Urethral bulking agents for SUI: Rethinking their indications
Rising interest in alternatives to sling procedures and increasing evidence of successful outcomes for urethral bulking agents make them a potential primary treatment option for patients with SUI
Indications for use
According to the FDA premarket approvals (PMAs) for the particle-based urethral bulking agents, their use is indicated for adult women with SUI primarily due to intrinsic sphincter deficiency (ISD).6 The PMA indication for the nonparticulate agent, however, allows it to be used for SUI as well as SUI-predominant mixed urinary incontinence (MUI) due to ISD.7 Traditionally, ISD is defined by urodynamic criteria that includes a maximal urethral closure pressure less than 20 to 25 cm of water and/or a Valsalva leak point pressure of less than 60 cm of water.4
The American Urological Association (AUA) guideline lists bulking agents as an option for women who do not wish to pursue invasive surgical intervention for SUI, are concerned about lengthier recovery after surgery, or have previously undergone anti-incontinence procedures with suboptimal results.8 In general, most urologists and urogynecologists who perform urethral bulking agree with the AUA guideline.
Perceptions of bulking agents have shifted
Urethral bulking agents traditionally have been thought of as a "salvage therapy." Perceived indications for these agents include use in women with persistent SUI after more invasive treatment options or in women who were medically fragile and thus could not undergo a more invasive procedure.9 As mentioned, however, circumstances related to mesh use have shifted the current perception of indications for urethral bulking agents from salvage therapy only to use as a possible first-line treatment in the appropriately selected patient.9
Recent data that note improved durability and patient satisfaction, as well as better appreciation of the fact that, if the bulking agent fails, a synthetic sling procedure still can be performed without significant concerns, have contributed to this shift in intervention strategy.10,11 There also has been the perception that urethral bulking agents should not be considered in women who have urethral mobility. However, studies have shown that outcomes are not significantly different in patients with urethral mobility compared with those with a fixed urethra.11
Types of bulking agents
The ideal bulking agent should be made of a material that is biocompatible--with low host reactivity, low carcinogenic potential, low risk of migration--and easy to administer.5 Currently available bulking agents are classified as particulate and nonparticulate agents. The TABLE provides summary details of the available agents FDA approved for use.
Particulate bulking agents
Durasphere, approved by the FDA in 1999, is composed of carbon-coated zirconium oxide in a water-based and beta-glucan carrier. The first generation of this agent had particles that ranged in size from 212 to 500 µm and required an 18-gauge needle for injection.4 The second-generation preparation has a smaller particle size, ranging from 90 to 212 µm, which permits injection with a smaller needle, typically 20 gauge.4 Theoretically, the larger bead size reduces the risk of migration as particles larger than 80 µm cannot be engulfed by macrophages.4
Coaptite is a calcium hydroxylapatite-based product approved by the FDA in 2005. The carrier media is composed of sodium carboxymethylcellulose, sterile water, and glycerin. The particle size ranges from 75 to 125 µm, with an average of 100 µm.5 This synthetic material historically has been used in orthopedics and dental applications. The aqueous gel carrier dissipates over months, resulting in tissue growth; thereafter, the particulate beads slowly degrade.12
Macroplastique, a polydimethylsiloxane compound, was approved by the FDA in 2006. It has a long history of use primarily in Europe where it has been used since 1991. It is composed of a nonbiodegradable silicone (polydimethylsiloxane) elastomer suspended in a water-soluble gel. The initial composition was of particles that ranged in size from 5 to 400 µm, with 25% of the particles smaller than 50 µm. Because of the large number of particles smaller than 50 µm, there were concerns for migration.5 The agent's current composition contains particles that range from 120 to 600 µm, with an average particle size of 140 µm.4
Nonparticulate bulking agent
Bulkamid has been available in Europe since 2003 and was FDA approved in January 2020. It is the only available nonparticulate urethral bulking agent; it is composed uniquely of a nonresorbable polyacrylamide hydrogel made of cross-linked 2.5% polyacrylamide and water. Its bulking effect is achieved through the actual volume of hydrogel injected, which integrates with host tissue by vessel ingrowth, suggestive of a persistent durable effect. Because Bulkamid contains no particles or crystals, the theoretical risk of migration is mitigated.4
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