Urinary Incontinence

Stress urinary incontinence, urge incontinence, mixed incontinence, overflow incontinence

1. What every clinician should know

Urinary incontinence, or the loss of bladder control, is a common condition and has been reported in up to 43% of women aged 37-54. The two phases of the bladder function include filling phase and emptying phase. When these functions are disrupted in women incontinence can occur. During the filling phase, the sympathetic system (via beta adrenergic receptors) inhibits the parasympathetic activity and helps in bladder filling without rise in detrusor pressure. The external urethral sphincter and levator ani muscle are under the influence of the pudendal nerve and sacral efferent nerves during the filling phase.

During the emptying phase, inhibition of pudendal and sacral efferents relaxes the external urethral sphincter and levator. Posterior slackening of the fascial hammock and rotational descent of the bladder neck occur. The cerebral cortex inhibits sympathetic relaxation of the bladder. The urethra shortens which lowers resistance to flow. Parasympathetic cholinergic receptors in detrusor stimulates bladder contraction.

Diagnostic definitions

Stress incontinence

This is the involuntary immediate loss of urine when the intravesical pressure is higher than urethral pressure. In other words, the loss of urine with activities such as coughing, laughing, exercising, etc. These patients generally have no associated irritating voiding symptoms. The prevalence of stress urinary incontinence in women aged 25-84 is 15%.

Intrinsic sphincter deficiency (ISD) is a severe form of stress urinary incontinence confirmed on urodynamic testing. Many clinicians use a Valsalva or cough leak point pressure below 60 cm of H20 and/or maximum urethral closure pressure of <= 20 cm of H2O to confirm the diagnosis of ISD. The definitions and clinical consequences of this diagnosis are not well established.

Urge incontinence

Often referred to as overactive bladder-wet, this is the loss of urine due to an uninhibited detrusor contraction usually preceded by a strong urge to void. In other words, patients get the urge to void and have an accident before they can get to a commode. These patients also have many irritating voiding symptoms, such as frequency, urgency and nocturia. Urge incontinence can be associated with abnormalities of the nervous system but is generally idiopathic in its etiology and the prevalence of overactive bladder in women aged 25-84 years is 13%.

Mixed urinary incontinence

This is a combination of stress and urge urinary incontinence. It has been estimated that 29%-62% of women with urinary incontinence have mixed urinary incontinence.

Overflow incontinence

This occurs with urinary retention and overdistention of the bladder leading to intravesical pressure higher than maximal urethral closure pressure. These patients often have symptoms of spontaneous or continuous leaking but can have stress incontinence type symptoms. Chronic urinary retention can occur from injury to sacral portion of the spinal cord or nerves within the cauda equina. Diabetes is also a common cause of an overflow incontinence due to peripheral neuropathy and a paralytic bladder.

Risk factors that are common to both stress and urge incontinence are:

• Age
• Obesity
• Family history
• Diabetes
• Hormone replacement therapy (systemic)

Risk factors for stress urinary incontinence:

• History of childbirth
• Vaginal delivery
• History of hysterectomy
• Caucasian vs. Black women

Risk factors for urge incontinence:

• Older age
• Diabetes mellitus
• Two or more urinary tract infections in previous year
• High caffeine intake
• Smoking
• Black vs. Caucasian women

2. Diagnosis and differential diagnosis

History can aid with the diagnosis of incontinence type but will be incorrect in up to 25% of women. Clinical history of urinary frequency and urgency preceding an incontinence episode has 61% sensitivity for diagnosing urge incontinence.Clinical history of only leaking with associated activity (i.e., cough, sneeze, etc.) is 92% sensitive and 56% specific for diagnosing urodynamic stress incontinence in women.

A clinical history similar to stress incontinence but with an inability to empty the bladder without strain is a common symptom complex for diagnosing overflow incontinence. These subjects will generally have an associated disease state such as chronic illness that can result in an autonomic neuropathy, an obvious neuropathic condition, or a history of urinary obstruction following reconstructive surgery. A clinical history of continuous leaking is commonly associated with a fistula.

Diagnostic testing (urodynamics) should be performed in all subjects who fail a trial of conservative therapy or in anyone contemplating surgical correction. The “Gold Standard” for diagnosing stress urinary incontinence is objective evidence of leaking of urine with increase in intra abdominal pressure (coughing or valsalva maneuvers) during urodynamic testing. This can be a simple cough stress test where the patients bladder is retrograde filled through a red rubber catheter to at least 150 cc’s and visually demonstrating gross urine leak per the urethra during a cough or Valsalva.

Complex multichannel urodynamic testing can also demonstrate stress incontinence but is not necessary in the routine (surgically naive) patient. Intrinsic sphincter deficiency requires complex multichannel urodynamics to diagnose. However, the clinical utility of making this diagnosis and its impact on clinical decision making has not been rigorously determined.

See Figure 1. Patient with indigo carmine-stained urine and positive urine stress test.

Figure 1.

Urge incontinence is diagnosed based on patients symptoms, after eliminating other conditions. A cystometrogram demonstrating uninhibited detrusor contractions during the filling phase of the test is confirmatory, but will not be demonstrated in up to 50% of subjects eventually diagnosed with urge incontinence. A cystometrogram that can document bladder capacity which if very small (less than 250 cc’s) should warrant referral to a specialist (either urologist or urogynecologist).

Overflow incontinence can be easily diagnosed with obtaining a Post Void Residual (a simple In and Out catheterization following a spontaneous void). A post void residual of greater then 300-800 cc’s would make the diagnosis of overflow incontinence. A post void residual of less than 100 cc’s is considered normal. Values in between present a diagnostic dilemma.

Differential diagnosis for urinary incontinence include urinary tract fistula, ectopic ureter and heavy vaginal secretions. Depending on the clinical scenario, the patient may need work up to exclude genitourinary fistula. This may include IVP or CT urogram and cystourethroscopy. A pyridium (or any agent that can stain urine) pad test can be used to rule out vaginal secretions that may mimic urinary incontinence.

Conditions that can be associated with urinary incontinence include:

• Dementia
• Urogenital atrophy
• Restricted mobility
• Urinary tract infection
• Pharmacologic agent side effects (particularly alpha blockers)
• Endocrine causes (polyuria)
• Stool impaction
• Urinary retention

3. Management

Management of stress urinary incontinence

Conservative/behavioral measures

Weight loss of 5-10% may result in up to 60% reduction in weekly incontinence episodes. Fluid restriction to 0.75L/ day is associated with significantly lower number of incontinence episodes. Continence pessaries are safe, inexpensive, and may be appealing to some women, but in randomized controlled trials, they have been shown to be inferior to physical therapy.

Kegel’s exercises or pelvic floor muscle rehabilitation involves contraction of the levator ani muscles in a set number of repetitions done on a daily basis. They are commonly recommended for stress or urge incontinence. The thought is that by strengthening the pelvic floor and urethral sphincter you can correct the defect causing stress incontinence and for urge incontinence the patient can hold the urethra closed by a levator /urethral sphincter contraction during the uninhibited detrusor contraction until it abates or the patient reaches a commode.

Kegel’s exercises improve incontinence in about 50% of subjects treated but often relief is short lived. Clinicians have augmented Kegel’s exercises by using weighted vaginal cones to increase resistance as well as using electrical stimulation to either augment contractions or help the patient with very weak levator ani muscles who is unable to contract her pelvic floor muscles.

In randomized controlled trials, comparing the effectiveness of conservative/behavioral measures to various combinations conservative/behavioral therapies, there were no clinically significant differences in single-modality or combination therapy at 12 months and beyond. Conservative/behavioral therapy is well tolerated, non-invasive and results in resolution of bothersome symptoms and treatment satisfaction in 49-75% of subjects.

Medications

Estrogen

This has an interesting relationship to incontinence. Incontinence incidence increases with use of systemic estrogens compared with placebo (risk ratio [RR] 1.32, 95% CI 1.17-1.48) in analysis of 6 trials.Conversely there is a significant improvement in incontinence symptoms with topical/vaginal estrogens compared with placebo (RR 0.74, 95% CI 0.64-0.86)

Imipramine

This is a tricyclic antidepressant that has anticholinergic, beta and alpha-2 agonistic properties.It has been proposed that imipramine induces norepinephrine reuptake inhibition, which might suppress detrusor activity, in addition it may increase the resting tone of smooth muscle cells in the bladder neck from alpha adrenergic stimulation. In the treatment of stress urinary incontinence with imipramine, although success rates of up to 70% have been reported, a review of literature suggests overall low efficacy. It has been recommended that imipramine be used for milder forms of stress incontinence and in patients who are not candidates for surgery.

Duloxetine

This blocks reuptake of serotonin and norepinephrine. Duloxetinetreatment can significantly improve the quality of life of patients with stress urinary incontinence, but it is unclear whether or not benefits are sustainable. Approximately 33% of participants in clinical trials allocated duloxetine reported adverse effects (most commonly nausea) related to treatment. Approximately 10% allocated duloxetine stopped treatment as a consequence.

Periurethral bulking agents

These are injectable agents that bulk the bladder neck and bring about a modest mechanical obstruction much like early prostativc hypertrophy. Results of a recent Cochrane review (12 randomized or quasi-randomized trials) include two trials that found bulking agents similar to standard anti-incontinence surgery with respect to subjective improvement. Surgery out performed bulking agents for objective improvement.

Eight comparison trials found similar outcomes with all injectable agents, but results had wide confidence intervals. Another trial found transurethral injection associated with fewer early complications than periurethral injection. No studies compared injection therapy to conservative treatment. Overall, injectable therapy may be beneficial in subjects who are poor surgical candidates or in subjects with good urethrovessical junction who do not respond as well to mid-urethral sling surgery.

Surgery

In evaluating surgical outcomes, both subjective outcomes (patient reported outcomes of via quality of life questionnaires) and objective outcomes are reported. The relative importance of either type of outcome is debatable.

Burch colposuspension

A Cochorane review of 46 randomized or quasi-randomized trials found that open retropubic colposuspension is an effective treatment modality for stress urinary incontinence, especially in the long term. Overall cure rates are 68.9% to 88.0%.After five years, approximately 70% of patients can expect to be dry. Laparoscopic colposuspension should allow speedier recovery but its relative safety and effectiveness are not known yet.

Minimally invasive synthetic midurethral sling procedures

A synthetic polypropelene sling is placed under the mid urethra using needles passed in one of two trajectories, either retropubic (referred to as TVT) or transobtruator (referred to as TOT).They are termed minimally invasive because they involve two small incisions in the skin and one small vaginal incision beneath the urethra. The retropubic approach can involve needles passed from the suprapubic area down through the vaginal incision (top down) or from the vaginal incision up through the skin (bottom up). The transobtruator approach can involve needles passed from the groin skin incision out through the vaginal incision (outside in) or from the vaginal incision out through. The sling is not attached to any structures and is left loose under the mid urethra.

A Cochrane review of 62 randomized and quasi-randomized trials evaluating minimally invasive synthetic midurethral slings found there was no significant difference in subjective cure rate at 12 months comparing midurethral slings with traditional slings open Burch colposuspension or laparoscopic Burch colposuspension. Suburethral slings are associated with fewer intra- or post-operative complications compared to other methods, except for more bladder perforations compared to open retropubic colposuspension. Retropubic bottom-to-top route significantly more effective than top-to-bottom route (RR 1.10, 95% CI 1.01 to 1.20) with less voiding dysfunction, bladder perforations and tape erosions (RR 1.06, 95% CI 1.01 to 1.11).

Significantly higher objective cure rates (RR 1.15, 95% CI 1.02 to 1.30) with fewer tape erosions (RR 0.25, 95% CI 0.06 to 1.00) with monofilament tapes compared with multifilament tapes. The retropubic route was associated with similar subjective cure rates but significantly higher objective cure rate and more perioperative complications compared with transobturator route (RR 0.96, 95% CI 0.93 to 0.99). The trans-obturator sling was associated with less voiding dysfunction, blood loss, bladder perforation (RR 0.14, 95% CI 0.07 to 0.26) and shorter operating time.

See Figure 2. Tension-free vaginal tape used for stress urinary incontinence.

Figure 2.

Autologous fascial sling

This procedure involves using autologous fascia harvested from the rectus fascia or the fascia lata. The sling is passed through the retropubic space and placed under the bladder neck. Unlike the midurethral slings the fasccial sling is placed snug under the bladder neck and attached to the rectusfascia. Success rates are higher for women who underwent the sling procedure than for those who underwent the Burch procedure, for both the overall category of success (47% vs. 38%, P=0.01) and the category specific to stress incontinence (66% vs. 49%, P<0.001). More women who underwent the sling procedure experienced difficulty voiding (6.1% vs. 0.0%).

There is insufficient data to comment on newer midurethral slings or mini slings.

Retropubic vs. transobturator synthetic slings

The rates of objective treatment success were 80.8% in the retropubic-sling group and 77.7% in the transobturator-sling group (3.0 percentage-point difference, 95% confidence interval [CI], -3.6 to 9.6).The rates of subjective treatment success were 62.2% in the retropubic-sling group and 55.8% in the trans-obtruator sling group (6.4percentage-point difference, 95% CI, -1.6 to 14.3). The rates of voiding dysfunction requiring surgery were 2.7% in those who received retropubic slings and 0.0% in those who received transobturator slings(P=0.004). There were no significant differences between groups in postoperative urge incontinence, patient satisfaction with the results of the procedure, or quality of life.

Postoperative recurrent urodynamic stress incontinence at six months was 21% (TVT Group) vs.45% (TOT Group)(p = 0.004).The requirement for repeat sling surgery in those with symptomatic urodynamic stress incontinence was 0.0% in the TVT Group vs. 12.7% in the TOT Group (p =0.003). There was no significant difference in hospital length of stay or postoperative complications among groups. Retropubic slings are preferred over transobturator slings in during intrinsic sphincter deficiency and recurrent stress urinary incontinence.

Intraoperative complications of retropubic mid urethral sling procedures include:

• Bladderperforation: 0.7-24%
• Hemorrhage:0.7-8%
• Bowelperforation <1%
• De novourgency and obstruction: 5.9-25%
• Erosion intourethra: 0.3%
• Groin and thigh pain is more common in patients who undergo a transobturator approach (OR 8.8, 95%CI: 2.6-29.5)

Bulking agents

Carbon coated zirconium oxide (Durasphere ®) (second-generation injectable bulking agent)

FDA approved for adult women with stress urinary incontinence due to intrinsic sphincter deficiency. At one year follow up, it is associated with up to 80% cure rate for treating stress urinary incontinence associated with intrinsic sphincter deficiency.

Calcium hydroxyaptite (CaHA) (Coaptite ®)

No systemic adverse events were observed with this product. At one year there was improvement of 60% with either agent. Subjects generally required fewer injections with CaHA then Collagen.

Silicone microimplants (Macroplastique ®)

Safe and effective at a median of 58 month follow up. It is associated with an overall subjective cure rate of 80%.

Management of urgent urinary incontinence

Conservative measures

Weight loss and diet changes are two ways to manage this incontinence. A 16% reduction in weight can result in 70% reduction in urge incontinence episodes. Fluid restriction to 0.75L/ day is associated with significantly decreased voiding frequency, urgency, and wetting episodes with improved quality of life.

Biofeedback

Biofeedback, including timed voids, relaxation techniques, pelvic floor muscle rehabilitation, and avoidance of certain dietary irritants is another technique. Behavioral treatment yielded a mean of 80.7% reduction of incontinence episodes and was significantly more effective than drug treatment (mean 68.5% reduction, P=.04) and both were more effective than the placebo control condition (mean 39.4% reduction, P<.001 and P=.009, respectively). Patient-perceived improvement was greatest for behavioral treatment (74.1% “much better” vs. 50.9% and 26.9% for drug treatment and placebo, respectively). Only 14.0% of patients receiving behavioral treatment wanted to change to another treatment vs. 75.5% in each of the other groups.

In a randomized controlled trial that tested whether individualized drug therapy (extended release oxybutynin) enhanced with behavioral training would result in better outcomes than individualized drug therapy alone, there were no significant differences in frequency of incontinence, patient satisfaction or global perception of improvement at 6 and 12 months.

Medications

Anticholinergic drugs: Oxybutynin, Tolterodine, Fesoterodine, Trospium, Solafenacin, Darifenacin

Several head-to-head trials involving the various medications have shown only modest differences favoring one drug over another. Most differences were inside-effects, rather than any major outcome criteria (incontinent episodes, number of micturitions, nocturia). The clinical significance of these differences is debatable.

Imipramine

Tricyclic antidepressant, anticholinergenic, and alpha agonist properties. Success rate of up to 90% in treating urge incontinence reported. The fluctuating nature of urge incontinence together with poor study design and conflicting results obtained in trials makes drawing definitive conclusions difficult. Imipramine can be used inpatients with mixed incontinence.

Hormone replacement

Estrogen therapy may be effective in alleviating the symptoms suggestive of OAB. Local administration (Topical) may be the most beneficial route of administration.

Botulinum toxin A intravesical injections

There is superiority of botulinum toxin A to placebo in such outcomes as incontinence episodes, bladder capacity, maximum detrus or pressure, and quality of life. Botulinum toxin appeared to have beneficial effects in overactive bladder that quantitatively exceeded the effects of intravesical resiniferatoxin. Botulinum toxin intravesical injections are associated with increased risk of elevated post void residual.

Sacral neuromodulation (SNS)

InterStim® is an FDA approved implantable device that provides electrical stimulation to the sacral nerve. The exact mechanism of action SNS is unknown. It is indicated for patients with urge incontinence, urgency-frequency syndrome or urinary retention who have failed more conservative treatments. A review of SNS suggest that after five years, 63% urge incontinent patients have at least a 50% reduction in leaking episodes per day, after four years, 53% urgency-frequency patients have at least a 50% reduction in voids per day, and after one year, 53% of 19 non-obstructive urinary retention patients have at least a 50% reduction in catheterized urinary volumes.

Factors associated with poor response to SNS are:

• Poor mobility and requirement of a wheelchair
• Age greater than 55
• Presence of three or more chronic medical conditions
• Intra- vertebral disk disease
• Duration of complaints of greater than seven months

In patients with non-obstructive urinary retention (which can cause overflow incontinence), predictors of success with SNS include hypertonic pelvic floor dysfunction (Fowler syndrome).This condition is associated with elevated urethral pressure profile.

Acupuncture

Limited evidence suggests that acupuncture may be helpful for irritating bladder symptoms. Percutaneous tibial nerve stimulation involves placing an acupuncture needle percutaneously in the ankle region near the tibial nerve and stimulating with an electrical generator for 30 minutes. A multicenter, double-blind, randomized, controlled trial comparing the efficacy of percutaneous tibial nerve stimulation to sham through 12 weeks of therapy demonstrated that percutaneous tibial nerve stimulation subjects achieved statistically significant improvement in bladder symptoms with 54.5% reporting moderately or markedly improved responses compared to 20.9% of sham subjects from baseline (p <0.001). Percutaneous tibial nerve stimulation may decrease symptoms of urge incontinence previously unresponsive to antimuscarinics based on a small randomized trial. There was more than 50% reduction in urge incontinence in 71% with tibial nerve stimulation vs. 0% with control (p < 0.001).

Overflow urinary incontinence

Treatment options for overflow incontinence include:

• Prolonged catheterization (either transurethral or supra pubic)
• Clean intermittent self catheterization
• Sacral neuromodulation (discussed above)

Subjects with overflow incontinence should be referred to an expert for management.

4. Complications

Psychosocial impact of untreated disease

Urinary urgency, frequency, and urge incontinence negatively impacts sleep, social interaction, and health-related quality of life. Depression is two to three times more common in women with urinary incontinence compared to those without. Severity of depression is directly proportional to the severity of incontinence. Urinary incontinence increases the risk for falls in elderly dementia patients. Other conditions associated with untreated urinary incontinence include increased risk for urinary tract infections and yeast vaginitis. It is also often perceived as a barrier to exercise.

5. Prognosis

Urinary incontinence is likely to worsen with time. In a nurses’ health study that followed 23,792 women aged 54-79 yrs for two years, it was observed that 2.1% of those who reported leakage at least monthly at baseline progressed to at least weekly and 8.9% of those who reported leakage at least weekly at baseline improved to monthly or less, and 2% had complete remission.

A prospective study demonstrated that menopausal transition was not associated with worsening of urinary incontinence symptoms over six years in midlife women. The results were that 52.9% had no change, 32.4% had decreased incontinence, and 14.7% had worsening. In a prospective, observational study of three hundred twenty-four incident cases of stroke with incontinence 1 week post stroke, age 75 and older was independently associated with poor recovery from post stroke urinary incontinence.

6. What is the evidence for specific management and treatment

Abrams, P, Cordoza, L, Fall, M, Griffiths, D, Rosier, P, Ulmsten, U, van Kerrebroeke, P, Victor, A, Wein, A. “The standardization of terminology of lower urinary tract function: Report from the Standardization Sub-committee of the International Continence Society”. Neurourol Urodynam. vol. 21. 2002. pp. 167-78. (Article on standard terms and their universally agreed upon definitions in lower urinary tract disorders.)

Cody, JD, Richardson, K, Moehrer, B, Hextall, A, Glazener, CMA. “Oestrogen therapy for urinary incontinence in post-menopausal women”. Cochrane Database Syst Rev. 2009. pp. CD001405(Review article on the effects of estrogen on urinary incontinence suggesting minimal if any benefit.)

Duthie, JB, Herbison, GP, Wilson, DI, Wilson, D. “Botulinum toxin injections for adults with overactive bladder syndrome”. Cochrane Database Syst Rev. 2007. pp. CD005493(Article on limited data regarding the use of Botox in women with recalcitrant OAB suggesting at least short term benefit.)

Keegan, PE, Atiemo, K, Cody, JD, McClinton, S, Pickard, R. “Periurethral injection therapy for urinary incontinence in women”. Cochrane Database Syst Rev. 2007. pp. CD003881(Review article suggesting some short term benefit of injectible therapy but less effective then other surgical therapies.)

Lapitan, MCM, Cody, JD, Grant, A. “Open retropubic colposuspension for urinary incontinence in women”. Cochrane Database Syst Rev. 2009. pp. CD002912(Article demonstrating long term efficacy of retropubic suspension in the treatment of stress urinary incontinence.)

Mariappan, P, Alhasso, AA, Grant, A, N’Dow, JOM. “Serotonin and noradrenaline reuptake inhibitors (SNRI) for stress urinary incontinence in adults”. Cochrane Database Syst Rev . 2005. pp. CD004742(Review article questioning any benefit of SNRIs in the treatment of stress urinary incontinence.)

Nabi, G, Cody, JD, Ellis, G, Hay-Smith, J, Herbison, GP. “Anticholinergic drugs versus placebo for overactive bladder syndrome in adults”. Cochrane Database Syst Rev. 2006. pp. CD003781(Review article suggesting that anticholinergics demonstrate better efficacy then placebo in relieving symptoms of OAB.)

Ogah, J, Cody, JD, Rogerson, L. “Minimally invasive synthetic suburethral sling operations for stress urinary incontinence in women”. Cochrane Database Syst Rev. 2009. pp. CD006375(Review article stating that minimally invasive slings (retropubic) have efficacy in treating stress urinary incontinence.)

Waetjen, LE, Feng, WY, Ye, J, Johnson, WO, Greendale, GA. “Study of Women’s Health Across the Nation (SWAN). Factors associated with worsening and improving urinary incontinence across the menopausal transition”. Obstet Gynecol. vol. 111. 2008. pp. 667-77. (Good epidemiologic study on urinary symptoms across various age groups.)

Ward, K, Hilton, P. “UK and Ireland TVT Trial Group. Prospective multicentre randomised trial of tension-free vaginal tape and colposuspension as primary treatment for stress incontinence”. BMJ. vol. 325. 2002. pp. 67

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