Botox
The only approved formulation for use is onabotulinum toxin A (Botox). Dysport (abobotulinum toxin A) is not available locally and is less potent than Botox.
Potent neurotoxin produced by clostridium botulinum.
- 7 different types (A – G) – we just use type A.
Mechanism of action
- Acts at the presynaptic cholinergic nerve terminal of the neuromuscular junction
- The heavy chain binds to a receptor on the presynaptic nerve terminal and the toxin is internalised
- It then cleaves SNAP-25 off the SNARE protein, rendering the SNARE protein inactive which prevents exocytosis and release of acetylcholine (and subsequently inhibits detrusor contraction)
- Also thought to inhibit sensory urgency by modulating or inhibiting release of glutamate, substance P and calcitonin gene-related peptide.
Indications
- Overactive bladder refractory to medical and conservative management
- Neurogenic detrusor overactivity
- ?Emerging role for bladder pain syndrome, sphincter dyssynergia
Contra-indications
- Pregnancy
- Untreated UTI
- Myasthenia gravis, motor neuron disease
- Inability or unwilling to self-catheterise (relative contra-indication, PBS exclusion)
- Max dose 360 units / 3 months
Efficacy
- No proven differences for those with or without detrusor overactivity at UDS
- About 70 % efficacy – reduction in UUI, all other OAB symptoms, and improved continence versus placebo in RCT.
- Onset may take a week or two.
- Effects last for 4 – 12 months, average around 6 months. No evidence that retreatments lose efficacy.
- Superior to oral anticholinergics and mirabegron
Adverse effects
Risks of cystoscopy
- UTI (bacteriuria 15 – 30 %), bleeding, GA risks
Risks of botox itself
- Urinary retention requiring ISC/IDC – 5 % – higher risk in DM and MS
- Bladder pain
- Systemic absorption/effects and hypersensitivity very rare
Technique
- GA or LA
- 1 mL aliquots injected submucosally or intramuscular
- Generally avoid trigone for OAB, theoretical risk of reflux
- 100 units – 200 units for idiopathic OAB
- Avoid gentamicin which may theoretically potentiate neuromuscular blockade
- Careful when mixing Botox to avoid denaturing the protein
Sacral neuromodulator / sacral nerve stimulator
Mechanism
- Electrodes placed adjacent to sacral nerve roots delivers electric currents to the area via attached battery implant, delivering low amplitude stimulation and modulation of bladder neural pathways.
- The detailed mechanisms of this are not fully understood.
- Possibly modulates voiding reflexes and afferent and/or efferent pathways
Indication
- Idiopathic OAB, failed conservative and medical therapy
- Non obstructive urinary retention
- Concurrent faecal incontinence
Contra-indications
- Unable to comply with device programming optimisation.
- Pregnancy – no data – recommended to turn device off during pregnancy.
- Need for ongoing regular MRI (NB some newer devices MRI compatible).
- Appears safe in conjunction with pacemakers despite theoretical risk of crosstalk.
- If needing diathermy, device should probably be turned off pre-operatively.
Efficacy
- 50 – 70 % proceed to implant after test period.
- 60 – 80 % satisfaction and success rates in some trials with test period.
- EAU – over half have > 50 % improvement in UUI and 15 % may be cured at 4 years.
- Trial vs botox – similar outcomes at 2 year mark
Adverse effects
- Pain at implant site (10 %)
- Lead migration, wound issues, battery migration.
- Transient minor electric shocks. Leg pain/buttock pain and paraesthesia.
- 30 % requiring surgical revision or removal (pain, infection), 5 – 10 year battery life
- MRI incompatible (although newer models OK with MRI)
Technique
- Trial
Implantation of permanent tined lead now preferred over percutaneous wire lead (although benefit of trialling wire is no GA).
Bladder diary prior to intervention mandatory.
Set-up:
- X-ray friendly table – prone with anus/perineum and foot on show.
- GA (but avoid long acting muscle relaxant / paralysis). Prone with care of pressure points
Accessing S3 foramen:
- Ideally superior and medial within S3 foramen
- AP shot and mark medial edge of foramina (usually parallel to sciatic notch), draw line
- Lateral shot to identify target – S2 is usually at SIJ level, S3 about 1 cm below
- Alternate – 9 cm from coccyx, 11 cm from anal verge, then 1 – 2 cm lateral from midline
- Insert provided needle at approx. 60 degrees angle, “walking” along bone aiming inferolateral until “drops” into foramen
- Apply needle stimulation and assess response
Ideal response:
- Perineal bellows, great toe plantarflexion, genital sensation
- S2 will cause plantarflexion of foot and heel rotation with anal sphincter clamping. S4 will give bellows only with no foot movement.
Place the tined lead:
- 1 cm skin incision at needle entry point
- Remove stylet from needle, place directional guide and remove needle
- Dilator and sheath over directional guide under II – marker halfway through bone
- Remove all except sheath then place tine through introducer. Test all 4 electrodes
Finishing test run:
- The lead is tunnelled through a small gluteal incision over the ipsilateral iliac crest (where the future internal pulse generator (IPG) will go and connected to a percutaneous extension cable
- The extension cable is passed subcutaneously to the contralateral hip and comes out percutaneously -> connected to external neurostimulator during trial
If bladder diaries show > 50 % improvement in symptoms, proceed to internal pulse generator placement
- GA, 1-2 weeks later, prone
- Open previous gluteal incision and widen medially
- Create pocket in subcutaneous fat, ensure haemostasis
- Device should fit comfortably but not too big a pocket
Troubleshooting:
- Pain – turn off device, if pain is from energy/stimulation, pain should stop. If pain continues, from mechanical effects of implant itself.
- If pain from stimulation, change programming or lead configuration.
- Try programs for a week (unless intolerable side effects)
- If no improvement in symptoms with reprogramming or turning off – image to assess for lead fracture or rotation
- Physician programmer can check battery etc. Use reps. Battery life about 5 years.
Tibial nerve stimulation
- Posterior tibial nerve has nerve roots from L4 – S3 (branch of the sciatic nerve).
- Stimulation of posterior tibial nerve has impulses travel back to S2 – S4 roots. Unclear mechanism of how this then modulates the bladder response.
- Less invasive than SNS – not permanent, only requires a needle placement.
- However more time consuming and inconvenient – frequent visits.
- Good evidence including in RCT against control/sham group. 50 – 70 % responders with > 50 % improvement in symptoms.
- Typical protocol – 12 x weekly treatments for 30 minutes. Can then have maintenance afterwards (tapering 5 sessions over 3 months, then monthly ongoing).
- No notable side effects.
- Contraindicated in pacemakers as per manufacturer.
Technique:
- 34 G needle inserted 3 – 4 cm cephalad to medial malleolus
- Grounding pad placed on same leg
- Low voltage applied from external generator
- Optimal effect – fanning/dorsiflexion of big toe, tickling sensation at sole of foot
- Tolerable intensity for 30 minutes
Transcutaneous placement also seems effective.
Bladder augmentation (ileocystoplasty)
Severe, refractory, debilitating OAB. Largely has been replaced by botox etc.
The principle is to bivalve the bladder coronally, and patch the defect with a piece of bowel, which increases capacity of the bladder, reduces contractility and lowers detrusor pressures.
Considerations
- Major abdominal procedures with need for GA, prolonged recovery.
- Must be willing and able for self-catheterisation if needed, for both drainage and flushing of mucus etc.
- Contraindicated in inflammatory bowel disease, previous pelvic radiation, short gut, significant renal impairment (cannot compensate for hyperchloraemic metabolic acidosis) or liver failure (cannot compensate for increased ammonium reabsorbed by the augmented bowel)
Risks
General / anaesthetic
- DVT/PE, MI, CVA, neuropraxias
Early:
- Bleeding
- Infection – urinary sepsis, wound, chest
- Leak – bowel anastomosis, bladder anastomosis (incl rupture from overdistension)
- Ileus / SBO
- Other organ injury
Late:
- Recurrent UTI
- Requirement for ISC
- Hyperchloraemic hypokalaemic metabolic acidosis (much higher cf. conduit due to dwell time of urine)
- Troublesome mucus production
- Stones
- Renal function deterioration
- B12 deficiency / pernicious anaemia
- Spontaneous rupture or perforation
- Malignancy – latent period > 10 years, generally adenocarcinomas at anastomosis
Outcomes
- Long term success or patient satisfaction is only 50 – 60 % for idiopathic OAB, cf. 90 % for neuropaths.
- Long term follow up required including assessing for stones (XR/USS), B12 deficiency, metabolic acidosis, renal and liver function and malignancy screening after 10 years.
Technique
- Supine with break. Arms out. Bowel prepped. Cef/flagyl. IDC with filling line.
- Lower midline. Develop retzius then open peritoneum.
- Fill bladder. Long vertical incision in sagittal plane to bivalve bladder – start 2 cm above bladder neck in midline, and continue in midline past dome back to middle of interureteric bar posteriorly
- Identify and take 20 – 30 cm ileum with stapler, at least 15 cm proximal to terminal ileum
- Side-to-side stapled anastomosis to restore bowel continuity, close mesenteric window and trouser suture – ensure mesentery of augmented/bladder segment runs underneath bowel continuity
- Irrigate the isolated augment segment. Ensure adequate length to reach bladder.
- Can use syringe filled with betadine. Then use the barrel of the syringe inside the lumen as a stabilising base and cut between the two ridges for detubularisation.
- Detubularise by opening the bowel on its antimesenteric side using cut diathermy
- Reconfigure in a U-shape, suture the medial cut anti-mesenteric edges together with 3-0 PDS, locking some sutures
- Place a big SPC through bladder prior to attaching augment
- Suture augment in place with interrupted 3-0 PDS. Consider ureteric catheters if worried about trigone.
- Leak test via SPC and oversew any leak points
- Urethral IDC, drain and SPC. Regular flushes on ward to stop mucus blockages.
- Consider cystogram prior to SPC removal.