Urge Incontinence

Etiology

The etiologies of urge incontinence often involve the detrusor muscle of the urinary bladder, which is the specialized smooth muscle in the bladder wall. These include detrusor muscle overactivity, poor compliance with the detrusor, and bladder hypersensitivity.

Detrusor Overactivity

Detrusor overactivity is believed to be the uninhibited (involuntary) contractions of the smooth muscle during bladder filling. Significant causes leading to this overactivity could be neurologic disorders (spinal cord injury), abnormalities in the urinary bladder, and an increase or alteration in the bladder microbiome.[4][5][6] This may also be completely idiopathic.[7]

Poor Detrusor Compliance

Poor detrusor compliance results in the failure of the bladder to stretch and thereby increase intravesicular pressure. It also involves discomfort during filling and limited capacity. Pelvic radiotherapy or prolonged periods of catheterization can often lead to this.

Bladder Hypersensitivity 

Bladder hypersensitivity and the sensory role of the urothelium are believed to be intertwined. It has recently been established that as the urothelium acts as a pivotal mediator of bladder function, the role of urothelial inflammation and infection can lead to an overactive bladder with or without urgency.[8] Here again, the balance of urinary microbiota can alter bladder function and sensation and, perhaps, lead to urgent incontinence.[9]

Epidemiology

The prevalence of urinary incontinence of any kind varies mainly with age and obesity. Other factors found to be associated with urinary incontinence of different subtypes include previous hysterectomy or pelvic surgery, parity, pulmonary disease, diabetes mellitus, dementia, or residing in a nursing home.[10][11][12][13]

The data regarding the true prevalence of different types of urinary incontinences vary widely depending on the population studied, the social stigma and lack of interest to self-report (respondent bias in observational studies), and also on the case definitions in the questionnaires used.[2] This is probably the reason why, in many epidemiological studies from earlier dates, there had been no differentiation between urge and stress urinary incontinence.

Accurate prevalence measurement for urinary incontinence via robust epidemiological studies and validated measures tend to exist more in the United States, and some developed European and Asian countries rather than in the developing world. Even then, the reported prevalence for any subtype of urinary incontinence in adult women is of a broad range (5%-72%), with an approximate convergence of 30% according to different studies).

Overall, the association between age and urinary incontinence is well established. When the whole population is considered as one, most studies pick either mixed or urge incontinence as less prevalent than stress incontinence.[12] Observational data from 4 European countries, as well as median prevalence data from a review of epidemiological studies from around the world, have revealed similar trends. Unlike stress incontinence, which reaches a peak mostly around the fifth decade of a patient's life and then shows a decline, both urge and mixed incontinence continue to increase in prevalence with increasing age.[10][14] The association of age with incontinence also prevails in men, but severe incontinence in elderly males is often half the number of that in women.[10][15]

When considering the prevalence of urge incontinence, specifically among women and men, a slightly different picture is depicted. Studies have shown that stress incontinence is of high prevalence among postmenopausal women, whereas urge incontinence may have a somewhat lower prevalence. Even then, it is this second type of incontinence that is often extraordinarily bothersome and is more likely to require treatment.[15] The prevalence of any subtype of urinary incontinence (3%-11%) in all ages of men is considered much lower than that for women. Interestingly, urge incontinence is often the predominant subtype among 40% to 80% of those within the male population.[16]

History and Physical

The care for any urinary incontinence almost always begins at a primary clinician's office. The presentation of incontinence symptoms can often be late due to the unwillingness of the patient population to report it. Therefore, the primary clinician should conduct a thorough and empathetic history-taking. History should include a discussion about the patient's typical voiding pattern, onset, and duration of incontinence symptoms, whether or not the patient is bothered by symptoms, and any associated factors that can affect incontinence (ie, amount and type of daily fluid intake and bladder irritants such as caffeine, carbonated beverages, artificial sweeteners, alcohol, etc). Most histories should also focus on triggering factors or events of urinary incontinence (eg, feeling of urgency, cough, sneezing, feeling of running water, lifting, bending, sexual activity, movement, changes in position), constant or intermittent leakage of urine, coexisting medical condition (such as diabetes mellitus, diabetes insipidus, urogynecological cancer, cardiorespiratory diseases, chronic cough, dementia, delirium, presence of a urinary tract infection, obesity and sleep apnea). 

Other factors requiring assessment should include urinary frequency (>7 micturition episodes in a day), urgency, pain with a full bladder, obstetric history (number and mode of deliveries), gynecological history (history of pelvic organ prolapse, anal incompetence, menopause, sexual dysfunction), any previous pelvic surgery (incontinence procedures, pelvic floor reconstruction, and hysterectomy), history of surgery of the central nervous system or spinal surgeries.[17] 

Clinicians should also do a thorough review of any current medicines that can exacerbate or lead to incontinence symptoms, eg, alpha-adrenergic agonists and antagonists, angiotensin-converting enzyme (ACE) inhibitors, anticholinergic drugs, calcium channel blockers, cholinesterase inhibitors (increases bladder contractility and can cause urgency incontinence), diuretics, lithium, psychotropic medications, sedatives, hypnotics, selective serotonin reuptake inhibitors (the increased cholinergic activity can lead to urge incontinence) and lastly opioid analgesics.[8]

It is well-validated that sometimes, symptom presentation is not enough to guide patient care for a specific type of urinary incontinence. A focused physical examination, therefore, should include pelvic and genitourinary examination as well as neurological, gait, mental status, and body mass index (BMI) assessment, all of which can be started in the primary care setting. An abdominal examination can reveal information regarding any costovertebral angle tenderness, pelvic masses, and palpable bladder. A positive Valsalva maneuver for more than 6 seconds might reveal evidence of pelvic organ prolapse. A digital examination of the pelvic floor discloses information regarding the tone and strength of the pelvic floor. Additionally, a speculum exam might reveal vaginal atrophy, incontinence-associated dermatitis, and extra-urethral urine loss or fistula.[8] 

Neurological examination should include details of mental status, perineal reflexes and sensation, patellar reflexes, gait, and a mobility assessment.[18] A postvoid residual gives valuable insight into bladder emptying in patients with obstructive symptoms or neurological diseases but should only be performed with ultrasonography for better accuracy and less invasiveness.[17][19] Congestive heart failure should also be ruled out with a cardiovascular examination in case of any lower extremity edema.[18]

While it is challenging to not have a single test to diagnose urge incontinence, other simple office-based examinations can aid in ruling out different types and pathophysiology of incontinence. A positive cough stress test (observation of immediate leakage of urine with cough when a bladder has at least 200 mL of urine) has excellent sensitivity and specificity for stress incontinence, especially in a standing position. A cotton swab test can be used to evaluate urethral hypermobility. Here, a cotton swab is inserted through a lubricated urethra up to the neck of the bladder, and the test is considered positive if the cotton swab angle changes greater than 30 degrees from the resting position with the Valsalva maneuver.[19]

Evaluation

The evaluation for urge incontinence of urine can be performed with a series of sequential steps. The first step should always involve a thorough history and physical examination. At this stage, some validated questionnaires can also be used. Commonly used questionnaires to quantify the amount of bother and bladder symptoms include the short-form Pelvic Floor Distress Inventory and the short-form Pelvic Floor Impact Questionnaire.[20] These questionnaires evaluate bladder symptoms, pelvic organ prolapse symptoms, and any bowel symptoms. Although the Pelvic Floor Distress Inventory weighs the measure of severity, the Pelvic Floor Impact Questionnaire assesses the impact of these symptoms on a person's social functioning and activities of daily living. Other questionnaires that are recommended by The International Consultations on Incontinence are the Urogenital Distress Inventory (UDI), King's Health Questionnaire, Urge UDI, etc.[21]

The second step can include urine analysis with microscopy and, if needed, culture to rule out any hematuria, glycosuria, and urinary tract infection (UTI). At this time, office-based examinations like a cough stress test, cotton swab test, post-void residue, and voiding diary can be utilized. A voiding diary can clarify fluid intake, symptoms, and situations in which the incontinence symptoms occur.[22]

Anytime during these steps, assessment should also aim to rule out reversible causes. Decisions should also be made when to refer to a urologist or urogynecologist. The reversible causes can be memorized with the mnemonic DIPPERS (delirium, infection, pharmaceutical, psychological morbidity, excess fluid intake, restricted mobility, and stool impaction). If present, any of these conditions need treatment and reassessment. Referral to a specialist should be considered if there is bladder pain, advanced urological prolapse, fistula, neurological symptoms, urogenital malignancy, urogenital surgery, recurrent UTI, sterile pyuria, hematuria, post-void residual volume of more than 50 mL, and insensible loss of urine.[8]

The third step is to try to decide the presumed type of urinary incontinence from the information gathered. Points in favor of urge incontinence include symptoms of urgency, typical frequency, and nocturia, no incontinence with cough, sneezing, lifting, position change, variable volume loss on the voiding diary, negative cough stress test, and postvoid residual volume of less than 50 mL.

The final step involves the utilization of urodynamic studies. These studies can acquire valuable information about the relationship between pressure and flow between the urethra and the bladder. They also often provide ample details on lower urinary tract function. Even though these studies are outside the scope of primary clinicians' offices, they can be crucial to achieving a correct diagnosis of mixed and urge incontinence.[23] Indications for these urodynamic studies are:

• Significant inconsistencies between symptom scale, history, and voiding diary
• Planned or previous surgery
• Hematuria
• The presence of neurological diagnoses such as multiple sclerosis
• Associated prolapse of pelvic organs
• Previous history of correction surgery for incontinence
• Elevated volume of post-void residual urine.
• Well-known components of urodynamic studies include:
  • Uroflowmetry
  • Cytometry
  • Postvoid residual urine volume
  • Urethral pressure profiles for urethral closure pressures
  • Leak point pressure measurement
  • Neurophysiologic studies [18]

Treatment / Management

The treatment of urge urinary incontinence is designed to achieve a degree of decrease in bladder contractility. It also aims to acquire increased bladder capacity and decreased afferent input to the bladder.[3] According to the American Urological Association guidelines, treatment options should be considered at 3 different levels.

First-line Treatment

First-line treatment includes teaching the patient some behavioral therapies such as bladder training and toileting habits, lifestyle modifications, voiding diaries, dietary changes, avoiding bladder irritants (such as caffeine and smoking), pelvic floor muscle training (PFMT), and biofeedback.

Second-line Treatment

Second-line treatment includes the use of medications, namely antimuscarinic and beta-3 agonist therapy.

Antimuscarinic agents

Some antimuscarinic agents currently available for the treatment of urge incontinence include oxybutynin, tolterodine, fesoterodine, trospium, darifenacin, and solifenacin. At present, no substantial evidence exists for the most efficacious antimuscarinic drug. Extended-release versions have been found to cause lesser side effects compared to immediate-release versions.[24] The common side effects related to these drugs are dry mouth, blurred vision, tachycardia, constipation, impaired cognition, and urinary retention. These side effect profiles have often culminated in high discontinuation rates and less than standard compliance rates.[17] Medicines like darifenacin and solifenacin (selective antimuscarinic agents) are sometimes preferred over non-selective agents to control cognitive side effects better.[25](A1)

Beta-3 adrenoreceptor agonists 

The beta-3 adrenoreceptor agonists cause direct relaxation of detrusor muscles. They achieve inhibition of spontaneous contractile activity in the bladder and reduction in bladder afferent activity. Mirabegron is the first of its class and the only beta-3 adrenoceptor agonist that is used as a second-line treatment for those who either poorly tolerate antimuscarinic agents or cannot tolerate them at all. Daily doses of mirabegron 25, 50, and 100 mg demonstrated significant efficacy in treating symptoms of urge incontinence in phase III clinical trials.[26] In some cases, combining an anticholinergic medication with mirabegron may result in increased efficacy and minimized side effect load.[27] This medication can theoretically lead to an increase in cardiovascular events, particularly hypertension, and headaches.(A1)

Third-Line Treatment

If patients with urge incontinence meet the following criteria, they are eligible for third-line treatment (refractory cases):

1. They demonstrate a failure to respond to behavioral therapy
2. They have either intolerance to or inadequate response to at least 2 second-line treatments.

Third-line treatment includes the 3 following unique types of neuromodulations that are FDA-approved:

1. Percutaneous stimulation of the tibial nerve (PTNS)
2. Temporary chemical denervation of the bladder detrusor muscle
3. Sacral neuromodulation.

PTNS involves weekly sessions for the initial 3 months and then monthly maintenance treatments. Contraindications to PTNS should be carefully assessed, which include patients with pacemakers or defibrillators, nerve damage involving tibial nerve or pelvic floor function, and patients who are pregnant.[17] Intravesical onabotulinum toxin A injection is also approved by the FDA and requires delivery via cystoscopy every 6 months if symptoms recur. It results in flaccid paralysis of the detrusor muscle with consistent improvement in urge incontinence symptoms and quality of life. Other neuromodulations, such as sacral, pudendal, and paraurethral nerve stimulators, can be surgically implanted. Intravesicular onabotulinum toxin A injection was shown to be superior to neuromodulation devices for the reduction of urgency symptoms in a 2016 study.[25]

Differential Diagnosis

The differential diagnoses for urge incontinence include all of the reversible causes discussed in the evaluation section. Then again, the classification and characterization of urinary incontinence are somewhat challenging. It is most often dependent on history and subjective complaints from the patient due to a lack of adherence to proper history and physical exam techniques. Therefore, urge incontinence symptoms can easily have a differential diagnosis of either stress or mixed-type incontinence. Another more common differential diagnosis can be overactive bladder syndrome (OAB). Although urge incontinence and OAB are often used interchangeably, most OAB cases do not have any incontinence symptoms. Other conditions, such as diabetes mellitus, recurrent UTI, and neurological diseases, can also be included in the differential diagnosis for urge incontinence.

Prognosis

The prognosis of urge incontinence differs from person to person, and hence, treatment plans should ideally be individualized after discussion with the patient. While behavioral therapy and medications have promising results in the younger patient population, the neuromodulation options should be considered early in the algorithm for the elderly population. According to the American Urological Association, the efficacy of treatment guidelines and prognosis of urge urinary incontinence depends on many factors related to the patient's age and comorbid conditions. Frailty, functional and cognitive impairment, family and caregiver support, and comorbid conditions play pivotal roles in a patient's participation in behavioral therapies. Comparatively, younger individuals have a higher success rate and increased quality of life with behavioral therapies alone or combined with medications.

The use of antimuscarinic agents in elderly patients with cognitive impairment and dementia might lead to further worsening of dementia and Alzheimer's disease. Coexisting medications with anticholinergic properties, such as medications for parkinsonism, donepezil, anti-nausea medications, and sedatives, leads to poor prognosis. Thus, third-line treatment options such as PTNS might need to be included in treatment and prognosis discussions earlier in the disease process for the elderly or affected population. A baseline mini-mental status exam score can prove vital while assessing the quality of life improvement. Beer's criteria for risk assessment or antimuscarinic risk scale can be considered essential for the elderly population, whereas, in the younger community, side effect management can lead to better disease prognosis and treatment success.[28] 

Again, while considering the third-line treatment options, cognitive assessment is essential to predict the outcome. Despite all these considerations, when left untreated or unattended, the prognosis of urge urinary incontinence is abysmal. It is socially burdensome and leads to significant morbidity.

Complications

Complications of urge urinary incontinence can be related to the disease process itself and also to the medications and surgical procedures.[29] Complications of chronic urinary incontinence include:

• Skin problems, including dermatitis, rashes, and bedsores from prolonged periods of wet skin
• Recurrent urinary tract infections
• Progressive cognitive impairment from the use of different antimuscarinic agents
• Significant impact on the quality of life and loss of independence in performing activities of daily living

Complications of all the surgical or bladder neuromodulation procedures can be:

• Injury to the genitourinary tract
• Chronic catheterization
• Persistent or recurrent urinary incontinence