Overactive Bladder Treatment & Management

Updated: Dec 09, 2016
  • Author: Pamela I Ellsworth, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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Treatment

Approach Considerations

Overactive bladder (OAB) can be managed with several different methods. [27, 28, 29, 30, 31] If a specific cause of OAB symptoms is identified, it should be treated appropriately; for example, urinary tract infection (UTI) should be treated with antibiotics; similarly, atrophic urethritis can be treated with topical application of estrogen vaginal cream.

Guidelines for the treatment of OAB by the American Urological Association (AUA) and the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU) include the following recommendations [2, 3] :

  • First-line therapy: Behavioral therapies and education should be offered first; starting antimuscarinic therapies at the same time as behavior therapies may prove clinically beneficial
  • Second-line therapy: Antimuscarinics; extended-release preparations should be used instead of immediate-release preparations when possible; transdermal oxybutynin can also be used. Beta-3 adrenoceptor agonists are also second-line pharmacologic therapies for the management of OAB and may be used as the initial pharmacologic therapy or when anticholinergic agents have failed or are contraindicated.
  • Third-line therapy: Sacral neuromodulation or peripheral tibial nerve stimulation (PTNS) for carefully selected patients with severe refractory OAB symptoms or those who are not candidates for second-line therapy and are willing to undergo a surgical procedure; intradetrusor injection of onabotulinumtoxinA is another option.

The choice of a particular treatment depends on the severity of the symptoms and the extent that the symptoms interfere with the patient’s lifestyle. [32] The three main approaches to treatment include pharmacotherapy, [33] behavioral therapy, and surgery.

A combined treatment approach using behavioral and pharmaceutical interventions is effective in most patients with OAB. Several drugs that have been proven safe and efficacious in clinical trials have been approved for the treatment of OAB. Behavioral interventions, such as the following should be part of every treatment plan:

  • Limiting bladder irritants (eg, caffeine, alcohol)
  • Bladder training
  • Urgency suppression techniques, including pelvic floor muscle exercises

Surgery is rarely used to treat OAB and is reserved for patients in whom pharmacologic and behavioral therapy fail. Various surgical options are available, including sacral nerve neuromodulation and, rarely, bladder augmentation. Percutaneous tibial nerve stimulation is a minimally invasive option for patients in whom pharmacologic therapy fails or is contraindicated.

Consultation with a pelvic floor physical therapist may be helpful.

Go to Pubovaginal Sling, Injectable Bulking Agents for Incontinence, and Surgical Treatment of Urinary Incontinence for complete information on these topics.

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Pharmacologic Therapy

Anticholinergics

Anticholinergic agents are currently the first-line therapy for OAB. [34, 35, 36, 37] These agents are thought to act primarily by inhibiting involuntary detrusor muscle contractions (at the level of the efferent pathway), but identification of muscarinic receptors in the urothelium/suburothelium suggests that they may also affect the afferent sensory pathway. The goals of therapy with anticholinergic agents are to prevent inappropriate detrusor contractions and to maintain normal bladder function, while minimizing adverse effects.

A meta-analysis of 50 randomized controlled trials involving more than 27,000 women with OAB found only modest improvement in symptoms with anticholinergic treatment. Daily treatment reduced urge incontinence by 1.73 episodes per day and voids by 2.06 per day, while placebo reduced urge incontinence episodes by 1.06 and voids by 1.2 per day. No individual agent was shown to be superior to the others. [38]

The duration of treatment is controversial, although many physicians would argue that OAB is a chronic condition with symptom severity that may vary over time. In a prospective randomized, open-label, multicenter trial of symptom change and retreatment rate after discontinuation of the antimuscarinic tolterodine (extended-release, 4 mg) in known responders, 65% of patients requested retreatment and 62% experienced symptom relapse. [39]

Symptom duration and baseline health-related quality of life (HRQol) were risk factors for retreatment according to univariate analysis. However, HRQol was the only independent risk factor. This article serves to highlight both the importance of patient education when managing those with OAB and the significant potential need for long-term anticholinergic therapy. [39]

Oxybutynin and tolterodine are the more commonly used anticholinergics in OAB treatment. Oxybutynin (Ditropan) was among the first anticholinergic agents to be used to treat detrusor overactivity; its efficacy in treating OAB is well documented. [40] However, the effects of oxybutynin are not tissue-specific, and studies have shown that oxybutynin has a greater inhibitory effect on salivation than on bladder contraction, resulting in a high incidence of dry mouth.

Tolterodine (Detrol, Detrol LA) is the first major drug to address the problems of treatment tolerability. [41] Unlike oxybutynin, tolterodine has a greater inhibitory effect on bladder contraction than on salivation. Therefore, it has fewer side effects (eg, dryness of mouth), but with comparable efficacy. [42, 43]

A long-acting, extended-release formulation of oxybutynin (Ditropan XL), which is associated with fewer adverse effects than its immediate-release predecessor, and efficacy that is comparable to the agents above, is also currently available. [44, 45, 46]

A study of 148 men aged 42-88 years with persistent OAB symptoms while receiving alpha-blocker therapy for bladder outlet obstruction found that behavioral and antimuscarinic therapy are effective in reducing these symptoms when added to alpha-blocker treatment. The study concluded that behavioral therapy is at least as effective as antimuscarinic therapy. [47]

Other anticholinergic agents used to treat OAB include the following:

  • Trospium chloride (Sanctura) [48, 49]
  • Propiverine hydrochloride (approved in Europe, not in the United States)
  • Solifenacin (Vesicare) [50, 51, 52, 53]
  • Darifenacin (Enablex), [54]
  • Oxybutynin patch (Oxytrol)
  • Fesoterodine (Toviaz)

The first over-the-counter (OTC) treatment for OAB in women aged 18 or older, Oxytrol for Women, was approved by the U.S. Food and Drug Administration (FDA) in January 2013. The drug is available only by prescription for men. [55]

No head-to-head trials of these agents have assessed efficacy and side effects. The available literature suggests that these agents are clinically similar and that none appears to offer a major distinct advantage over the others. However, slight differences in these agents may be clinically useful in drug selection.

In two placebo-controlled studies that compared tolterodine (Detrol LA) 4 mg and fesoterodine 8 mg, a statistically significant greater reduction in urge urinary incontinence episodes was found with fesoterodine 8 mg. [56]

In a 16-week randomized, double-blind, placebo-controlled study, increasing the solifenacin dose from 5 to 10 mg in OAB patients with more severe symptoms improved outcomes. [57] Patients who had their dose increased experienced greater reductions in the mean number of severe urgency episodes from week 8 through the end of the study and significant reductions in mean total urgency score, mean maximum Patient Perception of Intensity of Urgency Scale urgency rating, and mean micturition frequency.

Darifenacin has the most selective M3 activity and has shown the greatest degree of safety with respect to lack of impact on cognitive function, which suggests that it may offer a slight advantage in elderly patients. It is available in 2 formulations.

Trospium is a large-molecule quaternary amine with minimal central nervous system (CNS) penetration. It has a unique liver metabolic pathway, making it the most suitable for patients receiving multiple drugs with cytochrome P-450 (CYP-450) utilization.

The patch version of oxybutynin has minimal dry mouth or constipation adverse effects but is available in only a single, relatively small dosage and may irritate the skin. A gel formulation of oxybutynin is available that delivers 5 mg of oxybutynin and is not associated with the skin irritation of the patch.

Fesoterodine is the newest anticholinergic available for OAB. It shares the same active metabolite as tolterodine, 5-HMT; however, fesoterodine is efficiently and extensively metabolized to 5-HMT via ubiquitous esterases and thus does not have the pharmacokinetic variability associated with tolterodine. Furthermore, head-to-head studies have demonstrated superiority of the 8-mg dose of fesoterodine compared with tolterodine (Detrol LA) 4 mg in the reduction of UUI episodes.

Although efficacious, anticholinergic agents cause frequent adverse effects such as dry mouth, constipation, blurred vision, and drowsiness. These effects are dose-related and can severely limit tolerability, especially in elderly patients. Anticholinergics may also produce confusion, especially in elderly patients with pre-existing dementia.

Anticholinergics are contraindicated in patients with urinary retention, gastric retention, and untreated narrow-angle glaucoma. They should be used with caution in patients with clinically significant bladder outlet obstruction, decreased gastrointestinal motility, treated narrow angle glaucoma, and myasthenia gravis. More recently, cases of angioedema of the face, lips, tongue and/or pharynx have been reported with several of these agents, and patients should be counseled to seek care immediately if they experience swelling.

Various attempts have been made to improve the organ selectivity of these drugs to overcome their adverse effects. These include the development of new antimuscarinic agents with structural modifications [58, 59] and the use of innovative drug-delivery methods. The benefits of improved drug-delivery systems extends to the long-term therapeutic efficacy, with improved tolerability and patient compliance.

Prospective therapies aimed at novel targets with novel mechanisms of action are currently at different stages of clinical development. These include beta3-adrenoceptor agonists, K+ channel openers, and 5-HT modulators. [5]

Beta3-receptor agonists

In June 2012, the FDA approved the first beta3-receptor agonist, mirabegron (Myrbetriq), for symptoms of urge urinary incontinence, urgency, and urinary frequency associated with OAB.

Beta3-receptor agonists act directly to inhibit afferent nerve firing independent of the relaxing effects on the bladder smooth muscle. In one trial, mirabegron was shown to be safe and efficacious over a 1-year period [60] . In another multicenter, randomized, double-blind, parallel-group placebo- and tolterodine-controlled phase 3 trial, mirabegron significantly improved the number of incontinence episodes and the number of micturitions per 24 hours compared with placebo and was well tolerated. [61] \

In a prospective study in 26 elderly Japanese men with OAB who had been taking tamsulosin, the addition of mirabegron significantly improved OAB symptoms and significantly increased voided volume without impairing bladder contractility during voiding. [62] In a multinational phase II 12-week trial, the combination of mirabegron (25/50 mg) with solifenacin (5/10 mg) resulted in improved objective and subjective efficacy outcomes compared with placebo or solifenacin (5 mg) alone. [63]

Combination therapy

Ongoing studies are evaluating the use of combination therapy with an anticholinergic agent plus a beta3-adrenoceptor agonist. The goal is to achieve improvement in OAB symptoms with a decreased incidence of side effects. [64, 65]

A dose-ranging study by Abrams et al that explored six doses of combination therapy with solifenacin plus mirabegron, five doses of monotherapy with either agent, or placebo, concluded that mirabegron 25/50 mg plus solifenacin 5/10 mg improves objective and subjective efficacy outcomes compared with placebo or solifenacin 5 mg. Micturition frequency normalization was approximately twofold greater with solifenacin 10 mg plus mirabegron 25 mg and solifenacin 5 mg plus mirabegron 50 mg versus solifenacin 5 mg. [64]

In a 12-week study by Drake et al of patients who remained incontinent despite treatment with solifenacin at a dose of 5 mg, the addition of mirabegron (50 mg) significantly improved incontinence and frequent urination, and was superior to monotherapy with solifenacin at a dose of 10 mg. Combination therapy was well tolerated. [65]

 

Botulinum toxins

Detrusor injections of onabotulinumtoxinA are approved by the FDA for the treatment of adults with OAB who cannot use, or do not adequately respond to, anticholinergic medication. Most of the effects of botulinum toxin are thought to be the result of inhibition of the release of acetylcholine from the presynaptic nerve terminal, which prevents stimulation of the detrusor muscle. Review of the clinical data shows a profound effect of botulinum toxin on involuntary detrusor contractions and elevated detrusor pressures. Botulinum neurotoxin type A may also affect other neurotransmitters, such as sensory/afferent neurotransmitters. [66]

Approval was based on safety and efficacy data from two double-blind, randomized, multi-center, placebo-controlled 24-week clinical studies. By week 12 in both clinical trials, patients treated with onabotulinumtoxinA had a reduction of at least 50% in frequency of daily urinary incontinence episodes from baseline compared to placebo. Duration for efficacy with onabotulinumtoxinA at reducing urinary leakage and other symptoms of OAB was 135-168 days compared to 88-92 days with placebo. [67]

OnabotulinumtoxinA is also FDA approved for treatment of urinary incontinence due to detrusor overactivity associated with a neurologic condition (eg, spinal cord injury, multiple sclerosis) in adults who have an inadequate response to or are intolerant of an anticholinergic medication.

The benefits of repeated detrusor injections of botulinum neurotoxin type A were demonstrated in a prospective study by Khan et al in 137 patients with multiple sclerosis–neurogenic OAB. Before treatment, 83% of the patients were incontinent; 4 weeks after the first treatment, 76% were completely dry. The efficacy was sustained with repeat injections. The median interval between retreatments remained constant at 12-13 months. Furthermore, considerable improvement was noted in the mean urogenital distress inventory and incontinence impact questionnaire 7 scores initially and after subsequent treatments. [66]

However, a long-term follow-up study of 128 women who received intravesical onabotulinumtoxinA for idiopathic OAB found that 70% had discontinued treatment—27% because of insufficient effect and 43% of intolerance. Most patients discontinued treatment after the first (79%) and second (19%) injections. Only 2% of patients had discontinued treatment after more than two injections. [68]

Tricyclic antidepressants

Tricyclic antidepressants such as imipramine and doxepin have also been used to treat OAB. These block the reuptake of noradrenaline and serotonin. However, whether this mechanism mediates the beneficial effects on bladder hyperactivity is unclear. These agents have been associated with cardiac dysrhythmias and mental status changes and thus should be used with caution in elderly patients. Tricyclic antidepressants are not recognized as first-line therapy for the treatment of OAB.

Capsaicin

Capsaicin is an extract from Mexican red peppers. It has been investigated for intravesical administration in OAB. A similar agent, resiniferatoxin, has also been investigated.

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Behavioral Therapy

Behavioral therapy, also called behavioral modification, is a treatment approach that aims to alter an individual’s actions or environment to improve bladder control. Components of behavioral therapy include the following [69] :

  • Education
  • Dietary and lifestyle modification (see Dietary Measures)
  • Bladder training
  • Pelvic floor muscle therapy (PFMT)
  • Self-monitoring with bladder or voiding diaries

Bladder training

Bladder training involves a program of patient education and a scheduled voiding regimen. The goals of bladder training are to normalize urinary frequency, to improve control over bladder urgency, to increase bladder capacity, to decrease incontinence episodes, to progressively prolong voiding intervals, and to improve the patient’s confidence in bladder control. Occasionally, it is used in conjunction with electrical stimulation and biofeedback therapy (see below).

How bladder training works is not fully identified; but proposed mechanisms include the following:

  • Improved cortical inhibition over detrusor contractions
  • Improved cortical facilitation of urethral closure during bladder filling
  • Improved central modulation of sensory afferent impulses
  • Changes in behavior due to improved awareness of lower urinary tract function
  • Increased reserve capacity of the lower urinary tract

A program of bladder retraining involves becoming aware of patterns of incontinence episodes and relearning skills necessary for storage and proper emptying of the bladder. Bladder retraining alone is successful in 75% of patients treated for urge incontinence.

Bladder retraining involves developing a schedule of when the patient should try to urinate; the patient should then try to consciously delay urination between these times. One method is to urinate at definite intervals (eg, 30 min); then, as the patient becomes skilled at waiting, the time intervals are gradually increased by one half hour until the individual is urinating every 3-4 hours.

Because the desired level of bladder control may take months to achieve, the patient needs to be highly motivated. Furthermore, bladder training may be effective in the short term, but, because of the extensive effort required, its efficacy may decline over the long term.

Pelvic floor muscle therapy

PFMT involves exercises designed to improve the function of the pelvic floor muscles. The rationale for use of PFMT in urgency urinary incontinence and OAB is that contraction of the muscles can reflexively or voluntarily inhibit contraction of the detrusor muscle. PFMT is defined as any program of repeated voluntary pelvic floor muscle contractions taught by a healthcare professional. [70]

Regular daily exercising of pelvic muscles can improve, and even prevent, urinary incontinence. This is particularly helpful in younger women. PFM exercises should be performed 30-80 times daily for at least 8 weeks. The principle behind PFM exercises is to strengthen the muscles of the pelvic floor, thereby improving function of the urethral sphincter. The success of PFM exercises depends on proper technique and adherence to a regular exercise program. These exercises have limited value in elderly patients and in patients with poor mobility.

Another approach is to use vaginal cones to strengthen the muscles of the pelvic floor. A vaginal cone is a weighted device that is inserted into the vagina. The woman contracts the pelvic floor muscles in an effort to hold the device in place. The contraction should be held for up to 15 minutes and should be performed twice daily. Within 4-6 weeks, symptoms improve in about 70% of women who try this method.

Biofeedback-assisted therapy

Biofeedback is a method of positive reinforcement in which electrodes are placed on patient’s abdomen and the anal area. Biofeedback-assisted behavioral therapy uses biofeedback to teach patients how to control normal physiologic responses of the bladder and pelvic floor muscles that mediate incontinence. Used in conjunction with PFM exercises, biofeedback helps patients gain awareness and control of the pelvic muscles.

Early biofeedback for OAB consisted of bladder-pressure biofeedback. [71, 72] Feedback of pelvic floor muscular activity was subsequently added. [73] Bladder-pressure biofeedback was not widely adopted because of the need for catheterization during each training session. Biofeedback is most commonly used to teach individuals to identify and contract their pelvic floor muscles.

Some therapists place a sensor in the vagina (in women) or in the anus (in men) to assess contraction of the pelvic floor muscles. A monitor displays a graph that shows which muscles are contracting and which are at rest. The therapist can help the patient identify the correct muscles for performing Kegel exercises. About 75% of people who use biofeedback to enhance performance of Kegel exercises report symptom improvement, with 15% considered cured.

Pelvic floor electrical stimulation

Pelvic floor electrical stimulation involves the use of mild electrical pulses to elicit contractions in a specific group of muscles. The current may be delivered using an anal or vaginal probe. Pelvic floor electrical stimulation should be performed in conjunction with PFM exercises. The electrical stimulation therapy may be performed at the clinic or at home. Treatment sessions usually last 20 minutes and may be performed every 1-4 days. Some clinical studies have shown promising results in treating urge incontinence with electrical stimulation.

Recommendations

In 1989, the Consensus Conference on urinary incontinence in adults recommended that the least invasive or dangerous procedure should be tried first. [74] In its guidelines for urinary incontinence in adults, the Agency for Health Care Policy and Research recommended behavioral therapy as a first-line therapy for incontinence. [75] More recently, the Third International Consultation on Incontinence in June 2004 recommended behavioral therapy as a first-line therapy for incontinence. [70]

Success rates

In a study in an outpatient geriatric medicine clinic, behavioral therapy yielded a mean 80.7% reduction in incontinence episodes. [76] Behavioral therapy was significantly more effective than oxybutynin given at a dosage of 2.5 mg/day to 5 mg three times per day (mean reduction in incontinence episodes. 68.3%). Both therapies were better than placebo (mean reduction, 39.4%). In addition, patient-perceived improvement was also greatest in those treated with behavioral therapy. [76]

In a randomized clinical trial of bladder training, Fantl et al observed that episodes of incontinence decreased by a mean of 57% in women aged 55 years and older who underwent bladder training. Patients in a no-treatment control group showed little improvement. [77]

Burgio et al demonstrated an added benefit of combining drug and behavioral therapy in a stepped program. Individuals who were not completely continent or were unsatisfied with behavioral therapy or oxybutynin alone were offered combination therapy. [78] With the change to a combined strategy, substantial improvements were noted.

The International Continence Society (ICS) recommends that PFMT be offered as a first-line therapy to all women with stress, urge, or mixed urinary incontinence. Different techniques of PFMT are described in the literature. They vary in the training schedule; the frequency, force, and duration of contractions of the pelvic floor muscle; and the use of adjuncts, such as biofeedback, electronic prompting devices, and intravaginal pressure-monitoring devices. [79]

Patients seem to benefit most from a PFMT program that provides intensive supervision. Most patients do not appear to have any posttreatment benefit from biofeedback-assisted PFMT. [80] However, for individuals who have trouble identifying and contracting the pelvic floor muscles, biofeedback may be useful. PFMT has been effective in women of all ages. [81]

Biofeedback-assisted behavioral training has been effective in treating urge urinary incontinence, with 76-86% mean reductions in episodes. [73, 82, 83] However, biofeedback is not necessary for everyone.

Burgio et al evaluated biofeedback, verbal feedback based on vaginal palpation, and use of a self-help booklet about PFMT in a first-time behavioral therapy program in community-dwelling women aged 55-92 years. [81] All groups achieved similar reductions in episodes of urge incontinence. However, the groups differed significantly regarding patient satisfaction: complete satisfaction with treatment was reported by 75% of the biofeedback group, 85.5% of the verbal feedback group, and 55.7% of the self-help booklet group.

Limitations

Behavioral therapy relies on the active participation of an involved and motivated patient. In addition, it requires a practitioner who is well trained in such therapy. Behavioral therapy does not produce any permanent changes in bladder function (eg, decreased detrusor overactivity as measured on urodynamic studies). Therefore, regular adherence and long-term compliance are needed.

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Surgical Therapy

Augmentation cystoplasty is rarely necessary in idiopathic OAB. However, it may be used in individuals with refractory neurogenic OAB, particularly in those with poor compliance. In this reconstructive procedure, a segment of the bowel is removed and used to replace a portion of the bladder.

Neuromodulation (sacral nerve stimulation; InterStim, Medtronic, Minneapolis, Minn) is a new technique that is FDA approved for the management of OAB and urge urinary incontinence. It requires the surgical implantation of a small device at the S3 level. Typically, an external stimulator is placed initially, and if the patient experiences a 50% or greater reduction in symptoms, a permanent internalized stimulator is placed.

A prospective study in 272 patients undergoing neuromodulation reported an adverse event rate of 30%. Most were minor, but 13% of patients required surgical intervention, typically revision or replacement. [84]

Urgent PC (Cogentix Medical, Minnetonka, MN) is an office-based method of neuromodulation, using percutaneous tibial nerve stimulation. Typically, twelve 30-minute sessions are performed, followed by a maintenance regimen. Urgent PC is approved by the FDA.

Go to Pubovaginal Sling, Injectable Bulking Agents for Incontinence, and Surgical Treatment of Urinary Incontinence for complete information on these topics.

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Investigational Therapies

The future development of new modalities in OAB treatment appears promising. [85, 86, 87, 88, 89] Investigational therapies of considerable interest include the following:

  • Neurokinin receptor antagonists
  • Alpha-adrenoceptor antagonists
  • Nerve growth factor inhibitors
  • Gene therapy
  • Stem cell–based therapies

Six weeks of electro-acupuncture treatment significantly improved OAB symptom scores and King's Health Questionnaire scores in a study of 45 women with OAB. First sensation of bladder filling, first urge to void, and maximum cystometric capacity also significantly improved. [90]

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Dietary Measures

Elimination of dietary caffeine (in those with urge incontinence) and consumption of adequate dietary fiber is advisable. Some have suggested that the avoidance of certain foods and beverages may improve the symptoms of OAB in some cases. These include the following:

  • Alcohol
  • Spicy foods
  • Nuts
  • Chocolate
  • High-potassium foods
  • Carbonated and caffeinated beverages

Consider providing the patient with such a list and advise the patient to try systematically eliminating one item at a time, to see whether that results in any improvement in symptoms.

Adequate fluid intake is important because many persons with OAB restrict fluids in hopes of voiding less. However, concentrated urine may act as a bladder irritant.

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Management of Chronic Incontinence

Although management approaches such as medical therapy, pelvic muscle exercises, and bladder training improve continence in most patients, some never achieve complete dryness. Treatment failures are sometimes due to concurrent use of necessary medications such as diuretics, which can cause incontinence, or to restricted mobility. Other patients may have dementia or other physical impairments that keep them from being able to perform pelvic muscle exercises or to retrain their bladders.

The following recommendations can help keep persons with chronic incontinence improve symptoms and reduce their cost of care:

  • Scheduled toileting - Take the patient to the toilet every 2-4 hours or according to his or her toilet habits.
  • Prompted voiding - Check for dryness and encourage use of the toilet.
  • Improved access to toilets - Use assistive devices such as canes, walkers, and wheelchairs, and clear a well-lit path to the toilet. Raising the seating level of the toilet can facilitate toileting. Bedside commodes and urinals may be appropriate.
  • Managing fluids and diet - Eliminate dietary caffeine (for those with urge incontinence) and encourage adequate fiber in the diet. Modify fluid intake. Reduce volume overload (for nocturia).
  • Disposable absorbent pads or garments - Use these to keep patients dry.
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