Urinary Incontinence

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Urinary Incontinence
Mixed
Urge
Stress
Jan Busby-Whitehead, MD Chief, Division of
Geriatric Medicine University of North
Carolina
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Definition of Urinary Incontinence
The involuntary loss of urine which is
objectively demonstrable and a social or
hygienic problem.
The International Continence Society
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URINARY INCONTINENCE
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Prevalence

• Community 17 older men, up to 30 older women
• Hospital up to 50 older men and women
• LTCF 50-70 older men and women

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Prevalence of Incontinence in Women
Hunskaar, et.al., Int Urogynecol J, 2000
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Prevalence of Incontinencein Community-Dwelling
Women
Hunskaar, et.al., Int Urogynecol J, 2000
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Reversible causes of UI
D
- Delirium or Drugs -
Restricted mobility - Infection,
impaction - Polyuria
R
I
P
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Drugs Contributing to UI
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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

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Physiology
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Aging Changes

• Decreased bladder capacity
• Reduced voiding volume
• Reduced flow rates
• Increased urine production at night
• Nordling, J Experimental Gerontology, 2002,
  37991

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Stress UI
Abrams P et al. Urology. 20036137-49.

• The complaint of involuntary leakage with effort
  or exertion or on sneezing or coughing

Sudden increase in abdominal pressure
Urethral pressure
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Urge UI

• Abrams P et al. Urology. 20036137-49. Ouslander
  J. N Engl J Med. 2004350(8)786-799.

The complaint of involuntary leakage
accompanied by or immediately preceded by urgency
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Overactive bladder

• Includes urinary urgency with or without urge
  incontinence, urinary frequency, and nocturia
• Associated with involuntary contractions of the
  detrusor muscle

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Mixed UI
Abrams P et al. Urology. 20036137-49. Chaliha
C et al. Urology. 20046351-57.

• The complaint of involuntary leakage associated
  with urgency and also with exertion, effort,
  sneezing, or coughing

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Overflow

• Urethral blockage
• The Bladder is not able
• to empty properly

Neurogenic/Atonic
Obstruction
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Functional Incontinence

• Immobility
• Diminished vision
• Aphasia
• Environment
• Psychological

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Clinical 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?

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Office 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

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Basic 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

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Referral 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

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Cystometry

• 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

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Treatment Options

• Behavioral
• Pharmacological
• Functional Electrical Stimulation
• Surgery

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Are behavioral techniques effective? 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

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Behavioral Treatments for UI
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Self Management

• Fluid Intake
• Dont reduce amount
• Do not drink fluids 2 hr before bedtime
• Avoid caffeine, alcohol, nicotine

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Scheduled 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

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Pelvic 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

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Efficacy of Behavioral Treatment
PMFE Without Biofeedback
PMFE With Biofeedback
100 90 80 70 60 50 40 30 20 10 0
98
91
50
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Range of Improvement
Range of Improvement
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Randomized Trials of Behavioral Treatment for
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 199882181-191

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Behavioral 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

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Limitations of Behavioral Treatment Studies

• 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

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NIH Treatment Trial
Kincade, Dougherty, Busby-Whitehead

• 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

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Drug Treatment for UI What Works

• Stress UI
• Alpha adrenergic agents?
• Estrogen?
• Combination therapy?

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Alpha 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

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Duloxetine (Cymbalta)

• FDA application for stress UI withdrawn
• Warning for liver dysfunction, alcohol

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Estrogen

• 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 lt80 given combined HRT or placebo for
  ischemic heart disease.
• 55 had gt1 episode UI/week
• HRT group had worsening stress and urge UI sx

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Drug 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

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Muscarinic 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

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Hepatic 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

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Behavioral vs Drug Rx for Urge UI in Older Women

• 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 BFBgtdruggtplacebo

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Burgio et al JAMA 1998 2801995-2000
Oxybutynin vs Behavioral Treatment for Urge UI
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Oxybutynin

• 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

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Oxybutynin 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

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Tolterodine 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 pts47
  tolterodine, 71 oxybutynin, 19 placebo, dry
  mouth 86 oxybutynin, 50 tolerodine

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OBJECT Study
Appel et al Mayo Clin Proc 200176

• 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

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Trospium

• 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

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Darifenicin

• 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(lt2)

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Solefenacin

• 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)

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Desmopressin

• 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

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Functional 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

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Surgery for Urge/OAB

• If behavioral and pharmacological treatments
  dont 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

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Treatment 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

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Drug 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

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Summary

• 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