Transcript huffaker

Nerve Stimulation Therapies
for Bowel and Bladder
Continence
R. Keith Huffaker, MD, MBA, FACOG
Quillen/ETSU Center for Pelvic Surgery
and Urogynecology
Disclosures
• None
Objectives
• Sacral nerve stimulation (SNS)
– InterStim
– Diagnoses
• Percutaneous tibial nerve stimulation
(PTNS)
– Urgent PC
– Diagnoses
Overactive Bladder: Prevalence & Impact
35
30
25
20
15
10
5
0
OAB 1
OAB
Asthma 2
Asthma
Diabetes 3
Diabetes
Osteoporosis 4
Osteoporosis
Alzheimer's 5
Alzheimer’s
• It is estimated that overactive bladder (OAB) affects more than
33 million people in the U.S.1
• OAB is more prevalent than many well-known diseases.2-5
• The total U.S. economic cost of OAB is $12.6 billion
(year 2000 dollars).6
1. Serels S. The wet patient: understanding patients with overactive bladder and incontinence. Curr Med Res Opin. 2004;20(6):791-801.
2. Centers for Disease Control and Prevention Website. http://www.cdc.gov/asthma/brfss/03/lifetime/tableL1.htm. Accessed October 18, 2010.
3. National Diabetes Information Clearinghouse Website. http://www.diabetes.niddk.nih.gov/dm/pubs/statistics/#y_people. Accessed October 18,
2010.
4. National Osteoporosis Foundation Website. http://www.nof.org/node/40. Accessed October 18, 2010.
5. Alzheimer’s Association Website. http://www.alz.org/alzheimers_disease_facts_figures.asp. Accessed October 18, 2010.
6. Hu, TW et al. Costs of Urinary Incontinence and Overactive Bladder in the United States: A Comparative Study. Urology.2004;63(3):461-465.
Sacral Nerve Stimulation
Indications
--for urinary control is indicated for the following in patients who
have failed or could not tolerate more conservative treatments:
Overactive bladder
• Symptoms of urinary urge incontinence
• Symptoms of urgency-frequency
• Combination of both
Urinary retention/incomplete emptying
• Non-obstructive
It’s simply the
muscles or the
nerves
Where
Medications Work
Efferent
messages tell
muscles to work.
Medication may
help muscle
comply better
Where InterStim
works
Sensory Messages
(Afferent) tell the
brain what is
happening with
the bladder and
other voiding
components
InterStim
modulates
incorrect
messages.
InterStim: consider after two
medications fail. Unlikely third
or fourth will work.
Also has some
effect on
muscles/motor
Normal Micturition
• Filling: The detrusor muscle is relaxed
so that the bladder wall can stretch and
fill to capacity. Inhibition (efferent)
signals cause the sphincter and pelvic
floor to tighten (guarding reflex).
• Capacity: Sensory (afferent) receptors
in the bladder wall are stimulated,
causing a feeling of fullness or
discomfort (urge sensation).
• Voiding: Under conscious brain control,
the external sphincter and pelvic floor
relax, while the detrusor muscle
contracts (voiding reflex).
Mechanism of Action
• Mechanism of action for SNS is not fully
understood at this time - many theories
exist.
• Generally agreed that stimulation of the
sacral nerves modulates the neural
reflexes that influence the bladder,
sphincter and pelvic floor that
control/influence voiding. (Afferent
Reference: Chancellor MB, Chartier-Kastler EJ. Principles of sacral
pathways) nerve stimulation (SNS) for the treatment of bladder and urethral
sphincter dysfunctions. International Neuromodulation Society
2000; 3: 15-26.
Treatment Algorithm to Evaluate for InterStim Therapy
Urinary Urgency-Frequency and Urge Incontinence
Initial Screening
Voiding Diary
Urodynamic
Work-up
Behavioral Techniques
Interventional Techniques
Medications
+
Continue as
Appropriate
InterStim Therapy
Test Stimulation
Treatment Algorithm to Evaluate for InterStim Therapy
Urinary Retention
Initial Screening
Voiding Diary
Urodynamic
Work-up
Rule Out Obstruction
Medications and/or
Catheterization
+
Continue as
Appropriate
InterStim Therapy
Test Stimulation
InterStim Pre-test Requirements
• Patient has had condition for > 1 year
• Stress incontinence has been eliminated as
•
major urinary complaint
Patient failed conventional therapy:
– Behavior modifications
– Two medication failures
– Cannot comply with other treatment option (I.e. selfcath)
• Can complete urinary diary and use device
• Patient has improvement of 50% or > during
test
•
Therapy consists of 2 steps:
1. Test stimulation procedure –
allows trial of InterStim Therapy
-simple (30-45) minutes
-done in office (PNE) or
outpatient room (PNE or
Stage I)
--test for a ½ to 1 week
-percutaneous wire
-external pulse generator
-voiding diary
2. Implantation of device
--full implant
--Stage II
--both steps target S3 foramen
and nerves
Test Stimulation: Place the Temporary Test Lead
Click for video.
Lead parallel to nerve
Relate Sacral Anatomy to Lead Location
Look for Motor and Sensory Responses
Connect the Lead to External Test Stimulator
When desired
responses are
achieved, the lead is
secured and connected
to an external test
stimulator
Discuss:
• Antibiotics
• Anesthesia
• Dressing technique
• Documenting lead
location
Implant Procedure
• Patients with a
•
successful test
stimulation go on to
implantation of the
internal pulse
generator. (50%)
A pocket is typically
created for the
neurostimulator in
the upper buttock.
Complete InterStim System
1. Tined lead is placed
parallel to the sacral
(S2, S3, or S4) nerve.
3
2. Implantable
2
2
neurostimulator
generates mild electrical
pulses that are delivered
through the lead
electrodes.
3. Clinician and patient
1
programmers are used
to set the parameters
of the electrical pulses.
Estimated Battery Life
High, Moderate, and Low Energy Consumption
• These estimations of battery
life assume a new
neurostimulator with no
subsequent adjustments to
stimulation parameters.
• Battery life will be shortened if
stimulation parameters are
increased to consume more
energy.
• Accurate placement of the
InterStim lead will minimize
stimulation parameters and
energy consumption, thus
maximizing battery life.
InterStim Delivers Clinical Efficacy
1
12-month clinical success for Urinary Control
79% of urge incontinence
patients achieved clinical success
• 45% remained completely dry
• An additional 34% experienced 50%
reduction in leaking
64% of urgency-frequency
patients achieved clinical success
Urge
Incontinence
UrgencyFrequency
Urinary
Retention
(n=38)
(n=33)
(n=38)
1. Medtronic-sponsored research : InterStim
Therapy - Clinical Summary, 2011.
• 31% returned to normal voids
(4 to 7 voids/day)
• An additional 33% experienced 50%
reduction in number of voids
77% of urinary retention
patients achieved clinical success
• 61% eliminated use of catheters
• An additional 16% experienced 50%
reduction in catheterized urine volume
InterStim Therapy for Urinary Control
Lasting Efficacy - Proven in a 5-year Clinical Trial
Urge Incontinence1
Evaluable Patients – the subset of
subjects for whom both baseline and
5-year data were available
Intent-to-Treat Patients – all implanted
subjects, including those who dropped out
and were imputed as no change from baseline
• 59% of urge incontinent patients achieved  50% reduction in leaks/day*
• 71% of those urge incontinent patients who reported heavy leaks at
baseline achieved  50% reduction in leaks per day†
* 59% in evaluable patient population (n=61) and 37% in intent-to-treat population (n=96)
† 71% in evaluable patient population (n=49) and 42% in intent-to-treat population (n=84)
1. Medtronic-sponsored research : InterStim Therapy - Clinical Summary, 2011.
InterStim Therapy for Urinary Control
Lasting Efficacy - Proven in a 5-year Clinical Trial
Urinary Retention1
Evaluable Patients – the subset of
subjects for whom both baseline and
5-year data were available
Intent-to-Treat Patients – all
implanted subjects, including those
who dropped out and were imputed as
no change from baseline
78% of urinary retention patients achieved  50%
reduction in volume/catheterization*
* 78% in evaluable patient population (n=23) and 58% in intent-to-treat population (n=31)
1. Medtronic-sponsored research : InterStim Therapy - Clinical Summary, 2011.
Sacral Nerve Stimulation
Indications
Also indicated for the treatment of Chronic
Fecal Incontinence in patients who have
failed or are not candidates for more
conservative treatments.
Fecal IncontinenceMore Common Than You Might Think
35
30
25
20
15
10
5
0
OAB1,2
OAB
Asthma 3
Asthma
Diabetes 4
Diabetes
FIFI 5
Osteoporosis 6
Osteoporosis
Alzheimer's
7
Alzheimer’s
• It is estimated that more than 18 million adults in the United States
•
– 1 in 12 – suffer from fecal incontinence (FI)5
FI is nearly as prevalent as many other chronic diseases and more prevalent
than other illnesses well-known to impact many Americans.1-4,6-7
Stewart, W.F et al. Prevalence and Burden of Overactive Bladder in the United States. World Jrnl of Urol 2003:20:327-336
Serels S. The wet patient: understanding patients with overactive bladder and incontinence. Curr Med Res Opin. 2004;20(6):791-801.
Centers for Disease Control and Prevention Website. http://www.cdc.gov/asthma/brfss/03/lifetime/tableL1.htm. Accessed October 18, 2010.
National Diabetes Information Clearinghouse Website. http://www.diabetes.niddk.nih.gov/dm/pubs/statistics/#y_people. Accessed October 18,
2010.
5. Whitehead W.E. et al. Fecal Incontinence in US adults: epidemiology and risk factors. Gastroenterology. 2009; 137:512-517.
6. National Osteoporosis Foundation Website. http://www.nof.org/node/40. Accessed October 18, 2010.
7. Alzheimer’s Association Website. http://www.alz.org/alzheimers_disease_facts_figures.asp. Accessed October 18, 2010.
1.
2.
3.
4.
Patient Education Needed
Studies suggest that only 15%– 45% of FI patients seek
treatment1,2.
Consider the following statistics that support the claim that
fecal incontinence is a hidden condition:
• For 84% of patients with FI, the physician was unaware of the patient’s
•
•
disorder1
54% of patients with FI had not discussed the problem with a professional2
65% of patients with severe or major FI which had an impact on the quality of
life wanted help with their symptoms3
1. Damon H, Guye O, Seigneurin A, et al. Prevalence of anal incontinence in adults and impact on quality-of-life. Gastroenterol Clin Biol.
2006;30(1):37-43
2. Edwards NI, Jones D. The Prevalence of Faecal Incontinence in Older People Living at Home. Age Ageing. 2001;30(6):503-7
3. Perry S, Shaw C, McGrother C, et al. Prevalence of faecal incontinence in adults aged 40 years or more living in the community. Gut.
2002;50(4):480-484.
FI Impacts Quality of Life
Fecal Incontinence Quality of Life Scale (FIQOL) Scores
Note: Higher scores translate to higher quality of life
Medtronic data on file. InterStim Therapy for Bowel Control Prospective Clinical Study. PMA#P080025.
Treatment Algorithm to Evaluate InterStim Therapy
Chronic Fecal Incontinence
InterStim Therapy for Bowel Control
Percent of Patients with a 100%
Reduction in Accidents at 12 Months
Clinical Efficacy: Complete Continence
InterStim Therapy
Bowel Control Study1,2
Tjandra RCT3
47%
41%
36%
MWC
(n=120)
Per-protocol
(n=106)
SNS group
(n=53)
1. Wexner SD, Coller JA, et al. Ann Surg. 2010 Mar;251(3):441-9.
2. Medtronic-sponsored research : InterStim Therapy - Clinical Summary, 2011.
3. Tjandra JJ et al. Sacral nerve stimulation is more effective than optimal medical therapy for severe fecal
incontinence: a randomized, controlled study. Dis Colon Rectum. May 2008;51(5):494-502.
FIQOL ― Improvement in
Quality of Life
InterStim Therapy for Bowel Control
n = 120, p < 0.0001
MWC analysis
Medtronic-sponsored research. InterStim Therapy Clinical Summary Insert, 2010
InterStim Therapy for Bowel Control
Clinical Efficacy: Quality of Life
InterStim Therapy Bowel Control Study1
Mean FIQOL Score
(Completers Analysis)
4.0
3.5
3.0
2.5
2.0
1.5
1.0
Baseline
(n=119)
3-Months
(n=116)
6-Months
(n=109)
12-Months
(n=107)
24-Months
(n=68)
36-Months
(n=30)
Scale 1 - Lifestyle
2.31
3.22
3.26
3.36
3.32
3.52
Scale 2 - Coping/Behavior
1.49
2.64
2.69
2.77
2.69
2.7
Scale 3 - Depression/SelfPerception
2.53
3.33
3.48
3.54
3.58
3.77
Scale 4 - Embarrassment
1.6
2.73
2.75
2.81
2.76
2.95
1. Wexner SD, Coller JA, Devroede G, et al. Sacral nerve stimulation for fecal incontinence:
results of a 120-patient prospective multicenter study. Ann Surg. Mar 2010;251(3):441-449.
Sacral Neuromodulation Therapy for Bowel
Control Prospective Clinical Study
• Prospective, multicenter study
– Primary endpoint was a >50% reduction in
incontinence episodes per week
– 133 subjects underwent test stimulation
• 90% had a successful test trial
– 12 month follow-up:
• 83% success
• 41% complete continence
1. Wexner SD, Coller JA, et al. Ann Surg. 2010 Mar;251(3):441-9.
2. InterStim Therapy Clinical Summary, 2011.
Fecal Incontinence, Tjandra study
• Prospective randomized trial of SNM vs.
•
•
optimal medical management in patients with
severe fecal incontinence
SNM (n=60)
Optimal medical management (n=60)
– pelvic floor exercises, bulking agent, and dietary
manipulation.
• Assessment included endoanal ultrasound,
anorectal physiology, two-week bowel diary,
and fecal incontinence quality of life index.
Tjandra JJ, Chan MK, et al. Dis Colon Rectum. 2008 May;51(5):494-502.
Tjandra Study ― Safety Results
The most common adverse events
(≥5.0%) reported are:
• Excessive tingling in the vaginal region =
9%
• Implant site pain, especially in slimmer
patients = 6%
Tjandra JJ, Chan MK, et al. Dis Colon Rectum. 2008 May;51(5):494-502.
Fecal Incontinence, Tjandra study
• Follow-up at 12 months
• Two groups similar with demographics and
severity of symptoms
• SNM group – 90% successful stage 1
– Mean weekly incontinent episodes from 9.5 to 3.1
– Mean incontinent days/week 3.3 to 1
• Significant improvement in fecal incontinence
QOL index in all four domains in SNM group
• No improvement in the medical management
group
Tjandra JJ, Chan MK, et al. Dis Colon Rectum. 2008 May;51(5):494-502.
Chan and Tjandra. Sacral Nerve Stimulation for Fecal Incontinence: External
Anal Sphincter Defect vs. Intact Anal Sphincter. Diseases of the Colon and
Rectum:2008.
• Prospective study
• External anal sphincter defect, n=21
• External anal sphincter intact, n=32
• 3,6,12mo f/u
– Anorectal physiology
– Wexner’s score
– Bowel diary
– QOL Q’s
• All 53 benefited from SNS
• EAS defects: Weekly incont. episodes
decreased from 13.8 to 5 at 12 mos.
• EAS intact 6.7 to 2
• QOL scores improved for both groups
• +/- pudendal neuropathy irrelevant
• Size of EAS defect did not matter up to
120 degrees
LeRoi, et al. Efficacy of Sacral Nerve Stimulation for Fecal Incontinence
Results of a Multicenter Double-Blind Crossover Study. Annals of
Surgery:2005.
• n=27 (most were women)
• SNS implanted
• Double-blind crossover design
• Randomized to on or off for one month
periods
• Pt then chose the period of preference not
knowing whether was actually on or off
• Placed in preferred mode for 3 months
• On group preferential
Interstim Bottom Line
• Interstim is FDA approved for
–
–
–
–
–
refractory urgency and frequency
urge incontinence
incomplete bladder emptying
fecal incontinence
Not for pain (PBS/BPS/IC)
• Effective therapy with intermediate longterm follow-up.
• Support is critical
What is PTNS?
• Defined in a variety of ways:
– Percutaneous Tibial Nerve Stimulation
– Posterior Tibial Nerve Stimulation
– Posterior Tibial Neurostimulation
• Example: New CPT® code 64566
“Posterior tibial neurostimulation -
percutaneous electrode, single treatment,
includes programming”
Potential PTNS Patients
PTNS
• Easy to administer in twelve 30
minute sessions with maintenance
therapy variable
• Effective – Approximately 2/3 of
patients report a reduction in their
symptoms
• May work even if other treatments
have failed
• Low risk – Most common side-effects
include transient mild pain or skin
inflammation at or near the
stimulation site
Treatment with PTNS
• Stimulation
•
• Provides
Percutaneous
Tibial Nerve
Stimulation
(PTNS)
•
delivered via a 34
ga. needle
electrode
Needle electrode
inserted above
medial malleolus
The needle
electrode is
connected to a
battery-powered
stimulator
PTNS Neuromodulation System
Treatment with PTNS
• Impulse travels from the ankle along
the tibial nerve to the S2, 3, and 4
Office-based Treatment
• Patient is clothed and comfortable
• May be administered by qualified staff,
•
under physician supervision
Physician and staff
can treat multiple
patients at once
Treatment Frequency
• 12 weekly PTNS treatments
• Responders may need maintenance
treatments to sustain improvements
– Slowly increase time between treatments
– If symptoms reappear or increase in severity,
return to last frequency to sustain relief
– In OrBIT study, treatment interval increased
to 24 days between treatments during
months 6 – 12
PTNS Contraindications
• Patients who are pregnant or planning to become
•
•
•
•
•
•
pregnant while using this product
Patients with pacemakers or implantable defibrillators
Patients prone to excessive bleeding
Patients with nerve damage that could impact either
percutaneous tibial nerve or pelvic floor function
Not intended for intra-cardiac or
trans-thoracic use
Concurrent use of medical monitoring equipment during
stimulation is not recommended
Not suitable for use in the presence of a flammable
anesthetic mixture with air or with oxygen or nitrous
oxide
PTNS Clinical Effectiveness
• 30+ peer reviewed publications
demonstrate safety and efficacy
– Reduce urgency, urge incontinence &
frequency
– Significant objective and subjective
improvements
– No serious adverse events or
side-effects
– Improved quality of life
– Objective urodynamic data
– 2/3 of patients respond well
PTNS Studies
• Payne 1998, Freq & Incont, N=98, 80%
improved
• Vandoninck 2003, OAB, N=90, Freq 1310, incontinence 5-2/day
• Vandoninck 2003, Urge incontinence,
N=35, 16/35 dry, pads/nocturia/HRQOL all
improved
• Congregado-Ruiz 2004, OAB and UI,
N=51, all parameters stats improved
• De Dennaro 2004, OAB, N=23, 80%
improved
• Peters, et al.
• J Urol 2010
• N = 220
• 52% PTNS & 57% Sham correctly guessed
intervention
• PTNS pts showed significant
improvements: urgency, frequency, UI, sx
severity, QOL measures
Meta-Analysis of 7 PTNS Studies
Martinson, M. (2008). Meta-Analysis of PTNS for Urinary Disorders. Sponsored by Uroplasty, Inc.
60 – 80% Response
MacDiarmid, S., & Staskin, D. (2009). PTNS: A literature based assessment . Curr Bladder Dys , 4, 29-33.
OrBIT – PTNS vs. Detrol® LA
• Multicenter, RCT
• 12 week phase
• 12 month responder follow-up
• 1:1 randomization (n=100)
• Physician and patient GRA
• Voiding diaries, QoL measures
PTNS compared to Drug
• Patient perception of cure/improvement:
80% in PTNS group; 55% in tolterodine LA group
• Physician perception of cure/improvement: 80%
in PTNS group; 61% of tolterodine LA group
• Comparable reductions in voiding episodes and
urge incontinence
• Side-effects: No serious adverse events were
associated with either treatment. Constipation and
dry mouth reported more often in tolterodine LA
group
Peters, K.M., Leong, F.C., Shobeiri, S.A., MacDiarmid, S.A., Rovner, E.S., Wooldridge, L.S., et al. (2008). Randomized
multicenter study comparing percutaneous tibial nerve stimulation with pharmaceutical therapy for the treatment of overactive
bladder. Abstract, American Urologic Association, Annual Meeting, Orlando, FL.
OrBIT Results – Long-term
• Statistically significant improvement
sustained from 12 weeks thru 12 months
•
– Frequency -2.8 voids/day (p<0.001)
– Nighttime voids -0.8 voids/night (p<0.05)
– Urgency -3.7/day (p<0.01)
– Voided volume +39 cc (p<0.05)
– Incontinence episodes -1.6/day (p<0.001)
– QOL measure (p<0.01)
No serious adverse events or device malfunctions
OrBIT – Side Effects
• Constipation reported less often in PTNS
•
•
arm compared to drug arm (p=0.04)
Dry mouth reported less often in PTNS
arm compared to drug arm (p=0.0004)
PTNS group reported pain, discomfort or
redness at ankle (assessed for PTNS
group only)
PTNS Long-Term Follow-up
• Retrospective analysis of 256 patients (178 were
•
•
•
treated for OAB symptoms)
Sixty percent (107/178) of patients with OAB
symptoms were responders
Results stable at three-year mean follow-up
when initial series was followed by maintenance
therapy
Only 10% of patients showed significant
reduction of the obtained results
Cappellano F., Finazzi Agro E., Giollo A., Petta F., Catanzaro M., Miano R., Germani S., Catanzaro F. (2006). Percutaneous
tibial nerve stimulation (PTNS): results at long term follow-up. Abstract presented at the SIUD Congresso Nationale 2006, 2730 September, Rome, Italy.
Risks of Treatment
• The risks of PTNS are low
• Side-effects include:
– Transient moderate pain at or near the
stimulation site
– Transient mild pain or skin inflammation
at or near the stimulation site
– Transient mild bleeding at needle
insertion site
What’s Next for PTNS
• Shorter therapy protocols
• Determination of prolonged treatment
protocols
• Fecal urgency and incontinence
• Constipation
• Incomplete bladder emptying
• Chronic pelvic pain
• Chronic non-bacterial prostatitis pain
• Pediatric use for LUTS