No Pee? No Panic! Review of Lower Urinary Tract Disease in Cats Rachel Halpin, DVM, DACVECC

Home , Acepromazine

5% of all cats suffer from lower urinary disease

Almost 100 million cats in US

5 million cats with LUTS

Feline interstitial Young Cats cystitis LUTS Bladder Stones Lower Urinary Tract Signs

Urinary Tract Infection Urethral Old Cats Obstruction

OTHER – Neoplasia, Polyps, etc

10% 3% Other

UTI 20% FIC Stones 67%

Also known as “Bladder Pain Syndrome”

Increased urgency, frequency, and pain when urinating without any known cause, such as an infection

• Complex condition • “Pandora’s Syndrome” • Anxiopathy

Due to activation of the Central Threat Response System (CTRS) within the CNS

Why is there an association between “stressful” events and episodes of urinary signs?

Stress Epinephrine Disease affecting Mast Permeability Pain the bladder, not a Cells disease of the bladder

• The bladder wall is lined with glycosaminoglycans (GAGs) to protect the bladder wall from the irritating effects of urine • Defective in FIC • Allows irritation of the wall • Highly innervated organ • Responsive to increased release of catecholamines

Living in Using non- Living with No access to apartment clumping litter other cats vantage point 2.5x 2.5x 3x 4.6x

• Highly concentrated urine • Higher mineral content • Increased propensity for crystal formation • Increased mucous formation • Urethral spasm

Urinalysis (+/- culture) Abdominal x-rays Ultrasound

“Bladder Sweat”

• Actually common • 33% of UO (JVECC 2020) • None were urine • Scant to mild

Cooper, et. Al JVECC 2020

Chronic lower Acute onset urinary signs – lower urinary Feline Interstitial tract signs Cystitis

Non-obstructive Obstructive

Analgesia Anti-spasmodic Other

• Buprenorphine • Prazosin • Diet modification? • Robenacoxib • Acepromazine • Environmental? (Onsior®) • Phenoxybenzamine

Initial stabilization

Unblocking

Inpatient treatment

Outpatient treatment

Initial Stabilization Within the first hour

Place IV catheter

Administer analgesic

IV fluid therapy

There’s only one way to get potassium out of the body

The kidneys filter excess potassium into urine

If urinary obstruction, can’t excrete potassium – build up in the blood

Why do we give all those other drugs?

Copyright © 2020 Care Center. All rights reserved. • Insulin • Exogenous administration – ¼ unit per kg IV • MUST follow with dextrose • Monitor BG x 6 – 12 hours • Endogenous administration – 1 mL per kg 50% Managing dextrose • Albuterol Intracellular • 1-2 puffs per cat Shifting of • Reserved for dire emergencies Potassium • Risk of increasing heart rate/contractility • Bicarbonate • 1–2 mEq/kg IV over 15–20 min • Now things are getting crazy

K+

If hypotensive, repeat bolus until BP >90 (up to 4)

Follow with high fluid rate to account for post-obstructive diuresis

Trying to get that liquid gold General Procedure

• Sedate • Clip & prep area around prepuce • Extrude penis • Digital manipulation • Placement of a urinary catheter • Flushing as it is passed to relieve the obstruction • Obtain sample for urinalysis

Stabilization Procedure • Clippers • Sterile gloves • Scrub solution • Sterile lubricant • IV catheter • Scrub solution • IV fluids • 6mL empty syringe • Multiple 20mL syringes with saline • Calcium gluconate • Urinary catheter(s) • Dextrose/insulin • Tape/Suture • Collection system • Used IV fluid bag • IV drip set • Sedation

• Semi-rigid polypropelene Closed: No hole at the end, fenestrations further down. Less traumatic, difficult if distal obstruction • Inexpensive • Excellent for relieving obstructions • Most traumatic due to rigidity and fenestrations • Urethral tear • Uncomfortable & irritating if used as indwelling catheter

• Soft & pliable • Inexpensive • Atraumatic • Ideal for indwelling catheter • Requires butterfly tape & suture to secure • 3.5 vs 5 French

• Slippery Sam® • Made from Goretex® • Also used to make fabric-like mesh that is a conduit for vascular and skin grafts • Soft, pliable but more firm than red rubber • Built-in area for securing • Most expensive option • Mila® • Softest option (except Foley) • Difficult to place due to flexibility • Guidewire • Built-in area for securing • 18g IV catheter (without stylet) • Foley

• Numerous options • Choose cardio sparing medications • Combinations • Buprenorphine + Benzodiazepine + Ketamine • Buprenorphine + Midazolam + Propofol / Alfaxalone • Others?

• FLOW-BY OXYGEN • ECG monitoring

• Provides analgesia and relaxation x 1 hour • Can help with difficult unblocking, spasm

Injection site: between sacrum and first coccygeal vertebra

• 0.1 mL/kg lidocaine or bupivacaine – preservative-free, sterile • 25g needle on midline at 45° angle to the skin surface • If encounter bone, back-up & adjust angle • Once enters space, may feel “pop” • No resistance to injection • Should see local relaxation within 5 mins – if not, injection may have been SQ

Copyright © 2020 Care Center. All rights reserved. Inpatient Treatment Every cat’s dream Inpatient Treatment Does length of hospitalization affect • Hospitalize for 36 – 48 hours recurrence? • Analgesia - buprenorphine • Anti-spasmodics • Acepromazine • Prazosin • Phenoxybenzamine • IV fluids • Very high doses may be necessary • Replace dehydration • Keep up with post-obstructive diuresis (POD) • Antibiotics?

• May prevent urethral spasm • Acepromazine • Cheap • Sedation • Hypotension • Prazosin • Less risk of hypotension • No sedation • Dose 0.5mg PO q12 (per cat) • Decreased recurrence in retrospective but failed to prove in prospective study • Phenoxybenzamine • Expensive • No benefit over prazosin

• Infections are exceedingly rare • Bacteriuria reported 0 – 20% • Bacteriuria from catheter samples does not indicate infection • Ripe for contamination! • Is pyuria present? • Recent study – • 0% urine cultures positive for growth obtained via cystocentesis • 6% bacteriuria present on urinalysis • 13% developed positive culture within 24 hours • What does a positive culture tell us? • May not represent true urinary colonization

• Initiation while catheter in place will not prevent infection • May select for resistant bacteria • Indications for use • Pyuria + leukocytosis/leukopenia • Comorbidity • Always submit culture if starting antibiotics • Possible UTI? • Obtain urine via cystocentesis 2 – 5 days following discharge

• Closed collection system • Aspirate urine every 4 hours • Weigh bag every 4 hours • 1 gram = 1 mL • Change in weight in 4 hours = amount of urine produced

0 hours 4 hours 8 hours

Bag weight 45 g 245 g 495 g

Urine produced 0 mL 200 mL 250 mL

• Hydrostatic damage to the tubules causes impaired resorption • Build-up of urea results in osmotic diuresis • Results in MASSIVE urine production • Anecdotally 10 – 15 ml/kg/hr • Resolves in 24 – 48 hours • Expect high urine output – if not could be problem

• Used to monitor fluid rate and kidney function • Ensure adequate fluid therapy for diuresis • If inadequate fluids are administered, progressive dehydration and/or hypovolemia will develop

• Persistent dehydration Urine output LESS • Urinary catheter dysfunction than IV Fluid in • Declining renal function, relative oliguria

• Diuresis Urine output MORE • Polyuria than IV Fluid in • Renal Disease • Medullary washout

Copyright © 2020 Care Center. All rights reserved. Increase Fluid Rate Urine • Persistent dehydration • Urinary catheter Check output LESS dysfunction Weight than IV • Declining renal function, Fluid in relative oliguria Decrease Fluid Rate Urine • Diuresis output • Polyuria • Renal Disease MORE than • Medullary washout IV Fluid in

Sedated unblocking & discharge

• 30% will return with obstruction within 24 hours of unblocking • Not advised if severe dehydration or azotemia

Decompressive cystocentesis

• 10-20% develop uroabdomen • Many are severe, but mild self-limiting leakage can occur • Not recommended for routine treatment • Option for clients with financial constraints

• Sedate with acepromazine and buprenorphine • Single cystocentesis • 22G 1½" needle, extension set, 3-way stopcock • Empty the bladder as much as possible • Place the needle into the bladder at a 45⁰ angle near the neck of the bladder • Prevents the bladder shrinking off of the needle

VCNA Small Animal Practice. 29; 270, 1999

Hospitalize in Repeat sedation Decompressive quiet/dark area SQ Fluids and cystocentesis Cystocentesis away from dogs x as needed 2-3 days

Place 3.5fr Successful in 73% of cats indwelling 14% recurrence within 3 days catheter 27% of cats were euthanized

Decompressive 73% Prognosis success cystocentesis & hospitalization

95+% Inpatient hospitalization success with urinary catheter

Though good initially, high risk of recurrence

11% within 24 hours 24% within 1 month 58% in 6 months

1st offense: “This is a chronic condition, with up to 50% of cats experiencing recurrence within 6 months. In severe cases, there is a surgery that can be performed to prevent further episodes” 2nd offense: “There is a surgery that can be performed to prevent this again – not a procedure that is taken lightly, associated with risks, but if this continues, benefit may supersede risk. 3rd offense: Recommend PU 4th offense: Beg for PU

• High complication rates • 25% recurrent urinary tract infections • 5% urine scald / local irritation • Excellent owner satisfaction in 80% of cats

• MEMO • Environment • Enrichment • Litter Boxes • Diet & Feeding • Minimizing threats

• Drug therapy • Should be considered in conjunction with MEMO especially for cats that are refractory • Behavioral modification • GAGs • Pheromones

• Provide bedding in quiet, safe spaces • Warming pads (85-100°) • Ability to climb • Allows escape from other animals • Provides vantage point • Keep carrier in cat’s safe space • Open with comfortable bedding • Ideal “hiding place” • Prevents negative association with carrier

• Perching areas • Cat tree • Windows • Scratching Posts • Routine social interaction with owner • Access to toys • Most cats prefer to play vs be pet • “Ask the cat”

• 1 per cat + 1 extra • Different locations • Quiet areas • Avoid locations where the cat may be frightened • Near vents/appliances that automatically turn on • Areas other animals have access to • Heavily trafficked areas

• Prefer unscented clumping litter • Box should be at least 1 ½ - 2x the length of cat • Deep litter • Uncovered boxes • Scoop 1-2 times daily • Clean box every 1-2 weeks • “Ask the cat”

• Decreased recurrent LUTS • 30% LUTS on diet vs 80% on control • Canned may be superior • AAFCO approved • Variety • Different foods • Variable locations and containers • Generally prefer to eat alone in quiet, safe place • Natural hunters – hide food, puzzles • Weight loss • Add new food instead of replacing – ask the cat!

• Unique preferences regarding water • Freshness • Taste • Temperature • Movement – running water • Shape of container • Dislike whiskers hitting container • Dishes cleaned regularly

Copyright © 2020 Care Center. All rights reserved. • Most inter-cat conflict is “silent” • Conflict develops around social maturity, even if cats had been together since kittens Minimizing Threats • Outdoor cats can be threatening if visible or can be smelled by indoor cats • First: Identify there is a problem

Assertive Cat Threatened Cat

Doesn’t back away from other cats Spends majority of time alone or hiding

Stares at other cats Avoids eye contact with other cats

Denies access to resources for other cats Yields resources to other cats

Rub cheeks, head, chin and tail and people at “cat height”

When sees the threatened cat: lowers its When sees the assertive cat: head and neck while elevating hind end – Crouches, may cower, then flee. Does not stalking – growls, may spray vocalize, may spray

• Generally caused by competition for resources • Provide separate set of resources • Provide refuge area for threatened cat • Keep nails trimmed • Provide elevated areas • Adds space to smaller areas • Especially good if conflict is with dogs or kids

• Tricyclic Antidepressants • Have not been compared to MEMO • If MEMO alone insufficient • Consider amitriptyline, fluoxetine, or clomipramine • Generally 2 weeks before effective • Ideal for chronic treatment, not flare-ups • Benzodiazepines • Alprazolam x 2 weeks following UO • Neutraceuticals • Zylkene: contains a natural ingredient from cow’s milk with calming properties • Skeptical data • Unlikely to be harmful

• Proposed benefit given damaged layer noted in cats with FIC

• Two major studies 1. Compared oral glucosamine to placebo – No difference in incidence of LUTS, but strong placebo effect 2. Injectable pentosan polysulfate vs placebo - No difference

• Fatty acids that transmit highly specific information between animals of the same species • Feliway®: synthetic analogue of feline pheromone • Trend towards less LUTS episodes • Decreased negative behavioral traits • Increased grooming and food intake in hospital

• Very impactful to the human-animal bond • Complex set of conditions causing lower urinary signs in cats • Can range from chronic outpatient care to acute life-threatening emergency • Effective treatment options available • High cost & commitment • Recurrence is very common • Long-term care involves holistic approach

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Copyright © 2020 Care Center. All rights reserved. • Hetrick PF, Davidow EB. J Am Vet Med Assoc. 2013.8 This large study evaluated 192 cats with UO. Recurrence occurred in almost 11% of cats at 24 hours, and 24% at one month. Cats treated with prazosin (0.5 mg/cat) had recurrence far less often than cats treated with phenoxybenzamine. Cats with a 3.5-Fr catheter were less likely to re-obstruct than cats with a 5-Fr catheter. There was no association between rUO and duration of urinary catheterization, administration of antimicrobials or meloxicam, or consistent administration of pain medication during indwelling catheterization. • Eisenberg BW, et al. J Am Vet Med Assoc. 2013.9 This prospective study in 83 cats suggested that longer duration of catheterization (26.5 versus 24.5 average hours) might decrease risk of re- obstruction at 30 days. Catheter size (3.5 versus 5 Fr) was not a risk factor for re-obstruction in this study. • Dorsey TI, et al. J Am Vet Med Assoc. 2019.10 Male cats with urethral obstruction were randomly assigned to flush only to place the catheter (68 cats) or flush until clear (69 cats). There was no difference in the in hospital UO recurrence rate, catheter time or hospitalization time between the groups. • Reineke EL, et al. J Vet Emerg Crit Care. 2017.11 This prospective double-blind study evaluated the effect of prazosin on recurrence. Forty-seven cats were randomized to receive either placebo or prazosin. There was no in-hospital benefit detected to prazosin therapy, nor at 1 or 6 months. Side effects associated with prazosin administration included lethargy, ptyalism, diarrhea, anorexia, and malodorous stool. Prazosin was given at a dosage of 0.25 mg/cat in this study. • Dorsch et al. J Feline Med and Surgery. 2016.12 Following routine supportive care and un-obstruction, all 37 cats received buprenorphine and in-dwelling urinary catheter for 48 hours. Eighteen cats received meloxicam, and 19 cats received placebo for 5 days. There was no difference in the rate of re-obstruction, or any other parameter in treated cats compared to placebo- treated cats. • Seitz M, et al. J Am Vet Med Assoc. 2018.1 This study compared the risk of re-obstruction (rUO) within 30 days in 46 cats hospitalized with a urinary catheter and 45 cats catharized and then sent home. Incidence of rUO was 10.87% in the inpatient group and 31.1% in the outpatient group. Cats with indwelling catheters who had abnormal appearance to urine when catheter removed were more likely to re-obstruct. • Cooper ES, et al. J Am Vet Med Assoc. 2010.2 Financial limitations are common in owners of cats with UO. This study looked at 15 cats where standard therapy had been declined. Cats that were life-threatening ill were excluded as were those with stones. Cats were treated with acepromazine, medetomidine, and buprenorphine as well as decompressive cystocentesis and subcutaneous fluids. Treatment success was defined as spontaneous urination within 72 hours. Treatment was considered successful in 11/15 cats, and this protocol was suggested as potentially amenable for outpatient cases. However, 3 cats developed a uroabdomen and 1 cat developed a hemoabdomen during this treatment protocol. • Hall J, et al. 2015.3 There is occasionally debate if decompressive cystocentesis is useful or risky in cats with UO. Forty-seven cats were evaluated. All cats were treated with decompressive cystocentesis. No cats developed urinary bladder rupture. Otherwise, outcomes were similar to those previously reported. These results support the use of decompressive cystocentesis. • Reinke EL, et al. IVECCS. 2017.4 This prospective study is examining decompressive cystocentesis before placement of a urethral catheter. In 69 cats so far, there were no complications but also no reported changes in ease of catheterization or time to place a urinary catheter. • Galluzzi F, et al. J Small Anim Pract. 2012.5 The goal of this study was to determine if adding intra-urethral atracurium helped decrease the time to unblock cats. Forty-five cats were enrolled and randomized to treatment with atracurium or no atracurium. Treated cats were more likely to have the plug removed at the first attempt and to have a catheter placed more quickly. Atracurium should be considered in UO cats. There was no evidence of systemic side effects. • O’Hearn AK, et al. J Vet Emerg Crit Care; 2011.6 This article reported a procedure for providing local anesthesia during unblocking. • Pratt C, et al. IVECCS. 2015.7 In this double-blinded, prospective, interventional study, 88 cats were divided into 3 groups (sham, bupivacaine, and morphine-bupivacaine). The cats receiving an epidural required less sedation during unblocking and had a longer time until needing further analgesia. • Beer KS, Drobatz KJ. J Vet Emerg Crit Care. 2016.18 While it is common for urine from cats with urethral obstruction to be bloody, this manuscript described 17 cats that received blood transfusions for during treatment for urethral obstruction due to severity of urinary blood loss. Cats that required blood transfusions had a longer duration of clinical signs prior to presentation and were more likely to have had a prior episode of UO. Additionally, they more commonly had a gallop and/or murmur detected. Four of 17 cats were euthanized, in comparison to zero cats in a control group of 30 cats. While severe hemorrhage is uncommon, it may occur and will require closely monitoring and may result in a higher rate of euthanasia. Evidence Predicting Recurrence

JAVMA 2018 – Increased risk of recurrence if urine hadn’t cleared JVECC 2017 – No difference with prazosin (underpowered) JFMS 206 – meloxicam vs placebo, no difference JAVMA October 2013 – Longer catheterization decreased recurrence (24h vs 26h) JAVMA August 2013 – Prazosin decreased compared to phenoxybenzamine, decreased recurrence @ 24 hours with 3.5 fr JVIM 2012 – intravesicular application of lidocaine and bicarbonate did not decrease recurrence