Medial and Surgical Treatment of Incontinence

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Medial and Surgical Treatment of Incontinence
May 6, 2009 Symposium on Challenging
Geriatric Issues Satish Rangaswamy, M.D.,
F.R.C.S.(C)
2
Disclosures

• Investigator/Advisory Board Member /or Honoraria
  provided by the following companies
• Pfizer Canada
• Astellas Pharma Canada
• Novartis Pharmaceuticals Canada

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Overview

• OAB Incontinence

• Stress Incontinence

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Classification of Urinary Incontinence
Stress
Urge
Mixed
Overflow

• Urethral hypermobility
• Intrinsic sphincter deficiency

• Detrusor overactivity
• Sensitive bladder

• Combination of urge and stress

• Hypotonic or acontractile detrusor
• Obstruction

Cause

• Leakage during ? intra-abdominal pressure

• Involuntary leakage
• Strong desire to void

• Often one symptom predominant
• ? with age

• Bladder distension
• Frequent to constant dribbling

Symptoms
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Incontinence - acute and potentially treatable
causes

• D Delirium or confusion
• I Infection
• A Atrophic vaginitis or urethritis
• P Pharmaceutical agents (e.g. anticholinergic
  agents,
• diuretics, a-adrenoceptor agonists, calcium
  channel antagonists)
• P Psychological factors (e.g. depression,
  dementia)
• E Excess urine output (e.g. volume-expanded
  states, retention overflow)
• R Restricted mobility
• S Stool impaction

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Overactive Bladder

• Definition
• Screening and Assessment
• Management Approach
• Safety of Pharmacologic agents in the Elderly
• OAB in Males
• Emerging therapies/Surgical therapies

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DEFINITION

• The defining symptoms of overactive bladder
  syndrome (OAB) are
• urinary urgency with or without incontinence,
• frequency
• nocturia1
• Of these, urgency is the cardinal symptom.

1. Abrams P, Cardozo L, Fall M et al., The
standardization of terminology of lower urinary
tract function report from the Standardization
Sub-committee of the International Continence
Society, Neurourol. Urodyn. (2002)21 pp.
167178.
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Etiologies of Bladder Overactivity

• Obstruction (BPH)
• Neurological conditions
• Behavioural
• Aging-related
• DHIC (detrusor hyperactivity with impaired
  bladder contractility)

• Pelvic floor/urethral disorder
• Bladder hypersensitivity (sensory)
• Immature bladder (congenital)
• Combinations

• Idiopathic

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OAB Is Prevalent and Increases With Age
Comparison of Data From the SIFO Study 1997 and
the EPIC Study 2005
40
35
30
25
Prevalence,
20
15
10
5
0
18-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70
Age, y
Milsom I et al. BJU Int. 200187760-766. Irwin
DE et al. EAU 2006. EPIC Study. Data of file.
Pfizer Inc.
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OAB Impact on Quality of Life Physical

• Decreased ability to maintain an independent
  lifestyle
• More discomfort and skin irritation
• Increased dependence on caregivers
• Restriction of sexual activity
• Poor sleep
• Cause of falls at night

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OAB Impact on Quality of LifePsychological

• Loss of self-esteem self-confidence
• Feelings of shame, embarrassment
• Fear of losing control (life ruled by bladder)

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OAB Impact on Quality of LifeSocial

• Withdrawal/avoidance/restriction of
• social activity
• recreation
• occupation
• travel
• Negative impact on relationships
• Important influence on decision to
  institutionalize an elderly person

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Overactive Bladder

• Definition
• Screening and Assessment
• Management Approach
• Safety of Pharmacologic agents in the Elderly
• OAB in Males
• Emerging therapies/Surgical therapies

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Screening for Possible OAB

• Primary health care providers should question at
  risk patients to identify OAB
• Questions should be open-ended e.g.
• Are you having any trouble WITH BLADDER CONTROL

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Basic Evaluation of OAB

• Components of the basic evaluation should include
• patient history-voiding diary
• physical examination
• urinalysis
• PVR - if indicated

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Basic Evaluation of OAB Postvoid Residual Volume
(PVR)

• patients with symptoms of incomplete emptying
• longstanding diabetes mellitus
• past history of urinary retention
• failure of pharmacological therapy
• pelvic floor prolapse
• previous incontinence surgery

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Basic Evaluation of OAB Postvoid Residual Volume
(PVR)

• If clinically indicated accurate PVR can be done
  by
• catheterization
• ultrasound
• PVR of lt50 mL is considered normal, repetitive
  PVR gt200 mL is considered abnormal
• Clinical judgment must be exercised when
  interpreting PVR results in the intermediate
  range of 50 - 199 mL

Adapted from Clinical Practice Guideline on
Urinary Incontinence in Adults. Rockville, MD
Agency for Health Care Policy and Research March
1996.
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Nocturia vs Nocturnal Polyuria

• Nocturia is frequency of urination waking up the
  individual greater than once per night. It may be
  due to
• Nocturnal Polyuria
• Decreased nocturnal bladder capacity or
• Combination.
• Nocturnal Polyuria is passage of greater than 33
  of total voided volume during sleeping hours.
  Multiple causes

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Causes of Nocturnal Polyuria

• Congestive heart failure
• Hypoalbuminemia 
• Venous insufficiency 
• Excessive fluid intake
• Use of long-acting diuretics
• Chronic Renal Disease
• Sleep apnea 
• Nocturnal Polyuria Syndrome

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Sleep Apnea

• The nocturnal polyuria of sleep apnea is an
  evoked response to conditions of negative
  intrathoracic pressure due to inspiratory effort
  posed against a closed airway.
• The mechanism for this natriuretic response is
  the release of atrial natriuretic peptide due to
  cardiac distension caused by the negative
  pressure environment.
• This cardiac hormone increases sodium and water
  excretion and also inhibits other hormone systems
  that regulate fluid volume, vasopressin and the
  renin-angiotensin-aldosterone complex.

Mary Umlauff, Eileen Chasens Sleep
disordered breathing and nocturnal polyuria
nocturia and enuresis SLEEP MEDICINE REVIEWS
Volume 7, Issue 5, Pages 403-411 (October 2003)
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Nocturnal Polyuria Syndrome

• A disorder of the vasopressin system with
• very low or undetectable levels of vasopressin at
• night and in some cases throughout the entire
• 24-hour period has been designated the nocturnal
• polyuria syndrome, a condition characterised by
  an
• increase in the nocturnal urine output, which in
  the
• most extreme cases accounts for 85 of the
  24-hour
• diuresis. It has been estimated that the
  nocturnal polyuria syndrome
• occurs in 34 of the population aged gt 65 years

Pharmacotherapy for Nocturia in the Elderly
Patient Ragnar Asplund Drugs Aging 2007 24
(4) 325-343
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Voiding Diary 1
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Voiding Diary 2
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Overactive Bladder

• Definition
• Screening and Assessment
• Management Approach
• Safety of Pharmacologic agents in the Elderly
• OAB in Males
• Emerging therapies/Surgical therapies

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OAB Management

• Treatment approaches for overactive bladder

• Lifestyle changes and/or management
• Behavioral therapy
• Pharmacological therapy

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Lifestyle changes

• Moderate fluid intake
• Reduce or eliminate caffeine
• Avoid fluids before bed

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Behavioral Treatments

• Pelvic floor muscle exercises
• Kegel
• Biofeedback
• Electrical stimulation

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Behavioral Treatments

• Toileting assistance
• scheduled toileting
• prompted voiding
• Bladder education/retraining
• delayed/timed voiding
• urge suppression exercises

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Pharmacologic Therapy
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Pharmacologic Therapy for Bladder Overactivity
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Overactive Bladder

• Definition
• Screening and Assessment
• Management Approach
• Safety of Pharmacologic agents in the Elderly
• OAB in Males
• Emerging therapies/Surgical therapies

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OHIP Limited Use
290 For patients with urinary frequency, urgency
or urge incontinence who have Failed to respond
to behavioral techniques AND An adequate trial of
oxybutynin with gradual dose escalation has shown
to be either ineffective or resulted in
unaccepatable side effects. Note If after a
trial of 2 weeks patients continue to
experience similar side effects and no greater
efficacy than oxybutynin, continued therapy with
this more costly agent should be
reassessed. Authorization Period Indefinite
TOLTERODINE L-TARTRATE Detrol LA 2mg SR
Cap Detrol LA 4mg SR Cap Detrol 1mg Detrol 2mg Tab
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Overactive Bladder

• Definition
• Screening and Assessment
• Management Approach
• Safety of Pharmacologic agents in the Elderly
• OAB in Males
• Emerging therapies/Surgical therapies

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Men and Women Are Both Bothered by OAB Symptoms
Percentage of Respondents With OAB Symptoms Who
Reported That OAB Had an Effect on Daily Living
Men
Women
100
80
67
65
60
Percentage of Respondents
40
20
0
Bothered by OAB
Milsom I et al. BJU Int. 200187760-766.
From a survey of 16,776 adults.
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Fewer Men than Women Are Treated with
Antimuscarinics
25
OAB prescriptions
20
BPH prescriptions
15
Prescriptions, in thousands
10
5
0
Female
Male
Male
Women with OAB symptoms get treatment more than
men (41)
Men with LUTS are treated mainly for prostate
conditions
Data collected over 12 months. OAB
prescriptions include all antimuscarinics BPH
prescriptions include all alpha blockers and
5-alpha reductase inhibitors.
Verispan Patient Longitudinal Data, MAT.
2005. IMS NPA, MAT. 2005.
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Safety of Tolterodine IR in Men With OAB/DO and
BOO Study Design

• Multinational, double-blind study comparing 12
  weeks of tolterodine 2 mg bid with placebo
• Study objective
• Evaluate the safety of tolterodine IR in men with
  urodynamically proven BOO and DO
  (Abrams-Griffiths gt20) and no prior therapy for
  BPH
• Patient population
• 221 men with BOO and DO
• PVR lt40 of maximum cystometric capacity
• No history of urinary retention in the preceding
  12 months
• 21 randomization

Abrams P et al. J Urol 2006 175999-1004.
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Safety of Tolterodine IR in Men With OAB/DO and
BOO Results

• No difference between tolterodine and placebo
  effect on Qmax and PdetQmax at 12 weeks
• No difference in AUR between tolterodine and
  placebo

Abrams P et al. J Urol 2006 175999-1004.
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Tolterodine ER as Monotherapy in?-Blocker
Failures Results

• Open-label, 6-month study
• Objective
• To ascertain safety and efficacy of tolterodine
  ER in men with LUTS who previously discontinued
  an a-blocker
• Patient population
• 43 men with BPE and LUTS (50-83 years)
• Failed an a-blockers due to AEs (11pts) or lack
  of efficacy (32 pts)
• PSA lt10 mg, no history of urologic surgery

Kaplan S et al. J Urol. 2005 1742273-76
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Tolterodine ER as Monotherapy in?-Blocker
Failures Results

• Symptomatic improvement
• Frequency decreased from 9.8 to 6.3
  micturitions/day
• Night-time frequency decreased from 4.1 to 2.9
  per night
• AUA-SS decreased from 17.3 to 11.2
• Urodynamic results
• Qmax increased from 9.8 mL/s to 11.7 mL/s (P lt
  .001)
• PVR decreased from 97 mL to 75 mL (P lt .03)
• Safety
• 4 men (9) discontinued therapy because of dry
  mouth
• No incidence of AUR

Kaplan S et al. J Urol. 2005 1742273-76
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Recent Studies of Anticholinergics in Men with
OAB/LUTS Safety
Incidence of Urinary Retention in trials

• Tolterodine alpha blocker (3 months)
• 0/25 (Athanasopoulos)
• 1/60 (Lee)
• Tolterodine monotherapy (3-6 months)
• 0/149 (Abrams)
• 27 ml average increase in PVR not considered
  clinically significant
• 1/72 on placebo
• 0/43 (Kaplan)
• 1/77 (Roehrborn)
• Propiverine alpha blocker (2 months)
• 0/142 (Lee)

Incidence of Urinary Retention in BPH Patients
0.5-2.5 /year Roehrborn, 2001
Athanasopoulos A et al., J Urol 2003
1692253-6 Kaplan SA, Walmsley K, Te AE, J Urol
2005 1742273-6 Lee JY, Kim HW, Lee SJ, et al.,
BJU Int 2004 94817-20 Abrams P, J Urol 2006
175 999-1004. Lee K-S, Choo M-S, Kim D-Y, et al.
J Urol 2005 174 1334-8 Roehrborn C, et al.
BJUI 2006 971003
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Conclusions - OAB in Men

• Prevalence of OAB is similar in men and women and
  increases with age
• In both men and women with LUTS, storage symptoms
  are more bothersome than voiding symptoms
• Physicians are more likely to use BPH agents than
  OAB agents as a first-line therapy for OAB
  symptoms in men
• Early evidence that anti-muscarinics are safe and
  efficacious in males with OAB/LUTS
• Caution in patients with neurological disorders

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Overactive Bladder

• Definition
• Screening and Assessment
• Management Approach
• Safety of Pharmacologic agents in the Elderly
• OAB in Males
• Emerging therapies/Surgical therapies

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ß3 Adrenoceptor

• The b3-AR is the most abundant of the AR subtypes
• in human detrusor muscle, suggesting that
• this subtype mediates detrusor relaxation.

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ß3 Adrenoceptor Agonist

• The mechanism by which b-AR agonists induce
• relaxation of smooth muscles is not fully
• understood, but it is believed that an
  intracellular
• pathway for smooth muscle relaxation is activated
• by cAMP

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Animal Studies of ß3 Adrenoceptor Agonist

• No change in micturition pressure1
• Bladder capacity increased and
• No change in residual volume.2

1. Fujimura T, Tamura K, Tsutsumi T, et al.
Expression and possible functional role of the
b3-adrenoceptor in human and rat detrusor
muscle. J Urol 19991616805.
2. Takeda H, Yamazaki Y, Akahane M, et al. Role
of the b3-adrenoceptor in urine storage in the
rat comparison between the selective
b3-adrenoceptor agonist, CL316,243, and various
smooth muscle relaxants. J Pharmacol Exp Ther
200029393945.
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ß3 Adrenoceptor Agonist
Beta-3 AR agonist
Anticholinergic agent
M3
M3
ß3
ß3
Induction of relaxation
Inhibition of contraction
Bladder
ß3
ß3
M3
M3
a1
a1
a1
a1
Prostate
Sphincter muscle of urethra
ß2
ß2
ß2
ß2
Induction of relaxation without change in maximum
micturition pressure
Inhibition of contraction with decrease in
maximum micturition pressure
No affect on residual urine volume
? Increase in residual urine volume
The possibility of indication for urge
incontinence with BPH
? Contraindication for urge incontinence with BPH
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Normal Neuromuscular transmission
THE JOURNAL OF UROLOGY
Vol. 171, 21282137, June 2004
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Mechanism of ActionBotulinum toxin
THE JOURNAL OF UROLOGY
Vol. 171, 21282137, June 2004
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Botox injection

• 100 units diluted in 10ml saline in 30 injection
  sites, sparing the trigone
• Under local anesthesia (xylocaine 2 in 20ml, 20
  minutes)
• In the absence of a positive urine culture

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Interstim Sacral Neuromodulation
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Gastric Augmentation Cystoplasty
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Detubularized Ileal Augmentation Cystoplasty
Augmentation cystoplasty with simultaneous AUS
implantation
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Conclusion-Overactive Bladder

• Definition
• Urgency
• Nocturia NP vs DBC
• Screening and Assessment
• History, Physical, Voiding Diary is helpful
• Management Approach
• Lifestyle, Behavioural, Pharmacological and
  Surgical

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Conclusion-Overactive Bladder

• Safety of Pharmacologic agents in the Elderly
• Use selective M3 anti muscarinics where possible
• Use agents which dont cross the BBB
• OAB in Males
• Anticholinergics seem safe
• Surgical and Emerging therapies
• Newer agents and surgical procedures

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Stress Incontinence

• Female
• Hypermobility
• ISD
• Neurogenic

• Male
• Postprostatectomy
• Neurogenic

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Stress Incontinence

• Assessment

History, Physical Examination Pad test Cough
stress test Cystoscopy Voiding cystometrogram
Abdominal leak point pressure
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Stress Incontinence

• Medical therapy
• Kegel exercises M/F
• Alpha adrenergic agonists M/F

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Stress Incontinence

• Surgical therapy
• Periurethral Bulking Agents M/F
• Post./Midurethral Slings M/F
• Open Surgery (rarely)-Pubovaginal Sling,
  Retropubic Urethropexy F
• Artificial Sphincter M/F

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Stress Incontinence

• Female
• Hypermobility
• ISD
• Neurogenic

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Hypermobility
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Hypermobility
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ISD
Poor mucosal seal
Normal mucosal seal
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Original TVT
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TRANS-OBTURATOR SLINGS
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Third Generation Synthetic Midurethral Slings
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Peri-Urethral Bulking Agents

• Autologous fat
• Hyaluronic acid/Dextranomer
• Teflon particles

• Collagen
• Silicone particles
• Calcium hydroxylapatite
• Ethylene vinyl alcohol
• Carbon spheres
• Porcine dermal implant

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Treatment with Zuidex Implacement
4 x 0.7ml NASHA/Dx
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Stress Incontinence

• Male
• Postprostatectomy
• Neurogenic

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Male Slings
AMS Advance Male Sling
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AUS
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