Nerve Stimulation Therapies
for Bowel and Bladder
Continence
R. Keith Huffaker, MD, MBA, FACOG
Quillen/ETSU Center for Pelvic Surgery
and Urogynecology
Objectives
• Sacral nerve stimulation (SNS)
– InterStim
– Diagnoses
• Percutaneous tibial nerve stimulation
(PTNS)
– Urgent PC
– Diagnoses
Where do InterStim and Urgent PC
fit?
Interstim – Sacral
Neuromodulation
Indications
• Urinary Frequency
• Urinary Urgency
• Urge Urinary
•
•
•
Incontinence
Urinary Retention /
Incomplete Bladder
Emptying
Fecal Incontinence
Not for SUI
Micturition and Storage Reflexes
Leng & Chancellor UNA 2005
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
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
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.
But is it really
doing
anything?
• Dasgupta and Fowler. Changes in brain
activity following sacral
neuromodulation for urinary retention.J
Urol. 2005 Dec;174(6):2268-72.
•
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
After Test Procedure
• Voiding diary
– 50% improvement required for implantation
– Implantation is not required if you choose not
to do so
• Second step
– PNE wires removed in office, or
– OR for staged approach
• Place neurostimulator
• Remove lead
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.
Tined Lead
Patient Programmer
Physician Programmer
Clinical Study Overview
• Multi-center randomized, prospective study*
– 23 centers: 9 European & 14 North American
– 581 patients (1993 – 1998)
• Measurements:
– Urge incontinence
• Number of leaking episodes /day
• Severity of leaking episodes
• Number of pads/diapers replaced/day
– Urgency-frequency
• Number of voids/day
• Volume voided/void
• Degree of urgency prior to void
– Retention
• Volume per catheterization
* Staged Implant was not performed during this study
Efficacy: Overactive Bladder
Efficacy: Urinary Retention
Implantation:
Ranking of Adverse Events in
First 12 Months Post-implant
•
•
•
•
•
•
•
Pain at neurostimulator site
15.3%
New pain
9.0%
Suspected lead migration
8.4%
Infection
6.1%
Transient electric shock
5.5%
Pain at lead site
5.4%
Adverse change in bowel function
3.0%
Note: Additional events occurred – each less than 2.0%
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
• Outcome measures
– FI
– Fecal urgency
– Delay in postponing defecation
– Manometry
– QOL
– Etc.
• Significant improvement in all when on
• Clinical benefit not due to placebo
RKH SNS Results
Diagnosis
Procedure
Success
Implant
Implant success
IE
SNS PNE
No
No
NA
IE
SNS PNE
No
No
NA
UUI
SNS PNE
Yes
No
NA
IE and UUI
SNS PNE
Yes
Yes
Yes
UUI
SNS PNE
Yes
Yes
Yes
UUI and FI
SNS PNE
Yes
Yes
Yes
UUI
SNS PNE
Yes
Yes
Yes
UUI
SNS PNE
Yes
Yes
Yes
IE
SNS PNE
No
No
NA
IE and UUI
SNS PNE
Yes
Yes
Yes
UUI
SNS PNE
Yes
Yes
Yes
UUI
SNS PNE
Yes
Yes
Yes
IE and UUI
SNS PNE
Yes
Yes
Yes
UUI
SNS PNE
Yes
Yes
Yes
IE and MUI
SNS PNE
Yes
Yes
Yes
UUI and FI
SNS PNE
Yes
Yes
Yes
MUI
SNS PNE
Yes
Yes
Yes
IE and FI
SNS PNE
Yes
Yes
Yes
UUI
SNS PNE
Yes
Yes
Yes
IE and UUI
SNS PNE
Yes
Yes
Yes
IE=incomplete bladder emptying; UUI=urge urinary incontinence;
FI=fecal incontinence; MUI=mixed urinary incontinence
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
Urgent PC
®
An Option Between
Conservative and Surgical
Treatments
Simple,
Office-based
Neuromodulation
with Urgent® PC
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 Urgent PC Patients
®
Urgent
PC
• 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 Urgent® PC
• 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
Treatment with Urgent® PC
• Impulse travels from the ankle along
the tibial nerve to the sacral nerves
Urgent® PC Neuromodulation
System
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 Urgent PC 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
Urgent PC 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
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.
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.
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.
OrBIT – UPC 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
OrBIT Results at 12 Weeks
OrBIT Results at 12 Weeks
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)
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 Results – Long-term
• Responders continued treatment
– 90% for 6 months
– 73% for 12 months
• Sustained improvements at 12 months
OrBIT – Treatment Interval
Risks of Treatment
• The risks of Urgent PC 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
RKH PTNS Results
Diagnosis
Procedure
Success
UUI
PTNS
Yes
UUI
PTNS
Yes
n=2; both successful
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