Nerve Stimulation Therapies for Bowel and Bladder Continence

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Nerve Stimulation Therapies for Bowel and Bladder
Continence

• R. Keith Huffaker, MD, MBA, FACOG
• Quillen/ETSU Center for Pelvic Surgery and
  Urogynecology

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Objectives

• Sacral nerve stimulation (SNS)
• InterStim
• Diagnoses
• Percutaneous tibial nerve stimulation (PTNS)
• Urgent PC
• Diagnoses

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Where do InterStim and Urgent PC fit?
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Interstim Sacral Neuromodulation

• Indications
• Urinary Frequency
• Urinary Urgency
• Urge Urinary Incontinence
• Urinary Retention / Incomplete Bladder Emptying
• Fecal Incontinence
• Not for SUI

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Micturition and Storage Reflexes
Leng Chancellor UNA 2005
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Its 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 InterSti
m modulates incorrect messages. Also has some
effect on muscles/motor
InterStim consider after two medications fail.
Unlikely third or fourth will work.
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InterStim Pre-test Requirements

• Patient has had condition for gt 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.
  self-cath)
• Can complete urinary diary and use device
• Patient has improvement of 50 or gt during test

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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
  pathways)

Reference Chancellor MB, Chartier-Kastler EJ.
Principles of sacral nerve stimulation (SNS) for
the treatment of bladder and urethral sphincter
dysfunctions. International Neuromodulation
Society 2000 3 15-26.
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But is it really doing anything?

• Dasgupta and Fowler. Changes in brain activity
  following sacral neuromodulation for urinary
  retention.J Urol. 2005 Dec174(6)2268-72.

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• Therapy consists of 2 steps
• 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

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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

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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.

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Tined Lead
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• Patient Programmer

• Physician Programmer

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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
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Efficacy Overactive Bladder
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Efficacy Urinary Retention
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ImplantationRanking 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

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Chan and Tjandra. Sacral Nerve Stimulation for
Fecal Incontinence External Anal Sphincter
Defect vs. Intact Anal Sphincter. Diseases of the
Colon and Rectum2008.

• Prospective study
• External anal sphincter defect, n21
• External anal sphincter intact, n32
• 3,6,12mo f/u
• Anorectal physiology
• Wexners score
• Bowel diary
• QOL Qs

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• 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

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LeRoi, et al. Efficacy of Sacral Nerve
Stimulation for Fecal IncontinenceResults of a
Multicenter Double-Blind Crossover Study. Annals
of Surgery2005.

• n27 (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

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• Outcome measures
• FI
• Fecal urgency
• Delay in postponing defecation
• Manometry
• QOL
• Etc.

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• Significant improvement in all when on
• Clinical benefit not due to placebo

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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
IEincomplete bladder emptying UUIurge urinary
incontinence
FIfecal incontinence MUImixed urinary
incontinence
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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 long-term
  follow-up.
• Support is critical

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An Option Between Conservative and Surgical
Treatments
Urgent PC

• Simple, Office-based Neuromodulation with
  Urgent PC

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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

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Potential Urgent PC Patients
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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

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Treatment with Urgent PC

• Stimulation delivered via a 34 ga. needle
  electrode
• Needle electrode inserted above medial malleolus
• The needle electrode is connected to a
  battery-powered stimulator

• Provides Percutaneous Tibial Nerve Stimulation
  (PTNS)

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Treatment with Urgent PC

• Impulse travels from the ankle along the tibial
  nerve to the sacral nerves

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Urgent PC Neuromodulation System
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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

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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

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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

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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

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Meta-Analysis of 7 PTNS Studies
Martinson, M. (2008). Meta-Analysis of PTNS for
Urinary Disorders. Sponsored by Uroplasty, Inc.
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60 80 Response
MacDiarmid, S., Staskin, D. (2009). PTNS A
literature based assessment . Curr Bladder Dys ,
4, 29-33.
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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.
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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, 27-30 September, Rome,
Italy.
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OrBIT UPC vs. Detrol LA

• Multicenter, RCT
• 12 week phase
• 12 month responder follow-up
• 11 randomization (n100)
• Physician and patient GRA
• Voiding diaries, QoL measures

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OrBIT Results at 12 Weeks
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OrBIT Results at 12 Weeks
p-value 0.053  
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OrBIT Side Effects

• Constipation reported less often in PTNS arm
  compared to drug arm (p0.04)
• Dry mouth reported less often in PTNS arm
  compared to drug arm (p0.0004)
• PTNS group reported pain, discomfort or redness
  at ankle (assessed for PTNS group only)

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OrBIT Results Long-term

• Statistically significant improvement sustained
  from 12 weeks thru 12 months
• Frequency -2.8 voids/day (plt0.001)
• Nighttime voids -0.8 voids/night (plt0.05)
• Urgency -3.7/day (plt0.01)
• Voided volume 39 cc (plt0.05)
• Incontinence episodes -1.6/day (plt0.001)
• QOL measure (plt0.01)
• No serious adverse events or device malfunctions

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OrBIT Results Long-term

• Responders continued treatment
• 90 for 6 months
• 73 for 12 months
• Sustained improvements at 12 months

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OrBIT Treatment Interval
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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

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RKH PTNS Results
Diagnosis Procedure Success
UUI PTNS Yes
UUI PTNS Yes
n2 both successful
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Whats 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