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Urinary Retention in Adults: Diagnosis and Initial Management BRIAN A.

SELIUS, DO, and RAJESH SUBEDI, MD, Northeastern Ohio Universities College of Medicine, St. Elizabeth Health Center, Youngstown, Ohio Am Fam Physician. 2008 Mar 1;77(5):643-650. Urinary retention is the inability to voluntarily void urine. This condition can be acute or chronic. Causes of urinary retention are numerous and can be classified as obstructive, infectious and inflammatory, pharmacologic, neurologic, or other. The most common cause of urinary retention is benign prostatic hyperplasia. Other common causes include prostatitis, cystitis, urethritis, and vulvovaginitis; receiving medications in the anticholinergic and alpha-adrenergic agonist classes; and cortical, spinal, or peripheral nerve lesions. Obstructive causes in women often involve the pelvic organs. A thorough history, physical examination, and selected diagnostic testing should determine the cause of urinary retention in most cases. Initial management includes bladder catheterization with prompt and complete decompression. Men with acute urinary retention from benign prostatic hyperplasia have an increased chance of returning to normal voiding if alpha blockers are started at the time of catheter insertion. Suprapubic catheterization may be superior to urethral catheterization for short-term management and silver alloy-impregnated urethral catheters have been shown to reduce urinary tract infection. Patients with chronic urinary retention from neurogenic bladder should be able to manage their condition with clean, intermittent self-catheterization; low-friction catheters have shown benefit in these patients. Definitive management of urinary retention will depend on the etiology and may include surgical and medical treatments. Urinary retention is the inability to voluntarily urinate. Acute urinary retention is the sudden and often painful inability to void despite having a full bladder.1 Chronic urinary retention is painless retention associated with an increased volume of residual urine. 2 Patients with urinary retention can present with complete lack of voiding, incomplete bladder emptying, or overflow incontinence. Complications include infection and renal failure. SORT: KEY RECOMMENDATIONS FOR PRACTICE Evidence rating B C B A A A

Clinical recommendation In men with benign prostatic hyperplasia, initiation of treatment with alpha blockers at the time of catheter insertion improves the success rate of trial of voiding without catheter. Men with urinary retention from benign prostatic hyperplasia should undergo at least one trial of voiding without catheter before surgical intervention is considered. Prevention of acute urinary retention in men with benign prostatic hyperplasia may be achieved by long-term treatment with 5-alpha reductase inhibitors. Silver alloy-impregnated urethral catheters reduce the incidence of urinary tract infections in hospitalized patients requiring catheterization for up to 14 days. Suprapubic catheters improve patient comfort and decrease bacteriuria and recatheterization in patients requiring catheterization for up to 14 days. Low-friction, hydrophilic-coated catheters increased patient satisfaction and decreased urinary tract infection and hematuria in patients with neurogenic bladder who practice clean, intermittent self-catheterization.

References 36,37 31 3840 41 42 47,48

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 579 or http://www.aafp.org/afpsort.xml. Family physicians often encounter patients with urinary retention. In two large cohort studies of U.S. men 40 to 83 years of age, the overall incidence was 4.5 to 6.8 per 1,000 men per year. The incidence dramatically increases with age so that a man in his 70s has a 10 percent chance and a man in his 80s has a more than 30 percent chance of having an episode of acute urinary retention. 3,4 The incidence in women is not well documented. Although the differential diagnosis of urinary retention is extensive, a thorough history, careful physical examination, and selected diagnostic testing should enable the family physician to make an accurate diagnosis and begin initial management. Causes of Urinary Retention Although classification systems vary, causes of urinary retention can be categorized as obstructive, infectious and inflammatory, pharmacologic, neurologic, or other (Table 11,57). TABLE 1 Selected Causes of Urinary Retention Cause Obstructive Men Benign prostatic hyperplasia; meatal stenosis; paraphimosis; penile constricting bands; Women Organ prolapse (cystocele, rectocele, uterine prolapse); pelvic mass (gynecologic malignancy, uterine Both Aneurysmal dilation; bladder calculi; bladder neoplasm; fecal impaction; gastrointestinal or retroperitoneal malignancy/mass; urethral

Cause

Men phimosis; prostate cancer Balanitis; prostatic abscess; prostatitis

Infectious and inflammatory

Women fibroid, ovarian cyst); retroverted impacted gravid uterus Acute vulvovaginitis; vaginal lichen planus; vaginal lichen sclerosis; vaginal pemphigus

Both strictures, foreign bodies, stones, edema Bilharziasis; cystitis; echinococcosis; GuillainBarr syndrome; herpes simplex virus; Lyme disease; periurethral abscess; transverses myelitis; tubercular cystitis; urethritis; varicellazoster virus Disruption of posterior urethra and bladder neck in pelvic trauma; postoperative complication; psychogenic

Other

Penile trauma, fracture, or laceration

Postpartum complication; urethral sphincter dysfunction (Fowler's syndrome)

NOTE: For pharmacologic and neurologic causes of urinary retention, see Tables 2 and 3, respectively. Information from references 1 and 5 through 7. OBSTRUCTIVE Obstruction of the lower urinary tract at or distal to the bladder neck can cause urinary retention. The obstruction may be intrinsic (e.g., prostatic enlargement, bladder stones, urethral stricture) or extrinsic (e.g., when a uterine or gastrointestinal mass compresses the bladder neck causing outlet obstruction). The most common obstructive cause is benign prostatic hyperplasia (BPH).1,5 In a study of 310 men over a two-year period, urinary retention was caused by BPH in 53 percent of patients. Other obstructive causes accounted for another 23 percent. 7 Each year in the United States, there are approximately 2 million office visits and more than 250,000 surgical procedures performed for patients with BPH.4 BPH causes bladder neck obstruction through two mechanisms: prostate enlargement and constriction of the prostatic urethra from excessive alpha-adrenergic tone in the stromal portion of the gland.8 Other obstructive causes of urinary retention in men include prostate cancer, phimosis, paraphimosis, and external-constricting devices applied to the penis. Obstructive causes in women often involve pelvic organ prolapse such as cystocele or rectocele. Urinary retention can also result from external compression of the bladder neck from uterine prolapse and benign or malignant pelvic masses. In men and women, urethral strictures, stones, and foreign bodies can directly block the flow of urine. Fecal impaction and gastrointestinal or retroperitoneal masses large enough to cause extrinsic bladder neck compression can result in urinary retention. Urinary retention from bladder tumors is usually caused by blood clots from intravesicular bleeding and often presents with painless hematuria.9 INFECTIOUS AND INFLAMMATORY The most common cause of infectious acute urinary retention is acute prostatitis. Acute prostatitis is usually caused by gram-negative organisms, such as Escherichia coli and Proteus species, and results in swelling of the acutely inflamed gland. 1,10 Urethritis from a urinary tract infection (UTI) or sexually transmitted infection can cause urethral edema with resultant urinary retention, and genital herpes may cause urinary retention from local inflammation and sacral nerve involvement (Elsberg syndrome).11 In women, painful vulvovaginal lesions and vulvovaginitis can cause urethral edema, as well as painful urination, which also results in urinary retention. PHARMACOLOGIC Medications with anticholinergic properties, such as tricyclic antidepressants, cause urinary retention by decreasing bladder detrusor muscle contraction.12 Sympathomimetic drugs (e.g., oral decongestants) cause urinary retention by increasing alpha-adrenergic tone in the prostate and bladder neck.8 In a recently published population-based study, men using nonsteroidal anti-inflammatory drugs (NSAIDs) were twice as likely to experience acute urinary retention compared with those not using these agents. NSAID-induced urinary retention is thought to occur by inhibition of prostaglandin-mediated detrusor muscle contraction.13 Table 25 lists medications associated with urinary retention. TABLE 2 Pharmacologic Agents Associated with Urinary Retention Class Antiarrhythmics Anticholinergics (selected) Drugs Disopyramide (Norpace); procainamide (Pronestyl); quinidine Atropine (Atreza); belladonna alkaloids; dicyclomine (Bentyl); flavoxate (Urispas); glycopyrrolate (Robinul); hyoscyamine (Levsin); oxybutynin (Ditropan); propantheline (Pro-Banthine*); scopolamine (Transderm Scop) Amitriptyline (Elavil*); amoxapine; doxepin (Sinequan*); imipramine (Tofranil); maprotiline (Ludiomil*); nortriptyline (Pamelor) Brompheniramine (Brovex); chlorpheniramine (Chlor-Trimeton); cyproheptadine (Periactin*); diphenhydramine (Benadryl); hydroxyzine (Atarax*) Hydralazine; nifedipine (Procardia) Amantadine (Symmetrel); benztropine (Cogentin); bromocriptine (Parlodel); levodopa (Larodopa*); trihexyphenidyl (Artane*) Chlorpromazine (Thorazine*); fluphenazine (Prolixin*); haloperidol (Haldol); prochlorperazine (Compazine*); thioridazine (Mellaril*); thiothixene (Navane) Estrogen; progesterone; testosterone

Antidepressants Antihistamines (selected) Antihypertensives Antiparkinsonian agents Antipsychotics Hormonal agents

Class Muscle relaxants Sympathomimetics (alphaadrenergic agents) Sympathomimetics (betaadrenergic agents) Miscellaneous

Drugs Baclofen (Lioresal); cyclobenzaprine (Flexeril); diazepam (Valium) Ephedrine; phenylephrine (Neo-Synephrine); phenylpropanolamine; pseudoephedrine (Sudafed) Isoproterenol (Isuprel); metaproterenol (Alupent); terbutaline (Brethine*) Amphetamines; carbamazepine (Tegretol); dopamine (Intropin*); mercurial diuretics; nonsteroidal antiinflammatory drugs (e.g., indomethacin [Indocin]); opioid analgesics (e.g., morphine [Duramorph]); vincristine (Vincasar PFS)

* Brand not available in the United States. Levodopa is only available in combination drug products (e.g., carbidopa/levodopa [Sinemet]). Drug not available in the United States. Adapted with permission from Curtis LA, Dolan TS, Cespedes RD. Acute urinary retention and urinary incontinence. Emerg Med Clin North Am. 2001;19(3):600. NEUROLOGIC Normal functioning of the bladder and lower urinary tract depends on a complex interaction between the brain, autonomic nervous system, and somatic nerves supplying the bladder and urethra. Interruption along these pathways can result in urinary retention of neurologic etiology (Table 36). Neurogenic or neuropathic bladder is defined as any defective functioning of the bladder caused by impaired innervation.14 Urinary retention from neurologic causes occurs equally in men and women. 5 Although most patients with neurogenic bladder will experience incontinence, a significant number might also have urinary retention. 15 Up to 56 percent of patients who have suffered a stroke will experience urinary retention, primarily because of detrusor hyporeflexia. In a prospective study, 23 of 80 patients with ischemic stroke developed urinary retention, with the majority having resolution within three months.16 Up to 45 percent of patients with diabetes mellitus and 75 to 100 percent of patients with diabetic peripheral neuropathy will experience bladder dysfunction, which is likely to include urinary retention.17 Voiding dysfunction tends to correlate with the severity of multiple sclerosis and occurs in up to 80 percent of patients, with urinary retention being present in approximately 20 percent. 18 Disk herniation, spinal trauma, and cord compression from benign or malignant tumors may cause urinary retention through interruption of spinal pathways. 19 TABLE 3 Neurologic Causes of Urinary Retention and Voiding Dysfunction Lesion Type Autonomic or peripheral nerve Brain Spinal cord Causes Autonomic neuropathy; diabetes mellitus; Guillain-Barr syndrome; herpes zoster virus; Lyme disease; pernicious anemia; poliomyelitis; radical pelvic surgery; sacral agenesis; spinal cord trauma; tabes dorsalis Cerebrovascular disease; concussion; multiple sclerosis; neoplasm or tumor; normal pressure hydrocephalus; Parkinson's disease; Shy-Drager syndrome Dysraphic lesions; invertebral disk disease; meningomyelocele; multiple sclerosis; spina bifida occulta; spinal cord hematoma or abscess; spinal cord trauma; spinal stenosis; spinovascular disease; transverse myelitis; tumors or masses of conus medullaris or cauda equine

Adapted with permission from Ellerkmann RM, McBride A. Management of obstructive voiding dysfunction. Drugs Today (Barc). 2003;39(7):515. OTHER CAUSES Postoperative Complications. Family physicians often encounter urinary retention in patients who have had surgery. Pain, traumatic instrumentation, bladder over-distension, and pharmacologic agents (particularly opioid narcotics) are all thought to play a role. After rectal surgery, patients will experience urinary retention up to 70 percent of the time. 20 As many as 78 percent of patients who have had total hip arthroplasty and up to 25 percent of patients who have had outpatient gynecologic surgery will develop urinary retention. 21,22 During hemorrhoidectomy, the use of selective pudendal nerve block rather than spinal anesthesia may decrease urinary retention. 20 In some studies, perioperative administration of prazosin (Minipress) has also been shown to decrease postoperative urinary retention in men. 23 Pregnancy-Associated Urinary Retention. Urinary retention during pregnancy is usually the result of an impacted retroverted uterus that causes obstruction of the internal urethral meatus, most often at 16 weeks' gestation. 24 Post-partum, the incidence is reported to be 1.7 to 17.9 percent. Risk factors include nulliparity, instrumental delivery, prolonged labor, and cesarean section. 25,26 In a study of more than 3,300 deliveries, women who received epidural anesthesia were significantly more likely to experience urinary retention than those who did not.27 Trauma. Acute injury to the urethra, penis, or bladder may cause urinary retention. Bladder rupture and urethral disruption can occur with pelvic fracture or traumatic instrumentation.5 Approach to the Patient with Urinary Retention

Table 45,6,28,29 and Table 55,6,2830 summarize key aspects of the history, physical examination, and diagnostic testing that can help determine the etiology of urinary retention. TABLE 4 Possible Etiology of Urinary Retention Based on History and Physical Examination Findings Patient Men History* Previous history of urinary retention Physical examination Enlarged, firm, nontender, nonnodular prostate on digital rectal examination; prostate examination may be normal Tender, warm, boggy prostate; possible penile discharge Enlarged nodular prostate; prostate examination may be normal Edema of penis with nonretractable foreskin; externally applied penile device Possible etiology Benign prostatic hyperplasia

Fever; dysuria; back, perineal, rectal pain Weight loss; constitutional signs and symptoms Pain; swelling of foreskin or penis

Acute prostatitis Prostate cancer

Women

Men or women

Phimosis, paraphimosis, or edema caused by externally placed constricting device Pelvic pressure; protrusion of pelvic organ from Prolapse of bladder, rectum, or uterus on Cystocele; rectocele; uterine vagina pelvic examination prolapse Pelvic pain; dysmenorrhea; lower abdominal Enlarged uterus, ovaries, or adnexa on Pelvic mass; uterine fibroid; discomfort; bloating pelvic examination gynecologic malignancy Vaginal discharge; dysuria; vaginal itching Inflamed vulva and vagina; vaginal Vulvovaginitis discharge Dysuria; hematuria; fever; back pain; urethral Suprapubic tenderness; costovertebral Cystitis; urethritis; urinary tract discharge; genital rash; recent sexual activity angle tenderness; urethral discharge; infection; sexually transmitted genital vesicles infection; herpes infection Painless hematuria Gross hematuria with clots Bladder tumor Constipation Abdominal distention; dilated rectum; Fecal impaction retained stool in vault Constitutional symptoms; abdominal pain or Palpable abdominal mass; positive fecal Advanced gastrointestinal tumor or distention; rectal bleeding occult blood test; rectal mass malignancy Existing or newly diagnosed neurologic disease; Generalized or focal neurologic deficits Neurogenic bladder multiple sclerosis; Parkinson's disease; diabetic neuropathy; stroke; overflow incontinence

* Most patients will present with one or more lower urinary tract symptoms. Symptoms include frequency, urgency, nocturia, straining to void, weak urinary stream, hesitancy, sensation of incomplete bladder emptying, and stopping and starting of urinary stream. Patients with 150 to 200 mL of retained urine may have a percussible or palpable bladder Information from references 5,6,28, and 29. TABLE 5 Diagnostic Testing in Patients with Urinary Retention Test type Laboratory Diagnostic test Urinalysis Serum blood urea nitrogen, creatinine, electrolytes Serum blood glucose Prostate-specific antigen Rationale Evaluate for infection, hematuria, proteinuria, glucosuria Evaluate for renal failure from lower urinary tract obstruction Evaluate for undiagnosed or uncontrolled diabetes mellitus in neurogenic bladder Elevated in prostate cancer; may be elevated in benign prostatic hyperplasia, prostatitis, and in the setting of acute urinary retention Measure postvoid residual urine; evaluate for bladder and urethral stones, hydronephrosis, and upper urinary tract disease Evaluate for suspected pelvic, abdominal, or retroperitoneal mass or malignancy causing extrinsic bladder neck compression Evaluate for intracranial lesion, including tumor, stroke, multiple sclerosis (MRI preferred in multiple sclerosis) Evaluate for lumbosacral disk herniation, cauda equina syndrome, spinal tumors, spinal cord compression, multiple sclerosis Evaluate for suspected bladder tumor and bladder or urethral stones or strictures Evaluate bladder function (detrusor muscle and sphincter) in patients with neurogenic bladder to help

Imaging studies

Renal and bladder ultrasonography

Pelvic ultrasonography; CT of abdomen and pelvis

MRI or CT of brain MRI of spine

Other

Cystoscopy, retrograde cystourethrography Urodynamic studies (e.g., uroflowmetry, cystometry, electromyography, urethral pressure profile, video urodynamics,

Test type

Diagnostic test pressure flow studies of micturition)

Rationale guide management

NOTE: Imaging studies and diagnostic procedures are guided by the clinical context and suspected diagnoses. CT = computed tomography; MRI = magnetic resonance imaging. Information from references 5,6, and 28 through 30. BENIGN PROSTATIC HYPERPLASIA A common presentation of urinary retention is bladder outlet obstruction caused by BPH. Patients will generally present with a history of multiple lower urinary tract voiding symptoms, including frequency, urgency, nocturia, straining to void, weak urinary stream, hesitancy, sensation of incomplete bladder emptying, and stopping and starting of urinary stream. 31 The history may also include previous episodes of catheterization. The physician should inquire about precipitating factors, including alcohol consumption, recent surgery, UTI, genitourinary instrumentation, constipation, large fluid intake, cold exposure, and prolonged travel. 32 A detailed medication history should be obtained for prescribed and over-the-counter medications, with special attention to those that are known to cause urinary retention (Table 25). Abdominal examination should include percussion and palpation of the bladder. A bladder should be percussible if it contains at least 150 mL of urine; it may be palpable with more than 200 mL. 5,28 A rectal examination should be performed to estimate prostate size and to check for prostate nodules and fecal impaction. A urinalysis should be done to evaluate for possible infection. If the diagnosis remains in doubt, residual urine can be accurately measured by bladder ultrasonography or catheterization. 28 If available, bladder ultrasonography would be preferred because it is noninvasive and more comfortable for the patient, and because complications (e.g., UTI) can be avoided (Figure 1). The volume of residual urine considered to be significant varies in the literature, ranging from 50 to 300 mL.33 Because prostate-specific antigen will likely be elevated in acute urinary retention, it is unlikely to be helpful in this setting. 5 NEUROGENIC BLADDER Another cause of urinary retention that family physicians will likely encounter is neurogenic bladder. Patients can present with overflow incontinence or recurrent UTI. A history of neurologic disease, spinal trauma or tumor, diabetes, and any change in baseline neurologic status should be carefully noted. Patients with suspected neurogenic bladder should undergo a general neurologic examination, as well as specific examinations related to bladder function. These include the bulbo-cavernosus reflex (contraction of the bulbocavernosus muscle when the glans penis is squeezed), anal reflex (contraction of the anal sphincter when the surrounding skin is stroked), voluntary contractions of the pelvic floor, anal sphincter tone, and sensation in the S2 to S5 dermatomal distribution (Figure 2), which is in the perianal and saddle area.29 Imaging studies looking for tumors or other lesions in the brain and spinal cord may also be necessary. Once neurogenic bladder is diagnosed, the patient should be referred for urodynamic testing to guide ongoing management.

Figure 2. The S2 to S5 dermatomal distribution. Initial Management of Urinary Retention

Acute urinary retention should be managed by immediate and complete decompression of the bladder through catheterization. Standard transurethral catheters are readily available and can usually be easily inserted. If urethral catheterization is unsuccessful or contraindicated, the patient should be referred immediately to a physician trained in advanced catheterization techniques, such as placement of a firm, angulated Coude catheter or a suprapubic catheter.5 Hematuria, hypotension, and postobstructive diuresis are potential complications of rapid decompression; however, there is no evidence that gradual bladder decompression will decrease these complications. Rapid and complete emptying of the bladder is therefore recommended.34 In patients with known or suspected BPH, the optimal amount of time to leave a catheter in place is unknown. Up to 70 percent of men will have recurrent urinary retention within one week if the bladder is simply drained. 35 Recent studies have shown that men with BPH have a greater chance of a successful voiding trial without a catheter at two to three days if they are treated with alpha-adrenergic blockers (e.g., alfuzosin [Uroxatral], tamsulosin [Flomax]) for three days starting at the time of catheter insertion. 36,37 American Urological Association (AUA) guidelines recommend at least one attempted trial of voiding after catheter removal before considering surgical intervention.31 Prevention of acute urinary retention in BPH may be achieved by long-term treatment (four to six years) with dutasteride (Avod-art), finasteride (Proscar), or a combination of finaste-ride and doxazosin (Cardura).3840 The AUA guidelines recommend only using the 5-alpha reductase inhibitors finasteride and dutasteride in men with demonstrable prostate enlargement by digital rectal examination.31 For hospitalized patients requiring catheterization for 14 days or less, a Cochrane review found that silver alloy-impregnated urethral catheters have been associated with decreased rates of UTI versus standard catheters.41 Another Cochrane review concluded that patients requiring catheterization for up to 14 days had less discomfort, bacteriuria, and need for recatheterization when suprapubic catheters were used compared with urethral catheters.42 In a recent meta-analysis of abdominal surgery patients, suprapubic catheters were found to decrease bacteriuria and discomfort and were preferred by patients. 43 Although evidence suggests short-term benefit from silver alloyimpregnated and suprapubic catheters, their use remains somewhat controversial. If possible, the use of chronic urethral indwelling catheters should be avoided. Complications include UTI, sepsis, trauma, stones, urethral strictures or erosions, prostatitis, and potential development of squamous cell carcinoma.44,45 In a one-year prospective study of nursing home patients, catheter use was independently associated with increased mortality.46 Patients with chronic urinary retention, especially those with neurogenic bladder, should be able to manage their condition with clean, intermittent self-catheterization. This technique is considered first-line treatment for managing urinary retention caused by neurogenic bladder and can reduce complications, such as renal failure, upper urinary tract deterioration, and urosepsis.47 Two randomized trials found that in men with neurogenic bladder from spinal cord injury, low-friction, hydrophilic-coated catheters decreased the incidence of UTI and microhematuria and provided increased patient satisfaction in persons performing self-catheterization.47,48 Definitive management of urinary retention will depend upon the underlying etiology and may involve surgical and medical treatment

Differential Diagnosis and Treatment of Impaired Bladder Emptying Naoki Yoshimura, MD, PhD and Michael B Chancellor, MD Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA This article has been cited by other articles in PMC.

Other Sections Abstract Although much attention is paid to urinary incontinence, the condition of incomplete bladder emptying is becoming more common with the aging of the US population and the widespread use of anticholinergic drugs to treat overactive bladder. This disorder can often be silent until end-stage presentation of overflow incontinence. In this article, we review the pathophysiologic conditions of the bladder and urethra that can cause impaired bladder emptying and discuss how to evaluate and screen the patient with a bladder that does not empty. In addition, we provide an overview of treatment options available for impaired bladder emptying and consider the research that is under way to find the best therapies for the failing bladder. Key words: Bladder, Urethra, Urinary retention, Ultrasound, Bethanechol

Other Sections

We have heard a great deal about overactive bladder recently. But what if your patients have the opposite problema bladder that wont go? How do you evaluate the patient whose bladder does not empty? What are the most common and effective forms of therapy for impaired bladder emptying? Urinary retention and incomplete bladder emptying can be caused by an inadequately contractile bladder, urethral sphincter obstruction, or both. Because prostate enlargement has been addressed in a previous article in this supplement (see Lepor, p. S8), this article focuses on bladder dysfunction. The one unique case of urethral obstruction that is discussed is function retention due to non-neurogenic detrusorsphincter dyssynergia, also referred to as shy bladder syndrome.

Other Sections Micturition Reflexes Normal micturition is completely dependent on neural pathways in the central nervous system. These pathways perform 3 major functions: amplification, coordination, and timing.1 The nervous control of the lower urinary tract must be able to amplify weak smooth-muscle activity to provide sustained increases in intravesical pressures sufficient to empty the bladder. The bladder and urethral sphincter function must be coordinated to allow the sphincter to open during micturition but remain closed at all other times. Timing represents the voluntary control of voiding in the normal adult and the ability to initiate voiding over a wide range of bladder volumes. In this regard, the bladder is a unique visceral organ that exhibits predominantly voluntary rather than involuntary (autonomic) neural regulation. A number of important reflex mechanisms contribute to the storage and elimination of urine and modulate the voluntary control of micturition.

Other Sections Guarding Reflexes Against Stress Urinary Incontinence There is an important bladder-to-urethra reflex that is mediated by sympathetic efferent pathways to the urethra. This is an excitatory reflex that contracts the urethral smooth muscle and, thus, is called a guarding reflex. The positive reflex is not activated during micturition but activates when bladder pressure is increased, such as during a cough or exercise. A second guarding reflex is triggered by activation of sacral motoneurons that, in turn, activate urethral external sphincter efferent neurons, which send axons into the pudendal nerves and the nerves innervating the pelvic floor. 2 This somatic guarding reflex is activated by bladder afferents and/or directly by stress such as sneezing.3The activation of somatic urethral and pelvic floor efferent pathways contracts the

external urinary sphincter and the pelvic floor muscle, thus preventing stress urinary incontinence. The brain inhibits the guarding reflexes during micturition.

Other Sections Causes of Incomplete Bladder Emptying Urinary retention and incomplete emptying can result from a number of causes (Table 1). In some cases, the flow of urine is blocked, for example, in men with benign prostatic hyperplasia. This causes obstruction. Another form of impaired emptying is nonobstructive, that is, there is no problem with the urethra but the bladder muscle is less able to adequately contract. When the bladder cannot contract properly, some or all of the urine remains in the bladder. If left untreated, this condition can lead to urinary tract infection and damage to the kidneys.4 Table 1 Diagnosis, Evaluation, and Treatment of Impaired Bladder Emptying

Urethral Obstruction Functional obstruction at the pelvic floor external sphincter, sometimes called shy bladder syndrome, can cause just as much distress as prostatic mechanical obstruction of the urethra. At the University of Pittsburgh, we have seen a number of patients in end-stage renal failure resulting from the inability to relax the external sphincter over decades. The condition is believed to be an abnormal, learned, and upregulated guarding reflex. Before these patients are put on the transplant list, they are taught intermittent self-catheterization. Bladder Dysfunction Detrusor areflexia is defined as acontractility due to an abnormality of nervous control. In detrusor areflexia, the bladder cannot be demonstrated to contract during urodynamic studies. Detrusor areflexia can develop from various conditions in which the neurologic pathways innervating the bladder are damaged. However, the contribution of myogenic factors should not be ignored. Common Neurologic Causes of Impaired Bladder Emptying Spinal cord injury. Any injury to the spinal cord, including blunt, degenerative, developmental, vascular, infectious, traumatic, and idiopathic injury, can cause voiding dysfunction. Injury to the cauda equina and peripheral sacral nerves can have devastating effects on bladder and urethral sphincter function. The true incidence of lower urinary tract dysfunction as a result of cauda equina and pelvic plexus injury is unknown, mainly because of the lack of prospective studies with preoperative and postoperative neurourologic evaluation of patients. Pelvic surgery. The incidence of vesicourethral dysfunction has been reported to be 20% to 68% after abdominal perineal resection, 16% to 80% after radical hysterectomy, 10% to 20% after proctocolectomy, and 20% to 25% after anterior resection.5 Pelvic and sacral fractures. Pelvic trauma can result in cauda equina and pelvic plexus injury. The frequency of neurologic injury after pelvic fracture is estimated to be between 0.75% and 11%.5 The injury most closely correlated with neurologic damage is transverse sacral fracture. Approximately two thirds of these patients will have neurogenic bladder. 5 Because most of the injuries are incomplete, the majority of patients with neurourologic injury after pelvic and sacral fractures will improve over time. Herniated disc. Some reports indicate that the incidence of voiding dysfunction in patients with disc prolapse may approach 20%. Data have demonstrated that, once patients show evidence of bladder dysfunction following lumbar disc prolapse, detrusor recovery with treatment is uncommon.5 Therefore, cauda equina syndrome from lumbar disc herniation should be considered a surgical emergency.

Infectious neurologic processes. There are a number of infectious causes of incomplete emptying of the bladder:

Acquired immune deficiency syndrome (AIDS): Neurologic complications, involving both the central and peripheral nervous systems, occur in as many as 40% of patients with AIDS.5 Urinary retention is the most common presenting symptom. Neurosyphilis (tabes dorsalis): Neurosyphilis has long been recognized as a cause of central and peripheral nerve abnormalities. Voiding dysfunction related to neurosyphilis was common in the era before penicillin use. Herpes zoster and herpes simplex: Herpes zoster is an acute, painful mononeuropathy associated with a vesicular eruption in the distribution of the affected nerve. The viral activity is predominantly located in the dorsal root ganglia of the cranial nerves. However, sacral nerve involvement may be associated with loss of bladder and anal sphincter control.

Lyme disease: Caused by the spirochete Borrelia burgdorferi, Lyme disease is associated with a variety of neurologic sequelae. Urologic manifestations of Lyme disease can be primary or late manifestations of disease and affect both sexes and persons of all ages. Urinary urgency, nocturia, and urge incontinence are the most common urologic symptoms. 6

Myogenic Failure Degeneration of or damage to bladder smooth muscle can also induce detrusor hyporeflexia or areflexia. Chronic overdistension can result in detrusor myogenic failure, even if the neurologic disease is treated or reversed. Bladder management to avoid overdistension, such as institution of intermittent catheterization after spinal cord injury, may protect the bladder from permanent myogenic damage. Overactive Bladder Link to Impaired Bladder Emptying Anticholinergic drugs are now widely used to treat overactive bladder. A potential side effect of all anticholinergic agents is high residual urine volume and impaired bladder emptying. This can occur soon after initiation of therapy and is especially worrisome in the frail elderly and men with concomitant prostate hypertrophy.7 A simple ultrasound check of residual urine after initiation of anticholinergic therapy can rule out potential problems. Sensory Uropathy It is widely accepted that diabetes results in sensory and autonomic polyneuropathy. When sensory and/or autonomic neurons innervating the bladder are damaged, bladder dysfunction, characterized by impaired sensation of bladder fullness, increased bladder capacity, reduced bladder contractility, and increased residual urine volume, can be observed. 8 The prevalence of diabetic cystopathy is related to the duration of diabetes and not to the sex and age of the patient. It has also been reported that diabetic cystopathy can occur silently and early in the course of diabetes. 8 In such cases, the bladder dysfunction is often detected only after careful questioning and/or urodynamic testing. Thus, urodynamic testing in patients with diabetes is often key to the early diagnosis of bladder dysfunction.

Other Sections Diagnosis Table 2 lists some of the general symptoms of impaired bladder emptying. Patients with known or suspected neurologic damage due to pelvic or sacral injury should have a careful physical examination. The integrity of the sacral dermatomes is tested by assessing perianal sensation, anal sphincter tone, and control of the bulbocavernosus reflex. Table 2 Symptoms of Impaired Bladder Emptying

Many patients complain of straining to urinate, incontinence, and a sensation of incomplete bladder emptying. The urinary stream may be diminished and interrupted, since many of these patients rely on abdominal straining to urinate. On occasion, symptoms of voiding

dysfunction may be the only initial clinical manifestation of a cauda equina lesion. 9 The varied and mixed symptomatologies emphasize the need for a complete neurourologic evaluation. The physical examination may reveal a distended bladder, but the most characteristic features are elicited by a careful neurologic examination. Sensory loss in the perineum or perianal area is associated with the S2 through S4 dermatomes. The extent of perineal anesthesia can be a useful predictor in patients with lumbar disc prolapse. If saddle anesthesia of the S2 through S4 dermatomes continues after surgical laminectomy and decompression, the urinary bladder rarely recovers. A unilateral or mild sensory disturbance indicates a better prognosis. Deep tendon reflexes in the lower extremities, clonus, and plantar responses, as well as the bulbocavernosus reflex, should be routinely evaluated. Urodynamic Findings The typical cystometrogram finding of cauda equina injury is detrusor areflexia (Figure 1). On the uroflowmetry, an abdominal straining, sawtooth pattern is generally seen (Figure 2). Urodynamic abnormalities may be the only aberration documented, with no other overt neurologic manifestations, in some patients with cauda equina injury. In cases of herniated disc not induced by trauma or acute conditions, the protrusion is usually slow and progressive and may result in nerve irritation and, consequently, detrusor hyperreflexia. 10 Figure 1 Detrusor areflexia without any voluntary or involuntary detrusor contraction to 500 mL volume on urodynamic study in a 61-year-old insulin-dependent diabetic woman. The patient is receiving intermittent catheterization approximately 4 times per 24 hours.(more ...) Figure 2 Straining uroflowmetry of the diabetic woman in Figure 1. The patient complained of the sensation of incomplete emptying post-micturition, occasional incontinence, and straining to urinate. Although her maximum flow rate is normal (29.1 mL/s), the voiding (more ...) The integrity of the sacral reflex in men may be further studied with evaluation of the latency time of the sacral evoked potentials by stimulating the penile skin and recording the response with a needle electrode in the bulbocavernosus muscle. 11 In patients with complete cauda equina lesions, the sacral evoked response is either absent or significantly prolonged; this represents a more sensitive indicator of neuropathy than the classic electromyographic changes. In conclusion, the major urodynamic features in patients with cauda equina injury are an absent or diminished detrusor areflexia, neuropathic changes on perineal floor electromyography, and absent evoked electromyographic responses. Risks of Catheterization When evaluating impaired bladder emptying, it is important to avoid catheterizing a patient who has a large residual urine volume. Even with a sterile technique, it is difficult to avoid introducing bacteria into the bladder with catheterization. This is of little concern in the normal patient; however, in a patient with high residual urine, just a few bacteria can quickly multiply in the warm and wet environment of the bladder and can overgrow and become stagnant. Therefore, not only does an ultrasonographic residual urine check avoid the pain and irritation of urethral catheterization, it is medically safer. Use of the portable bladder ultrasound machine, rather than catheterization, is recommended for routine residual urine check (Figure 3). Figure 3 Checking residual urine volume is quicker, less irritating, and safer with a bladder scanner.

Other Sections Treatment Catheterization Indwelling urethral or suprapubic catheters and clean intermittent catheterization are the options available when the bladder must be drained. Both urethral and suprapubic catheterization achieve this end; however, if long-term catheterization is required, most patients prefer a minor

surgical procedure to place a suprapubic catheter. Suprapubic catheterization is more comfortable than urethral catheterization, allows the patient to have sexual intercourse, and is easier to change. Long-term urethral catheterization should especially be avoided in women, because of risk of chronic catheter pressure causing erosion damage and fistula formation to the vagina. Without question, if the patient can perform clean intermittent self-catheterization, it is almost always preferred over indwelling catheterization. Biofeedback Bladder retraining and biofeedback can help the patient with a spastic pelvic floor and external urinary sphincter to relearn how to relax during micturition. This technique is typically performed with perineal electromyographic electrodes connected to an electronic biofeedback machine. Over several sessions, patients get visual and auditory signals of what it feels like when they contract the pelvic floor muscles. Positive and negative feedback then can be used to teach the patient to relax specific muscles. Drug Treatment Bethanechol chloride, 25 mg tid/qid, is the only drug available for the treatment of urinary retention. Bethanechol is an agonist for the parasympathetic nerve-mediated, acetylcholine-mediated detrusor muscle contraction.12,13 It helps to increase bladder muscle tone and contractility. Bethanechol works within an hour after the pill is administered. Therefore, it takes only a few days to determine whether the medication is effective for a particular patient. Because of absorption issues, bethanechol generally should be taken on an empty stomach. Adverse effects include upset stomach, vomiting, dizziness, wheezing, sweating, and flushing. Urethral Botulinum Toxin Injection Another method of treating refractory sphincter spasticity is injection of botulinum toxin into the spastic pelvic floor. Although this technique may sound highly unusual, we have had great success with it at our institution. Botulinum toxin is a powerful site-specific muscle relaxant. We have employed the injection of botulinum toxin A in the lower urinary tract, as an FDA off-label use, in more than 125 patients since 1998. This therapy should not be used as first-line treatment; however, it can avoid the need for lifelong catheterization in patients who are refractory to therapy.14 The technique is simple to perform and has been described in a previous issue ofReviews in Urology.15 Sacral Nerve Stimulation Why would sacral nerve neuromodulation promote voiding in patients with voiding dysfunction? To understand this, it should be recognized that, in adults, functioning of brain pathways is necessary to turn off sphincter and urethral guarding reflexes and allow efficient bladder emptying. Spinal cord injury produces bladder sphincter dyssynergia and inefficient bladder emptying by interfering with these brain mechanisms (Figure 4). This may also occur with more subtle neurologic lesions in patients with idiopathic urinary retention; for example, after a bout of prostatitis or a urinary tract infection. Figure 4 In cases of neurologic disease, the brain cannot turn off the guarding reflex and retention can occur. Sacral nerve stimulation (SNS) restores voluntary micturition in cases of voiding dysfunction and urinary retention by inhibiting the guarding reflex. (more ...) It has been demonstrated in animals that, before the development of brain control of micturition, stimulation of somatic afferent pathways passing through the pudendal nerve to the perineum can initiate efficient voiding by activating bladder efferent pathways and turning off the excitatory pathways to the urethral outlet.1 Tactile stimulation of the perineum in the cat also inhibits the bladder sympathetic reflex component of the guarding reflex mechanism. Sacral nerve stimulation can elicit similar responses in patients with urinary retention, turning off excitatory outflow to the urethral outlet and promoting bladder emptying.16 Because sphincter activity can generate afferent input to the spinal cord that can, in turn, inhibit reflex bladder activity, an indirect benefit of suppressing sphincter reflexes would be a facilitation of bladder contraction.

Other Sections Research Muscle Cell Transplantation The aim of stem cell tissue engineering is to replace, repair, or enhance the biologic function of damaged tissue or organs. The process involves harvesting cells from patients or donors, isolating stem cells from the sample, expanding the cell number through cell culture

techniques, and subsequently injecting or implanting the cells into the patient. One particular advantage of muscle stem cell transplantation is that it may augment impaired detrusor muscle function. It has been demonstrated that skeletal muscle stem cells, when injected into the failing bladder, can improve detrusor contractility and may be able to differentiate into bladder smooth muscle. 17This treatment offers the only hope for patients with detrusor myogenic failure. Gene Therapy What can you do when the impaired bladder emptying is caused by damage to the nerve that innervates the bladder? We are studying the feasibility of gene therapy using a replication- deficient herpes simplex viral vector encoding neurotrophic factors that is injected into the bladder wall.18 The herpes vector would hone in on the nerves that innervate the bladder. It is hoped that the payload it delivers, the transcription of neurotrophic factor proteins, will help improve nerve function. Thus, in the future, neurotrophic factors or other growth factors combined with targeted gene therapy techniques may be beneficial for patients with diabetic cystopathy or other forms of urologic nerve damage (Figure 5). Figure 5 Herpes vector neurotrophic factor gene therapy: the herpes vector for nerve growth factor (HSV-NGF) is injected into the bladder and taken up by the sensory C-fiber afferent nerves.

Other Sections Conclusion Impaired bladder emptying is a common and underdiagnosed condition. With overactive bladder being treated more often, physicians should especially be on the lookout for impaired bladder emptying. Screening is simple and safe with portable bladder ultrasound scanners. Treatment ranges from bethanechol for stimulation of detrusor contraction to clean intermittent self-catheterization. Injection of botulinum toxin and acupuncture, like sacral nerve neuromodulation, can help a number of patients with refractory impaired bladder emptying. Exciting research on muscle stem cell transplantation and neurotrophic gene therapy is under way. Main Points

Urinary retention and incomplete bladder emptying can result from urethral obstruction (such as in men with benign prostatic hyperplasia), shy bladder syndrome, or detrusor areflexia (acontractility of the bladder due to an abnormality of nervous control). Incomplete bladder emptying is often neurologic in nature, as in patients who have had spinal cord injury, pelvic surgery or trauma, or herniated disc; it can also result from an infectious cause, presenting as a neurologic sequela of AIDS, Lyme disease, herpes zoster, or neurosyphilis.

Patients with incomplete bladder emptying should undergo a careful physical and neurologic examination to assess for distended bladder, sensory loss in the perianal and perineal areas, deep tendon reflexes in the lower extremities, clonus, plantar responses, and bulbocavernosus reflex.

Catheterization to evaluate impaired bladder emptying is not recommended in patients with a large residual urine volume because of the risk of bacteriuria. Ultrasonographic residual urine check, which is safer and more comfortable for the patient, should be employed in this population.

Treatment options for patients with urinary retention include biofeedback to teach muscle relaxation, drug therapy with bethanechol chloride, and sacral nerve neuromodulation. In addition, injection of botulinum toxin to suppress pelvic floor spasticity has shown success in patients refractory to first-line therapy. Stem cell transplantation and gene therapy for impaired bladder emptying are also being investigated.