Mirinda van Schoor BVSc(Hons); MMedVet(Med)
Bakenkop Animal Hospital, Centurion
The urinary bladder is responsible for storing urine until it is convenient and appropriate to void urine. Both urine storage and bladder emptying require normal functioning and interaction of the autonomic and somatic nervous systems. In addition, these two processes also require that the parts of the lower urinary tract (ureters, bladder, bladder sphincter, urethra) are intact and functioning normally. For an animal to consciously and voluntarily initiate voiding, the cerebrum, brainstem, lumbar and sacral spinal cord also need to be intact and functioning.
Urinary incontinence is defined as the loss of voluntary control over voiding. Rather than intentionally voiding urine and emptying the bladder, the patient suffers from intermittent or continuous dribbling of urine. Most animals are still able to voluntarily empty their bladder at appropriate times and in appropriate places but dribbling of urine occurs throughout the day and night in inappropriate places, especially when the animal is lying down or sleeping. Many pets are not aware of the fact that they are dribbling urine. The prevalence of urinary incontinence varies between 5-20%.
Urinary incontinence can result from a large number of neurogenic or non-neurogenic causes with non-neurogenic incontinence being the most common cause in small animal practice. Of all the non-neurogenic causes of urinary incontinence, primary urethral sphincter mechanism incompetence is the most common urinary storage disorder in dogs.
When a patient is presented with a complaint of urinary incontinence it is important to have a systematic approach during the diagnostic process. Information that needs to be collected includes the signalment, complete medical and surgical history, observation of the voiding process, a complete physical examination, a detailed neurological examination, palpation of the bladder, complete urine analysis with urine culture and antibiogram, haematology and serum chemistry if indicated, imaging of the urinary tract which may include radiography, ultrasonography, contrast studies (cystography and urethrography) and urethroscopy and cystoscopy.
When inappropriate urination is reported the clinician will need to distinguish between loss of voluntary control versus behavioural causes (submissive urination), urge incontinence, consciously urinating in inappropriate places or diseases resulting in polyuria and polydipsia such as chronic renal failure. The owner also needs to be questioned about the dog’s ability to voluntarily initiate a urine stream, the force of the urine stream, interruptions in the urine stream during urination, presence of haematuria and any pain the dog may be experiencing during urination. Perineal soiling and urine scalding needs to be investigated.
Physical examination may reveal an enlarged/overdistended bladder which is more commonly seen in cases with neurologic disease or partial urinary tract obstruction. In cases with non-neurogenic disease the bladder is usually normal sized or small at examination. Palpation of a fairly full bladder after voiding may indicate incomplete voiding and urine retention. Passing a urinary catheter may determine the possibility of a partial urinary tract obstruction.
Neurogenic causes include upper motor neuron diseases of the brain or spinal cord, lower motor neuron damage seen in trauma for example and reflex dyssynergia. A complete neurological examination will aid in diagnosing these causes. A rectal examination to assess anal tone may also be useful in determining neurologic diseases (lower motor neuron) as the cause of the incontinence.
Although the most common non-neurogenic cause is urethral sphincter mechanism incompetence (USMI), other non-neurogenic causes need to be investigated and excluded. These causes include urinary tract inflammation and infection (which results in urge incontinence), ectopic ureters, urethral diverticulum, pelvic bladder, post-prostatectomy incompetence in male dogs, ureterocoele and a few other less common causes. The rest of this paper will focus on the management of USMI and the reader is referred to other texts for detailed discussions on diagnostic procedures and management of other causes of inappropriate urination and urinary incontinence mentioned in this section.
Urethral sphincter mechanism incompetence (USMI)
As mentioned before, USMI is the most common cause of urinary incontinence in small animal practice (60% of urinary incontinence cases) and is most commonly seen in adult spayed female dogs.
Optimal functioning of the urethral sphincter depends on the smooth muscle of the urethra as well as tissues surrounding the urethra, the urethral submucosal vasculature, collagen content and the urothelium. Decreased tone and responsiveness of the muscle together with changes in the peri-urethral tissue results in sphincter failure. In female dogs these changes are associated with a reduction in oestrogen and oestrogen receptors and an increase in follicle-stimulating hormone and luteinizing hormone after being spayed. The condition was previously referred to as hormone responsive or oestrogen responsive incontinence, but with a better understanding of the complexity of the pathophysiology involved, this name has mostly been abandoned.
USMI generally occurs around from about 3 years after ovariohysterectomy in up to 20% of female dogs spayed between the first and second heat. Some authors report that dogs spayed before the first heat had a 9.7% incidence of USMI. Urethral closure pressure was shown to decrease within 12-18 months after spaying a bitch. In one study in dogs spayed before 3 months of age the risk of USMI appears to be increased, but other studies have failed to show any relationship to the age at which the dogs were spayed. Dogs showing signs of incontinence since birth or since acquiring the puppy shortly after weaning should be examined for congenital deformities such as ectopic ureters.
A recent study investigated the relationship of age at spaying and the projected adult weight of the dogs. This study found that dogs weighing more than 25 kg adult weight were more likely to develop USMI if they were spayed at a younger age. It is possible that the impact of decreasing oestrogen may have less of an effect on developed adult tissues compared to developing tissues.
Several breeds seem to be predisposed to USMI and the incidence in large breed dogs weighing more than 20 kg is reported to be up to 30%. Doberman Pinchers, Giant Schnauzers, Old English Sheep Dogs, Rottweilers, Weimeraners and Boxers are some of the breeds that seem to be overrepresented. Female dogs of predisposed breeds may benefit from delaying time of spaying and thus decrease the risk of USMI. The same tendency was not seen in small breed dogs and therefor timing of spaying can still be based on potential benefits such as decreased risk of mammary neoplasia with early spaying.
Previously body condition score (BCS) was thought to be associated with development of USMI with obese dogs supposedly being predisposed to UMSI. The latest study did not confirm this relationship, but the authors commented that assessment of BCS is not standardized and future studies need to consider using more accurate and standardized evaluation methods before any concrete conclusions can be made regarding the role of obesity.
Conformational predisposing factors may also increase the risk of PSMI. These include pelvic bladder, short urethra and recessed/juvenile vulva. Dogs with USMI usually have adequate bladder capacity and are able to empty the bladder normally. Incontinence in these cases occur due to increased pressure intra-abdominally. This occurs for example when an animal lies down, especially when it is relaxed, or when pressure increases due to barking or coughing or after exertion.
The reasons for incontinence in male dogs is poorly understood, but a decrease in testosterone leading to an increase in follicle-stimulating hormone and luteinizing hormone may play a role.
In a clinically healthy spayed female dog that was urinary continent before being spayed and has a normal result on complete urine analysis, a presumptive diagnosis of USMI is justified. In all other cases a more intensive investigation is warranted.
Medical treatment of USMI
Medical management of USMI is usually considered the first line of treatment, but some clinicians prefer surgical options and in cases that do not respond to medical management surgical options should be considered. The aim of medical management is to either increase the sensitivity of alpha-receptors, increase the number of alpha-receptors in the urethral sphincter or both.
Many clinicians consider phenylpropanolamine (PPA) to be the first choice in the treatment of USMI. PPA is an alpha-adrenergic agonist which is associated with treatment success rates of 75-90%. The dosage for individual animals may vary quite widely but starting doses of 1.0-1.5 mg/kg per os every 8-12 hours appears to be effective in most cases. Over time the response to treatment may decrease and increases in dosage may be required. A 2011 study showed that once daily dosing may be adequate. A single daily dose of 1.5 mg/kg was successful in controlling incontinence in 88.9% of clinical cases in this study. It was shown in healthy beagles that PPA reached therapeutic levels 2 hours after a single dose and then progressively decreased to baseline by 24 hours. Despite higher plasma levels of PPA with more frequent dosage, urethral pressure profiles were not significantly different. The reasons for clinical efficacy is not clearly understood, but it may be possible that certain individuals can be managed with once daily dosing which is more convenient and cost effective for owners.
In South Africa PPA can be used in the form of a cold and flu mixture sold as Rinex®. Rinex® contains phenylpropanolamine hydrochloride, chlorpheniramine maleate (an antihistamine) and phenylephrine hydrochloride (another alpha-adrenergic agonist). The drug is available in capsules (30mg PPA per capsule), syrup (1mg PPA per ml) and paediatric syrup (0.5 mg/ml). Most patients have some kind of response to this drug. The dosage may need to be increased over time as the drug does seem to become less effective over time. Side effects may include restlessness, hypertension, aggressiveness, changes in sleeping patterns and gastrointestinal side effects. These can usually be limited by decreasing the dose.
Contraindications for the use of PPA include pre-existing cardiac disease, chronic kidney disease, protein losing nephropathy, hyperthyroidism and hypertension. Although hypertension does not seem to develop to a clinically significant degree in dogs receiving PPA it is recommended that blood pressure is monitored regularly. In many cases PPA is combined with oestrogen drugs and there seems to be a synergistic effect when these two drugs are used together.
PPA is also usually prescribed in incontinent male dogs. Some clinicians combine PPA with testosterone, but efficacy of this approach has not been well documented. Approximately 43% of male dogs are responsive to PPA, much lower than what is seen in female dogs.
This drug is an alpha-adrenergic agonist which is used to treat hypotension. It is usually used as a constant rate infusion to improve peripheral vascular resistance and increase mean arterial pressure. The drug is compounded and sold as an oral solution to treat USMI in incontinent dogs. In South Africa it is compounded by Kyron laboratories as a syrup which contains 20 mg/ml. The recommended dose is 1.2 mg/kg three times daily. As with PPA, it is contraindicated in cases with cardiac disease, renal disease or hypertension. It is advisable to monitor blood pressure regularly.
Oestrogens can be administered less frequently than PPA which may be more convenient for most owners. However, with some formulations response rate is lower than with PPA and only 60-65% of patients respond to treatment with diethylstilboesterol. For the newer oestriol formulation a response rate of up to 80% or higher was reported.
Oestrogens increase the sensitivity of the urethral alpha-adrenergic receptors to catecholamines and possibly also increase the number of alpha-adrenergic receptors. Diethylstilboesterol (DES) and oestriol are the most commonly used oestrogens.
Side effects of oestrogen therapy could include signs of oestrus such as mammary gland enlargement, vulvar swelling and attractiveness to intact males; perineal alopecia and bone marrow suppression. In most cases bone marrow suppression is not a clinically significant complication unless dosages of around 10 times the recommended doses are used and it is not listed as a side effect for oestriol. It is recommended that as a precaution a complete blood count should be performed prior to treatment and repeated a month after initiating treatment and again at 3 months and 5 months. Its use is contraindicated in intact female dogs and the drug should be used with extreme caution in male dogs as it could result in prostatic metaplasia.
DES is compounded by compounding pharmacies such as V-Tech. DES is dosed at 0.1-1 mg (0.02 mg/kg) per dog perios for 3-5 days and then every 3-7 days depending on the response. Once a week dosing may be more convenient for some owners. After two months the dosing frequency can be decreased to once every 10 days, and in some cases even to every 14 days. The formulations available from V-Tech in South Africa include 30 mg capsules and a syrup which contains 1mg/ml.
Oestriol (Incurin®) is a naturally occurring short acting oestrogen which is registered for use in dogs. Each tablet contains 1 mg oestriol. It is dosed at 1 tablet per dog per day for 1-2 weeks after which the dose is reduced to the lowest controlling/effective daily dose, usually ½ tablet per dog per day. After this stage, alternate day dosing can be implemented. Dose is not related to body weight and needs to be adjusted for the individual animal. In cases that do not respond to 1 tablet per day the dose can be doubled to 2 tablets per dog per day. If this regimen still has no effect on the incontinence the diagnosis should be reconsidered and a more intensive diagnostic approach should be taken.
Premarin® tablets (0.3 mg, 0.625 mg, 1.25 mg) is a preparation used in postmenopausal women. It is derived from pregnant mare urine and contains conjugated oestrogens which are converted to oestradiol. This drug can be dosed at 20µg/kg per os every 3 or 4 days.
Testosterone injections have anecdotally been reported to improve incontinence in male dogs. It is given at 1.5 mg/kg every 4 weeks. The exact mechanisms which result in an effect are unclear, but could involve increased urethral smooth muscle tone, improved tone in urethral supporting structures and increased prostatic urethral resistance. It is reported to be less effective than PPA. Potential side effects in male dogs include development of perianal adenomas and prostatic enlargement. The use of testosterone in female dogs cannot be recommended as its use may lead to clitoral hypertrophy, masculinisation and aggression. It is also contraindicated in dogs with renal disease, cardiac disease and hepatic insufficiency.
Gonadotropin releasing hormones
Although not often recommended and not commonly used, gonadotropin releasing hormone (GnRH) analogues may be effective in some cases of USMI. GnRH analogues decrease follicle stimulating hormone (FSH) and luteinizing hormone (LH) by down regulating gonadotropin receptors in the pituitary gland. Because spaying causes a decrease in oestrogens and a subsequent increase in FSH and LH, GnRH may have a role to play in the management of post ovariohysterectomy USMI. This medication will need further investigation as analysis to date showed that FSH and LH in spayed incontinent dogs were actually lower than FSH and LH in spayed continent dogs. GnRH analogues had no effect on maximum urethral closing pressure and urethral pressure profiles compared to PPA and oestrogens.
In a small group of dogs, a response rate of (7/11 dogs) 60% was seen when using leuprolide. The fact that a response is seen clinically when using the drug lead to the speculation than GnRH may have a direct effect on the bladder which causes detrusor muscle relaxation. The GnRH analogue, leuprolide (Lupron®) can be used at 5-10 mg intramuscularly every 3 months. This drug may be useful in cases where oetrogens and PPA are contraindicated.
Imipramine (Tofranil®) is a norepinephrine reuptake inhibitor and potential anticholinergic. It is available in 10 mg, 25 mg and 50 mg tablets. It indirectly increases alpha-receptor stimulation in urethral smooth muscle and may lead to an increase in bladder relaxation. It is dosed at 5-15 mg/dog ( ½ to 1 ½ of the 10mg tablets) per os every 12 hours. It is not commonly used in the treatment of PSMI. Side effects include vomiting, diarrhoea, hyperexcitability, seizures and sedation. It decreases the seizure threshold and should not be used in epileptic animals.
Interventional procedures for USMI
A complete discussion on these procedures are beyond the scope of this text as this paper describes the medical management of USMI. However, it is worth mentioning the surgical options available for patients in South Africa. Various surgical specialists can be contacted regarding these procedures should a patient require surgical intervention.
This procedure involves the injection of bulking agents such as bovine crosslinked collagen submucosally into the proximal urethra during cystoscopy. By bulking up the tissues an increase in resting urethral pressure is achieved. There is a variable response rate (50-80%) and duration of effect with response periods varying from 8 months to 2 years. This procedure can be combined with medical management and renders PPA more effective.
See the article on Surgical Procedures for Urethral Sphincter Mechanism Incompetence in Bitches on page 30-34 in this edition
References on www.vetlink.vet360.co.za