Introduction

A bulking agent is a material injected into the wall of the urethra to improve urethral coaptation in women suffering from stress incontinence. The concept was initially described in the 1930s when sodium morrhuate and paraffin were used to augment urethral resistance. Sclerosing agents were also used for inducing permanent urethral scaring to improve urinary leakage. Eventually, collagen, Teflon, and autologous fat were found to be efficacious, and only collagen demonstrated proven safety and endured extensive testing, becoming the gold standard for injectable agents. Since then, multiple other products have been developed by industry, each with its particular success rates and complications.

Although the cause of stress incontinence remains unknown, the most accepted theory divides patients into 3 groups. Group 1 includes patients who have urethral mobility with an intact urethral sphincter. Historically, these patients are thought not to be good candidates for injection of a bulking agent because outcomes of suspension procedures or slings have been very good. Group 2 includes patients with a mobile urethra who are thought to have a deficient urethral sphincter and group 3 includes women who have a well-supported urethra with a deficient sphincter (intrinsic sphincter deficiency [ISD]). ISD was defined in 1992 as the damage to the urethral sphincteric system regardless of the cause. The goal of using bulking agents is to maintain urethral coaptation during the storage phase and control during transient abdominal pressure variations while permitting voiding as needed. Injecting a material into the proximal urethra provides bulk and mucosal resistance, resulting in resistance to passive urine flow. Success with the use of bulking agents is reported to occur when the functional length of the urethra increases, which results in an increase in the efficiency of pressure transmission in the proximal quarter of the urethra. This process resists bladder neck opening during increases in intraabdominal pressure as would happen with stress urinary incontinence (SUI). Klarskov reported that certain bulking agents actually increase the strength of the sphincter, possibly by increasing the volume of the muscle cell and thereby its ability to contract and generate power.

Indications

Bulking agents are used to manage stress incontinence in women, with the main indication being ISD. This indication, however, includes the need for touchup or rescue urinary control after the patients with incontinence have had meager outcomes with alternative incontinence techniques such as slings. Other indications include the need to operate under local or no anesthesia, such as in patients who are medically fragile or unstable. Being elderly with the inability to succumb to the postoperative discomfort and subsequent immobility is yet another indication. Because of the way urethral coaptation works, bulking may be used in patients who have poor bladder emptying with concurrent sphincter weakness. Other potential indications are in patients who are still interested in child bearing, patients whose anticoagulation cannot be reversed long enough to allow for alternative incontinence surgical management, and patients who refuse to undergo a more invasive surgical procedure such as a sling or suspension.

Indications

Bulking agents are used to manage stress incontinence in women, with the main indication being ISD. This indication, however, includes the need for touchup or rescue urinary control after the patients with incontinence have had meager outcomes with alternative incontinence techniques such as slings. Other indications include the need to operate under local or no anesthesia, such as in patients who are medically fragile or unstable. Being elderly with the inability to succumb to the postoperative discomfort and subsequent immobility is yet another indication. Because of the way urethral coaptation works, bulking may be used in patients who have poor bladder emptying with concurrent sphincter weakness. Other potential indications are in patients who are still interested in child bearing, patients whose anticoagulation cannot be reversed long enough to allow for alternative incontinence surgical management, and patients who refuse to undergo a more invasive surgical procedure such as a sling or suspension.

Injectable agents

The success of any material implanted refers to its efficacy over time while maintaining a low–side-effect profile. Successful use of bulking agents depends on the nature of the material injected, ease of administration of the material, and the host milieu including integrity of the paraurethral tissue and fascia. Material biocompatibility, including low host reactivity, low carcinogenesis potential, and low risk of migration, is also important. Historically, sodium morrhuate and paraffin as well as sclerosing agents were used with questionable outcomes. Autologous fat injections were also used, with poor outcomes and complication rates reaching 32%. Teflon (polytetrafluoroethylene), marketed as Polytef (DuPont, USA), was also tested but was not approved by the Food and Drug Administration (FDA) because of particle migration. Two products with high potential were Tegress (CR Bard, Inc, Covington, GA, USA) and Deflux (Q-Med, Uppsala, Sweden). Deflux, made of dextranomer/hyaluronic acid, was proven to have high efficacy in vesicoureteral reflux, but trials did not prove its efficacy in the treatment of SUI. Deflux was also associated with the formation of sterile pseudoabscesses in 16% of the patients. Tegress, also marketed as Uryx (Genyx Medical, Inc, Aliso Viejo, CA, USA), was made of a copolymer of ethylene vinyl alcohol, which was highly efficacious in the treatment of SUI, but urethral erosions (up to 37% of patients) precluded its use and was withdrawn from the market in 2006. Contigen (CR Bard, Covington, GA, USA), made of glutaraldehyde cross-linked bovine collagen, has been studied the most and is used as a reference for testing newer agents. However, in 2011, its production ceased.

Zuidex (Q-Med AB, Uppsala, Sweden), made of hyaluronic acid with dextronomer, was highly effective in controlling reflux in the pediatric population but was withdrawn from the market because of high rates of erosion.

These agents can be injected submucosally by either a transurethral or a periurethral technique. In the transurethral technique, the agent is injected under direct guidance using a needle introduced through the operative channel of a cystoscope. In the periurethral technique, the needle is introduced lateral to the urethral meatus and positioned submucosally. Administering a dye before injecting the bulking agent can help localize the tip of the needle. Schultz and colleagues in a prospective randomized trial showed no difference in the long-term outcomes between the 2 techniques, although immediate postoperative urinary retention was slightly higher in the patients undergoing periurethral technique.

In 2008, Kuhn and colleagues randomized 30 patients to either a midurethral or bladder neck injection site. The study showed no difference in outcomes, with slightly higher patient satisfaction in the midurethral group. In a similar study by Lightner and colleagues, proximal injections of Contigen were associated with better outcomes (84% vs 65%) compared with midurethral injections of Zuidex. However, conclusions from this study are not possible because it compared different products at different injection sites.

The following is a detailed discussion of the various bulking agents currently in use.