Intradetrusor onabotulinumtoxinA Injections Research Articles

Review of simultaneous treatment with intradetrusor onabotulinumtoxinA injections during transurethral prostate surgery for men with bladder outlet obstruction and overactive bladder

ABSTRACT Bladder outlet obstruction (BOO) is common in males with benign prostate enlargement (BPE) and often presents with different lower urinary tract symptoms. Overactive bladder (OAB) has been reported to be related to BOO, although it can also be idiopathic. The storage symptoms of BOO are often similar to those of OAB. The etiology and pathophysiology of both BPE and OAB are multifactorial with metabolic syndrome known as one of the factors. As of today, transurethral prostate surgery remains the gold standard for treating BOO associated with BPE. Intradetrusor onabotulinumtoxinA (BoNT-A) injections have been shown to be effective in treating OAB. However, they are usually administered after transurethral prostate surgery. In view of the strong therapeutic effects of both surgery and injections, the feasibility of combining them in one setting to increase patient comfort, convenience, and possibly results while decreasing costs is appealing to physicians. However, patient safety and possible complications have to be considered. In this article, we review available studies of concurrent intradetrusor BoNT-A injections during transurethral prostate surgery. Although there is no definitive evidence supporting the concurrent use of intradetrusor BoNT-A during transurethral prostate surgery, there are no reports of increased complications too. Further large-scale randomized controlled trials would be necessary to validate the feasibility of combining the treatments in one setting and observe for possible complications.

Cost Analysis of Oral Phenazopyridine vs Intravesical Lidocaine for Preprocedural Analgesia for Intradetrusor OnabotulinumtoxinA Injections.

Office administration of intradetrusor onabotulinumtoxinA is commonly used to treat overactive bladder. For preprocedure analgesia, either 50 mL 2% intravesical lidocaine instillation for 20 to 30 minutes or 200 mg oral phenazopyridine can be used. Phenazopyridine is associated with shorter appointment times and is noninferior to lidocaine for pain control in this setting. We performed a cost analysis of phenazopyridine vs lidocaine for analgesia before office intradetrusor onabotulinumtoxinA injection for the treatment of idiopathic overactive bladder. A health care sector-perspective cost analysis was performed. The following assumptions were made: (1) similar efficacy of each medication in providing adequate analgesia, (2) similar physician ease of performing the procedure with either analgesic, and (3) similar patient satisfaction with either analgesic. Average cost of medications, adverse reactions, nursing tasks, and office visit time were found in publicly available data. Sensitivity analyses were performed using TreeAge Pro 2021, R1 software. Phenazopyridine is less costly compared to lidocaine per visit for office intradetrusor onabotulinumtoxinA injection ($827 vs $925). A difference of $98 per procedure provides a total annual cost savings of over $24 million if all procedures are performed with phenazopyridine instead of lidocaine. Sensitivity analysis showed that phenazopyridine remained less costly under most circumstances, and threshold analysis provided exact circumstances under which phenazopyridine is no longer cost saving. Phenazopyridine provides cost savings compared to lidocaine for analgesia before office intradetrusor onabotulinumtoxinA injection for the treatment of idiopathic overactive bladder. If adopted by providers nationwide, phenazopyridine may reduce health care spending and minimize office visit time while maintaining patient pain control and satisfaction.

OnabotulinumtoxinA is now an important tool for managing pediatric neurogenic lower urinary tract dysfunction.

Initial urologic management of pediatric neurogenic lower urinary tract dysfunction (NLUTD) includes clean intermittent catheterization (CIC) regimen and use of anticholinergic or beta3 agonist medications. Historically, NLUTD that did not respond to these initial management strategies received open surgical procedures such as augmentation cystoplasty (AC) to increase bladder capacity and create a lower-pressure reservoir. Since its first reported use in 2002, intradetrusor onabotulinumtoxinA (BTX-A) injections has developed an emerging role in management of pediatric NLUTD, culminating in its recent FDA-approval in 2021. In this review, the current evidence regarding the safety, tolerability, and efficacy of BTX-A use in pediatric NLUTD will be summarized. Additionally, we will attempt to define the current role of BTX-A in the management of patients with NLUTD, discuss limitations to the current body of literature, and suggest future avenues of study.

Lower Urinary Tract Dysfunction in Pediatric Patients with Multiple Sclerosis: Diagnostic and Management Concerns.

Multiple sclerosis (MS) is increasing in the pediatric population and, as in adults, symptoms vary among patients. In children the first manifestations can sometimes overlap with acute neurological symptoms. Urological symptoms have not been much studied in childhood. We shared our experience with MS urological manifestation in children. This article is a retrospective evaluation of all children with MS, according to the Krupp criteria, who also present with urological symptoms. We collected demographic and clinical history, the MR localization of demyelinating lesions, urological symptoms, and exams. We report on six MS pediatric cases with urological manifestation. Urinary symptoms, characterized by urinary incontinence in five patients and urinary retention in one patient, appeared in a different time frame from MS diagnosis. Urodynamic exams showed both overactive and underactive bladder patterns. Treatment was defined according to lower urinary tract dysfunction, using clean intermittent catheterization, oxybutynin, and intradetrusor Onabotulinum Toxin-A injection. A low acceptance rate of invasive evaluation and urological management was observed. The MS diagnosis was traumatic for all our patients. We believe it is important to address urological care in young people from the time of diagnosis for prompt management; it could be useful to include a pediatric urologist in multidisciplinary teams.

Bladder instillations vs onabotulinumtoxinA injection for interstitial cystitis/bladder pain syndrome: a randomized clinical trial

Interstitial cystitis/bladder pain syndrome is an unpleasant sensation related to the bladder with lower urinary tract symptoms lasting more than six weeks, unrelated to an otherwise identifiable cause. The etiology is likely multifactorial including urothelial abnormalities, neurogenic pain upregulation, and potentially bladder and vaginal microbiome alterations. Despite treatment effectiveness of both bladder instillations and intradetrusor onabotulinumtoxinA injection for this condition, a head-to-head comparison has not been performed. To compare the efficacy of bladder instillations and intradetrusor onabotulinumtoxinA injection for treatment of interstitial cystitis/bladder pain syndrome. Patients with O'Leary-Sant (OLS) questionnaire scores of ≥ 6, meeting clinical criteria for interstitial cystitis/bladder pain syndrome, and desiring procedural management were randomized to bladder instillations or intradetrusor onabotulinumtoxinA injection. The primary outcome was the difference in OLS scores at 2 months post-treatment between groups. Secondary outcomes included evaluation of sexual function, physical/mental health status, pain, patient satisfaction, treatment perception, retreatment, and adverse event rates. 47 patients were analyzed with 22 randomized to bladder instillations and 25 to onabotulinumtoxinA injection. There were no differences in demographic and clinical characteristics between groups. From baseline to 2 months post-treatment, there was a decrease in OLS subscales in all patients (Interstitial Cystitis Symptom Index (ICSI) -6.3 (CI -8.54, -3.95), p<.0001; Interstitial Cystitis Problem Index (ICPI) -5.9 (CI -8.18, -3.57), p<.0001). At 2 months post-treatment, patients in the onabotulinumtoxinA group had significantly lower OLS scores compared to those in the bladder instillation group (ICSI 6.3 ± 4.5 [onabotulinumtoxinA] versus 9.6 ± 4.2 [instillation], p=.008; ICPI 5.9 ± 5.1 [onabotulinumtoxinA] versus 8.3 ± 4.0 [instillation], p=.048). The difference in OLS scores between groups did not persist at 6-9 months post-treatment. There were no statistically significant differences between baseline and post-treatment time points for the remaining questionnaires. Eight percent of patients who received onabotulinumtoxinA injection experienced urinary retention requiring self-catheterization. Patients who underwent onabotulinumtoxinA injection were significantly less likely to receive retreatment within 6-9 months compared to patients who received bladder instillations (relative risk 13.6; 95% CI, 1.92-96.6; P=.0002). There were no differences between groups regarding patient satisfaction, perception of treatment convenience, or willingness to undergo retreatment. Both onabotulinumtoxinA injection and bladder instillations are safe, effective treatments for patients with interstitial cystitis/bladder pain syndrome, with significant clinical improvement demonstrated at 2 months post-treatment. Our findings suggest that intradetrusor onabotulinumtoxinA injection is a more effective procedural treatment for this condition than bladder instillation therapy and associated with decreased rates of retreatment.

Does the setting for intradetrusor onabotulinumtoxinA injection for management of overactive bladder matter?

Intradetrusor onabotulinumtoxinA (Botox) injections, to treat idiopathic overactive bladder (OAB), can be performed in the office setting under local analgesia alone or in the operating room (OR) under local and/or sedation. The objective of this study was to compare the symptomatic improvement in patients with OAB who underwent treatment with intradetrusor onabotulinumtoxinA injections in an in-office versus the OR setting. We performed a multicenter retrospective cohort study of women with the diagnosis of refractory non-neurogenic OAB who elected to undergo treatment with intradetrusor onabotulinumtoxinA injections between January 2015 and December 2020. The electronic medical records were queried for all the demographic and peri-procedural data, including the report of subjective improvement post procedure. Patients were categorized as either "in-office" versus "OR" based on the setting in which they underwent their procedure. Five hundred and thirty-nine patients met the inclusion criteria: 297 (55%) in the in-office group and 242 (45%) in the OR group. A total of 30 (5.6%) patients reported retention after their procedure and it was more common in the in-office group (8.1%) versus the OR group (2.5%), (P = 0.003). The rate of urinary tract infection within 6 months of the procedure was higher in the OR group (26.0% vs. 16.8%, P = 0.009). The overall subjective improvement rate was 77% (95% confidence interval: 73%-80%). Patients in the OR group had a higher reported improvement as compared to the in-office group (81.4% vs. 73.3%, P = 0.03). In this cohort study of patients with OAB undergoing intradetrusor onabotulinumtoxinA injections, post procedural subjective improvement was high regardless of the setting in which the procedure was performed.

Antibiotics for UTI Prevention After Intradetrusor OnabotulinumtoxinA Injections.

Urinary tract infections (UTIs) occur in 8.6% to 48.1% of patients after intradetrusor onabotulinumtoxinA injections. The objective of this study was to evaluate both choice and duration of antibiotic prophylaxis on the incidence of UTI within 30 days after in-office onabotulinumtoxinA injections. We included a single-site, retrospective cohort of 305 patients with overactive bladder or bladder pain syndrome receiving postprocedure prophylactic antibiotics for in-office, 100-unit intradetrusor onabotulinumtoxinA injections from 2019 to 2023. Categories of antibiotic prophylaxis compared included (1) nitrofurantoin 100 mg twice daily for 3 days, (2) nitrofurantoin 100 mg twice daily for 5 days, (3) trimethoprim-sulfamethoxazole 160 mg/800 mg twice daily for 3 days, and (4) "other regimens." Primary outcome was incidence of UTI within 30 days. Variables were compared via χ2 test. Crude/adjusted odds were estimated using binary logistic regression. Incidence of UTI was 10.4% for 3-day nitrofurantoin, 20.5% for 5-day nitrofurantoin, 7.4% for 3-day trimethoprim-sulfamethoxazole, and 25.7% among "other regimens" (P = 0.023). Differences among primary regimens were substantial but not statistically significant: 3-day trimethoprim-sulfamethoxazole had 31% lower odds of UTI versus 3-day nitrofurantoin (odds ratio [OR], 0.689; P = 0.518). Compared with 3-day nitrofurantoin regimen, the 5-day nitrofurantoin regimen had twice the odds of UTI (OR, 2.22; P = 0.088). Those receiving "other regimens" had nearly 3 times the odds of UTI (OR, 2.98; P = 0.018). Results were similar adjusting for age and race. Overall urinary retention rate was 1.97%. Prophylactic antibiotic choice and duration of treatment potentially affect UTI incidence after in-office, intradetrusor onabotulinumtoxinA injections. Nitrofurantoin and trimethoprim-sulfamethoxazole for 3 days have the lowest UTI incidence.

Anatomical location and number of injection sites of intravesical OnabotulinumtoxinA for females with refractory idiopathic overactive bladder: Ascoping review.

The negative impact on quality of life and the economic-related burden to the patient and the health care system associated with idiopathic overactive bladder (iOAB) is well-documented. Intradetrusor OnabotulinumtoxinA (BTN/A) injections are a well-used treatment modality for the management of overactive detrusor refractory to medical management, with well-documented efficacy and safety profiles. There is currently no best practice guideline for the administration of BTN/A for this procedure and historically the trigone of the bladder has been excluded from the injection paradigm given the risk of vesicoureteral reflux (VUR). A scoping review methodology was employed to assess available literature to evaluate current techniques used. There is emerging literature that the inclusion of the trigone may increase the efficacy of the procedure, while maintaining a similar adverse effect profile. Similar results could also be obtained by decreasing the number of injection sites. A scoping review was completed with systematic methodology using the Preferred Systematic Reviews and Meta Analyses extension for Scoping Review checklist. The search strategy looked to evaluate BTN/A and number of injection sites and the inclusion of the trigone in female patients with iOAB. Studies with male or neurogenic bladder only were excluded. Mixed studies were included. A specialist research librarian was engaged, with supervision from a functional urologist using a combination of MeSH and natural language terms. Two investigators independently reviewed the titles and abstracts. Twelve articles were included and were published between 2005 and 2021. There was no evidence of VUR in any of the results. All but one study reported similar if not improved efficacy of trigone-inclusion. Lower number of injection sites had similar efficacy profiles to higher numbers of intradetrusor injections. Further high-quality randomized control trials of trigone inclusion and reduction of injection sites are required. It is hoped that with further exploration of intraoperative methods for BTN/A injections, the development of universally accepted guidelines may optimize management and experiences for patients with iOAB.

Fluid intake behavior in women with refractory overactive bladder undergoing third line therapy.

Fluid intake has been shown to be related to urinary symptoms, but no studies to date have investigated the effect of fluid intake on urinary symptoms in women with refractory overactive bladder (OAB). As this group of women are considered to have a possible unique pathophysiologic mechanism of OAB, we investigated the relationship between fluid intake, fluid intake behavior, and urinary symptoms in women with refractory OAB. A prospective cross-sectional study of women with refractory OAB was conducted by assessing the relationship between fluid intake and lower urinary tract symptoms (LUTS) in women undergoing third line OAB therapies. Fluid intake and behavior were measured by the questionnaire based voiding diaryand urinary symptoms were measured by the International Consultation on Incontinence Questionnaire for Female Lower Urinary Tract Symptoms (ICIQ-FLUTS). The relationship between fluid intake and symptom severity was assessed using Spearman's rankcorrelation and χ2 tests. Of the 126 individuals undergoing third line therapy for OAB, 60 (48%) underwent intradetrusor onabotulinumtoxinA injection (BTX) injection, 42 (33%) peripheral tibial nerve stimulation,and 24 (19%) sacral neuromodulation.The mean total daily fluid intake was 2567.0 ± SD 1292.4 mL and did not differ significantly across treatment groups. Total fluid intake was weakly correlated with worse filling-type LUTS (r = 0.241, p = 0.007), and there was no relationship between LUTS and caffeinated fluid intake. Half (52%) of the subjects reported current fluid restricting behavior to control urinary symptoms, but this behavior was not correlated with LUTS severity (all p > 0.05). Patients that currently use tobacco have greater LUTS (current = 25.8 ± SD 9.5, former = 14.8 ± SD 6.1, never = 15.0 ± SD 6.1; p < 0.001). BMI was also positively correlated with worse incontinence symptoms (r = 0.351, p < 0.001). Fluid intake along with other lifestyle factors, including tobacco use and weight, are minimally related to the symptomatology seen in women with refractory OAB. Further studies are needed to assess if behaviors change during treatment with third line therapies, and if these behavioral changes may affect treatment response.

Analgesia Using Transcutaneous Electric Nerve Stimulation in Office Bladder Chemodenervation, a Randomized Controlled Trial.

Office bladder chemodenervation, performed via cystoscopy with intradetrusor onabotulinumtoxinA (BOTOX) injections, is a common treatment for overactive bladder/urge urinary incontinence. Transcutaneous electric nerve stimulation (TENS) has shown to provide analgesia during office hysteroscopy. Adjuvant analgesia using TENS during bladder chemodenervation has not been studied. The primary outcome is a clinically significant (10-mm) difference in pain visual analog scale (VAS) measurements during injections for chemodenervation using active TENS compared with placebo TENS. We hypothesize that active TENS use will significantly change pain VAS scores. Secondary outcomes include 5-point pain Likert scale, satisfaction 10-point scale, and adverse events. This was a double-blind randomized control trial of men and women with urinary urge incontinence undergoing office chemodenervation performed in an academic and private setting. Participants were randomized into 2 groups: chemodenervation with active TENS or placebo TENS. Power calculation determined 100 patients would be required detect a difference of 10 mm on pain VAS. One hundred one (85 female and 16 male) participants were recruited. No differences were noted in the demographics. Participants in the active TENS group reported a difference of greater than 10 mm in pain VAS scores (48 ± 23 vs 31 ± 23, P = 0.01). Satisfaction index scores were high but no difference was noted between groups (8.6 vs 8.7, P = 0.68). Most participants were eligible to use TENS units. Transcutaneous electric nerve stimulation is a safe and noninvasive adjuvant analgesia option for patients undergoing this procedure. Lower pain levels and high satisfaction rates suggest that this is an additional analgesic option during outpatient chemodenervation.

Response to: "Simultaneous Intradetrusor OnabotulinumtoxinA Injections with Holmium Laser Enucleation of the Prostate: What Is the Hurry?" by P.N. Maheshwari.

Journal of EndourologyAhead of Print Response to: “Simultaneous Intradetrusor OnabotulinumtoxinA Injections with Holmium Laser Enucleation of the Prostate: What Is the Hurry?” by P.N. MasheshwariNicholas S. Dean, Mitchell M. Huang, and Amy E. KrambeckNicholas S. DeanAddress correspondence to: Nicholas S. Dean, MD, Northwestern Memorial Hospital, 676 N. Street Clair, Suite 2300, Chicago, IL 60611, USA E-mail Address: nicholas.dean@northwestern.eduDepartment of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.Search for more papers by this author, Mitchell M. HuangDepartment of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.Search for more papers by this author, and Amy E. KrambeckDepartment of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.Search for more papers by this authorPublished Online:15 Jun 2023https://doi.org/10.1089/end.2023.29138AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Response to: “Simultaneous Intradetrusor OnabotulinumtoxinA Injections with Holmium Laser Enucleation of the Prostate: What Is the Hurry?” by P.N. Masheshwari." Journal of Endourology, , pp. FiguresReferencesRelatedDetails Volume 0Issue 0 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Nicholas S. Dean, Mitchell M. Huang, and Amy E. Krambeck.Response to: “Simultaneous Intradetrusor OnabotulinumtoxinA Injections with Holmium Laser Enucleation of the Prostate: What Is the Hurry?” by P.N. Masheshwari.Journal of Endourology.ahead of printhttp://doi.org/10.1089/end.2023.29138Online Ahead of Print:June 15, 2023PDF download

Evaluating the utility of routine urine culture and antibiotic treatment in children with neurogenic bladder undergoing intradetrusor OnabotulinumtoxinA injection

OnabotulinumtoxinA is used as treatment for refractory idiopathic and neurogenic detrusor overactivity in children. Many patients perform intermittent self-catheterization and therefore have higher rates of asymptomatic bacteriuria, which may increase their risk of symptomatic urinary tract infection (UTI) following treatment. Multiple injections are often needed due to the short-term efficacy of onabotulinumtoxinA treatment, which may also increase the risk of UTI. We aim to evaluate whether a sterile urinary tract is necessary to decrease the risk of postoperative UTI in pediatric patients treated with onabotulinumtoxinA. A retrospective review of patients undergoing intradetrusor onabotulinumtoxinA injection from 2014 to 2021 was performed. Demographic data, clinical characteristics, antibiotic treatment and culture results were collected. A positive urine culture was defined as ≥ 103CFU/ml of uropathogenic bacteria. Our primary outcome was symptomatic UTI within 14 days of the procedure. 103 patients underwent 158 treatments with onabotulinumtoxinA. The incidence of postoperative UTI was 3.2%. The incidence of symptomatic postoperative UTI in patients with asymptomatic bacteriuria compared to those with sterile urine was not significantly different (3.8% vs 0%, p=0.57). Obtaining a preoperative urinalysis or urine culture did not affect the incidence of postoperative UTI (p=0.54). The number needed to treat with antibiotics to prevent one postoperative UTI was 27. The incidence of postoperative UTI was highest in patients with low-risk bladders (p=0.043). Prior history of multi-drug resistant UTI was a risk factor for postoperative UTI (p=0.048). For children undergoing onabotulinumtoxinA injection, there are no evidence-based recommendations regarding antibiotic prophylaxis and the need to screen for and treat asymptomatic bacteruria prior to treatment. Our study addresses this important clinical question, and shows no difference in the rate of postoperative UTI between patients with asymptomatic bacteriuria and those with sterile urine. Patients with a history of multi-drug resistant UTI are at increased risk of symptomatic postoperative UTI and may benefit from preoperative urine testing and treatment. Limitations of our retrospective study include its small sample size in the face of such a low incidence of our primary outcome. The risk of UTI following onabotulinumtoxinA injection in children is low. The presence of sterile urine at the time of surgery does not significantly decrease the risk of postoperative UTI. Routine treatment of asymptomatic bacteriuria prior to surgery results in a large number of patients receiving unnecessary antibiotics. As a result, we recommend against preoperative urine testing for most asymptomatic patients.

Simultaneous Intradetrusor OnabotulinumtoxinA Injections with Holmium Laser Enucleation of the Prostate: What Is the Hurry?

Journal of EndourologyJust Accepted Editorial Comment on END-2023-0074-OR.R1Dr. Pankaj N MaheshwariDr. Pankaj N MaheshwariSearch for more papers by this authorPublished Online:11 May 2023https://doi.org/10.1089/end.2023.0235AboutSectionsPDF/EPUB Permissions & CitationsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetails Volume 0Issue ja InformationCopyright 2023To cite this article:Dr. Pankaj N Maheshwari.Editorial Comment on END-2023-0074-OR.R1.Journal of Endourology.ahead of printhttp://doi.org/10.1089/end.2023.0235Online Ahead of Editing: May 11, 2023PDF download

Intradetrusor OnabotulinumtoxinA Injections at the Time of Holmium Laser Enucleation of the Prostate for Men with Severe Storage Symptoms.

Introduction: Intradetrusor onabotulinumtoxinA (OTA) injection is a well-established treatment option for refractory overactive bladder; however, its use at the time of holmium laser enucleation of the prostate (HoLEP) for men with bladder outlet obstruction (BOO) and severe storage symptoms has not been previously reported. Materials and Methods: We retrospectively identified men with BOO and severe storage symptoms who underwent treatment with 200 U of intradetrusor OTA (Botox®) at the time of HoLEP. Patients were propensity score matched to a cohort of HoLEP-only patients based on age, Michigan Incontinence Symptom Index (M-ISI) score, preoperative urinary retention, urge incontinence, and prostate size. Perioperative, postoperative, and patient-reported outcomes were examined between groups. Results: We identified 82 men who underwent HoLEP, including 41 patients in the OTA group and 41 patients in the control group. There was no difference in operative times (59 minutes OTA vs 55 minutes control, p = 0.2), rates of same-day trial of void (TOV) (92% OTA vs 94% control, p = 0.7), or rates of same-day discharge (88% OTA vs 85% control, p = 0.6) between groups. There was no difference in temporary postoperative urinary retention (7% OTA vs 2% control, p = 0.3) between groups. Patients who received OTA injections had a significant reduction in their incontinence scores at 3-month follow-up (M-ISI -8, interquartile range [IQR]: -13 to 0, p < 0.001), whereas control patients did not (M-ISI -5, IQR: -8 to -1, p = 0.2). There was no difference in rates of 90-day complications between groups (OTA 10% vs control 5%, p = 0.7). Conclusions: Intradetrusor OTA at the time of HoLEP is safe and is associated with improved urinary incontinence scores and AUA Symptom Score. Rates of same-day discharge and same-day TOV after HoLEP were not affected by OTA. These findings support the role of OTA as an adjunct to surgical intervention in men with incontinence in the presence of BOO.

Treating Lower Urinary Tract Symptoms in Older Adults: Intravesical Options.

This article provides an overview of the diagnosis and the treatment of lower urinary tract symptoms in older adults complicated by the neurodegenerative changes in the micturition reflex and further confounded by age-related decline in hepatic and renal clearance raising the propensity of adverse drug reactions. The first-line drug treatment for lower urinary tract symptoms, orally administered antimuscarinics, fails to reach the equilibrium dissociation constant of muscarinic receptors even at their maximum plasma concentration and tends to evoke a half-maximal response at a muscarinic receptor occupancy of just 0.206% in the bladder with a minimal difference from exocrine glands, which raises the adverse drug reaction risk. On the contrary, intravesical antimuscarinics are instilled at concentrations 1000-fold higher than the oral maximum plasma concentration and the equilibrium dissociation constant erects a downhill concentration gradient that drives passive diffusion and achieves a mucosal concentration around ten-fold lower than the instilled concentration for a long-lasting occupation of muscarinic receptors in mucosa and sensory nerves. A high local concentration of antimuscarinics in the bladder triggers alternative mechanisms of action and is supposed to engage retrograde transport to nerve cell bodies for neuroplastic changes that underlie a long-lasting therapeutic effect, while an intrinsically lower systemic uptake of the intravesical route lowers the muscarinic receptor occupancy of exocrine glands to lower the adverse drug reaction relative to the oral route. Thus, the traditional pharmacokinetics and pharmacodynamics of oral treatment are upended by intravesical antimuscarinics to generate a dramatic improvement (~ 76%) noted in a meta-analysis of studies enrolling children with neurogenic lower urinary tract symptoms on the primary endpoint of maximum cystometric bladder capacity as well as the secondary endpoints of filling compliance and uninhibited detrusor contractions. The therapeutic success of intravesical multidose oxybutynin solution or oxybutynin entrapped in the polymer for sustained release in the pediatric populationbodes well for patients with lower urinary tract symptoms at the other extreme of the age spectrum. Though generally used to predict oral drug absorption, Lipinski's rule of five can also explain the ten-fold lower systemic uptake from the bladder of positively charged trospium over oxybutynin, a tertiary amine. Chemodenervation by an intradetrusor injection of onabotulinumtoxinA is merited for patients with idiopathic overactive bladder discontinuing oral treatment because of a lack of efficacy. However, age-related peripheral neurodegeneration potentiates the adverse drug reaction risk of urinary retention that motivates the quest of liquid instillation, delivering larger fraction of onabotulinumtoxinA to the mucosa as opposed to muscle by an intradetrusor injection can also probe the neurogenic and myogenic predominance of idiopathic overactive bladder. Overall, the treatment paradigm of lower urinary tract symptoms in older adults should be tailored to individual's overall health status and the risk tolerance for adverse drug reactions.

Postprocedural Pain Associated With 5 Versus 20 Intradetrusor Injections of OnabotulinumtoxinA for Treatment of Overactive Bladder: A Multicenter Randomized Clinical Trial

(Abstracted from Urogynecology 2022;28:518–525) For treating nonneurogenic overactive bladder, female pelvic medicine and urogenital reconstruction guidelines given by the American Urological Association and Society of Urodynamics recommend that onabotulinumtoxinA (botoxA) may be used as third-line therapy following a failure of both first-line lifestyle and behavioral changes and second-line cholinergic or β-agonist therapy. Wide variations on the acceptable number of injections per treatment episode (as much as 1 injection to 40) have been promulgated for botoxA.

Neurogenic Lower Urinary Tract Dysfunction in the First Year After Spinal Cord Injury: A Descriptive Study of Urodynamic Findings.

We aimed to provide a real-world description of neurogenic lower urinary tract dysfunction within the first year after spinal cord injury with a focus on unfavorable urodynamic parameters that are associated with urological morbidity. Urodynamic investigations from 97 patients with traumatic or ischemic acute spinal cord injury and managed according to the European Association of Urology Guidelines on Neuro-Urology were analyzed at a single university spinal cord injury center at 1 month, 3 months, 6 months, and 12 months after injury. Unfavorable urodynamic parameters were defined as detrusor overactivity in combination with detrusor sphincter dyssynergia, maximum storage detrusor pressure of 40 cm H2O or higher, bladder compliance less than 20 mL/cm H2O, and vesicoureteral reflux of any grade. One or more unfavorable urodynamic parameter was observed in 87 out of 97 patients (90%) within the first year after spinal cord injury. Eighty-eight percent of the patients showed detrusor overactivity with detrusor sphincter dyssynergia, 39% a maximum storage detrusor pressure of 40 cm H2O or higher, and 7% vesicoureteral reflux. No patient developed a low-compliance bladder. Using a standardized urodynamic follow-up schedule, we found unfavorable urodynamic parameters in a majority of the population within the first year after spinal cord injury. As early treatment based on urodynamic findings might reduce the risk of deterioration of upper and lower urinary tract function, thereby improving long-term outcomes, there is need for further research regarding recommendations for a urodynamic follow-up schedule during the first year after spinal cord injury.

This Month in Adult Urology

This Month in Adult Urology

Intravesical Instillation of OnabotulinumtoxinA in the Treatment of Refractory Overactive Bladder in Participants with Urinary Incontinence.

Intradetrusor injections of onabotulinumtoxinA are efficacious for the treatment of overactive bladder with urgency urinary incontinence in adults refractory to or intolerant of anticholinergics. Delivery of onabotulinumtoxinA via instillation would reduce the need for intradetrusor injections. The objective of this trial was to assess the efficacy and safety of intravesical instillation of an onabotulinumtoxinA + hydrogel admixture. After review of a stage 1 safety phase by an independent committee, participants were recruited into stage 2 and randomized to either onabotulinumtoxinA 100, 300, 400, or 500 U, or placebo, all with hydrogel admixture. End points included change from baseline to week 12 in the number of urinary incontinence episodes (primary); micturition, urgency urinary, and nocturia episodes/day; volume voided per micturition; proportion of participants with a ≥50% decrease from baseline in urinary incontinence episodes/day; and Overactive Bladder Questionnaire total score. Adverse events were reported. Change from baseline to week 12 in number of urinary incontinence episodes was -2.72 with placebo and ranged from -0.89 to -1.85 in the onabotulinumtoxinA + hydrogel treatment groups. No difference from placebo was observed for any efficacy end point. The proportions of participants with treatment-emergent adverse events were similar among all groups, with asymptomatic bacteriuria the highest reported (6.7%-15.5%). There were no reports of urinary retention or elevated post-void residual volume. Intravesical instillation of an onabotulinumtoxinA + hydrogel admixture for the treatment of refractory overactive bladder was well tolerated, but it showed no improvement over placebo.

Urinary tract infection following intradetrusor onabotulinumtoxina injection for non-neurogenic urgency incontinence: single- vs. multi-dose prophylactic antibiotic treatment regimens.

Urinary tract infection is one of the most common adverse events following onabotulinumtoxinA injection for urgency incontinence. Our hypothesis was that those undergoing injection for urgency incontinence who received more than one dose of prophylactic antibiotics have lower post-procedure urinary tract infection rates compared to those who receive a single dose. We conducted a multi-center retrospective cohort study in females who underwent onabotulinumtoxinA injection for non-neurogenic urgency incontinence to evaluate the effect of single- vs. multi-dose prophylactic antibiotic regimens on the risk of post-procedure urinary tract infection. The primary outcome was the rate of urinary tract infection within 30 days of injection. Our sample size calculation required 136 subjects per group. Two hundred eighty-one patients were included from four centers. The single-dose cohort included 145 patients (51.6%), and the multi-dose cohort included 136 patients (48.4%). The mean age was 65 years, and patients were primarily Caucasian (81.4%). There was no difference in the rate of urinary tract infections diagnosed within 30 days of injection between the cohorts (single dose 13.8% vs. multi-dose 10.3%, p = 0.369). Those with a positive urine culture within 30 days of injection had a 15.2 times greater odds of having a post-procedure infection than those who did not (95% CI 3.19-72.53). There was no significant difference between the two cohorts in terms of adverse health events following injection. In females with non-neurogenic urgency incontinence undergoing onabotulinumtoxinA injection, multi-dose prophylactic antibiotic regimens were not associated with lower post-procedure urinary tract infection rates.