Urethral Bulking Agents in SUI

TOG 2020

Introduction

• Urinary incontinence (UI) → involuntary loss of urine 
• ≥20 years → 25% UI
• SUI in 50% of all cases 36% Mixed UI(MUI)  11% Urgency UI
• UI has financial as well as significant effect on QoL

Pathophysiology of SUI

• SUI→ involuntary loss of urine associated with effort/exertion like sneezing, coughing, straining
• There are two causes

• Associated with urethral hyper-mobility: usually due to pelvic floor damage during childbirth. Demonstrated when there is descent & anterior rotation of anterior vaginal wall during cough + urine leaking
• Primary urethral weakness: no urethral hyper-mobility. Urethra appears fixed/rigid. Usually in women with previous failed SUI surgery

Treatment of SUI

• Current NICE recommendations: All women with SUI/MUI should have

1. lifestyle modifications,
2. limit fluid intake,
3. ↓ alcohol/caffeine intake,
4. stop smoking &
5. ↓ weight if BMI ≥30

• First line treatment: trial of supervised PFMT for at least 3 months 
• Cochrane review→ after PFMT 8x more cure rate & 17x more cure/improvement
• Non surgical treatments (duloxetine) have limited efficacy in treatment of SUI. Available for those who prefer pharmacological t/m or are not suitable for surgery
• NICE recommends use of mechanical device if occasional leakage like during exercise
• Offer surgery only if conservative measures fail
• If pure SUI or stress-predominant MUI→ surgery can be offered without urodynamics
• Majority of SUI surgery involved use of mesh, but its complications have risen issues
• Mesh:Complications rates up to 10%
• Removal rates 1.4% @ 1 yr 2.7% @ 2yrs  3.3% @ 5 yrs
• Overall re-operation rate 6.9% [either tape removal and/or repeat surgery for SUI]

Currently there is pause restriction on use of MESH until NICE conditions met

According to NICE 2019: 

• women to be offered choice of

1. open/laparoscopic colposuspension and
2. autologous rectus fasciae sling

• Retropubic mid-urethral mesh sling to be included in options but must be explained its restrictions, being permanent implant and complete removal may be impossible 
• Do not offer transobturartor approach unless specific clinical circumstances (e.g. previous pelvic procedures) in which the retropubic approach should be avoided.
• Do not use ‘top-down’ retropubic mid-urethral mesh sling approach or single-incision sub-urethral short mesh sling insertion except as part of clinical trial
• 48% reduction in tape insertion procedures in 2016-17 vs 2008-9

As there are pause restrictions on use of mesh procedures, urethral bulking agents likely to be popular as non-mesh treatment option

Indications for bulking agents (injection synthetic material around urethra)

1. Wishing to avoid major surgery/mesh
2. Recurrent SUI after failed primary surgery
3. Willing to accept less cure rate in favor of less invasive procedure with less risk of voiding difficulty
4. Co-morbidities
5. Desire future pregnancy 

Inform all these women that 

• Permanent material & may need repeat injections to have efficacy
• Lesser efficacy than alternate surgical procedures
• Poor durability  Limited evidence on long-term efficacy & side effects 
• NICE: give written information comprising agent name, manufacturer, injection date & surgeons details 

Five agents currently available in UK

1. Polyacrylamide hydrogel (Bulkamid)
2. Polydimethlsiloxone
3. Carbon beads
4. Calcium hydroxyapatite
5. Cross linked vinyl dimethyl polydimethylsiloxane

Mechanism of action 

• Intramural bulking agents creat additional submucosal bulk by providing artificial mucosal cushion & help in coaptation (adaption of urethral muscles to remain closed at rest)
• The ideal bulking agent should be

1. easy to inject,
2. retain volume and durability,
3. be biocompatible with minimal inflammatory and fibrotic response.
4. no migration from the site of injection (normally meaning particles with a diameter of >80 μm suspended in a gel).

There is no ideal bulking agent

Efficacy of bulking agents evidence

• More effective than conservative management in short term but do have complications which may have impact on long term
• May be an effective treatment option for recurrent SUI
• Can be used in women who undergo subsequent surgery
• Periurethral & transurethral route have similar outcomes

Collagen most widely used injectable

• Efficacy: 50% @12 month 32% @34-47 months   30% @ ≥48 months
• Superior to many agents like carbon bead, calcium hydroxyapatite and polyacrylamide hydrogel
• Require skin testing prior to use

Macroplastique:  

• Better cure & symptom improvement than collagen
• Does not need skin testing
• Higher re-injection rates associated with improved long-term outcomes

Polyacrylamide Hydrogel(Bulkamid): 

• Does not need skin testing
• Subjective success: 87% @ 1 month 71% @ 6 months 67% @ 12 months
• Repeat injection rate 12-35%
• TVT is superior to Bulkamid
• Current evidence not sufficient to recommend bulking agents as first-line treatment of SUI

Complications of bulking agents 

• Overall complications 32%
• Most adverse effects are minor & transient 
• 3% risk of major complication
• Most common→ urinary retention & infection 
• Most common complication with Bulkamid & Macroplastique → UTI followed by pain
• Other complications→

1. hypersensitivity reactions,
2. prolapse,
3. diverticula,
4. de novo detrusor overactivity,
5. injection site complications like sterile/infected abscess, pseudo cyst & mass formation.

Major complications→ pulmonary embolism/death

Bulkamid:

overall complications 18%

infection 5%

pain 4%

urinary retention 3.5%  

periurethral abscess & erosion

Macroplastique: infection 6% urinary retention 10%  erosion 1% higher risk of transient haematuria & dysuria

Operative technique to be read from original article (Click Here). Only few points covered below

• Pre-requisites of procedure: 

• Preoperative urinalysis antibiotic prophylaxis +/- local/general anaesthesia 
• Lithotomy position  
• Bulking agents given during cystoscopy  either transurethral or periurethral injection 
• Site of injection: 
• Bulking material injected into urethral submucosa at ≥2 sites at same level just distal to bladder neck or into mid-urethra

• Coughing and straining may be used to check adequate coaptation before stopping the procedure
• After the procedure:

• Avoid indwelling catheters
• Monitor for post-void & any difficulties with urination
• Must have at-least one satisfactory post-void residual before discharge (residual <100 ml & voided volume at-least 200 ml)

• Follow-up 3-6 months on phone
• All procedural & outcome data to be entered into BSUG surgical database

Conclusion 

• Durability of many agents not know beyond 1 year
• Insufficient evidence to recommend urethral bulking agents as first-line treatment
• Need more research

 

CPD Urethral Bulking Agents SUI

The use of urethral bulking agents in the treatment of stress urinary incontinence

Regarding urinary incontinence,

1. it occurs in 15% of women. FALSE
2. stress urinary incontinence (SUI) most commonly occurs as a result of intrinsic sphincter deficiency (ISD).FALSE

Regarding first‐line treatment for SUI,

3. all women should be offered a trial of supervised pelvic floor muscle training of at least 3 months’ duration. TRUE
4. bulking agents are not currently recommended. TRUE

With regard to surgical treatment of urinary incontinence,

5. women with stress‐predominant mixed urinary incontinence can be considered for surgery without urodynamic testing. TRUE
6. bulking agents cannot be used following other surgery for SUI. FALSE

Regarding the mechanism of action of bulking agents,

7. coaptation involves the adaptation of the urethral mucosa to remain closed at rest. TRUE

Regarding collagen as a bulking agent,

8. glutaraldehyde cross‐linked bovine collagen is the most widely used injectable worldwide. FALSE
9. collagen has demonstrated efficacy of almost 60% at 12 months. FALSE
10. carbon bead, calcium hydroxylapatite and polyacrylamide have all shown non‐inferiority to collagen. TRUE
11. collagen requires skin testing before administration. TRUE

Regarding the effectiveness of bulking agents,

12. the ideal bulking agent should have particles larger than 60 µm. FALSE
13. they have been shown to be more effective than pelvic floor physiotherapy. TRUE
14. they have been shown to be more effective than synthetic tapes and slings. FALSE
15. they have been shown to be more effective than no treatment. TRUE

Regarding side effects and complications of bulking agents,

16. most side effects are considered minor. TRUE
17. one of the most common side effects is urinary infection. TRUE
18. significant complications are rare. TRUE

When administering bulking agents,

19. the bulking material is injected into the urethral submucosa at two or more sites at the same level of the proximal urethra (at a level just distal to the bladder neck) or into the mid‐urethra. TRUE
20. coughing and straining is useful in demonstrating adequacy of the procedure before stopping. TRUE

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