Injectable Bulking Agents for Incontinence 

Background

Injectable therapy using bulking agents composed of synthetic materials, bovine collagen, or an autologous substance augments the urethral wall and increases urethral resistance to urinary flow. Injection of bulking agents to treat a dysfunctional urethra is a minimally invasive method of correcting intrinsic sphincteric deficiency (ISD) that results in stress urinary incontinence (SUI).^{[1, 2, 3, 4, 5, 6]}

Injectable agents have been used to manage SUI for more than a decade, but their application has been limited by placement, durability, antigenicity or compatibility issues. The lack of a single reproducible agent has led to the development and application of several agents that provide reasonable efficacy with minimal associated morbidity. Continuous development of techniques and materials provides the basis for multiple new bulking agents. Clinical trials continue to provide evidence-based experience with this form of minimally invasive treatment of SUI.

Urethral bulking procedures are designed to treat SUI due to intrinsic sphincter deficiency by artificially inflating the submucosal tissues of the bladder neck. These procedures involve injecting synthetic and autologous fillers into the wall of the urethra to make it fuller. Bulking up the bladder neck with particulate matter effectively closes the lumen of the urethra, which improves urethral coaptation and restores the mucosal seal mechanism of continence.

Bulking procedures are minimally invasive and are extremely useful for treating women with incontinence who wish to avoid open surgical procedures for various reasons. Methods used to bulk up the female urethra include transurethral and periurethral injection techniques (see the images below). The delivery techniques for the male urethra include transurethral and antegrade injection.

Urethral bulking agents reported in the literature (see below) include autologous fat, bovine collagen (Contigen), calcium hydroxylapatite (Coaptite), carbon beads (Durasphere), polydimethylsiloxane (Macroplastique), and polytetrafluoroethylene (PTFE; Teflon). Because of the risk of migration, PTFE is not approved by the US Food and Drug Administration (FDA) for treatment of female SUI.

Autologous fat is harvested from the lower abdomen and injected around the urethra. Glutaraldehyde, cross-linked collagen, is an extracted and purified bovine collagen. Durasphere is composed of pyrolytic carbon-coated beads suspended in a water-based gel. Other agents under clinical trial evaluation include synthetic calcium hydroxylapatite, cross-linked hyaluronic acid (HA), and ethylene vinyl alcohol copolymer suspended in dimethyl sulfoxide.

The initial introduction of injectable bulking agents has provided physicians with an additional option to treat SUI. The advent of newer agents with unique individualized merits and newer injectable techniques promises to dramatically alter the role of injectable bulking agents in the overall management of SUI.

Careful patient selection appears to be important but is not required for a successful outcome when this form of minimally invasive therapy is considered, especially in those who are less active and are at higher risk for the complications inherent in more invasive procedures.

Some recent studies have focused on the use of stem cells for treatment of SUI, both for female SUI and for postprostatectomy incontinence in men. Current research has focused on autologous cells, derived either from muscle or from adipose tissue.^[7] These stem-cell therapies for urinary incontinence may have the ability to regenerate a damaged or weakened rhabdosphincter. Because their effect is improved sphincter function rather than coaptation from a bulking effect, they are not discussed further in this article.

Go to Urinary Incontinence and Surgical Treatment of Urinary Incontinence for complete information on these topics.

Indications

Social indications for surgical intervention include any SUI that interferes with the patient’s quality of life. Pathologic indications for correcting ISD include primary urethral dysfunction, failed previous bladder neck surgery, and severe attenuation of endopelvic fascia.

Treating ISD secondary to severe ISD is often more difficult than treating ISD induced by urethral hypermobility, which is why severe ISD is referred to as complex or complicated SUI. If the urethra displays low outlet resistance, treatment must be designed to increase outflow resistance.

Candidates for periurethral bulking agents include women with ISD and men who are incontinent after prostate surgery. In women with severe ISD or urethral hypermobility–induced ISD, the best long-term results are obtained with a pubovaginal sling or retropubic bladder neck suspension procedure.^[8] However, periurethral injection therapy has been introduced because of excellent short-term results as a minimally invasive procedure.

In women with urethral hypermobility–induced ISD, early studies have reported favorable short-term results with injectables; however, long-term (>1 y) data are lacking. Incontinent men who fare best with injectable therapy are those who have SUI after transurethral prostatectomy (TURP). Men with SUI after radical prostatectomy have the least significant success rate with bulking agents, and these men may be treated best with a sling procedure or an artificial urinary sphincter.^[9]

Contraindications

Periurethral bulking agents should not be used in the setting of pure urge incontinence or bladder outlet obstruction. A patient with mixed incontinence (eg, SUI and urge incontinence) in whom the urge component is the predominant problem may elect to address the symptoms of bladder overactivity before bulking up the urethra but may find that treatment of the SUI also improves the urge incontinence. Patients with a hypersensitivity to collagen, noted on skin testing before injection, should not undergo this type of therapy.

Anesthesia

For autologous fat injection, the patient should be completely anesthetized. Injection of other materials may be performed with the patient under local anesthesia in the office or in the operating room. After careful preparation and draping, induce local anesthesia by gently instilling 2% lidocaine jelly directly into the urethra. If additional anesthesia is needed, 1% lidocaine may be injected into the periurethral tissues next to the urethral opening.

Equipment

Urethral bulking agents reported in the literature (see below) include autologous fat, bovine collagen (Contigen), calcium hydroxylapatite (Coaptite), carbon beads (Durasphere), polydimethylsiloxane (Macroplastique), and polytetrafluoroethylene (PTFE; Teflon). Because of the risk of migration, PTFE is not approved by the US Food and Drug Administration (FDA) for treatment of female stress urinary incontinence (SUI).

Autologous fat

Autologous fat, extracted from the patient’s lower abdomen, is an ideal bulking agent because it is inexpensive, readily available, and nonallergenic. However, it is less efficacious than other alternatives, and because of the rare possibility of fat emboli, its use is limited. Ideal candidates are women with a clinical history of severe urinary incontinence who have good anatomic support. Although some investigators also use autologous fat for urethral hypermobility, long-term results of this application remain undetermined.

The injection technique is simple, and it does not employ foreign materials such as Teflon or bovine collagen. Injections may be repeated as required; however, the operative time of the procedure is prolonged because suprapubic fat must be harvested before periurethral injection.

Before the FDA approved collagen for use, fat injections were used to treat intrinsic sphincter deficiency (ISD) by bulking up the urethra.^[10] The short-term result of periurethral fat injection is extremely good. Over time, however, the injected adipocytes tend to be phagocytized by the patient’s own body. This high degree of fat absorption is the major detriment to long-term cure.

Bovine collagen

A third type of bulking agent, bovine collagen, received FDA approval in 1993 for treating women with ISD. Collagen is a natural protein commonly found in animal bones and connective tissue. The collagen used to treat female urinary incontinence is extracted from cattle and then purified and prepared for use as a bioinjectable agent (cross-linked with glutaraldehyde). When collagen is injected around the urethra, the resultant bulking of periurethral tissue closes off the urethral lumen, which maintains urinary continence.

Collagen implantation usually is performed in the hospital in an outpatient setting, but it also can be performed in the office. During this procedure, collagen paste is injected carefully around the urethra near the bladder neck to bulk up the urethral tissue and stop urine from leaking. The injected bovine collagen gradually is replaced by the host collagen over the next 9-19 months. Usually, more than 1 treatment is necessary, and the procedure may have to be repeated after 1 year.^{[11, 12]}

Bovine collagen injection is not known to have any long-term complications. It is approved by the US FDA for treatment of both male and female ISD. Patients being considered for periurethral bovine collagen injection must undergo a skin test approximately 4-6 weeks before surgery to determine if they are allergic to this material.

Calcium hydroxylapatite

The FDA approved calcium hydroxylapatite for periurethral injection in 2005. The particles are combined with sodium carboxymethylcellulose as a carrier and are injected at the level of the bladder neck to provide a bulking effect. Animal studies have suggested that, after dissipation of the carrier, the calcium hydroxylapatite particles remain, eventually resulting in tissue ingrowth and new collagen formation.

A multicenter, prospective, randomized, single-blind study compared calcium hydroxylapatite injection with bovine collagen injection in women with ISD. At 12 months, 83 (63.4%) of 131 patients receiving calcium hydroxylapatite had improved by 1 Stamey grade. The 2 therapies were equally tolerated. However, a higher proportion of patients who received calcium hydroxylapatite required only 1 injection (38.1% vs 26.1%). In addition, the initial volume of calcium hydroxylapatite needed was less than that of bovine collagen (2.15 mL vs 3.39 mL).^[13]

Whereas a skin test is required before bovine collagen injection, no such test is required before calcium hydroxylapatite injection, which can be performed on an outpatient basis or in the office. As is the case with bovine collagen, most patients who receive calcium hydroxylapatite require additional injections after the first year because the effects tend to fade over time.

Carbon bead particles

Carbon bead particles are an attractive alternative to currently available injectable agents. These particles are nonbiodegradable bulking agents that may be as efficacious as bovine collagen while causing fewer adverse effects. Carbon bead particle injection has been reported to yield outcomes similar to those of collagen injection, without the problem of early reabsorption.^[14]

Carbon bead particles may be more difficult to inject than collagen because of increased viscosity; an 18- to 19-gauge needle is required for the injection. If any resistance to the injection is encountered (eg, from scar tissue), the suspension gel tends to be injected first, leaving the carbon bead particles behind in the syringe.

Dextranomer/hyaluronic copolymer

Dextranomer/hyaluronic copolymer (Zuidex) has been used in Europe, administered via the injection system Implacer, for treatment of SUI in women.^[15] In the United States, it has been used extensively in children with vesicoureteral reflux. At present, however, though studies are ongoing, dextranomer/hyaluronic acid is not FDA-approved for treatment of urinary incontinence in women.

Polydimethylsiloxane

Polydimethylsiloxane is a permanent material that can be administered via periurethral injection to treat SUI.^{[16, 17]} The FDA approved its use in 2006. A recent randomized prospective study that compared polydimethylsiloxane with bovine collagen found that the former achieved excellent efficacy at 12 months.^[18] However, because polydimethylsiloxane was approved relatively recently, no studies have yet been able to assess its long-term efficacy.

Polytetrafluoroethylene paste

PTFE is an inert plastic material that initiates a foreign body reaction and granuloma formation in the injection site. It stimulates an ingrowth of fibroblasts that help to hold the PTFE particles within the periurethral tissues to facilitate inward compression of the urethral lumen. The best candidates for PTFE injections are women experiencing SUI and incompetent urethra after a failed anti-incontinence operation, those with good anatomic support, and those with no history of pelvic radiation therapy.

The goal of PTFE injection is to create better coaptation and a better mucosal seal for the incompetent urethra by generating a cushioning effect with the PTFE paste. Simply stated, the paste adds bulk to the periurethral tissues and effectively closes the urethral lumen. The long-term success of a PTFE injection depends on whether a capsule forms around the injected paste. It is a simple procedure with a good cure rate, making it an excellent method for restoring urinary control.

The 2 disadvantages of PTFE injection are (1) that it requires using a large-bore needle and (2) that the FDA has withheld approval because of possible local and distant migration of the PTFE particles into the lymph nodes, lung, and brain.

Ethylene vinyl alcohol

Ethylene vinyl alcohol (Tegress) has been discontinued and is no longer recommended for periurethral injection. Recent reports have demonstrated significant complication rates, including 37% of patients in 1 case-series who experienced urethral erosion.^[19]

Positioning

Place the patient in the lithotomy position. Prepare and drape the vaginal area (and, for autologous fat injection, the suprapubic area) in a sterile fashion.

Complication Prevention

Injectable bulking therapy is performed predominantly in an outpatient setting, including in-office. Use a preoperative urine culture to check for infection. If using bovine collagen, administer a special skin test to patients 30 days before surgery to test for possible allergic reactions. Patients are typically given 1 dose of a prophylactic antibiotic because of the low risk of a bladder infection due to urethral manipulation.

Overview

The advantages of urethral bulking procedures include their simplicity, their minimal risk of associated complications, and their repeatability. These procedures may be performed on an outpatient basis. They can often be done quickly and painlessly in the surgeon’s office if transurethral or periurethral techniques are used. When an antegrade approach is chosen, the procedure must be performed in the operating room because suprapubic access is necessary. After the injection, patients notice immediate results.

The disadvantage of urethral bulking procedures is that the injectable agents may not produce a permanent cure. If stress urinary incontinence (SUI) persists after the initial injection, the surgeon can implant more material during subsequent follow-up visits. Long-term success is possible, but multiple reinjections are typically necessary.

Autologous Fat Injection

Initially, make a small surgical opening into the suprapubic area, and insert the end of a large-bore (7-10 mm) hollow probe that is connected to a high-pressure suction device. Using a liposuction technique, carefully extract 20-30 mL of fatty tissue from the lower abdomen. Meticulously transfer the harvested fatty tissue to several syringes for urethral injection.

Perform the entire procedure under direct vision using a cystoscope. Inject the fat periurethrally (ie, next to the urethra) or transurethrally (ie, directly into the urethra). Because the fat is low density, injections do not require a high-pressure injector.

For periurethral injection, connect the syringe containing the autologous fat to an 18-gauge needle. Slowly insert the needle next to the urethral opening and into the submucosal tissues. After ascertaining the proper position of the needle in the proximal half of the urethra, carefully inject the fatty tissue at 3 places around the urethra: the 2-, 6-, and 10-o’clock positions. The lumen is visualized closing as the injection progresses.

To ensure success, observe complete apposition (closure) of the urethral mucosa at the end of the procedure. Complete urethral closure may require injecting 1-2 tubes.

For transurethral injection insert the cystoscope into the mid-urethra. Under cystoscopic vision, connect the tip of the needle to a fat-filled syringe and gently slide it underneath the urethral mucosa. Slowly inject the fatty tissue into the submucosal tissues until complete coaptation of the urethral mucosa is visualized.

Bovine Collagen Injection

Insert the cystoscope into the urethra. Meticulously perform the entire procedure under direct vision using the cystoscope.

Inject the collagen in 1 of 2 ways, periurethrally (ie, placed next to the urethra) or transurethrally (ie, placed directly into the urethra).^{[20, 21]} Although continence results are comparable with either approach, the transurethral route is generally preferred by the less-experienced physician because more precise and efficient placement of collagen may result in a lower re-treatment rate and higher patient satisfaction. One or more (2.5-mL) syringes of collagen may be required.

For periurethral injection, slowly insert a straight or bent needle next to the urethral opening and into the submucosal tissues. After ascertaining the proper position of the needle in the proximal half of the urethra, slowly inject the paste at 3 sites around the urethra: the 2-, 6-, and 10-o’clock positions. As the injection progresses, the urethral lumen is visualized closing. To ensure success, complete apposition of the urethral mucosa must be observed at the end of the procedure. One or more syringes may be needed to produce complete closure.

For transurethral injection, use a special needle to inject collagen paste under direct vision underneath the urethral mucosa. Insert the cystoscope into the mid-urethra. Under cystoscopic vision, carefully insert the tip of the needle underneath the urethral mucosa. Precisely deposit the collagen paste into the submucosal tissues until complete coaptation of the urethral mucosa is visualized.

The antegrade route is reserved for men who are incontinent after prostatectomy. Create a suprapubic tract under adequate anesthesia. General anesthesia is preferred. Insert a flexible cystoscope into the bladder via the suprapubic tract. Identify the bladder neck. Under cystoscopic vision, carefully insert the tip of the needle underneath the bladder neck mucosa. Precisely deposit the collagen paste into the submucosal tissues until complete coaptation of the bladder neck is noted.

Calcium Hydroxylapatite Injection

Insert the cystoscope into the urethra. Meticulously perform the entire procedure under direct vision using the cystoscope.

Inject the calcium hydroxylapatite in 1 of 2 ways, periurethrally or transurethrally. Although continence results are comparable with either approach, the transurethral route is generally preferred by the less-experienced physician because more precise and efficient placement of collagen may result in a lower re-treatment rate and higher patient satisfaction. One or more (1-mL) syringes of calcium hydroxylapatite may be required.

For transurethral injection, use a special needle to inject the calcium hydroxylapatite under direct vision underneath the urethral mucosa. Insert the cystoscope into the mid-urethra. Under cystoscopic vision, carefully insert the tip of the needle underneath the urethral mucosa. Precisely deposit the calcium hydroxylapatite into the submucosal tissues until complete coaptation of the urethral mucosa is visualized. Coaptation of the bladder neck and/or urethra should be visualized during irrigation through the cystoscope.

Carbon Bead Injection

The intraoperative protocol and the technique of carbon bead particle injection are identical to those of collagen injection, except that preoperative skin testing is not required.

Insert the cystoscope into the urethra. Meticulously perform the entire procedure under direct vision using the cystoscope. Inject the carbon bead particles in 1 of 2 ways, periurethrally or transurethrally. One or more (1.0-mL) syringes of carbon bead particles may be required.

For periurethral injection, dispense the carbon bead paste into a special syringe connected to an 18-gauge bent needle. Slowly insert the needle next to the urethral opening and into the submucosal tissues. After ascertaining the proper position of the needle in the proximal half of the urethra, slowly inject the paste at 3 places around the urethra: the 2-, 6-, and 10-o’clock positions. As the injection progresses, the urethral lumen is visualized closing.

To ensure success, complete apposition of the urethral mucosa must be observed at the end of the procedure. One or more syringes may be needed to produce complete closure.

For transurethral injection, use a special needle to inject carbon bead paste under direct vision underneath the urethral mucosa. Insert the cystoscope into the mid-urethra. Under cystoscopic vision, carefully insert the tip of the needle underneath the urethral mucosa. Precisely deposit the carbon bead paste into the submucosal tissues until complete coaptation of the urethral mucosa is visualized.

Polydimethylsiloxane injection

The intraoperative protocol and the technique of polydimethylsiloxane injection are identical to those of collagen injection; however, preoperative skin testing is not required.

Insert the cystoscope into the urethra. Meticulously perform the entire procedure under direct vision using the cystoscope. Advance the needle through the working channel of the scope to visualize the needle tip. Then, insert the needle into the urethral wall, taking care to ensure that the needle bevel is facing the center of the urethral lumen. The needle should be advanced.

Inject the material in 3 locations, instilling a maximum of 1.25 mL at the 10 o’clock position, a maximum of 1.25 mL at the 2 o’clock position, and a maximum of 2.5 mL at the 6 o’clock position using a tissue-tunneling technique.

Implant the product slowly and wait a few seconds between pulls of the administration device lever. Wait approximately 30 seconds before withdrawing the needle from the tissue to limit product loss from the implantation site. Use caution and avoid passing the cystoscope over the implantation site, as this could disrupt product placement.

Polytetrafluoroethylene Paste Injection

Insert the cystoscope into the urethra. Perform the entire procedure under direct vision using the cystoscope. Inject the polytetrafluoroethylene (PTFE) paste in 1 of 2 ways: periurethrally or transurethrally. Use one or two 7-mL tubes of PTFE paste. Because PTFE is an extremely dense material, use a high-pressure injector to implant the dense paste into the periurethral tissues.

For periurethral injection, dispense the PTFE paste into the special high-pressure syringe connected to a 17-gauge needle. Slowly insert the needle next to the urethral opening and into the submucosal tissues. After ascertaining the proper position of the needle, inject the paste at 3 places around the urethra: the 2-, 6-, and 10-o’clock positions. As the injection progresses, the urethral lumen can be observed closing, and then the opening disappears.

To ensure success, visualize complete apposition (ie, kissing) of the urethral mucosa at the end of the procedure. One or 2 tubes may be injected to produce complete closure of the urethra.

For transurethral injection, use a special high-pressure syringe to inject PTFE paste under direct vision underneath the urethral mucosa. Insert the cystoscope into the mid-urethra. Under cystoscopic vision, insert the tip of the needle precisely underneath the urethral mucosa. Carefully inject the PTFE paste into the submucosal tissues until complete coaptation of the urethral mucosa is visualized.

Immediate Postoperative Period

After autologous fat injection, do not place a Foley catheter, because it promotes molding of the urethra around the catheter. If molding occurs, the urethral lumen cannot properly close. Prescribe oral antibiotics for 3 days. This procedure results in minimal urethral pain that responds to simple analgesics.

After bovine collagen injection, patients notice immediate results. Perform a cough stress test immediately after the injection to assess for cure. If stress urinary incontinence (SUI) persists, immediately reinject additional collagen. If the patient remains dry, allow her to void before discharging home.

Do not place a Foley catheter routinely after bovine collagen injection, because it may cause molding of the urethra. If patients experience difficulty in urination, they may need to self-catheterize with a small (eg, 12F) catheter. Permanent urinary retention is rare. If repeat injection is necessary for delayed stress incontinence, reschedule for 4-6 weeks later.

After calcium hydroxylapatite injection, most patients are able to void immediately postoperatively and notice effects. Forty-one percent of women may have some voiding difficulty initially, requiring temporary intermittent self-catheterization with a small (12F) catheter. Permanent urinary retention is rare.

After carbon bead particle injection, postoperative care is identical to that after collagen injection. If antegrade injection has been performed, a urethral catheter is unnecessary. Avoidance of a urethral catheter prevents molding of the bulking agent around the urethral catheter.

After polydimethylsiloxane injection, postoperative care is identical to that after collagen injection.

After polytetrafluoroethylene (PTFE) paste injection, leave a Foley catheter indwelling for 24 hours and administer oral antibiotics for 3 days. This procedure results in minimal urethral pain that responds to simple analgesics. Do not perform repeat injections for 6 months.

Expected Outcomes

Autologous fat injection

After fat injection, initial subjective improvement is reported to be as high as 83%; however, the cure rate declines to 57% after 1 year. Patients require 1-4 injections (average, 2.5) to achieve continence. Again, because of the limited clinical efficacy compared with other methods and rare but serious complications such as fat emboli, autologous fat is rarely used in periurethral injection.

Bovine collagen injection

Available medical literature indicates that 67%-96% of women with intrinsic sphincter deficiency (ISD) remain dry 1 year after injection. After 2 years, 40%-49% of incontinent women were cured, and 67%-83% were either cured or improved. Reports indicate that collagen is a more effective bulking agent than fat.^{[22, 23]} After 4 years, 27% remained cured and 36% remained improved.

The number of injections required to achieve continence varies from patient to patient. Kieswetter et al reported injecting 8 mL of bovine collagen at a single session.^[24] Corcos et al reported that the average number of injections in the first 6 months was 2.2, with an average volume of 9 mL of bovine collagen injected.^[25] Elsergany et al reported that in their series, the average cumulative collagen volume injected per patient was 6.1 mL for the first 11 cases, whereas in the last 22 cases, the average volume was 3.5 mL.^[26]

Collagen injection appears to be less efficacious in men with postprostatectomy incontinence than in women with SUI.^{[27, 28]} Tiguert et al performed transurethral collagen injection in 21 consecutive men with ISD. The mean total volume of collagen injected per patient was 18.4 mL (range, 1-44.5 mL), and the average number of injections was 2.9 (range, 1-5 injections). At a mean follow-up of 12.5 months, 1 (5%) patient became dry, 12 (57%) had significant improvement, and 8 (38%) had no change.^[29]

Antegrade injection of collagen has also been studied.^[30] Early work with this approach by Wainstein and Klutke demonstrated an overall positive response rate of 70%; that is, 70% of men who were incontinent after prostatectomy reported cure or significant improvement.^[31] However, in another study, Klutke et al reported only a 10% cure rate and a 35% improvement rate at a mean follow-up of 28 months.^[32] Although antegrade delivery of collagen appears promising, this therapy fails in a substantial number of patients at 2-year follow-up.

Calcium hydroxylapatite injection

In a multicenter, randomized, prospective trial comparing calcium hydroxylapatite with collagen, Dmochowski and Appell reported that 63.4% of patients who underwent calcium hydroxylapatite injection saw significantly improved continence at 1 year. Additionally, 38% of women required only 1 injection in total. The total amount injected during this trial was 4 mL, significantly lower than the amount of collagen injected (6.6 mL).^[33] To date, there have been no reported trials of calcium hydroxylapatite in men with postprostatectomy incontinence.

Carbon bead particle injection

The US Food and Drug Administration (FDA) approved carbon bead particle injections in 1999 after this material underwent a randomized, multicenter, double-blinded study comparing it with collagen. Carbon bead particle injection yielded outcomes similar to (and slightly better than) those of collagen injection.

Polydimethylsiloxane injection

Polydimethylsiloxane was approved by the FDA for use in the United States in 2006. A recent randomized trial showed that at 12 months after treatment, 61.5% of patients who received polydimethylsiloxane and 48% of patients who received bovine collagen had improved 1 Stamey grade. In the polydimethylsiloxane group, the dry/cure rate was 36.9%, compared to 24.8% in the collagen group.^[18]

Polytetrafluoroethylene paste injection

In incontinent men, the success rate of PTFE injection was 75% with a follow-up of 6 months to 16 years. However, the use of PTFE paste has been halted because of particle migration.

Complications

Most women are able to void easily after the procedure; however, temporary urinary retention from urethral edema or urethral sphincter spasm is the most common complication of any injectable bulking procedure. Patients may treat urinary retention with self-catheterization using a small catheter (eg, 12F) until urethral edema disappears (within a few days).

Autologous fat injection

Temporary urinary retention (24-48 h) is expected after autologous fat injection. This is the major postoperative problem, occurring in 7% of women after this procedure. The patient can use self-catheterization with a small catheter (eg, 12F-14F) until it resolves. Permanent urinary retention has not been reported. Recurrent urinary incontinence may arise from poor tissue coaptation or absorption of the fat by the host tissue.

Lower abdominal pain at the site of liposuction has been reported (3%) but is only temporary. Fat embolization resulting in death has been reported.

Bovine collagen and carbon bead particle injection

The most common complications include uncomplicated urinary tract infections (UTIs), temporary urinary retention, and transient urethral irritation. Uncommon complications such as periurethral pseudocyst and urethrovaginal fistula have also been reported.^{[34, 35]}

Uncomplicated UTI occurs in 5% of cases. Urge incontinence may develop in 12% of patients who receive collagen. Temporary urinary retention has been reported in 15% of cases. Transient urethral irritation has been reported in 1% of cases.

Calcium hydroxylapatite injection

With calcium hydroxylapatite injection, as with collagen injection, the most common adverse events include uncomplicated UTIs, temporary urinary retention, and dysuria. Permanent urinary retention has not been reported. De novo urge incontinence may occur in 6% of patients.

Polydimethylsiloxane injection

Complications are similar to those of calcium hydroxylapatite and bovine collagen injection. No serious long-term adverse events have been reported.

Polytetrafluoroethylene paste injection

PTFE is not approved for female SUI in the United States because of concerns regarding local and distant migration of the PTFE particles into the lymph nodes, lung, and brain. However, PTFE has been used in Europe with no reported significant clinical complications. The complications discussed herein are based on studies in men who have undergone prostatectomy.

Temporary urinary retention is the major postoperative problem (20%-25%) after PTFE injection. Expect temporary urinary retention (24-48 h after the procedure). Permanent urinary retention is very rare, and intermittent self-catheterization may be initiated in selected cases. Irritative voiding symptoms have been reported in 20% of cases.

Recurrent urinary incontinence may arise from poor tissue coaptation or paste leaking into the urethral lumen. The inflammatory reaction and granuloma formation around the injected PTFE paste require several weeks to subside. If a second injection is needed, do not attempt it until 3 months after the first procedure.

Infection of the injection site and abscess formation lead to erosion of the urethral mucosa and result in infected fluid draining into the urethral lumen. This urethral ulceration heals spontaneously and does not lead to any permanent adverse sequelae.

Despite the theoretical health hazard and the consequent lack of FDA approval, no human cases of death or carcinoma related to PTFE injections have been reported. Clinical trials show that many active women with ISD have benefitted from the use of this biomaterial. Currently, the safety and efficacy of PTFE injections for the treatment of incontinent women are being investigated in multicenter trials.

Long-Term Monitoring

Postprocedural pain medications are rarely needed. Call the patient on the telephone 24 hours after the injection therapy to inquire about possible urinary retention. If the patient is experiencing urinary retention, advise her to initiate the clean intermittent catheterization protocol after nursing educational training.

If, as in rare and complex cases, the patient has a suprapubic tube in place, she may clamp and unclamp the tube using a voiding schedule. The suprapubic tube is removed once the patient demonstrates a normal voiding pattern. Subsequent follow-up occurs at 3 months, 6 months, and annually thereafter.