1. Medial and Surgical Treatment of Incontinence
May 6, 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

3. Overview
OAB Incontinence
Stress Incontinence

4. 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 6

5. 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

6. Overactive Bladder Definition Screening and Assessment
Management Approach
Safety of Pharmacologic agents in the Elderly
OAB in Males
Emerging therapies/Surgical therapies

7. 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. 2

8. 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 5

9. OAB Is Prevalent and Increases With Age
Comparison of Data From the SIFO Study and the EPIC Study 2005 40 35
Men – SIFO 1997
Men – 2005 30
Women – SIFO 1997 25
Women ̶ 2005
Prevalence, % 20 15 10 5
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:
Irwin DE et al. EAU 2006.
EPIC Study. Data of file. Pfizer Inc.

10. 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 17

11. OAB Impact on Quality of Life Psychological
Loss of self-esteem & self-confidence
Feelings of shame, embarrassment
Fear of losing “control” (life ruled by bladder) 18

12. 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 19

13. Overactive Bladder Definition Screening and Assessment
Management Approach
Safety of Pharmacologic agents in the Elderly
OAB in Males
Emerging therapies/Surgical therapies

14. 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” 30

15. Basic Evaluation of OAB
Components of the basic evaluation should include
patient history-voiding diary
physical examination
urinalysis
PVR - if indicated 32

16. 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

17. 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 mL
Adapted from Clinical Practice Guideline on Urinary Incontinence in Adults. Rockville, MD: Agency for Health Care Policy and Research; March 1996. 36

18. 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

19. 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

20. 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 (October 2003)

21. 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):

22. Voiding Diary 1 Time of Day Amount voided (ml) Amount Intake (ml)
0700h
400
1100h
250
300
1400h
200
500
1800h
350
2100h
2200h
150
Total
1750 ml
1900 ml

23. Voiding Diary 2 Time of Day Amount voided (ml) Amount Intake (ml)
0700h
250
400
1100h
1600h
200
500
2000h
300
0100h
0200h
150
0300h
0500h
0600h
Total
1900ml
2200 ml

24. Overactive Bladder Definition Screening and Assessment
Management Approach
Safety of Pharmacologic agents in the Elderly
OAB in Males
Emerging therapies/Surgical therapies

25. Treatment approaches for overactive bladder
OAB Management
Treatment approaches for overactive bladder
Lifestyle changes and/or management
Behavioral therapy
Pharmacological therapy 51

26. Lifestyle changes Moderate fluid intake Reduce or eliminate caffeine
Avoid fluids before bed 52

27. Behavioral Treatments
Pelvic floor muscle exercises
Kegel
Biofeedback
Electrical stimulation 53

28. Behavioral Treatments
Toileting assistance
scheduled toileting
prompted voiding
Bladder education/retraining
delayed/timed voiding
urge suppression exercises
This slide emphasizes the major role that caregivers can play. 52

29. Pharmacologic Therapy

32. Pharmacologic Therapy for Bladder Overactivity
In addition to antimuscarinic effect oxybutinin has a direct smooth muscle inhibitory and topical local anaesthetic effect

33. Overactive Bladder Definition Screening and Assessment
Management Approach
Safety of Pharmacologic agents in the Elderly
OAB in Males
Emerging therapies/Surgical therapies

46. 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

47. Overactive Bladder Definition Screening and Assessment
Management Approach
Safety of Pharmacologic agents in the Elderly
OAB in Males
Emerging therapies/Surgical therapies

48. 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
100
Men
Women 80
65%
67% 60
Percentage of Respondents 40 20
Bothered by OAB
From a survey of 16,776 adults.
Milsom I et al. BJU Int. 2001;87:

49. Fewer Men than Women Are Treated with Antimuscarinics25
‘OAB’ prescriptions 20
‘BPH’ prescriptions 15
Prescriptions, in thousands 10 5
Female
Male
Male
Women with OAB symptoms get treatment more than men (4:1)
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
IMS NPA, MAT

50. 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:

51. 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:

52. 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:

53. 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:

54. 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/ (Kaplan)
1/ (Roehrborn)
Propiverine + alpha blocker (2 months)
0/ (Lee)
Incidence of Urinary Retention in BPH Patients: % /year
Roehrborn, 2001
Athanasopoulos A et al., J Urol 2003: 169: Kaplan SA, Walmsley K, Te AE, J Urol 2005: 174:2273-6
Lee JY, Kim HW, Lee SJ, et al., BJU Int 2004: 94: Abrams P, J Urol 2006; 175:
Lee K-S, Choo M-S, Kim D-Y, et al. J Urol 2005; 174: Roehrborn C, et al. BJUI 2006; 97:1003

55. 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

56. Overactive Bladder Definition Screening and Assessment
Management Approach
Safety of Pharmacologic agents in the Elderly
OAB in Males
Emerging therapies/Surgical therapies

57. β3 Adrenoceptor The b3-AR is the most abundant of the AR subtypes
in human detrusor muscle, suggesting that
this subtype mediates detrusor relaxation.

58. 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

59. 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.

60. β3 Adrenoceptor Agonist
Beta-3 AR agonist
Anticholinergic agent M3 β3 β3 M3
Induction of relaxation
Inhibition of contraction
Bladder β3 β3 M3 M3 α1 α1 α1 α1
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

61. BTX Efficacy:
BTX has been shown to decrease or eliminate urge urinary incontinence for 6 to 9 months in 67% to 73% of patients experiencing neurogenic or idiopathic detrusor overactivity.
Optimal dosing and duration have yet to be determined
Been suggested that BTX will become an accepted therapeutic option in patients with OAB refractory to antimuscarinic therapy.
Contraindicated in patients with an infection at the injection site or hypersensitivity to BTX

62. Normal Neuromuscular transmission
THE JOURNAL OF UROLOGY®
Vol. 171, 2128–2137, June 2004

63. Mechanism of Action Botulinum toxin
THE JOURNAL OF UROLOGY®
Vol. 171, 2128–2137, June 2004

64. 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

65. Interstim
Sacral Neuromodulation

66. Gastric Augmentation Cystoplasty

67. Detubularized Ileal Augmentation Cystoplasty
Augmentation cystoplasty with simultaneous AUS implantation;

68. 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

69. Conclusion-Overactive Bladder
Safety of Pharmacologic agents in the Elderly
Use selective M3 anti muscarinics where possible
Use agents which don’t cross the BBB
OAB in Males
Anticholinergics seem safe
Surgical and Emerging therapies
Newer agents and surgical procedures

70. Stress Incontinence Female Hypermobility ISD Neurogenic Male
Postprostatectomy
Neurogenic

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

72. Stress Incontinence Medical therapy Kegel exercises M/F
Alpha adrenergic agonists M/F

73. 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

74. Stress Incontinence
Female
Hypermobility
ISD
Neurogenic

75. Hypermobility

78. Hypermobility

79. ISD
Normal mucosal seal
Poor mucosal seal

81. Original TVT

84. TRANS-OBTURATOR SLINGS

85. Third Generation Synthetic Midurethral Slings

86. Peri-Urethral Bulking Agents
Autologous fat
Hyaluronic acid/Dextranomer
Teflon particles
Collagen
Silicone particles
Calcium hydroxylapatite
Ethylene vinyl alcohol
Carbon spheres
Porcine dermal implant

87. Treatment with Zuidex Implacement
4 x 0.7ml
NASHA/Dx

88. Stress Incontinence
Male
Postprostatectomy
Neurogenic

89. Male Slings
AMS Advance Male Sling

90. AUS