Transcript Overactive Bladder - Grand River Hospital

Medial and Surgical
Treatment of
Incontinence
May 6, 2009
Symposium on Challenging Geriatric
Issues
Satish Rangaswamy, M.D., F.R.C.S.(C)
Disclosures

Investigator/Advisory Board Member /or Honoraria provided by the
following companies:
 Pfizer Canada
 Astellas Pharma Canada
 Novartis Pharmaceuticals Canada
Overview
• OAB Incontinence
• Stress Incontinence
Classification of Urinary Incontinence
Stress
 Urethral
Cause
hypermobility
 Intrinsic
sphincter
deficiency
 Leakage
Symptoms
Mixed
 Detrusor
overactivity
 Sensitive
 Combination of Hypotonic or
urge and stress acontractile
detrusor
bladder
 Involuntary
Overflow
 Obstruction
 Often one
during  intra- leakage
symptom
abdominal
predominant
 Strong desire
pressure
to void
  with age
 Bladder
distension
 Frequent to
constant
dribbling
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, α-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
Overactive Bladder
1.
Definition
2.
Screening and Assessment
3.
Management Approach
4.
Safety of Pharmacologic agents in the Elderly
5.
OAB in Males
6.
Emerging therapies/Surgical therapies
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. 167–178.
Etiologies of Bladder Overactivity

Obstruction (BPH)

Pelvic floor/urethral disorder

Neurological conditions

Bladder hypersensitivity (sensory)

Behavioural

Immature bladder (congenital)

Aging-related

Combinations

DHIC (detrusor hyperactivity
with impaired bladder
contractility)

Idiopathic
OAB Is Prevalent
and Increases With Age
Comparison of Data From the SIFO Study 1997
and the EPIC Study 2005
40
30
Men – SIFO 1997
Men – 2005
Women – SIFO 1997
25
Women ̶ 2005
Prevalence, %
35
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. 2001;87:760-766.
Irwin DE et al. EAU 2006.
EPIC Study. Data of file. Pfizer Inc.
OAB Impact on Quality of Life
Physical
 Decreased
ability to maintain an independent
lifestyle
 More
discomfort and skin irritation
 Increased
dependence on caregivers
 Restriction
 Poor
of sexual activity
sleep
 Cause
of falls at night
OAB Impact on Quality of Life
Psychological
 Loss
of self-esteem & self-confidence
 Feelings
 Fear
of shame, embarrassment
of losing “control” (life ruled by
bladder)
OAB Impact on Quality of Life
Social

Withdrawal/avoidance/restriction of
- social activity
- recreation
- occupation
- travel

Negative impact on relationships

Important influence on decision to
institutionalize an elderly person
Overactive Bladder
1.
Definition
2.
Screening and Assessment
3.
Management Approach
4.
Safety of Pharmacologic agents in the Elderly
5.
OAB in Males
6.
Emerging therapies/Surgical therapies
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”
Basic Evaluation of OAB
 Components of the basic evaluation should
include
- patient history-voiding diary
- physical examination
- urinalysis
- PVR - if indicated
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
Basic Evaluation of OAB
Postvoid Residual Volume (PVR)
 If clinically indicated accurate PVR can be done by
- catheterization
- ultrasound
 PVR of <50 mL is considered normal, repetitive PVR >200 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.
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
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
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)
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 3–4% of the population aged > 65 years
Pharmacotherapy for Nocturia in the Elderly Patient
Ragnar Asplund Drugs Aging 2007; 24 (4): 325-343
Voiding Diary 1
Time of Day
0700h
Amount voided (ml)
400
Amount Intake (ml)
400
1100h
250
300
1400h
200
500
1800h
350
300
2100h
300
200
2200h
150
200
Total
1750 ml
1900 ml
Voiding Diary 2
Time of Day
Amount voided (ml)
Amount Intake (ml)
0700h
250
400
1100h
250
400
1600h
200
500
2000h
250
300
0100h
200
400
0200h
150
200
0300h
200
0500h
200
0600h
200
Total
1900ml
2200 ml
Overactive Bladder
1.
Definition
2.
Screening and Assessment
3.
Management Approach
4.
Safety of Pharmacologic agents in the Elderly
5.
OAB in Males
6.
Emerging therapies/Surgical therapies
OAB Management
Treatment approaches for overactive bladder
 Lifestyle changes and/or management
 Behavioral therapy
 Pharmacological therapy
Lifestyle changes
 Moderate fluid intake
 Reduce or eliminate caffeine
 Avoid fluids before bed
Behavioral Treatments
 Pelvic floor muscle exercises
- Kegel
 Biofeedback
 Electrical stimulation
Behavioral Treatments
 Toileting assistance
- scheduled toileting
- prompted voiding
 Bladder education/retraining
- delayed/timed voiding
- urge suppression exercises
Pharmacologic Therapy
Pharmacologic Therapy for Bladder Overactivity
Overactive Bladder
1.
Definition
2.
Screening and Assessment
3.
Management Approach
4.
Safety of Pharmacologic agents in the Elderly
5.
OAB in Males
6.
Emerging therapies/Surgical therapies
OHIP Limited Use
TOLTERODINE L-TARTRATE
Detrol LA 2mg SR Cap
Detrol LA 4mg SR Cap
Detrol 1mg
Detrol 2mg Tab
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
Overactive Bladder
1.
Definition
2.
Screening and Assessment
3.
Management Approach
4.
Safety of Pharmacologic agents in the Elderly
5.
OAB in Males
6.
Emerging therapies/Surgical therapies
Men and Women Are Both
Bothered by OAB Symptoms
Percentage of Respondents
Percentage of Respondents With OAB Symptoms
Who Reported That OAB Had an Effect on Daily Living
100
80
Men
65%
Women
67%
60
40
20
0
Bothered by OAB
From a survey of 16,776 adults.
Milsom I et al. BJU Int. 2001;87:760-766.
Fewer Men than Women Are Treated
with Antimuscarinics
Prescriptions, in thousands
25
‘OAB’ prescriptions
‘BPH’ prescriptions
20
15
10
5
0
Female
Male
Women with OAB symptoms get
treatment more than men (4:1)
Data collected over 12 months.
‘OAB’ prescriptions include all antimuscarinics
‘BPH’ prescriptions include all alpha blockers
and 5-alpha reductase inhibitors.
Male
Men with LUTS are treated
mainly for prostate conditions
Verispan Patient Longitudinal Data, MAT. 2005.
IMS NPA, MAT. 2005.
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 >20) and no prior therapy
for BPH

Patient population
- 221 men with BOO and DO
- PVR <40% of maximum cystometric capacity
- No history of urinary retention in the
preceding 12 months
- 2:1 randomization
Abrams P et al. J Urol 2006; 175:999-1004.
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; 175:999-1004.
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 α-blocker

Patient population
- 43 men with BPE and LUTS (50-83 years)
- Failed an α-blockers due to AEs (11pts)
or lack of efficacy (32 pts)
- PSA <10 mg, no history of urologic surgery
Kaplan S et al. J Urol. 2005; 174:2273-76
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 < .001)
- PVR decreased from 97 mL to 75 mL (P < .03)

Safety
- 4 men (9%) discontinued therapy because of dry mouth
- No incidence of AUR
Kaplan S et al. J Urol. 2005; 174:2273-76
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: 169:2253-6
Lee JY, Kim HW, Lee SJ, et al., BJU Int 2004: 94:817-20
Lee K-S, Choo M-S, Kim D-Y, et al. J Urol 2005; 174: 1334-8
Kaplan SA, Walmsley K, Te AE, J Urol 2005: 174:2273-6
Abrams P, J Urol 2006; 175: 999-1004.
Roehrborn C, et al. BJUI 2006; 97:1003
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
Overactive Bladder
1.
Definition
2.
Screening and Assessment
3.
Management Approach
4.
Safety of Pharmacologic agents in the Elderly
5.
OAB in Males
6.
Emerging therapies/Surgical therapies
β3 Adrenoceptor
The b3-AR is the most abundant of the AR subtypes
in human detrusor muscle, suggesting that
this subtype mediates detrusor relaxation.
β3 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
Animal Studies of β3 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 1999;161:680–5.
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 2000;293:939–45.
β3 Adrenoceptor Agonist
Beta-3 AR agonist
Bladder
Induction of
relaxation
Anticholinergic agent
Inhibition of
contraction
Prostate
Sphincter muscle
of urethra
β2
β2
β2
β2
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
Normal Neuromuscular transmission
THE JOURNAL OF UROLOGY®
Vol. 171, 2128–2137, June 2004
Mechanism of Action
Botulinum toxin
THE JOURNAL OF UROLOGY®
Vol. 171, 2128–2137, June 2004
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
Interstim
Sacral Neuromodulation
Gastric Augmentation Cystoplasty
Detubularized Ileal Augmentation
Cystoplasty
Augmentation cystoplasty with simultaneous AUS implantation;
Conclusion-Overactive Bladder
1.
Definition
 Urgency
 Nocturia – NP vs DBC
2.
Screening and Assessment
 History, Physical, Voiding Diary is helpful
3.
Management Approach
 Lifestyle, Behavioural, Pharmacological and Surgical
Conclusion-Overactive Bladder
1.
Safety of Pharmacologic agents in the Elderly
 Use selective M3 anti muscarinics where possible
 Use agents which don’t cross the BBB
2.
OAB in Males
- Anticholinergics seem safe
3.
Surgical and Emerging therapies
 Newer agents and surgical procedures
Stress Incontinence
Female
Male
• Hypermobility
• ISD
• Neurogenic
• Postprostatectomy
• Neurogenic
Stress Incontinence
Assessment
History,
Physical Examination
Pad test
Cough stress test
Cystoscopy
Voiding cystometrogram
Abdominal leak point pressure
Stress Incontinence
Medical therapy
Kegel exercises
M/F
Alpha adrenergic agonists
M/F
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
Stress Incontinence
Female
• Hypermobility
• ISD
• Neurogenic
Hypermobility
Hypermobility
Normal mucosal seal
ISD
Poor mucosal seal
Original TVT
TRANS-OBTURATOR SLINGS
Third Generation Synthetic Midurethral Slings
Peri-Urethral Bulking Agents
•
•
•
•
•
•
Collagen
Silicone particles
Calcium hydroxylapatite
Ethylene vinyl alcohol
Carbon spheres
Porcine dermal implant
• Autologous fat
• Hyaluronic
acid/Dextranomer
• Teflon particles
Treatment with Zuidex Implacement
4 x 0.7ml
NASHA/Dx
Stress Incontinence
Male
• Postprostatectomy
• Neurogenic
Male Slings
AMS Advance Male Sling
AUS