Introduction
In 1938 reported the use of morrhuate sodium for injection management of urinary incontinence. In the early 1990s, bovine collagen was introduced for the treatment of stress urinary incontinence and was the gold standard with which all later studies are compared, although production of this material was halted in 2011. Since the 1990s, several urethral bulking agents have been introduced for this purpose, although some have been removed due to a high rate of adverse events, difficulties with injection, or expense. The ideal urethral bulking material is biocompatible, nonimmunological, and hypoallergenic. It should retain its bulking characteristics for a prolonged interval and therefore should not biodegrade, nor should it migrate (particle size should be greater than 80 μm). The material should be easy to prepare and easy to inject. The ideal material is safe, readily obtainable, inexpensive, efficacious, and durable and induces minimal tissue reaction. The theory on how injectable materials can be used to treat stress incontinence is by mucosal coaptation of the bladder neck and proximal urethra with subsequent increased urethral resistance to outflow of urine. While transmission of pressure to the urethra during increased intra-abdominal pressure may not change in patients treated with urethral bulking injections, the pressure forcing the urine from the bladder through the urethra is resisted by the bulking of the mucosa in the immediate proximal urethra. This essentially prevents involuntary bladder neck opening.
Indications and Contraindications
The most common indications for urethral bulking agents are (1) intrinsic sphincter deficiency with or without urethral hypermobility, (2) persistent stress urinary incontinence after a urethral sling or urethropexy, (3) stress urinary incontinence in women who cannot undergo surgery due to multiple comorbidities (e.g., poor surgical candidate and/or cannot discontinue anticoagulation), and (4) stress urinary incontinence in women who do not desire a more invasive anti-incontinence surgery (e.g., prefer to avoid mesh material, desire future fertility, treat occult stress incontinence after successful pessary placement, etc.). Relative contraindications to the use of urethral bulking injections include active urinary tract infection, high postvoid residual urine (>100 mL), urinary stricture/obstruction, severe detrusor overactivity, and fragile urethral mucosa.
The ideal patient for urethral bulking has both limited mobility of the bladder neck and a poorly functioning sphincteric mechanism. Retropubic mid-urethral slings work poorly in women with a fixed (nonhypermobile) urethra and intrinsic sphincter deficiency. Urethral hypermobility is diagnosed when the angle of the urethra with the patient supine exceeds 30° to 40° from horizontal during straining efforts (Valsalva or cough). In classic teaching, intrinsic sphincter deficiency is diagnosed when (1) the maximal urethral closure pressure is less than 20 to 25 cm H 2 O and/or (2) the abdominal (Valsalva) leak point pressure is less than 60 cm H 2 O when the bladder is filled to 150 to 250 mL.
Certain patients respond better to urethral bulking injections. Should the procedure provide no relief after two or three injections, it is usually futile to attempt subsequent injections. A suburethral sling can be performed before or after urethral bulking injections. Theoretically, in a woman with a previous urethral bulking injection, there is a risk of encountering the bulking material during the dissection for a urethral sling. Conversely, in a woman with a previous urethral sling, there may be difficulty placing the bulking material in the correct space, because the sling may compress the urethra and not allow sufficient room for tissue expansion. If stress incontinence persists or recurs after a urethral sling or other pelvic reconstructive surgery, a urethral bulking agent may be used, and often it is very effective. This may be done as early as 6 weeks after surgery, except for Macroplastique ® , which is not recommended until after 12 weeks.
Bulking agents generally are not the first-line treatment for patients with urethral hypermobility and stress urinary incontinence, as the mid-urethral sling is highly efficacious. However, there are situations in high-risk patients who are poor surgical candidates with pelvic organ prolapse and stress incontinence when a pessary has provided excellent control of prolapse and has provided temporary stabilization of bladder neck mobility. Urethral bulking may be used in this patient to treat occult stress incontinence that was unmasked after the prolapse was reduced. In addition, treatment of stress urinary incontinence in women who have not completed childbearing is a difficult situation in which urethral bulking may be considered as an alternative to physical therapy, mid-urethral sling, or expectant management. Last, due to the current mesh controversy in the media, some women may desire treatment with nonmesh alternatives.
Evaluation
Evaluation before therapy consists of a history and physical examination to include a postvoid residual urine determination and urinalysis and/or urine culture. This is usually complemented by a bladder diary and urodynamic evaluation to establish the diagnosis of intrinsic sphincter deficiency. A voiding diary and/or a measured voided volume gives an estimate of bladder capacity, assuming the patient has been instructed to present with a full bladder. A free-flow uroflowmetric examination gives additional information regarding maximum flow rate, in addition to voided time and volume. A cystometrogram evaluates for detrusor overactivity, bladder compliance, bladder capacity, and abdominal (Valsalva) leak point pressure determination. The urethral pressure profile measures the maximum urethral closure pressure to aid in the diagnosis of intrinsic sphincter deficiency. Another evaluation technique to aid in diagnosis of intrinsic sphincter deficiency is direct urethroscopic visualization of the bladder neck and proximal urethra to evaluate for urethral coaptation/open bladder neck.
The procedure needs to be fully explained to the patient, including the predicted effectiveness and the possible need for repeat injections. Patients should have a basic understanding that all currently marketed bulking procedures involve the injection of nonbiodegradable material. Despite good initial subjective success by the patient and with coaptation of the proximal urethra noted by the surgeon, the improvements may be short-lived as the carrier medium is absorbed over time, leaving behind the permanent implant. The permanent material volume may be less than the volume of the material plus the carrier medium, leading to reduced coaptation in the initial few weeks after surgery. Thus, setting the expectation that additional bulking procedures may be required is essential.
Materials
All currently available materials are nonbiodegradable and nonimmunological, do not require refrigeration, and do not require skin testing ( Table 22.1 ).
| Trade Name | Bulking Material | Company | Approval | Carrier Media | Syringe | Needle Gauge/Type | Approaches | Ancillary Components |
|---|---|---|---|---|---|---|---|---|
| Contigen ® | Bovine dermal collagen cross-linked with gluteraldehyde | Bard, Inc., Covington, GA | 1993 (Off market in 2011) | Phosphate-buffered physiological saline | 2.5 mL | 22- to 23-gauge, rigid or flexible needle | Transurethral or periurethral | None |
| Durasphere ® EXP | Pyrolytic carbon–coated graphite beads | Coloplast Corporation, Minneapolis, MN | 1999 | Beta glucan and water gel | 1.0 and 3.0 mL | 18- or 20-gauge, pencil point tip, rigid needle, bent spiral tip needle | Transurethral or periurethral | None |
| Coaptite ® | Calcium hydroxylapatite | Boston Scientific Corporation, Natick, MA | 2005 | Sodium carboxymethyl cellulose, sterile water, and glycerine | 1.0 mL | 21-gauge, sidekick rigid needle | Transurethral | None |
| Macroplastique ® | Polydimethyl-siloxane macroparticle | Uroplasty, Geleen, The Netherlands, and Minnetonka, MN | 2006 | Polyvinylpyrrolidone gel | 2.5 mL | 18- or 20-gauge, rigid needle | Transurethral | Administration device/pressure gun |
Approved by the Food and Drug Administration (FDA) in 1993, Contigen ® (Bard Inc., Covington, GA) was the primary urethral injectable agent until 1999. It consists of glutaraldehyde cross-linking of bovine dermal collagen. Unfortunately, the manufacturing of bovine collagen was halted in June 2011. Of note, this was the only material that was biodegradable and not permanent. Additionally, this was the only material that required skin testing, as allergic reactions occurred in 2% to 5% of women. All currently marketed urethral bulking materials used bovine collagen as the control material in their representative comparative studies.
Durasphere ® (Carbon Medical Technologies Inc., St. Paul, MN) was initially approved by the FDA in 1999. It consisted of pyrolytic carbon to coated zirconium oxide beads with a particle size of 212 to 500 μm and required injection using an 18-gauge needle. The second-generation material, Durasphere ® EXP (Coloplast Corporation, Minneapolis, MN), consists of pyrolytic carbon–coated graphite beads suspended in a water-based carrier gel containing 3% beta glucan. Beta glucan is a simple polysaccharide that causes a subtle inflammatory response. The current preparation has a smaller particle size of 90 to 212 μm and is injected through a smaller (20-gauge) needle. The material is nonbiodegradable. According to the manufacturer, it should not migrate because the particle size is greater than 80 μm and thus theoretically cannot be engulfed by macrophages. The product is versatile and is the only material that is approved for periurethral methods, as well as transurethral methods. It is available in 1- and 3-mL syringes. Typically, 2 to 4 mL is injected at the 4 and 8 o’clock positions. Importantly, for women with “fragile urethral mucosa” (possibly from prior radiation therapy or prior urethral surgery), Durasphere ® EXP is the only material that is not contraindicated.
Coaptite ® (Boston Scientific Corporation, Natick, MA) was approved by the FDA in 2005. It consists of 75- to 125-μm (average 100-μm) calcium hydroxylapatite spheres suspended in an aqueous gel of sodium carboxylmethylcellulose. This synthetic material is a natural constituent of bones and teeth and has been used in dental and orthopedic applications for many years. In the urethra, it does not encapsulate but allows for ingrowth of native tissues with time as the gel carrier dissolves. It has not been shown to induce heterotopic bone formation. It is biocompatible, nonbiodegradable, and radiopaque; is injected through a 21-gauge needle; and is available in 1-mL syringes. Typically, 2 to 4 mL is injected at the 4 and 8 o’clock positions. According to the manufacturer’s instructions for use, Coaptite ® is contraindicated in patients with a “fragile urethral mucosal lining.”
Macroplastique ® (Uroplasty, Geleen, the Netherlands, and Minnetonka, MN) has been approved for use in Europe since 1991 and was approved by the FDA in 2006 for use in the United States. It is made from highly textured polydimethyl-siloxane macroparticles suspended in a bioexcretable carrier hydrogel of polyvinylpyrrolidone. It consists of silicone microimplants of 120 to 600 μm (average 140 μm) and is prepared in 2.5-mL syringes injected through an 18- or 20-gauge needle. Typically, two syringes are required with 2.5 mL delivered to the 6 o’clock position and 1.25 mL delivered to each of the 2 and 10 o’clock positions, for a total of 5 mL. It requires a special administration device for transurethral injection ( Fig. 22.1 ). According to the manufacturer’s instructions for use, Macroplastique ® is contraindicated in patients (1) with “fragile urethral mucosal lining (e.g., post radiation therapy or post surgery to the bladder neck)” or (2) within 12 weeks of previous Macroplastique injection or a minimally invasive sling procedure.
Bulkamid ® (Contura International, Soeborg, Denmark, and Ethicon, Somerville, NJ) is under clinical investigation in the United States. It is a nonresorbable polyacrylamide hydrogel made of cross-linked polyacrylamide and water. Bulkamid ® contains no solid particles (crystals or particulates), theoretically abolishing the risk of migration. Being a gel, it can be injected through the operative channel of a regular cystourethroscope using a special 23-gauge needle or the Bulkamid ® Urethral Bulking System—a specially designed lightweight urethroscopic instrument that facilitates injection ( Fig. 22.2 ). In 2012, a prospective study that followed 135 women over 2 years showed good maintenance of the durability of success, with 67% subjective cure rate at 1 year and 64% at 2 years.
