There is controversy regarding the characteristics of patients best treated with bulking agents. In 1992 the term “intrinsic sphincter deficiency” (ISD) was coined to describe patients with a damaged urethral sphincteric mechanism (Fig. 15.1), regardless of cause (7). While many, including the author of this chapter, believe the ideal patient for urethral bulking has both limited mobility of the bladder neck and a poorly functioning sphincteric mechanism, others consider that any patient desiring conservative treatment of stress urinary incontinence is a candidate. One of the aspects against use in young patients is that repeat injections of current agents are usually required to maintain effect, and this could mean many injections for such a patient. While some reports indicate equal effectiveness in patients with hypermobility of the bladder neck (8, 9, 10), others have noted impaired effect in these patients (11). Medicare guidelines for reimbursement require immobility of the bladder neck (5). It was not specified as to how immobility was to be determined, but most physicians use a Q-tip test with a straining value of less than 30 to 40 degrees as the cut-off value for hypermobility. Hypermobility has also been determined radiologically by a standing stress test with 2 cm or greater descent of the bladder neck, but there is no indication that imaging provides any more information than the standard Q-tip test. Other techniques include ultrasound and voiding cystourethrography (12). Medicare still requires a leak point pressure of 100 cm of water or less for reimbursement (6). The guidelines for this measurement require at least 150 mL of bladder filling, but there is no requirement regarding maximum bladder volume, position of the patient, size of urethral catheter, or kind of effort used to increase the intra-abdominal pressure. Without study confirmation, it is the author’s opinion that the most important pretreatment indication is impaired mobility of the bladder neck. If an anti-incontinence procedure or other
pelvic floor surgery has been performed, and stress incontinence persists or occurs, there is no contraindication to using a bulking agent, and often it is effective. This may be done as early as 6 weeks after surgery.

Generally, bulking agents are not indicated for patients with urethral hypermobility, especially now where there are minimally invasive tension-free slings that have excellent cure rates (see Chapter 14, Surgical Treatment of Stress Urinary Incontinence). There are situations in high-risk patients where a pessary has provided excellent control of pelvic organ prolapse, and there has been some temporary stabilization of bladder neck mobility. Periurethral bulking has been considered in this patient since when the prolapse is reduced by the pessary, the masking effect of the prolapse on the urethra is removed, and stress incontinence can result. This has not been studied definitively. The result of periurethral bulking after radiation therapy has not been encouraging. Contraindications include active urinary tract infection, high residual urine, severe detrusor overactivity, and reduced bladder capacity (less than 250 mL).

The ideal candidate for bulking therapy may be the patient with an immobile urethra and symptomatic stress incontinence, although there are other patients who could benefit from this approach (Table 15.1).

Evaluation prior to therapy includes the basic evaluation consisting of history, physical examination, neurological screening examination, 24-hour voiding diary, residual urine determination, Q-tip test, and urinalysis and/or culture (see Chapter 5, Basic Evaluation of the Incontinent Female Patient). This is complemented by a cystometrogram (CMG) with leak point pressure determination and urethrocystoscopy. The procedure needs to be fully explained to the patient, including the need for repeat injections.

Bulking agents should be of uniform spheroidal particle size over 110 microns in order to avoid phagocytization by macrophages and possible migration to distant locations. The injection performed under a low-pressure technique may prevent introduction into the vascular system.

Contigen® was approved by the Food and Drug Administration (FDA) in 1993. The material is prepared by glutaraldehyde cross-linking of bovine dermal collagen that is dispersed in phosphate-buffered physiologic saline, which may represent up to 65% of the total volume. The material contains 95% type I collagen and 1% to 5% type III collagen. It requires a skin test to be placed 30 days prior to injection to ensure absence of an allergic response, which occurs in 2% to 5% of women. The material biodegrades in 3 to 19 months and repeat injections may be required to re-establish efficacy. However, patients have been satisfactorily managed by one injection for as long as 6 years. The material is readily available and up to 1999 was the only injectable agent approved in the United States. The material comes in 2.5-mL syringes, injects through a 22-gauge needle, and requires one to three syringes injected transurethrally, and more as a periurethral injection. The contraindications to therapy include positive
skin test for Contigen® implant, history of allergy to any bovine collagen products, patients undergoing desensitization to meat products, or in patients with a history of severe allergies.

Durasphere® (Boston Scientific, Natick, MA) was approved by the FDA in 1999. It consists of pyrolytic carbon-coated zirconium oxide beads suspended in a water-based carrier gel containing beta-glucan. The newer preparation (Durasphere EXP) has a particle size of 95 to 200 μm compared to the older material, which had particle size of 251 to 300 μm. The material is nonbiodegradable and is radiopaque but requires injection with an 18-gauge needle. The material comes in 1-mL syringes and requires two to four syringes for injection. The initial evaluation showed efficacy equal to Contigen® (13).

Tegress® (C.R. Bard, Inc., Covington, GA) is an ethylene vinyl copolymer dissolved in dimethyl sulfoxide (DMSO), approved in the United States in the fall of 2004. Upon contact with a liquid medium, diffusion of DMSO occurs, and a solid polymer precipitates. It comes in a 2.8-mL vial and is injected through a 25-gauge needle at a total of three sites, with no more than 1 mL at any one site and the total injection not to exceed 2.5 mL (14).

Macroplastique® (Uroplasty, Inc., Minneapolis, MN) is approved for use in Europe and in Canada but remains in study protocols 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 size 73 to 100 μm and is prepared in 2.5-mL syringes. It requires a special injection apparatus for transurethral injection, but recently it has been applied periurethrally using the Macroplastique Implantation System (15). The silicone name will most likely inhibit ease of approval in the United States.

Calcium hydroxylapatite (Coaptite®; BioForm Medical, Inc., San Mateo, CA) consists of 100-μm hydroxylapatite spheres suspended in an aqueous gel of sodium carboxylmethylcellulose. The material is a natural constituent of bones and teeth and has been used in dental and orthopaedic applications for a number of years. It was approved by the FDA in the spring of 2006 for use in the United States. It is injected via a 21-gauge needle, requires only 2.5 mL on initial injection, and can be visualized radiographically or by ultrasound (16).

Permacol^TM (Tissue Science Laboratories plc [TSL], Aldershot, Hampshire, UK) is approved for use in Europe and is under study protocol in the Unites States. It is a sterile injectable suspension of acellular cross-linked porcine collagen matrix. It is a 60% suspension in saline of cryogenically milled Permacol® surgical implant. Its safety has largely been assumed through thousands of implants of porcine collagen sheets in pelvic reconstructive surgery. No skin test is required prior to use and comparative studies are favorable (17).