23 Jun 2014
Danièlle Gunn-Moore
Job Title
DANIÈLLE GUNN-MOORE BSc, BVM&S, PhD, FHEA, MACVSc, MRCVS discusses a multimodal approach to cystitis in felines, including easing stress, diet, increased water intake and, if necessary, urethral spasm relief and glycosaminoglycan replacement
Feline cystitis, that is to say, feline lower urinary tract disease (FLUTD), is common, with most cases being stress-associated feline idiopathic cystitis (FIC). FIC and the associated condition of urethral plugs account for approximately 75 per cent of all cases of FLUTD, and up to 90 per cent of urethral obstruction. The key to successful treatment is a correct diagnosis. Where no underlying cause can be found, treat for FIC.
FELINE cystitis is common, with most cases being stress-associated feline idiopathic cystitis (FIC).
FIC and the associated condition of urethral plugs account for approximately 75 per cent of all cases of FLUTD, and up to 90 per cent of urethral obstruction.
In cats, most uroliths are struvite and calcium oxalate. Since oxalate stones cannot be dissolved they should be surgically removed. Struvite stones may be dissolved using an appropriate diet – for example, Royal Canin Urinary S/O – in an average of 18 days (Houston et al, 2011), Hill’s s/d in as little as 14 days or Hill’s c/d Multicare in as little as four weeks (Lulich et al, 2013). Measure the number and size of stones prior to changing the diet, then remeasure them after a month. If the stones are struvite they should be much smaller and fewer (Lulich et al, 2013). If this has not occurred they should be removed surgically and sent for quantitative analysis.
The cat will need to drink as much water as possible (see FIC later). Dietary manipulation aims to create less concentrated urine (ideally, urine specific gravity [USG] less than or equal to 1.035), with reduced relative supersaturation (RSS) of the minerals that predispose to urolithiasis: feed an appropriate, ideally wet diet. Some manufacturers achieve this by adding extra salt (NaCl) – for example, Royal Canin Urinary S/O, Purina UR St/Ox – while others add potassium citrate, for instance, Hill’s Prescription Diet c/d Urinary Stress. All three diets have extra vitamin B6 (to reduce oxalate formation), omega 3 and 6 fatty acids (anti-inflammatory), plus vitamin E and beta-carotene (as antioxidants).
Few treatments for FIC have been investigated by well-controlled double- blinded experimental studies. Most are recommended from uncontrolled clinical observations and, since FIC is usually self-limiting, many treatments appear effective, so all treatments should be considered with appropriate caution.
Stress plays a key role in FIC.
Potential stressors include:
• living with another cat with which the FIC sufferer is in conflict (different social groups);
• abrupt changes in diet, environment or weather;
• overcrowding;
• owner stress; or
• the addition of new pets/people to the household.
Cats are naturally solitary hunters that may choose to live in groups of related individuals – being hostile to cats from other social groups. Cats do not like to share essential resources with cats from other social groups and the provision of adequate resources in the home is a key factor in minimising stress. The five key resources are water stations, feeding stations, latrines/litter boxes, resting places (preferably high up), and places to hide or ways of escaping.
Much can be said about environmental changes that may reduce the risk of FIC (Buffington et al, 2006; Gunn-Moore and Caney, 2009), for example, relating to litter box number, type, access, content and hygiene; provision of suitable feeding and watering stations; reducing inter-cat disharmony; and positive environmental enrichment (http://indoorpet.osu.edu) – for example, climbing frames and games that stimulate natural cat behaviour (paper bags and boxes to play in, fishing rod toys [hunting games, such as hiding toys filled with cat nip or bits of food] Gunn-Moore and Caney, 2009).
Provision of synthetic feline pheromone may help reduce anxiety in cats with FIC in multicat households (Gunn-Moore and Cameron, 2004). Using a diffuser 24 hours a day evenly distributes it throughout the house. However, it is not enough alone to override signals of social incompatibility. Work still needs to be done to reduce stress and integrate the cats.
Milk protein hydrolysates may help to reduce anxiety in cats (Beata et al, 2007). They are found in Zylkene (MSD), Royal Canin Calm and Hill’s c/d Urinary Stress, which also contains L-tryptophan to further reduce stress, plus glycosaminoglycans (GAGs, see later). A recent year-long study with Hill’s c/d Multicare resulted in an 89 per cent reduction in signs of FIC compared to a normal diet (Kruger et al, 2013).
Encourage the cat to drink by placing large, well-filled water bowls away from feeding areas (and even add fish or chicken juice). Altering the diet will reduce the USG most easily, ideally to approximately 1.035 (Markwell et al, 1999; Gunn-Moore and Shenoy, 2004). Transition should be made to a new diet gradually and an appropriate, ideally wet, diet fed (for example, as listed above). However, while reducing the USG and signs of cystitis, it will not alter the underlying pathology of FIC – the cat will still be stressed (albeit less painful) – so environmental modification and stress reduction are also needed.
Glycosaminoglycans may be beneficial if exogenous GAG attaches to the defective urothelium and decreases its permeability. They may also have analgesic and anti-inflammatory properties. They have been effective in some human studies with interstitial cystitis (IC). There are five published double-blinded, placebo-controlled studies in cats. Oral N-acetyl glucosamine (NAG) resulted in no significant difference in a six month-long study (Gunn-Moore and Shenoy, 2004), and a slight reduction in haematuria and unquantified reduction in pain in a one month study (Panchaphanpong et al, 2011). Pentosan polysulphate (PPS) has not proved beneficial, either when given orally in a six-month study (Chew et al, 2009), or by subcutaneous injections (3mg/kg on days one, two, five, seven and 10) in a 12-month study (Wallius and Tidholm, 2009).
However, some individual cats do appear to benefit from GAG supplementation and a pilot study suggested GAG (hyaluronic acid, chondroitin sulphates and NAG; A-Cyst, Dechra) instilled into the bladder on three occasions within 24 hours showed potential to reduce the risk of recurrence of re-obstruction in the first week (Bradley and Lappin, 2013). From human studies it appears there are differences in the relative efficiency of different GAGs, and the same may also be true in cats. Supplements may be given at higher doses at the time of the initial presentation and then reduced to a maintenance level. Possible side effects include prolonged bleeding times, inappetence and, possibly, insulin resistance.
There are a number of different GAG supplements – some of which often have other potentially beneficial compounds added, such as Cystease (Ceva Animal Health), which contains NAG and hyaluronic acid, plus L-tryptophan (to reduce stress). Injectable PPS is available as Cartrophen Vet (Biopharm).
Reducing urethral spasm may reduce clinical signs of cystitis and the risk of urethral obstruction (Straeter-Knowlen et al, 1994 and 1995; Marks et al, 1996). Even female cats with FIC have increased urethral muscle tone (Wu et al, 2011). Spasms may be initiated by local pain or inflammation and may affect smooth and/or skeletal muscle. While antispasmodic drugs are rarely associated with side effects, the risk of concurrent renal or cardiac disease should be assessed and systemic blood pressure measured, as hypotension and/or hepatotoxicity can occur. Injectable drugs (for example, acepromazine) may be given at the time of relieving urethral obstruction, followed by a seven to 14-day course of prazosin (Hetrick and Davidow, 2013). Dantrolene may also help (Straeter-Knowlen et al, 1995). Longer or intermittent courses may be required.
• Acepromazine 0.05mg/kg-0.2mg/kg IV, IM, SC or 1mg-3mg/kg PO.
• Prazosin 0.25mg/cat- 1mg/cat PO q8-12h.
• Phenoxybenzamine 0.5mg/kg-1mg/kg PO q12h – takes five days to work.
• Amitriptyline 0.5mg/kg-1mg/kg PO q24h.
• Dantrolene 0.5mg/kg-2mg/kg PO q12h (0.5mg/kg-1mg/kg IV).
• Atracurium besylate 0.2ml of 10mg/ml solution in 3.8ml of 0.9 per cent saline as an intraurethral flush (Galluzzi et al, 2012).
Tricyclic antidepressants (TCAs) have anticholinergic (increase bladder capacity, relax urethra and ureters), anti-inflammatory, anti-α adrenergic, analgesic and antidepressant effects. Amitriptyline may be beneficial in some humans with IC. However, two well-controlled studies in cats showed short courses (seven days) actually increased the risk of recurrence (Kraijer et al, 2003; Kruger et al, 2003), while a single open-label, year-long study did appear to reduce clinical signs (Chew et al, 1998).
TCAs should be reserved for severe chronic cases, or when stress is predicted, but not avoidable – for example, moving home or staying in a cattery. Side effects include somnolence, obesity, urinary retention and hepatotoxicity. Liver function should be monitored before and during treatment.
• Amitriptyline 0.5mg/kg-2mg/kg PO q24h.*
• Clomipramine 0.25mg/kg-0.5mg/kg PO q24h.*
*Give in the evening, and wean to as low as possible.
Serotonin re-uptake inhibitors (SSRIs) – for example, fluoxetine – may cause fewer side effects than TCAs, but are not licensed in cats and have not been studied in the treatment of FIC.
NSAIDs, buprenorphine (10μg/kg-30μg/kg PO, SQ, IM or IV q8-12h) and/or maropitant (NK-1 antagonist, potent visceral analgesic [Niyom et al, 2013] and blocker of substance P activation) may reduce clinical signs. However, they are rarely sufficient alone – combine with environmental and dietary modifications.
All treatments are merely palliative. The best results are gained using a multimodal approach, that is, reduce stress (paying particular attention to social stress), feed an appropriate diet, increase water intake and, if necessary, relieve urethral spasm and replace GAGs. When tailored to the individual cat, this may reduce or prevent further episodes. TCAs (SSRIs) should be reserved for severe recurrent cases. Referral to a veterinary behaviourist may be necessary to identify and resolve chronic stress.
Be proactive; observant owners can notice prodromal signs of an oncoming episode of FIC, such as increased hind end grooming or altered behaviour (for example, inter-cat aggression initiated by the FIC sufferer). Signs probably relate to increasing bladder pain. Reinforcing management changes may reduce the severity or duration of the episode, that is, reduce stress (give the cat more cuddles, install or refill a pheromone diffuser), increase fluid intake and/or give prazosin or a GAG supplement, or increase their dosage (Buffington et al, 2006; Gunn-Moore and Caney, 2009). This can also be used if a stressful episode is anticipated, such as builders in the home.
Treatment for urethral plugs consists of reducing the inflammatory protein matrix and urethral spasm (see FIC) and reducing crystalluria (see uroliths).
Ideally, treat bacterial infections according to culture and sensitivity. Address underlying problems. Prolonged courses may be required with concurrent nephropathy or thickened bladder wall (potential sequestered infection) for approximately four to six weeks. Recurrent infections require repeated courses, so repeated cultures are needed to check for antibacterial resistance.
In cases of bladder neoplasia, whenever possible surgically resect. Transitional cell carcinoma may be palliated with meloxicam: mean survival time 246 days (in some cases more than five years; Bommer et al, 2012). Gastrointestinal and nephro-toxicity are possible so monitor renal function before starting and during treatment.
• Meloxicam 0.05mg/ kg PO q24h long term.
• Bacterial cystitis responds favourably, unless underlying conditions cannot be addressed. FIC carries an increased risk of bacterial cystitis as the urothelium is poor at repelling bacterial colonisation, especially following iatrogenic intervention (Griffin and Gregory, 1992).
• Bladder stones that can be surgically removed or dissolved with diet, then prevented with diet, usually carry a reasonable prognosis; underlying hypercalcaemia (with oxalate stones) must be assessed and corrected.
• FIC without obstruction rarely proves fatal unless the owner feels the cat’s quality of life is so poor he or she opts for euthanasia.
• Neoplasia carries a guarded prognosis.
• Urinary obstruction carries a significant risk recurrence if management changes are not made. FIC-associated obstructions may recur in up to 60 per cent of cats in a year, with most occurring in the first seven days. In a study of cats with obstruction – due to FIC, plugs or stones – approximately 50 per cent continued to have cystitis, approximately 30 per cent to 40 per cent re-obstructed, and approximately 20 per cent were euthanised because of continued disease (Gerber et al, 2008). However, when appropriate treatment is instigated, these cats can be successfully managed in 85 per cent to 97 per cent of cases (Gunn-Moore and Shenoy, 2004; Buffington et al, 2006).
• Please note few of the drugs listed are licensed for this use in cats. Refer to the BSAVA Small Animal Formulary for more information about them and potential side effects.
The graph shows mean health scores at the start and end of a sixmonth double-blinded, placebo-controlled study. Forty cats with recurrent obstructive feline idiopathic cystitis were recruited, of which 20 received 125mg of N-acetyl glucosamine orally per day, while the other 20 received a placebo. The owners were asked to grade the severity of their cat’s signs using a scale from zero (very severe signs of cystitis) to five (normal cat). The error bars show the standard deviation. There is no statistical difference between the groups (Gunn-Moore and Shenoy, 2004).
Danièlle Gunn-Moore
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