4Interstim – Sacral Neuromodulation IndicationsUrinary FrequencyUrinary UrgencyUrge Urinary IncontinenceUrinary Retention / Incomplete Bladder EmptyingFecal IncontinenceNot for SUI
5Micturition and Storage Reflexes Leng & Chancellor UNA 2005
6It’s simply the muscles or the nerves Where Medications WorkEfferent messages tell muscles to work.Medication may help muscle comply betterWhere InterStim worksSensory Messages (Afferent) tell the brain what is happening with the bladder and other voiding componentsInterStim modulates incorrect messages.Also has some effect on muscles/motorConscious control occurs in the brain (pontine micturition center).As bladder stores urine, the detrusor relaxes and the pelvic floor tightens around the urinary sphincter.When bladder is full, and it is time to release the stored urine, the detrusor contracts and the sphincter/pelvic floor relaxes.InterStim: consider after twomedications fail. Unlikely thirdor fourth will work.
7InterStim Pre-test Requirements Patient has had condition for > 1 yearStress incontinence has been eliminated as major urinary complaintPatient failed conventional therapy:Behavior modificationsTwo medication failuresCannot comply with other treatment option (I.e. self-cath)Can complete urinary diary and use devicePatient has improvement of 50% or > during test
8Mechanism of ActionMechanism 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)Basic science research is being conducted to better understand the mechanism of action of sacral nerve modulation.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:
9But is it really doing anything? Dasgupta and Fowler. Changes in brain activity following sacral neuromodulation for urinary retention.J Urol Dec;174(6):
10Therapy 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 diary2. Implantation of device--full implant--Stage II--both steps target S3 foramen and nervesSystem includes a lead placed near the sacral nerve and programmable implantable neurostimulator – system provides stimulation to the sacral nerve.Two phases of therapy:Acute: test stimulation is done as an outpatient procedure usually in a clinic.Chronic: inpatient procedure where the patient is implanted with the InterStim system.
12After Test Procedure Voiding diary Second step 50% improvement required for implantationImplantation is not required if you choose not to do soSecond stepPNE wires removed in office, orOR for staged approachPlace neurostimulatorRemove lead
13Implant ProcedurePatients 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.
16Clinical Study Overview Multi-center randomized, prospective study*23 centers: 9 European & 14 North American581 patients (1993 – 1998)Measurements:Urge incontinenceNumber of leaking episodes /daySeverity of leaking episodesNumber of pads/diapers replaced/dayUrgency-frequencyNumber of voids/dayVolume voided/voidDegree of urgency prior to voidRetentionVolume per catheterizationSuccess was defined as a minimum of 50% improvement in at least one primary diary variable as compared to baseline. This same definition was used for qualifying after test stimulation but also to define clinical success after randomization.This 50% improvement has been chosen in other studies as well (behavior/ biofeedback training; NIH studies) and has been accepted by the NIH and AHCPR as a standardized measure. For this reason also in this study a 50% improvement in symptoms was chosen.Study initiated by Medtronic in December 1993 using the traditional implantation procedure (Staged Implant was not performed during this study; tined lead was not available for this study)Included voiding dysfunctions of: urge incontinence (184 patients), retention (177 patients), urgency/frequency (220 patients).Urge incontinence indication approved for market clearance on September 29, 1997 by U.S. Food & Drug Administration.Urgency/frequency and retention indications approved for market clearance on April 15, 1999 by U.S. Food & Drug Administration.* Staged Implant was not performed during this study
19Implantation: 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%Additional adverse events include technical problems (1.7%); suspected device problem (1.6%); change in menstrual cycle (1.0%); Adverse change in voiding function (0.6%); persistent skin irritation (0.5%); suspected nerve injury (0.5%); device rejection (0.5%).Overall surgical revision rate at 12 months = 29%.No reports of serious adverse device effects or permanent injury associated with the devices or the use of sacral nerve stimulation.At database closure, 9% of reported events were unresolved.
20External anal sphincter defect, n=21 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 studyExternal anal sphincter defect, n=21External anal sphincter intact, n=323,6,12mo f/uAnorectal physiologyWexner’s scoreBowel diaryQOL Q’s
21All 53 benefited from SNSEAS defects: Weekly incont. episodes decreased from 13.8 to 5 at 12 mos.EAS intact 6.7 to 2QOL scores improved for both groups+/- pudendal neuropathy irrelevantSize of EAS defect did not matter up to 120 degrees
22Double-blind crossover design 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 implantedDouble-blind crossover designRandomized to on or off for one month periodsPt then chose the period of preference not knowing whether was actually on or offPlaced in preferred mode for 3 months
23Outcome measures FI Fecal urgency Delay in postponing defecation ManometryQOLEtc.
24Significant improvement in all when on Clinical benefit not due to placebo
25IE=incomplete bladder emptying; UUI=urge urinary incontinence; RKH SNS ResultsDiagnosisProcedureSuccessImplantImplant successIESNS PNENoNAUUIYesIE and UUIUUI and FIIE and MUIMUIIE and FIIE=incomplete bladder emptying; UUI=urge urinary incontinence;FI=fecal incontinence; MUI=mixed urinary incontinence
26Interstim Bottom Line Interstim is FDA approved for refractory urgency and frequencyurge incontinenceincomplete bladder emptyingfecal incontinenceNot for pain (PBS/BPS/IC)Effective therapy with intermediate long-term follow-up.Support is critical
27An Option Between Conservative and Surgical Treatments Urgent® PCAn Option Between Conservative and Surgical TreatmentsSimple, Office-based Neuromodulation with Urgent® PC
28What is PTNS? Defined in a variety of ways: Percutaneous Tibial Nerve StimulationPosterior Tibial Nerve StimulationPosterior Tibial NeurostimulationExample: New CPT® code “Posterior tibial neurostimulation - percutaneous electrode, single treatment, includes programming”
30Urgent® PCEasy to administer in twelve 30 minute sessions with maintenance therapy variableEffective – Approximately 2/3 of patients report a reduction in their symptomsMay work even if other treatments have failedLow risk – Most common side-effects include transient mild pain or skin inflammation at or near the stimulation site
31Treatment with Urgent® PC Stimulation delivered via a 34 ga. needle electrodeNeedle electrode inserted above medial malleolusThe needle electrode is connected to a battery-powered stimulatorProvides Percutaneous Tibial Nerve Stimulation (PTNS)
32Treatment with Urgent® PC Impulse travels from the ankle along the tibial nerve to the sacral nerves
34Office-based Treatment Patient is clothed and comfortableMay be administered by qualified staff, under physician supervisionPhysician and staff can treat multiple patients at once
35Treatment Frequency 12 weekly Urgent PC treatments Responders may need maintenance treatments to sustain improvementsSlowly increase time between treatmentsIf symptoms reappear or increase in severity, return to last frequency to sustain reliefIn OrBIT study, treatment interval increased to 24 days between treatments during months 6 – 12
36Urgent PC Contraindications Patients who are pregnant or planning to become pregnant while using this productPatients with pacemakers or implantable defibrillatorsPatients prone to excessive bleedingPatients with nerve damage that could impact either percutaneous tibial nerve or pelvic floor functionNot intended for intra-cardiac or trans-thoracic useConcurrent use of medical monitoring equipment during stimulation is not recommendedNot suitable for use in the presence of a flammable anesthetic mixture with air or with oxygen or nitrous oxide
37PTNS Clinical Effectiveness 30+ peer reviewed publications demonstrate safety and efficacyReduce urgency, urge incontinence & frequencySignificant objective and subjective improvementsNo serious adverse events orside-effectsImproved quality of lifeObjective urodynamic data2/3 of patients respond wellChange reference to MacDiarmid, Staskin, Current Bladder DysfunctionC01/10
38Meta-Analysis of 7 PTNS Studies Martinson, M. (2008). Meta-Analysis of PTNS for Urinary Disorders. Sponsored by Uroplasty, Inc.
3960 – 80% ResponseKari: Use the newest patient response chart from PTNS brochure.MacDiarmid, S., & Staskin, D. (2009). PTNS: A literature based assessment . Curr Bladder Dys , 4,C01/10
40PTNS compared to DrugPatient perception of cure/improvement: 80% in PTNS group; 55% in tolterodine LA groupPhysician perception of cure/improvement: 80% in PTNS group; 61% of tolterodine LA groupComparable reductions in voiding episodes and urge incontinenceSide-effects: No serious adverse events were associated with either treatment. Constipation and dry mouth reported more often in tolterodine LA groupPeters, 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.
41PTNS 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 respondersResults stable at three-year mean follow-up when initial series was followed by maintenance therapyOnly 10% of patients showed significant reduction of the obtained resultsCappellano 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, September, Rome, Italy.
42OrBIT – UPC vs. Detrol® LA Multicenter, RCT12 week phase12 month responder follow-up1:1 randomization (n=100)Physician and patient GRAVoiding diaries, QoL measures
45OrBIT – Side EffectsConstipation 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)
49Risks of Treatment The risks of Urgent PC are low Side-effects include:Transient moderate pain at or near the stimulation siteTransient mild pain or skin inflammation at or near the stimulation siteTransient mild bleeding at needle insertion site
50RKH PTNS Results n=2; both successful Diagnosis Procedure Success UUI Yesn=2; both successful
51What’s Next for PTNS Shorter therapy protocols Determination of prolonged treatment protocolsFecal urgency and incontinenceConstipationIncomplete bladder emptyingChronic pelvic painChronic non-bacterial prostatitis painPediatric use for LUTS