排尿障礙治療中心 版權所有 urgency frequency syndrome hann-chorng kuo department of...
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排尿障礙治療中心 版權所有
Urgency Frequency Syndrome
Hann-Chorng Kuo
Department of Urology
Buddhist Tzu Chi General Hospital Hualien
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排尿障礙治療中心 版權所有
Lower Urinary Tract Symptoms
• Storage symptoms --
Frequency, urgency, urge incontinence, nocturia, suprapubic pain
• Empty symptoms --
Hesitancy, intermittency, dysuria, poor stream, terminal dribble, residual sensation, micturition pain
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The Urge Syndrome
Sensory urgency – hypersensitivity of bladder or urethra or both, which causes
-- a constant desire to void which is unrelieved by voiding
-- a desire to void at a low bladder volumeMotor urgency – occurrence of involuntary de
trusor contractions which make patients urge to void and/or urine leakage
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排尿障礙治療中心 版權所有
Frequency & Polyuria (Pollakisuria)
• A number of patients may have large daily urine output >2800ml/day
• Polydipsia, high water intake
• Frequency with voided volume >350ml is physiologically normal
• Should check metabolic status (DM, azotemia, hyperlipidemia, etc.) or diuretics
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Sensory Urgency & Frequency
• Reduced capacity of first desire (<150mL) or urgency (<350mL) subjectively
• Absence of detrusor instability
• Absence of urinary tract infection
• The incidence of sensory urgency has been estimated 6%, compared with an incidence of 31% for detrusor instability
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排尿障礙治療中心 版權所有
Known Causes of Sensory urgency freqency
• Urinary tract infection
• Lower ureteral stone or bladder stone
• Bladder tumor
• Irradiation cystitis
• Interstitial cystitis
• Chonic cystitis and reduced capacity
• Foreign body or bladder injury
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Etiology of Idiopathic Urgency Frequency
• Psychological factors
• Urothelial leak syndrome
• Reduced bladder compliance
• Diuresis
• Learned habit
• Detrusor instability
• Occult neuropathy
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Sensory UrgencyA Psychosomatic Complaint ?
• Bladder retraining is effective in treating sensory urgency
• Relaxation training, biofeedback, hypnosis, acupuncture have a 85% initial response, but relapse rate is 50%
• Cognitive factor to maintain high stress and arousal levels, increase vigilance concerning bladder sensation and fullness
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Psychological Social & Psychiatrical Factors
• High level of distress
• High level of anxiety
• Symptoms may worsen in relation to work or stress
• Belief of relationship with disease – uremia, infection, cancer
• Overestimate the significance of symptoms
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Sensory Urgency Frequency
• A disease of exclusion• Acute symptoms and chronic symptoms?• Related to empty symptoms or not?• Related to painful syndrome (painful
bladder, painful perineum, urethral pain)?• Intermittent? Persistent? Waxing & waning? • Related to urge or stress incontinence?
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Diagnostic Work-up
• Urinalysis
• Uroflowmetry & residual urine amount
• Voiding diary – 3 days
• KUB or Cystoscopy
• Ultrasound of bladder and urethra
• Cystometry & sphincter EMG
• Pressure flow study or videourodynamics
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Pathophysiology of LUTS in 256 Taiwanese Women
• Normal bladder and urethra 46
• Hypersensitive bladder 102
• Detrusor instability 44
• Low detrusor contractility 77
• Poor relaxation of urethral sphincter 76
• Genuine stress urinary incontinence 49
• Bladder outlet obstruction 21
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Urethral sensitivityAn etiology of urgency frequency?
• Increased urethral sensitivity was found in reduced bladder capacity and in women with normal CMG who complain of frequency urgency & dysuria
• A higher incidence of bladder neck incompetence in patients with urgency frequency than the controls
• Pelvic floor exercises and bladder neck suspension improves urgency frequency symptoms
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Bladder Neck Incompetence in Urgency Frequency Syndromes
Frequency-
Urgency
Syndrome
N PVL(cm) PVS(degrees)
Resting Straining Increment Resting Straining Increment
Bladder neck
incompetence
43
(55.1%)
1.99±0.40 2.07±0.46 0.08±0.2225.7±21.
851.2±30.4 25.5±18.9
Bladder neck
competence
35
(44.9%)
2.12±0.37 2.14±0.39 0.03±0.16 9.4±9.5 20.4±15.0 11.0±11.7
Statistics NS NS NS P<0.005 P<0.005 P<0.005
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排尿障礙治療中心 版權所有
Ultrasound of Bladder neck incompetence in urgency frequency
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Bladder Neck Decsent & Incompetence before Pelvic Floor exercises
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Improved Bladder neck Incompetence after Pelvic Floor exercises
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Detrusor Instability as an etiology of urgency frequency
• Minute detrusor contraction occur in the normal bladder – C-fiber dominates?
• Increased perception of bladder fullness during diuresis
• No significant difference in perception of bladder fullness between sensory urgency and detrusor instability
• Similar clinical efficacy of oxybutynin in treating sensory urgency (62.5%) and DI (60.4%)
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排尿障礙治療中心 版權所有
Increased amplitude of detrusor contractions in bladder filling
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Sensory nerves of bladder
• Dual sensory innervation of mammalian bladder
• Myelinated A-delta fibers – mediate stretch and micturition reflex
• Unmyelinated C-fibers (capsaicin sensitive sensory fibers) – mediate pain, temperature, noxious stimuli
• Sensory axons are present in lamina propria
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Sensory Innervation of Bladder
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Capsaicin sensitive sensory fiber
• Sensory function – regulating micturition threshold (especially after spinal cord transection), mediating pain, activating cardiovascular responses
• Efferent function – activating local motor responses, regulating nerve excitability, local control of vascular blood flow and permeability (neurogenic inflammation ?)
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排尿障礙治療中心 版權所有
Treatment of sensory urgency by intravesical capsaicin
• Capsaicin in 10 micro-M can effectively treat hypersensitive disorders
• Transient desensitization of capsaicin-sensitive afferents without interfering motor function
• Little effect was found in classical Interstitial cystitis
• Resiniferatoxin may have similar effects
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Role of Potassium in pathogenesis of Urgency Frequency Syndrome
• Chronic diffusion of urinary potassium into bladder interstitium may induce sensory symptoms, damage tissue, and possibly cause interstitial cystitis
• Intravesical potassium test (40ml, 0.4M) is a reliable method for detecting abnormal urothelium permeability
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排尿障礙治療中心 版權所有
Potassium test in Urgency Frequency Syndrome
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Nerve Growth Factor
• Increased nerve growth factor levels in the bladder biopsies from sensory urgency, chronic cystitis, and interstitial cystitis than in controls
• Immunostaining showed increased NGF expression in the urothelium, most marked in idiopathic sensory urgency
• Anti-NGF treatment may be rational
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NGF immunostaining in Idiopathic Sensory Urgency
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Urgency frequency associated with Bladder or perineal pain
• Suprapubic pain or perineal pain at bladder fullness
• The pain may/not disappear after voiding
• A tight sphincter EMG at bladder capacity
• Reduced bladder compliance
• Urethral obstruction due to stricture or spastic urethral sphincter as etiologies
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Reduced bladder capacity and Frequency urgency bladder pain
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Frequency urgency & pain Spastic pelvic floor & sphincter
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Differential diagnosis of Urgency Frequency Syndrome
• History – Bladder injury, foreign body• Urinalysis – UTI• Uroflowmetry – BOO• Cystoscopy – bladder tumor, bladder stone,
irradiation cystitis, chronic cystitis• Ultrasound – bladder neck and/or urethral i
ncompetence• Cystometry – low compliance, DI, DESD
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Pressure flow study for Urgency frequency syndrome
• Cystometry can only detect capacity, detrusor instability, compliance, and bladder sensation during filling phase
• Pressure flow study can diagnose bladder outlet obstruction, low detrusor contractility, poor relaxation of urethral sphincter, and DESD accurately
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Urodynamic study in Urgency frequency syndrome- Detrusor overactivity
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Urodynamic study in Urgency frequency syndrome- Detrusor underactivity
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Urodynamic study in Urgency frequency syndrome- Bladder outlet obstruction
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Urodynamic study in Urgency frequency syndrome- Low compliant bladder
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Urodynamic study in Urgency frequency syndrome- Pseudodyssynergia
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Urodynamic study in Urgency frequency syndrome- Idiopathic Sensory Urgency
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LUTS Analysis of Voiding dysfunction
Frequency
(n=233)
Urgency
(n=98)
Dysuria
(n=104)
Incontinence
(n=129)
Bladder pain
(n=34)
Normal bladder & urethra(n=46) 44 17 17 20 5
Hypersensitive bladder (n=102) 90 38 44 47 25
Detrusor instability (n=44) 37 22 18 30 6
Low detrusor contractility (n=77) 68 34 34 38 17
Poorly relaxed sphincter (n=76) 68 20 40 28 19
Genuine stress incontinence (n=49) 45 17 6 44 2
Bladder outlet obstruction (n=21) 21 20 13 9 5
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Treatment of Frequency urgency syndrome & Normal UDS
• Reassurance
• Bladder biofeedback
• Restrict fluid intake
• Avoid diuretics and certain acid foods
• Sedatives or mild tranquilizers
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Foods to be Avoided
Acid foodsAll alcoholic beverages Guava
Apple juice,red and green apples Lemon juice
Apricots Nectarines
Cantaloupes Peaches
Chilis/spicy foods Plums
Citrus fruits (lemon,lime, orange,etc) Strawberries
Coffee Tea
Cranberries Tomatoes
Grapes Vinegar
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Foods high in tyrosine, typtophan, aspartate, and phenylalanineAvocados Nutrasweet
(Aspartame)
Chocolate Saccharine
Bananas Nuts Corned beef Sour cream
Beer Onions Cranberries Soy sauce
Brewer’s yeast Pickled herring Fava beans Vitamins buffered with aspartate
Canned figs Pineapple Lima beans Wines
Champagne Prunes Marmite Yogurt
Cheeses Raisins Mayonnaise
Chicken livers Rye bread
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Bladder biofeedback for Urgency frequency syndrome
• Urodynamic proven sensory urgency• Bladder biofeedback – increased each voidi
ng interval by holding urine for 5 min more• Increase fluid intake gradually• Improved functional capacity (296 v 96ml)
and decreased daytime frequency (5.7 v 15.8) and nocturia (0.3 v 2.3) after treatment
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Intravesical Heparin therapy
• Patients with urgency frequency and a positive potassium test
• Intravesical Heparin 25000u/10ml saline and holding for 2 hours
• 2x or 3x per week for 12 weeks
• 67% patients have improvement in symptoms and increase in bladder capacity
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The changes of urodynamic parameters before and after heparin treatment
Baseline 3 months Statistics P value
FSF(ml) 96.5±46.4 146.1±55.4 0.001
US(ml)225.4±96.
2 264.9±84.2 0.009
Cystometric capacity(ml)
262.0±89.8 304.3±84.8 0.002
PdetQmax(cmH2O) 25.7±9.1 28.3±9.3 0.07Qmax (ml/sec) 12.9±5.7 15.1±7.7 0.063Residual urine(ml) 29.4±38.4 14.5±25.7 0.096IPSS (points) 19.5±4.6 9.0±4.0 0Nocturia (times/night) 5.7±2.0 2.3±1.1 0
Pain scale of KCl (points)
3.2±0.5 0.7±0.7 0
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Urodynamic finding before and after Heparin Therapy
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Intravesical Capsaicin Therapy
• Patients who are refractory to conventional treatment
• Capsaicin 10 -5 M in 30ml N/S instilled to bladder for 30 minutes
• Resiniferatoxin 10-8 M in 30ml N/S
• A burning sensation or urge at instillation
• Relief of pain and urge in the later days
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Cystometric Results after Capsaicin Instillation
Hypersensitive Bladder
(n=10)
IC
(n=10)
Before After Before After
FSF(ml) 59±21* 27±7.5 75±33* 21±15
FS(ml) 110±28* 55±17 109±32* 34±13
Capacity(ml) 189±30* 82±14 143±31* 59±17
Qmax(ml/sec) 22.8±7.5* 16.5±2.9 19.3±5.4* 12.5±4.7
Corredcted Qmax 1.65±0.5 1.83±0.3 1.62±0.3* 1.63±0.2
*P<0.05
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A Cocktail Preparation for Idiopathic Urgency Frequency ?
• Mixture of Xylocaine, Resiniferatoxin, Heparin, Oxybutynin with certain vehicle
• To provide local anesthesia, C-fiber desensitization, repair of defected glycosaminoglycan layer, anticholinergic effect together in one instillation
• Clinical trial is undergoing
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Anticholinergics Treatment
• Oxybutynin – the most effective and safe drug currently available
• Detrusitol – M3 antagonist, less salivary and GI side effects than ditropan
• Flavoxate – mild effect in detrusor
• Imipramine – central and anticholinergics
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DDAVP – Alternative for Urgency Frequency Polyuria
Baseline Post-treatment Paired t-test
Nocturnal frequency
(times/night)5.20±1.16 2.24 ±1.12 P<0.0001
Noctunal urine volume(ml) 955.6±255.9 522.8 ±210.5 P<0.0001
Quality of Life 4.47±1.07 1.05 ±0.91 P<0.0001
Urine specific gravity 1.012 ±0.007 1.016 ±0.005 P 0.011≒
Serum Na (meq/L) 139.5 ±4.34 139.7 ±3.84 P 0.761≒
Serum K (meq/L) 4.46 ±0.35 4.31 ±0.44 P 0.022≒
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Pelvic Floor Exercises for Urgency frequency syndrome
• 3 sets of 8 to 12 slow velocity maximal
pelvic floor muscle contractions
• Sustained for 6 to 8 seconds each
• Performed 3 to 4 times a week
• Continued for at least 15 to 20 weeks
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Results of Pelvic Floor Exercises
• Increased maximal cystometric capacity• Fewer detrusor contractions• Less incontinence episodes• Expected cure/improvement rates 65-75
%• About 50% of patients avoid surgery
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Changes of Bladder sensation after Pelvic Floor Exercises
Pre-treatmen
t
Post-treatment
Statistics (p value)
Qmax (mL/s) Total22.6 ± 13.
0 20.9 ± 10.2 0.390
Successful
26.0 ± 10.77 23.4 ± 10.7 0.236
Failure18.3 ± 14.
9 17.8 ± 9.2 0.881
Voided volume
Total340.5 ± 12
3.4 386.1 ± 152.9 0.240
Successful
395.4 ± 69.8 414.1 ± 176.3 0.780
Failure273.3 ± 14
4.5 351.9 ± 119.4 0.021
FSF (mL) Total101.0 ± 26.
8 128.2 ± 41.6 0.025
Successful
96.1 ± 21.1 136.4 ± 45.8 0.027
Failure107.0 ± 32.
7 118.1 ± 35.7 0.484
FS (mL) Total189.0 ± 47.
5 229.5 ± 46.9 0.006
Successful
190.4 ± 51.4 245.0 ± 47.4 0.015
Failure187.3 ± 45.
2 210.4 ± 40.9 0.218
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Increased Voluntary Contractility after Pelvic Floor Exercises
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Cystometrographic Biofeedback
• Under direct visualization of detrusor activity or involuntary detrusor contractions, patients are instructed to hold urine as strongly as possible
• Pressure flow study with patient sitting on commode with a uroflowmeter
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Detrusor instability and Holding urine during involuntary DI
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Neuromodulation for Urgency frequency syndrome
• Surface neuromodulation at suprapubic area
• Sacral nerve stimulation from sacral foramina
• Electromagnetic stimulation
• Interferential current electrostimulation of pelvic floor muscles
• Other transcutaneous neuromodulation
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The Anxious Bladder