTI caused by urease-producing microbes may induce struvite urolith formation.67 The prophylactic benefits of minimizing recurrent urethral obstruction by urethrostomy must be weighed against a longterm predisposition to recurrent bacterial UTI and urolith formation. We recommend that perineal urethrostomies be avoided unless (1) irreversible mural or extramural lesions exist that cause recurrent or persistent obstruction of the penile urethra or (2) frequent outflow obstruction of the distal urethra occurs despite properly designed medical management. CLIENT EDUCATION CONSIDERATIONS Because of the self-limiting nature of iLUTD and the

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uncertainty of the efficacy of specific or symptomatic therapy, client education assumes a prominent role in the management of affected cats. Owners should be sufficiently educated about the natural biologic behavior of the disease and lack of credible evidence regarding the safety and efficacy of therapeutic agents to make reasonable decisions about therapeutic options (see Answering Owner Questions). We also recognize that client- or self-imposed psychologic pressure to “do something” is occasionally overwhelming. Our desire to do something, however, must be evaluated in light of the potential risks and benefits of our therapeutic actions.

REFERENCES 1. Lawler DF, Evans RH: Urinary tract disease in cats: Water balance studies, urolith and crystal analyses, and necropsy findings. Vet Clin North Am 14:537–553, 1984. 2. Bartges JW: Lower urinary tract disease in geriatric cats. Proc 15th ACVIM Forum:322–324, 1997. 3. Lees GE, Rogers KS, Wolf AM: Diseases of the lower urinary tract, in Sherding RG (ed): The Cat: Disease and Clinical Management. New York, Churchill Livingstone, 1989, pp 1397–1454. 4. Martens JG, McConnell S, Swanson CL: The role of infectious agents in naturally occurring feline urologic syndrome. Vet Clin North Am 4:503–511, 1984. 5. Schechter RD: The significance of bacteria in feline cystitis and urolithiasis. JAVMA 156:1567–1573, 1970. 6. Barsanti JA, Finco DR, Shotts EB, et al: Feline urologic syndrome: Further investigations into therapy. JAAHA 18:387– 390, 1982. 7. Schechter RD: Heinz body anemia associated with use of urinary antiseptics containing methylene blue in the cat. JAVMA 162:37, 1973. 8. Harvey JW, Kornick HP: Phenazopyridine toxicosis in the cat. JAVMA 169:327–331, 1976. 9. Jonsson E, Coombs DW, Hunstad D: Continuous infusion of intrathecal morphine to control acquired immunodeficiency syndrome–associated bladder pain. J Urol 147:687– 689, 1992. 10. Hanno PM, Buehler J, Wein AJ: Use of amitriptyline in the treatment of interstitial cystitis. J Urol 141:846–848, 1989. 11. Buffington CAT, Chew DJ: Feline lower urinary tract disease in cats: The Ohio State experience. Proc 15th ACVIM Forum:343–346, 1997. 12. Elcock L: Feline urological syndrome. Feline Pract 11:6, 1981. 13. Engle GC: A clinical report of 250 cases of feline urological syndrome. Feline Pract 7:24, 1977. 14. Gaskell CJ, Denny HR, Jackson OF: Clinical management of the feline urological syndrome. J Small Anim Pract 19: 301–314, 1978. 15. Holzworth J: Urolithiasis in cats, in Kirk RW (ed): Kirk’s Current Veterinary Therapy. Small Animal Practice. Philadelphia, WB Saunders Co, 1965, p 410. 16. Lewis LD, Morris ML: Feline urological syndrome: Causes and clinical management. Vet Med 79:323, 1984. 17. Mandelker L: What’s hot and what’s not. Vet Forum 12(7): 54, 1995. 18. Osbaldison GW, Taussig RA: Clinical report on 46 cases of feline urological syndrome. Vet Med/Small Anim Clin 64:461, 1970.

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About the Authors Dr. Kalkstein is currently a resident in Small Animal Internal Medicine and Dr. Kruger is affiliated with the Department of Small Animal Clinical Sciences at the College of Veterinary Medicine, Michigan State University, East Lansing, Michigan. Dr. Osborne is affiliated with the Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota. Drs. Kruger and Osborne are Diplomates of the American College of Veterinary Internal Medicine.