Post on 04-Feb-2016
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Jan Busby-Whitehead, MDChief, Division of Geriatric Medicine University of North Carolina
University of North Carolina School of Medicine Center for Aging and Health
Definition of Urinary IncontinenceDefinition of Urinary Incontinence
* The International Continence Society
URINARY INCONTINENCEURINARY INCONTINENCE
University of North Carolina School of Medicine Center for Aging and Health
University of North Carolina School of Medicine Center for Aging and Health
PrevalencePrevalence
• Community: 17% older men, up to 30% older women
• Hospital: up to 50% older men and women
• LTCF: 50-70% older men and women
University of North Carolina School of Medicine Center for Aging and Health
Hunskaar, et.al., Int Urogynecol J, 2000
University of North Carolina School of Medicine Center for Aging and Health
Hunskaar, et.al., Int Urogynecol J, 2000
University of North Carolina School of Medicine Center for Aging and Health
Reversible causes of UI
- Delirium or Drugs
- Restricted mobility
- Infection, impaction
- Polyuria
IIPP
RRDD
University of North Carolina School of Medicine Center for Aging and Health
University of North Carolina School of Medicine Center for Aging and Health
Bladder Anatomy
Hollow, distensible, muscula organ
Reservoir of urine• Capacity ~600 mL• Desire ~200 mL• Normal void ~300 mL
Organ of excretion• Behind symphysis pubis• Female – against anterior wall of
uterus• Trigone• Sphincter
University of North Carolina School of Medicine Center for Aging and Health
Physiology
University of North Carolina School of Medicine Center for Aging and Health
Aging ChangesAging Changes
• Decreased bladder capacity
• Reduced voiding volume
• Reduced flow rates
• Increased urine production at night
* Nordling, J Experimental Gerontology, 2002, 37:991
University of North Carolina School of Medicine Center for Aging and Health
University of North Carolina School of Medicine Center for Aging and Health
Stress UIStress UI
The complaint of involuntary leakage with effort or exertion or on sneezing or coughing
Sudden increase in abdominal pressure
Urethral pressure
Abrams P et al. Urology. 2003;61:37-49.
University of North Carolina School of Medicine Center for Aging and Health
Urge UIUrge UIAbrams P et al. Urology. 2003;61:37-49. Ouslander J. N Engl J Med. 2004;350(8):786-799.
The complaint of involuntary leakage accompanied by or immediately preceded by urgency Involuntary detrusor
contractions
Urethral pressure
University of North Carolina School of Medicine Center for Aging and Health
Overactive bladderOveractive bladder
• Includes urinary urgency with or without urge incontinence, urinary frequency, and nocturia
• Associated with involuntary contractions of the detrusor muscle
University of North Carolina School of Medicine Center for Aging and Health
Mixed UIMixed UI
The complaint of involuntary leakage associated with urgency and also with exertion, effort, sneezing, or coughing
Abrams P et al. Urology. 2003;61:37-49. Chaliha C et al. Urology. 2004;63:51-57.
Sudden increase in abdominal pressure
Involuntary detrusorcontractions
Urethral pressure
University of North Carolina School of Medicine Center for Aging and Health
OverflowOverflow
Neurogenic/Atonic
Obstruction
•Urethral blockage•The Bladder is not able to empty properly
University of North Carolina School of Medicine Center for Aging and Health
Functional IncontinenceFunctional Incontinence
• Immobility
• Diminished vision
• Aphasia
• Environment
• Psychological
University of North Carolina School of Medicine Center for Aging and Health
Clinical QuestionsClinical Questions
? How do you evaluate for incontinence?
? Are behavioral techniques effective? For which patients?
? What drug treatments are useful and how do you use them?
University of North Carolina School of Medicine Center for Aging and Health
Office Evaluation of UIOffice Evaluation of UI
• Identify presence of UI
• Assess for reversible causes and treat
• If UI persistent, determine type and initiate treatment
• Identify patient who needs further evaluation and referral
University of North Carolina School of Medicine Center for Aging and Health
Basic Evaluation of UIBasic Evaluation of UI
• History: Bladder diary
• Physical examination, especially Genitourinary and Neurological
• Bladder stress test
• Postvoid residual
• Urinalysis, urine culture if indicated
• BUN, creatinine, fasting glucose
University of North Carolina School of Medicine Center for Aging and Health
Referral CriteriaReferral Criteria
Recurrent urinary tract infections
Hematuria
Elevated postvoid residual or other evidence of possible obstruction
Recent gynecological or urological surgery or pelvic radiation
Failed treatment of stress or urge UI
University of North Carolina School of Medicine Center for Aging and Health
CystometryCystometry
• Gold standard for diagnosis
• New definition for detrusor overactivity: Any rise in detrusor pressure during filling cystometry associated with symptoms and not related to abnormal bladder compliance
• Provocative stimuli
• Ambulatory monitoring
University of North Carolina School of Medicine Center for Aging and Health
Treatment OptionsTreatment Options
• Behavioral
• Pharmacological
• Functional Electrical Stimulation
• Surgery
University of North Carolina School of Medicine Center for Aging and Health
Are behavioral techniques effective? Are behavioral techniques effective? For whom?For whom?
• Behavioral techniques are effective for treatment of stress and urge UI, and overactive bladder, but generally do not cure
• Behavioral techniques are effective in community dwelling men and women
• Behavioral techniques are most appropriate for cognitively intact, motivated persons
University of North Carolina School of Medicine Center for Aging and Health
University of North Carolina School of Medicine Center for Aging and Health
Self ManagementSelf Management
• Fluid Intake
– Don’t reduce amount– Do not drink fluids 2 hr before bedtime– Avoid: caffeine, alcohol, nicotine
University of North Carolina School of Medicine Center for Aging and Health
Scheduled VoidingScheduled Voiding
• Scheduled voiding with systematic delay of voiding– Schedule based on time interval pt can
manage in daytime– Void at scheduled time even if urge not
present; suppress urge if not time with “Quick Kegels”
– Increase voiding interval by 30 min each week until continent for up to 4 hr
University of North Carolina School of Medicine Center for Aging and Health
Pelvic Muscle ExercisesPelvic Muscle Exercises
• Isolation of the pelvic muscles
• Avoidance of abdominal, buttock or thigh muscle contractions
• Moderate repetitions of strongest contraction possible
• Ability to hold contraction 10 seconds, repeat in groups of 10-30 TID
University of North Carolina School of Medicine Center for Aging and Health
Range of Improvement
100
90
80
70
60
50
40
30
20
10
0
PMFE Without PMFE Without
BiofeedbackBiofeedback
PMFE With PMFE With
BiofeedbackBiofeedback
Range of Improvement
98%
50%
91%
38%
University of North Carolina School of Medicine Center for Aging and Health
Randomized Trials of Behavioral Treatment Randomized Trials of Behavioral Treatment for Stress UIfor Stress UI
• 24 RCTs, but only 11 of high quality
• Pelvic floor exercises were effective (up to 75%)in reducing symptoms of stress UI
• Limited evidence for high vs low intensity
• Benefits of adding biofeedback unclear
* Berghmans et al. Br J Urol 1998:82:181-191
University of North Carolina School of Medicine Center for Aging and Health
Behavioral Treatment for Urge/OABBehavioral Treatment for Urge/OAB
• Bladder training
– Initial approach
–3 RCT: 47-90% cure rate with 6 mo f/u
–Recurrence in 43-58% after 2-3 yr
–35% fewer UI episodes vs controls: Cochrane Review 2004
University of North Carolina School of Medicine Center for Aging and Health
Limitations of Behavioral Treatment Limitations of Behavioral Treatment StudiesStudies
• Studies varied in
– types of UI– characteristics of subjects– intervention strategies– outcome measures used– duration of follow-up
• Few studies compared the efficacy of PFME performed with and without biofeedback
University of North Carolina School of Medicine Center for Aging and Health
NIH Treatment TrialNIH Treatment Trial
Purpose:• Compare pelvic floor muscle exercises alone to
PFME plus biofeedback in women with stress and mixed urge and stress UI
• Design– 315 women randomized to 3 groups, including an
attention control group– Followup up at 2 weeks, 6 months, 1 year
Kincade, Dougherty, Busby-Whitehead
University of North Carolina School of Medicine Center for Aging and Health
Drug Treatment for UI: What WorksDrug Treatment for UI: What Works
• Stress UI
– Alpha adrenergic agents?
– Estrogen?
– Combination therapy?
University of North Carolina School of Medicine Center for Aging and Health
Alpha Adrenergic DrugsAlpha Adrenergic Drugs
• Phenylpropanoloamine– Once a first line drug– 8 randomized controlled trials– Study duration: 2-6 weeks– % cure: 0-14– % side effects: 5-33%
• WITHDRAWN FROM MARKET due to report of hemorrhagic stroke
University of North Carolina School of Medicine Center for Aging and Health
Duloxetine Duloxetine (Cymbalta) (Cymbalta)
• FDA application for stress UI withdrawn
• Warning for liver dysfunction, alcohol
University of North Carolina School of Medicine Center for Aging and Health
EstrogenEstrogen
• Combined study with Phenylpropanolamine suggested improvement in combination
• Improves urogenital atrophy
• Heart and Estrogen/Progestin Replacement Study 2001: 4 yr, randomized trial, 2763 postmenopausal women <80 given combined HRT or placebo for ischemic heart disease.– 55% had >1 episode UI/week– HRT group had worsening stress and urge UI sx
University of North Carolina School of Medicine Center for Aging and Health
Drug Treatment of Overactive BladderDrug Treatment of Overactive Bladder
• Anticholinergic Drugs are mainstay– Oxybutynin IR 2.5-5 mg bid-qid – Ditropan XL 5-20 mg daily– Oxytrol patch TDS 3.9 mg 2x/wk – Tolterodine tartrate IR 1-2 mg bid– Detrol LA 2-4 mg daily
New Drugs:– Trospium chloride (Sanctura) 20 mg bid– Darifenicin (Enablex) 7.5-15 mg daily– Solefenicin (Vesicare) 5-10 mg daily
University of North Carolina School of Medicine Center for Aging and Health
Muscarinic ReceptorsMuscarinic Receptors
• M1 – Brain (cortex, hippocampus), salivary• glands, sympathetic ganglia
• M2 – Heart, hindbrain, smooth muscle (80% of detrusor)
• M3 – Smooth muscle (20% of detrusor), salivary glands, brain, eye (lens, iris)
• M4 – Brain (forebrain, striatum)
• M5 – Brain (substantia nigra), eye
University of North Carolina School of Medicine Center for Aging and Health
Hepatic metabolismHepatic metabolism• Oxybutynin CYP 3A4
• Tolterodine CYP 3A4, CYP 2D6
• Darifenacin CYP 3A4, CYP 2D6
• Solifenacin CYP 3A4
• CYP 3A4: Interactions with macrolides, ketoconazole, nefazadone
• CYP 2D6: interactions with TCAs, fluoxetine
University of North Carolina School of Medicine Center for Aging and Health
Behavioral vs Drug Rx for Urge UI in Older Behavioral vs Drug Rx for Urge UI in Older WomenWomen
• Randomized, controlled trial by Burgio et al JAMA 1998; 280; 1995-2000
• 197 women aged 55-92
• 8 weeks of BFB, 8 weeks of oxybutynin
• 2.5 to 5 mg qd to tid, or placebo control
• All 3 groups reduced UI frequency
• Effectiveness: BFB>drug>placebo
University of North Carolina School of Medicine Center for Aging and Health
Burgio et al JAMA 1998; 280:1995-2000
0
2
4
6
8
10
12
14
16
Leaks per
week
Behavioral Control
Pre
Post
University of North Carolina School of Medicine Center for Aging and Health
OxybutyninOxybutynin
• Both anticholinergic and smooth muscle relaxant properties
• 6/7 RCTs show benefit
• 15-58% greater reduction in urge UI than placebo
• Dose: 2.5 -5 mg qd-qid, 20 mg/d maximum
University of North Carolina School of Medicine Center for Aging and Health
Oxybutynin Controlled ReleaseOxybutynin Controlled Release
• Once daily dosing
• RCT showed rate of daytime continence similar to that for immediate release (53 vs 58%)
• Lower rate of dry mouth than immediate release form
University of North Carolina School of Medicine Center for Aging and Health
Tolterodine tartrateTolterodine tartrate
• Pure muscarinic receptor antagonist
• Dry mouth most common side effect
• 3 RCT compared tolterodine (2 mg bid) to oxybutynin (5 mg tid): Equally effective and superior to placebo
• Decreased urge U(I in study of 293 pts:47% tolterodine, 71% oxybutynin, 19% placebo, dry mouth 86% oxybutynin, 50% tolerodine
University of North Carolina School of Medicine Center for Aging and Health
OBJECT StudyOBJECT Study
• Compared efficacy and tolerability of extended release oxybutynin and tolterodine tartrate
• 12 weeks
• Prospective randomized,double-blind, parallel group study
• 276 women and 56 men
• Oxybutynin more effective for weekly urge UI, total incontinence, and urinary frequency
Appel et al Mayo Clin Proc 2001:76
University of North Carolina School of Medicine Center for Aging and Health
TrospiumTrospium• Dose 20 mg bid
• Renal metabolism
• Nonselective for muscarinic receptors
• Effective for detrusor overactivity in placebo-controlled double-blind studies:
• Trospium 20 mg bid vs tolterodine 2 mg bid in 232 pts reduced voiding frequency and number of UI episodes
• Dry mouth 7% and 9% respectively
University of North Carolina School of Medicine Center for Aging and Health
DarifenicinDarifenicin• Dose 7.5 to 15 mg daily
• Selective M3 receptor antagonist
• Several RCTs
• Mundy et al 2001 Randomized double-blind trial compared darifenacin 15 mg and 30 mg to oxybutynin 5 mg tid in 25 pts , similar efficacy
• Side effects: Dry mouth, constipation(<2%)
University of North Carolina School of Medicine Center for Aging and Health
SolefenacinSolefenacin
• Dose 5 to 10 mg daily
• Long acting muscarinic receptor antagonist, selective for M3
• Undergoes hepatic metabolism involving cytochrom P450
• Several multinational trials with over 800 pts, vs placebo, showed efficacy low side effects (2% dry mouth)
University of North Carolina School of Medicine Center for Aging and Health
University of North Carolina School of Medicine Center for Aging and Health
DesmopressinDesmopressin
• Decreases urine production
• Helps nocturia
• Dose: 20-40 mcg intranasal spray q hs
• Double-blind crossover trial showed decreased nighttime voids vs placebo, 1.9 vs 2.6
• Contraindications: CHF, HTN, ASCVD
University of North Carolina School of Medicine Center for Aging and Health
Functional Electrical StimulationFunctional Electrical Stimulation• Frequency of 10-50 Hertz for 15-20 minutes daily
• RCT: 50% cured after 8 weeks compared to sham controls
• 52-77% symptomatic improvement in short-term studies, non RCT
• Implantable electrodes at S2-3, 76% improvement for refractory urge UI x 18 mo
• BUT 33% required surgical revision
University of North Carolina School of Medicine Center for Aging and Health
Surgery for Urge/OABSurgery for Urge/OAB
• If behavioral and pharmacological treatments don’t work
• Augmentation enterocystoplasty
• One series of 267 patients had a 93% continence rate with 3 yr f/u
• Complications: urinary retention, stones, small bowel obstruction, reservoir rupture
University of North Carolina School of Medicine Center for Aging and Health
Treatment of Overflow UI Due to Mild BPHTreatment of Overflow UI Due to Mild BPH
• Alpha adrenergic antagonists
– Possibly relaxes prostate smooth muscle and stroma and urethra smooth muscle to increase urine flow
– Tamsulosin, doxazosin, terazosin
– Tamsulosin trials: 53 weeks, 31% and 36% improvement in maximal flow rate with 0.4mg and 0.8 mg/day vs 21% placebo
– Uroselective alfuzosin in late stage clinical trials
University of North Carolina School of Medicine Center for Aging and Health
Drug Treatment of Mild BPHDrug Treatment of Mild BPH
• Type II 5 alpha reductase inhibitor– Results in atrophy of the prostatic glandular
epithelium due to decreased synthesis of dihydrotestosterone
– Slow onset, 20-30% reduction in prostate volume and LUTS over time
– Side effects: Ejaculatory dysfunction (8%), loss of libido (10%), erectile dysfunction (16%)
– Finasteride , Dutasteride
University of North Carolina School of Medicine Center for Aging and Health
SummarySummary
• Behavioral treatment is effective for treating stress and urge UI and OAB
• Drugs are effective for treating urge UI and OAB and mild BPH
• New selective agents for urge and OAB based on new understanding of bladder and urethral function
• Caution needed in dosing, especially in older patients