OnabotulinumtoxinA Urethral Sphincter Injection as Treatment for Non-neurogenic Voiding Dysfunction – A Randomized, Double-Blind, Placebo-Controlled Study

Abstract

Non-neurogenic voiding dysfunction including dysfunctional voiding and detrusor underactivity caused by a spastic or non-relaxing external urethral sphincter can theoretically be treated by injections of botulinum A toxin into the external urethral sphincter. This randomized, double-blind, placebo-controlled trial was designed to determine the clinical efficacy of onabotulinumtoxinA urethral sphincter injections in patients with dysfunctional voiding or detrusor underactivity. Patients with medically refractory dysfunctional voiding (n = 31) or detrusor underactivity (n = 31) were randomly allocated in a 2:1 ratio to receive either onabotulinumtoxinA (100 U) (n = 38) or placebo (normal saline) (n = 24). There were no significant differences in subjective or objective parameters between patients who received onabotulinumtoxinA and those who received saline injection therapy, and the overall success rate was 43.5% (reduction in Patient perception of Bladder Condition by ≥2: onabotulinumtoxinA 36.8% vs placebo 54.2%, p = 0.114). The results were similar between the dysfunctional voiding and detrusor underactivity subgroups; however, a significant reduction in detrusor voiding pressure was only observed in dysfunctional voiding patients who received onabotulinumtoxinA. Repeat urethral sphincter onabotulinumtoxinA injections offered greater therapeutic effects in both dysfunctional voiding and detrusor underactivity patients. For patients with non-neurogenic voiding dysfunction, the success rate of onabotulinumtoxinA urethral sphincter injection was not superior to placebo.

The Therapeutic Effects and Pathophysiology of Botulinum Toxin A on Voiding Dysfunction Due to Urethral Sphincter Dysfunction

“…Data discussing the therapeutic effect of sphincteric BoNT-A injections in adults with DV are limited and are mostly provided by Kuo and his colleagues [48,55,71]. In a prospective nonrandomized study without controlled variables, the authors performed sphincteric injections using 50 to 100 units of Botox in 20 adults with DV and reported a subjectively excellent outcome in 30% of the patients, where the remaining 70% showed improvement [48].…”

“…A randomized, double-blind, placebo-controlled study was conducted in 31 adults with DV to compare the therapeutic effect of 100 units of Botox with normal saline [71]. Even though the detrusor voiding pressure and voided volume were significantly improved in the BoNT-A group, there were no significant between-group differences in the subjective success rate.…”

“…Even though the detrusor voiding pressure and voided volume were significantly improved in the BoNT-A group, there were no significant between-group differences in the subjective success rate. The author hypothesized that the local injection itself might have some unknown therapeutic effects on the relaxation of the EUS [71]. This concept is similar to the dry needling effect on myofascial trigger point pain, which can relax the actin-myosin bonds and normalize muscle tone [74].…”

Mechanism of Action of Botulinum Toxin A in Treatment of Functional Urological Disorders

“…Patients with non-neurogenic voiding dysfunction classically present with open bladder neck but poorly relaxed urethral sphincter and normal-to-high voiding pressure during micturition by urodynamic study and are mostly refractory to medical treatment [59]. Several recent clinical studies have shown BoNT-A injection to the external urethral sphincter could be a safe and efficient treatment method for refractory DV patients [60][61][62]. Post-treatment, improvements were noticed in several clinical aspects in those studies, such as maximal flow rate, voided urine amount, decreased detrusor voiding pressure, international prostate symptom score (IPSS), and quality of life index.…”

“…Poor bladder neck relaxation in BND may lead to weak stream and increased residual urine amount after voiding [63]. Recent studies demonstrated that BoNT-A injections in the external urethral sphincter, pelvic floor muscle, or bladder neck may offer promising therapeutic effects for DV symptoms improvement [61,64,65]. Synchronous significant reduction of the bladder outlet resistance and the pelvic floor pressure were observed in a study after BoNT-A injection treatment to the pelvic floor muscle, which indicates a more complex mechanism in DV symptoms.…”