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Treatment of Voiding Dysfunction by Urethral Injection of Botulinum A toxin

Treatment of Voiding Dysfunction by Urethral Injection of Botulinum A toxin. Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital. Voiding Dysfunction. Neurogenic detrusor external sphincter dyssynergia Dysfunctional voiding due to spastic urethral sphincter

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Treatment of Voiding Dysfunction by Urethral Injection of Botulinum A toxin

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  1. Treatment of Voiding Dysfunction by Urethral Injection of Botulinum A toxin Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital

  2. Voiding Dysfunction • Neurogenic detrusor external sphincter dyssynergia • Dysfunctional voiding due to spastic urethral sphincter • Poor relaxation of sphincter & low detrusor contractility • Detrusor underactivity or Detrusor failure • Detrusor areflexia

  3. Therapeutic modalities for voiding dysfunction • Medication: alpha-blocker, skeletal muscle relaxants, nitric oxide donors • Behavioral therapy: biofeedback, electrical stimulation, neuromodulation • Surgery: transurethral sphincterotomy, TUI-bladder neck, urethral stent • Clean intermittent catheterization • Indwelling Foley catheter or cystostomy

  4. Background of Botulinum A toxin • Botulinum A toxin is an inhibitor of acetylcholine release at the presynaptic neuromuscular junction • Inhibition of acetylcholine release results in regional decreased muscle contractility at the injection site • This chemical devervation is a reversible process, axons resprout in about 3-6 months

  5. Mechanism of Botulinum A Toxin in Neuromuscular Junction

  6. Clinical usefulness of Botulinum A toxin • Focal dystonia, blepharospasm (Scott et al 1985) • Dysphonia (Whurr et al 1993) • Limb spasticity ( Hesse et al 1994) • Dysphagia (Schneider, et al 1994) • No severe adverse effects ever reported

  7. Clinical application of botulinum A toxin in voiding dysfunction Botulinum A toxin 20-80 U successfully treated 11 SCI & DESD (Dykstra et al 1988) • In 21 of 24 SCI & DESD, BTX-A toxin 100 U reduced residual urine and MUCP (Schurch et al 1996) • Transperineal injection of BTX-A in 6 SCI improved voiding function (Schurch et al 1997)

  8. Clinical application of botulinum A toxin in voiding dysfunction Relief of voiding dysfunction due to prostatitis in 4 men (Maria et al 1998) • Improved bladder capacity and decreased maximal detrusor pressure after BTX-A in 5 SCI (Gallien et al 1998) • Effective in treating DESD (12), pelvic floor spasticity (8), and acontractile detrusor (1) by BTX-A 80-100 IU (Michael et al 2001)

  9. Improved Voiding Efficiency • Increased detrusor contractility in detrusor underactivity – nerve stimulation, increased nerve density • Reduced urethral resistance – urethral smooth muscles and striated muscles • Recovery of detrusor contractility in idiopathic detrusor acontractility

  10. Patients suitable for Botulinum A toxin Treatment • Patients with voiding dysfunction who were refractory to medication or behavioral therapy • Chronic SCI & DESD with low empty efficiency • Cauda equina lesion and difficult urination • Peripheral neuropathy and difficult urination • Dysfunctional voiding • Idiopathic detrusor underactivity • Poor relaxation of urethral sphincter

  11. Enrolled Patients Criteria • Patient is unable to void spontaneously, indwelling catheter, or on CISC • Difficult urination with low Qmax and large residual urine • Moderate to severe obstructive IPSS (>10 points) • High voiding pressure (>50 cm water) & low flow rate (Qmax <10ml/s) during urodynamic study • Poor relaxation or hyperactivity of sphincter EMG activity during pressure flow study

  12. Pretreatment evaluation • Conventional treatment at least 3 months • Cystoscopy to exclude anatomical BOO • Postvoid residual urine volume • Videourodynamic study: voiding pressure, abdominal leak point pressure, Qmax, sphincteric EMG activity, urethral patency in VCUG • Obstructive score in IPSS

  13. Obstructive symptom scoresand Quality of life index (IPSS) • Residual urine sensation or retention 0-5 • Intermittency 0-5 • Small caliber of urine or retention 0-5 • Straining to void 0-5 • Quality of life index 0-6 • Indwelling Foley catheter or on CISC

  14. Botulinum A toxin

  15. Botulinum A toxin therapy • 100 units (1vial) is diluted to 2ml • 50-100 units are used, 4 equivalent aliquot are injected via cystoscopy guide in men and around the urethra in women • Complete cardiorespiratory monitoring in OR • Foley catheter is indwelled for 1 day • Report adverse effect (AD, hematuria, UTI)

  16. Evaluation of Treatment Outcome • Subjectively improved in voiding efficiency • Increase in voided volume • Reduction of residual urine volume • Decrease of voiding pressure (detrusor or abdominal pressure) • Decrease in frequency of catheterization • Removal of indwelled Foley catheter

  17. * * * * * * * * Botulinum A Toxin Urethral Injection in Woman

  18. Sphincter Injection Cystoscopy

  19. Cystoscopic Urethral Injection in Men

  20. Identification of External Sphincter in Man

  21. Injection of 3,6, 9, and 12 o’clock Position of Urethral Sphincter

  22. Clinical Results after Botulinum A toxin Urethral injection • 50 –100 units of botulinum A toxin injected to urethral striated muscles • Effect appears 2-3 days after injection • Detrusor pressure or abdominal leak point pressure decreased and facilitate spontaneous voiding • Minimal adverse effect was noted

  23. Materials & Methods • A total of 103 patients received urethral Botox injection • 48 men and 55 women • Aged 16 to 94, mean 54 years old • 45 patients had urinary retention • 48 patients received 50U, 55 patients received 100U

  24. Diseases and Enrolled Patients

  25. Outcome assessment • Excellent: (1) spontaneous voiding by reflex or abdominal straining in urinary retention patients; (2) improvement in voiding pressure (Pabd or Pdet), Qmax, and residual urine by >25% • Improved: improvement in voiding pressure, Qmax, and residual urine but <25%, patient is satisfactory to therapeutic effect • Failed: subjectively no improvement, persistent urinary retention, or persistent large residual urine

  26. Therapeutic Results of Urethral Botox for Voiding Dysfunction

  27. Therapeutic Results of Urethral Botox for Voiding Dysfunction

  28. Changes in Urodynamic Parameters in All Patients with Successful Results

  29. Urethral Botox in Treatment ofDysfunctional Voiding • 20 patients with dysfunctional voiding • 7 men and 13 women • High voiding pressure & a hyperactive urethral sphincter activity • 6 had excellent result, 14 had improved result, no failed case • Success rate was 100%

  30. Dysfunctional Voiding (Pseudodyssynergia) in CVA

  31. Changes in Urodynamic Parameters in Patients with Dysfunctional Voiding

  32. Urethral Botox in Treatment of Poor Relaxation of Sphincter • 19 patients (12 men & 7 women) had a low voiding pressure and intermittent sphincter activity during voiding • 8 had excellent result, 7 had improved result, 4 failed (all had psychological disorder) • In 5 patients with retention, 3 had excellent and 1 had improved result

  33. Severe dysuria in Poor Relaxation of Urethral Sphincter

  34. Changes in Urodynamic Parameters in Patients with Poor Relaxation of Urethral Sphincter

  35. Urethral Botox in Treatment of DESD • 29 patients with DESD, 24 men & 5 women • 27 had spinal cord lesion, 2 had multiple sclerosis • 8 had excellent result, 15 had improved result, 6 failed • 4 patients with retention had excellent result • High pressure or low pressure DESD had similar success rate (84.6% v 75%)

  36. DESD in Multiple Sclerosis with Urinary Retention

  37. Reduction of voiding pressure in a SCI patient with DESD

  38. Changes in Urodynamic Parameters in Patients with DESD

  39. Urethral Botox in Treatment of Cauda Equina Lesion • 8 patients with cauda equina lesion • 4 men and 4 women • 5 had excellent, 1 had improved result • In 6 patients with urinary retention, 4 had excellent result, 1 improved • Repeat urethral Botox injection was necessary in 1 with hypertonic sphincter

  40. Cauda Equina Lesion with Detrusor Areflexia & Isolated Sphincter Obstruction

  41. Reduction of abdominal pressure in patient with cauda equina lesion

  42. Detrusor Areflexia due to Cauda Equina Lesion in MS

  43. Changes in Urodynamic Parameters in Patients with Cauda Equina Lesion

  44. Urethral Botox in Treatment of Detrusor Failure • 13 patients with detrusor failure or underactivity, 1 man & 12 women • 8 had excellent, 4 had improved result • All 7 patients with retention could void after urethral Botox treatment • Detrusor contractions reappeared in patients with detrusor failure

  45. Recovery of Detrusor Contractility in Detrusor Failure after Botox

  46. Changes in Urodynamic Parameters in Patients with Detrusor Failure

  47. Urethral Botox in Treatment of Detrusor Areflexia • 14 women had detrusor areflexia after previous radical hysterectomy • Patients voided by abdominal straining • 5 had excellent, 6 had improved result • 2 failed cases had bladder neck obstruction • Improved voiding noted after TUI-BN • 1 patient received 2nd injection successfully

  48. Detrusor Areflexia after Radical Hysterectomy,s/p Botox injection

  49. Reduction of Abdominal Voiding Pressure in Detrusor Areflexia after Radical Hysterectomy

  50. Changes in Urodynamic Parameters in Patients with Detrusor Areflexia

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