Intravesical Oxybutynin Research Articles

Intravesical oxybutynin treatment for neurogenic detrusor overactivity : Efficacy and safety data from clinical practice with the first intravesical oxybutynin treatment authorized in Germany

Existing therapies for neurogenic detrusor overactivity (NDO), i.e. oral anticholinergics and botulinum toxin injections, can be associated with serious adverse effects or are not always sufficiently effective. Therefore, there is aneed for alternative safe and effective treatment options for NDO. Intravesical oxybutynin has been successfully used for several years as a prescription drug in adults and children with spinal cord injury and spina bifida. In 2019, VESOXX® (FARCO-PHARMA, Cologne, Germany) became the first registered intravesical oxybutynin product in Germany, which is indicated for the suppression of neurogenic detrusor overactivity (NDO) in children from 6years of age and adults, who are managing bladder emptying by clean intermittent catheterisation (CIC), if they cannot be adequately managed by oral anticholinergic treatment due to lack of efficacy and/or intolerable side effects. Overall, there are limited data regarding therapy with intravesical oxybutynin, with the majority of publications being retrospective case series. To date, there are limited data on the efficacy and safety of the newly approved intravesical oxybutynin therapy (VESOXX®) in NDO patients. This noninterventional case series from daily routine treatment which evaluated the physician reports of 38patients suggests that intravesical oxybutynin effectively improves maximum detrusor pressure (Pdet max) by decreasing it by 59% from 51.94 cmH2O ± 26.12 standard deviation (SD) to 21.07 cmH2O ± 17.32 SD (P < 0.001, n = 34). Maximum bladder pressure (MBC) increased by 34% from 260.45 ml ± 200.26 SD to 348.45 ml ± 175.90 SD. Positive or similar effects compared to previous therapies were seen in bladder morphology, number of incontinence episodes, urinary tract infections and adverse drug effects. This case series demonstrates that intravesical oxybutynin is an important addition to current therapies for the treatment of NDO and it is also efficacious in the rare setting of other underlying diseases beyond spinal cord injury or spina bifida. The approved intravesical oxybutynin preparation VESOXX® may be auseful alternative for patients who do not respond to other therapies or suffered side effects.

Intravesical sustained release system of lidocaine and oxybutynin results from in vitro and animal study.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic debilitating condition of unknown etiology. Intravesical lidocaine demonstrated pain relief in patients with IC/BPS. Intravesical oxybutynin has shown therapeutic efficacy in patients with urinary bladder disorders. However, loss of drug with urination requiring multiple administrations and immediate dilution of drug concentration by residual urine in the bladder mitigated intravesical use of both drugs in clinical practice. The aim of this study was to evaluate the efficacy and safety of fixed-dose combination of lidocaine and oxybutynin, forming in the urine a sustained delivery system named TRG-042. In-vitro, we have quantitatively tested the concentration of lidocaine and oxybutynin released from TRG-042 in artificial urine. Following the successful in-vitro study weekly formulation of TRG-042 was instilled intravesically to six pigs. All pigs were followed with cystoscopy to assess the gradual degradation of the delivery system and to evaluate bladder response over 7 days. Daily blood samples were tested for drug quantization. In-vitro studies have demonstrated oxybutynin and lidocaine sustained release over 1-week period coupled with full degradation of the matrix. None of the animals demonstrated any side effects following instillation. Cystoscopy examination observed gradual disintegration of TRG-042 over 1-week with no adverse reaction to the mucosa. Plasma concentrations of oxybutynin and lidocaine were uniformly stable over the 1-week period [1.46 ± 0.176ng/ml and 4.29 ± 2.48ng/ml respectively(mean ± SEM)] with almost undetectable concentration of N-desethyloxybutynin (NDO)[0.032 ± 0.068ng/ml]. The in-vitro and animal data demonstrated that TRG-042 can safely be used for intravesical sustained release of lidocaine and oxybutynin in the treatment of BPS/IC.

Intravesical oxybutynin therapy for patients with neurogenic detrusor overactivity: a systematic review and meta-analysis.

To evaluate the effectiveness and safety of intravesical oxybutynin therapy for patients with neurogenic detrusor overactivity. A systematic search in PubMed, MEDLINE, EMBASE, ClinicalTrial.gov, and Cochrane Controlled Trials Register was conducted from 1990 to 2021. Nineteen studies were included for analysis, of which 392 patients including both adults and children were treated with intravesical oxybutynin. The analysis was performed by Cochrane RevMan® software, version 5.3. The primary outcomes were maximum bladder capacity (MBC), detrusor pressure at MBC, and bladder compliance. The secondary outcomes were episodes of urinary incontinence and side effects. MBC displayed an increase of 77.8ml (95% CI 56.9 to 98.7) in kids, 110.8ml (95% CI 58.95 to 162.7) in adults, respectively. Detrusor pressure at MBC demonstrated an improvement of -18.8cm H2O (95% CI -26.2 to -11.3) in kids, -23.2cm H2O (95% CI -32.6 to -13.8) in adults, respectively. The bladder compliance increased 5.8ml/cm H2O (95% CI 3.4 to 8.1) among kids. The mean percentage of patients "dry or improved" after treatment accounted for 76.9% in adults and 74.6% in kids, respectively. Among all patients, 53 (13.5%) reported side effects, 80 (20.4%) discontinued this treatment, 26 (6.6%) withdrew because of side effects, and 35 (8.9%) quit due to inconvenience. Intravesical oxybutynin treatment could be a feasible treatment for both adults and children with neurogenic detrusor overactivity, because of its good effect and less side effects.

Intravesical oxybutynin – A better option to treat catheter-related bladder discomfort?

Intravesical oxybutynin – A better option to treat catheter-related bladder discomfort?

Pilot study on the effects of intravesical oxybutynin hydrochloride instillations on the validity of doping control urine samples.

According to class M2.1 of the World Anti-Doping Agency (WADA) Prohibited List, the manipulation of doping control urine samples to alter their integrity and validity is prohibited both in- and out-of-competition. However, some paraplegic athletes with an overactive bladder need to be regularly treated with anti-cholinergic and anti-spasmodic drugs such as oxybutynin, which are often administered intravesically to reduce the substantial side effects observed after oral application. So far, it remains unclear whether such bladder instillations have a negative impact on analytical procedures and thus represent an anti-doping rule violation. Within this pilot study, urine samples were collected from five paraplegic athletes before and after an intravesical oxybutynin hydrochloride instillation. The samples were routinely tested for the presence of performance-enhancing drugs and afterwards fortified with 25 model compounds representing different classes of doping agents (anabolic agents, cannabinoids, diuretics, glucocorticoids, hormone and metabolic modulators, and stimulants) at low and medium concentrations. Additionally, the pH value and specific gravity were measured and the presence of oxybutynin was qualitatively determined by gas chromatography-mass spectrometry (GC-MS). In initial testing procedures, all samples were tested negative. Oxybutynin was present in most of the samples but found to have no significant effect on the detectability of the 25 model compounds subsequently added to each urine specimen. Therefore, it can be concluded that intravesical instillations with oxybutynin hydrochloride do not alter the integrity and validity of doping control urine samples.

Can Oral Fesoterodine Be an Alternative for Intravesical Oxybutynin Instillations in Children with Neuropathic Bladder Dysfunction?

Purpose: A low-pressure bladder in children with neuropathic bladder dysfunction can be achieved using anticholinergic medication. Due to the significant side effects of oral oxybutynin, our patients are treated with daily intravesical oxybutynin instillations. Newer oral anticholinergic medication, such as fesoterodine, claim to have fewer side effects in a once daily formulation. Because once-daily oral intake is easier than performing twice-daily intravesical instillations, we studied the effects of switching from intravesical oxybutynin to oral fesoterodine and compared the clinical response, urodynamic parameters and side effects. Patients and Methods: Twenty children (11 girls, 9 boys, 4–17 years) with neuropathic bladder dysfunction who perform clean intermittent catheterization and use intravesical oxybutynin instillations twice daily were included in this prospective study. Voiding diaries, a behavioural checklist, urodynamic investigations, vital signs and blood samples were evaluated at baseline during treatment with intravesical oxybutynin and repeated after 40 days of oral fesoterodine. Results: Out of 20, 13 (65%) children showed an identical objective dryness (pad-test), 2 (10%) improved and 5 (25%) got worse. Seven (35%) children reported equal dryness, 7 (35%) reported improvement and 6 (30%) reported that it got worse. From a urodynamic perspective, 13 (65%) children remained identical, 3 (15%) improved and 4 (20%) got worse. Four (20%) children reported a light to moderate dry mouth, 1 (5%) a headache, 1 (5%) behavioural changes during fesoterodine administration, 1 (5%) an increased appetite, 1 (5%) nausea and 1 (5%) hot flushes. Conclusions: The urodynamics after 40 days of fesoterodine were in 16 (80%) identical or better and could be a safe alternative for oxybutynin instillations in children with neuropathic bladder dysfunction.

Long-Term Efficacy, Safety, and Tolerability of Modified Intravesical Oxybutynin Chloride for Neurogenic Bladder in Children.

BackgroundChildren with spinal cord disorders can present with neurogenic bladder, a condition in which the bladder partly or completely loses its ability to store urine and void at low pressure. A bladder with low compliance may cause urinary incontinence, which negatively impacts quality of life and renal function. Long-term high pressure neurogenic bladder can increase the risk of deterioration in renal function. Antimuscarinic pharmacotherapy with clean intermittent catheterization is currently considered one of the most effective treatments for these patients. However, some patients do not respond to oral medication or have unacceptable adverse events (AEs), which may result in medical withdrawal for these patients. Intravesical oxybutynin is an effective treatment with less AEs compared with oral medication. However, an important issue with this treatment is retention of the solution in the bladder. Moreover, as yet no data are available on the very long-term use and outcome of modified intravesical oxybutynin therapy. In the present study, we report on the efficacy, safety, and side effects of long-term modified intravesical oxybutynin therapy in children with neurogenic bladder.MethodsModified intravesical oxybutynin (1.25 mg/5 mL, twice a day) was administered to four children (three boys and one girl) with neurogenic bladder (detrusor overactivity and/or low compliance bladder), who were previously unresponsive to or experienced intolerable AEs from oral medications. Results of pretreatment cystometrograms were compared to those from follow-up urodynamic studies. Anticholinergic AEs, occurrence of urinary tract infection, and degree of incontinence during this treatment were also evaluated.ResultsAfter 1 year, bladder compliance improved in three of the four patients. After 3 years, detrusor overactivity was undetectable in all patients. Bladder compliance at 3 years and 10 years after initiation of therapy was similar for three patients, and they are continuing modified intravesical oxybutynin therapy. One patient discontinued therapy at 118 months due to worsening of bladder compliance and upper urinary tract infection. No anticholinergic systemic AEs were observed in any of the patients.ConclusionsThese results suggest that modified intravesical oxybutynin is an effective and relatively safe long-term therapeutic option for children with neurogenic bladder.

Investigating Detrusor Muscle Concentrations of Oxybutynin After Intravesical Delivery in an Ex Vivo Porcine Model

Intravesical oxybutynin is highly effective in the treatment of overactive bladder. Traditionally the mechanism of action was explained by antagonism of muscarinic receptors located in the detrusor, however evidence now suggests antimuscarinics may elicit their effect by modifying afferent pathways in the mucosal region. This study aimed to investigate the bladder wall distribution of oxybutynin in an ex vivo setting providing tissue - layer specific concentrations of drug achieved after intravesical delivery. Whole ex vivo porcine bladders were intravesically instilled with 0.167 mg mL(-1) oxybutynin solution. After 60 min, tissue samples were excised, serially sectioned parallel to the urothelial surface and extracted drug quantified. Drug distribution into the urothelium, lamina propria and detrusor was determined. Oxybutynin permeated into the bladder wall at a higher rate than other drugs previously investigated (apparent transurothelial Kp = 1.36 × 10(-5) cm s(-1) ). After 60 min intravesical instillation, concentrations achieved in the urothelium (298.69 μg g(-1) ) and lamina propria (43.65 μg g(-1) ) but not the detrusor (0.93 μg g(-1) ) were greater than reported IC50 values for oxybutynin. This work adds to the increasing body of evidence suggesting antimuscarinics elicit their effects via mechanisms other than direct inhibition of detrusor contraction.

A pilot prospective study to evaluate whether the bladder morphology in cystography and/or urodynamic may help predict the response to botulinum toxin a injection in neurogenic bladder refractory to anticholinergics

BackgroundWe have observed different clinical responses to botulinum toxin A (BTX-A) in patients who had similar urodynamic parameters before the procedure. Furthermore, some bladders evaluated by cystography and cystoscopy during the procedure had different characteristics that could influence the outcome of the treatment. The aim of this study was to assess whether cystography and urodynamic parameters could help predict which patients with neurogenic detrusor overactivity (NDO) refractory to anticholinergics respond better to treatment with injection of BTX-A.MethodsIn total, 34 patients with spinal cord injury were prospectively evaluated. All patients emptied their bladder by clean intermittent catheterization (CIC) and had incontinence and NDO, despite using 40 mg or more of intravesical oxybutynin and undergoing detrusor injection of BTX-A (300 IU). Pretreatment evaluation included urodynamic, and cystography. Follow-up consisted of urodynamic and ambulatory visits four months after treatment. The cystography parameters used were bladder shape, capacity and presence of diverticula. Urodynamic parameters used for assessment were maximum cystometric capacity (MCC), maximum detrusor pressure (MDP), compliance and reflex volume (RV).ResultsAfter injection of BTX-A, 70% of the patients had success, with 4 months or more of continence. Before the treatment, there were significant differences in most urodynamic parameters between those who responded successfully compared to those who did not. Patients who responded successfully had greater MCC (p = 0.019), higher RV (p = 0.041), and greater compliance (p = 0.043). There was no significant difference in the MDP (0.691). The cystography parameters were not significantly different between these groups bladder shape (p = 0.271), capacity (p > 0.720) and presence of diverticula (p > 0.999). Statistical analyses were performed using SPSS (version 20.0) and included Student’s t-test for two paired samples and Fisher’s exact test, with a significance threshold of 0.05.ConclusionsThis study suggests that the cystography parameters evaluated cannot be used to help predict the response to injection of BTX-A in the treatment of refractory NDO. However, the urodynamic parameters were significantly different in patients who responded to the treatment, with the exception of the MDP.

Long-term outcome of intravesical oxybutynin in children with detrusor-sphincter dyssynergia: With special reference to age-dependent parameters

Intravesical instillation of oxybutynin is an accepted and effective treatment in children with neuropathic bladder-sphincter dysfunction, when oral oxybutynin results in inadequate suppression of detrusor overactivity or intolerable side effects. However, as yet no data are available on long-term use and outcome. A patient cohort with detrusor-sphincter dyssynergia that started oral oxybutynin between 1995 and 1997 was re-evaluated 15 ± 1 years after the switch from oral to intravesical (n = 10), with urodynamic investigations, renal ultrasounds, DMSA-scintigraphy, (51)Cr-EDTA-clearance, and validated questionnaires on incontinence and quality of life. At follow-up, cystometric bladder capacity (CBC) had increased to the 25-50% percentiles for age, from the 5% percentile; mean end-filling pressure, 24.5 ± 14.4 cm H2O, had returned to the safe zone; bladder compliance expressed as a fraction of normal compliance for age (Wahl units) showed a statistically significant increase. At follow-up, the prevalence of renal scars was 30% (95% CI: 6-65%). Kidney lengths correlated with scarring at DMSA-scintigraphy, (51)Cr-EDTA-clearance did not. In 2 years of oral oxybutynin we documented 10 pyelonephritic episodes, in 15 years of intravesical oxybutynin only three. Urinary continence was reported as satisfying, its impact on quality of life as acceptable. Percentile charts for cystometric bladder capacity and individual kidney lengths, age-dependent parameters, were invaluable in estimating long-term outcome, and the same goes for bladder compliance in Wahl units. We can conclude that intravesical oxybutynin provided more than adequate suppression of detrusor activity, without side effects, over a period of 15 years.

Pharmacokinetics of Intravesical Versus Oral Oxybutynin in Healthy Adults: Results of an Open Label, Randomized, Prospective Clinical Study

We investigated the pharmacokinetics of intravesical oxybutynin and discuss the clinical implications of the results. We performed an open label, randomized, 3-period crossover clinical study in 20 healthy adults. In periods 1 and 2 subjects received a single dose of 10 mg oxybutynin HCl solution intravesically or a 5 mg tablet orally. Period 3 comprised repeat intravesical applications (7 doses) of 10mg oxybutynin HCl. Enantioselective concentrations of oxybutynin and N-desethyloxybutynin were quantified by liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental methods, analyzed by descriptive statistics and compared using the average bioequivalence approach. Systemic exposure to racemic oxybutynin after intravesical administration was significantly greater, yielding 294% (90% CI 211-408) of that after oral intake of immediate release preparations, as measured by the dose normalized area under the plasma concentration time curve. In contrast, systemic exposure to racemic N-desethyloxybutynin reached only 21% (90% CI 15-29). The area under the plasma concentration time curve ratio of N-desethyloxybutynin to oxybutynin was 14-fold decreased for intravesical administration. After intravesical multidose administration, the cumulation of oxybutynin (1.3-fold) and N-desethyloxybutynin (1.6-fold) was weak, absorption was prolonged and apparent elimination half-lives were longer. The study medication was well tolerated with a third of participants reporting anticholinergic adverse effects. Our study provides evidence of significantly higher bioavailability of intravesical vs oral administration of oxybutynin due to circumvention of the intestinal first pass metabolism. Given the high efficacy and decreased rate of adverse effects, intravesical oxybutynin should be considered in patients with neurogenic lower urinary tract dysfunction who do not tolerate oral administration or in whom oral preparations fail to improve detrusor overactivity.

Intravesical Oxybutynin for Neurogenic Bladder in Children

Neuropathic bladder dysfunction caused by spinal cord disease may lead to irreversible renal damage and urinary incontinence. The majority of affected children can be successfully managed with standard medical treatment such as oral anti-cholinergic medication (typically oxybutynin or tolterodine) with or without Clean Intermittent Catheterization (CIC). The efficacy of this treatment, however, may be hampered as some of these patients experience severe Adverse Events (AEs) or insufficient suppression of detrusor over activity following oral anti-muscarinic pharmacotherapy. Intravesical oxybutynin chloride is an effective therapy for neurogenic bladder dysfunction; this review considers the indications, administration, safety, and efficacy of intravesical oxybutynin chloride instillation. In addition, some cases of children treated with intravesical oxybutynin chloride solution supplemented with hydroxypropylcellulose (modified intravesical oxybutynin) are described.

Urodynamic effects of propiverine in children and adolescents with neurogenic bladder: Results of a prospective long-term study

ObjectiveTo evaluate prospectively the efficacy and tolerability of propiverine for long-term treatment of neurogenic detrusor overactivity (NDO) in children. Materials and methods17 children and adolescents with NDO (10 female, 7 male; average age at last consultation 13.0 years) were evaluated during long-term treatment with propiverine (0.8 mg/kg body weight/day). Outcome measurements included urodynamic parameters, continence, hydronephrosis and tolerability of propiverine. ResultsAverage follow-up was 3.6 years (range 2.0–5.9). The average maximum detrusor pressure was 33.2 ± 4.8 cmH2O and bladder compliance was 20.0 ± 5.4 ml/cmH2O at the last follow-up visit. Maximum cystometric bladder capacity (MCBC) within the normal range was attained in 11 patients; it was still reduced (average of 61% of expected MCBC) in the remaining 6. Incontinence occurred on average once per day. Hydronephrosis was classified for each renal unit separately: grade 0 was measured in 26 and 22 cases, grade 1 or 2 in 6 and 8 cases, grade 3 or 4 in 2 and 4 cases pre and post treatment, respectively. In 6/17 patients adjuvant intravesical oxybutynin was applied, in 4 out of these 6 patients more invasive procedures, such as untethering, augmentation cystoplasty or botulinum toxin injections, were necessitated. Propiverine monotherapy was well tolerated in 11/17 patients. No serious adverse events were encountered during the study period. ConclusionLong-term efficacy and tolerability of propiverine for NDO in children and adolescents is promising: clinically relevant improvements in key urodynamic outcomes were paralleled by improvements in incontinence score.

The effects of long-term medical treatment combined with clean intermittent catheterization in children with neurogenic detrusor overactivity

To assess whether conservative treatment of pediatric patients with neurogenic detrusor overactivity (NDO) results in lower bladder pressure and increased expected bladder volume (EBV), we investigated the clinical and urodynamic effects of long-term intravesical oxybutynin instillation compared with a standard treatment of oral anticholinergic medication in patients with clean intermittent catheterization (CIC). A retrospective study was performed including 21 patients suffering from myelomeningocele and NDO. Initially, all patients were treated with oral anticholinergics and CIC. Ten of the 21 patients showed a sufficient response to the treatment and were included in group I (anticholinergics and CIC). The other 11 patients responded poorly to the initial treatment or developed side effects to oral medication. These patients were included in group II and treated with intravesical oxybutynin and CIC. The two groups were compared using clinical, sonographic and urodynamic examinations performed prior to starting treatment and repeated on an annual basis. Changes from baseline were analyzed with the Mann-Whitney U test. Ten patients in group I and 11 in group II were investigated. Two of the 11 patients in group II stopped the treatment. The mean starting age was 8.1 (± 6.6) years in group I and 12.5 (± 4.5) years in group II. The mean follow-up time was 7.1 (± 5.5) years in group I and 3.6 (± 1.8) years in group II. Bladder capacity increased from 173 (± 99) to 371 (± 115) ml in group I and from 245 (± 133) to 370 (± 156) ml in group II. Six of the 10 patients in group I and 6/9 patients in group II reached normal EBV. Three of the 10 subjects in group I and 6/9 in group II had bladder compliance values >10 ml/cm H(2)O. At final follow-up, the overall rate of urinary tract infections was equal. Social continence was achieved in 6/10 in group I and 7/9 in group II. Altogether, 19/21 patients responded to conservative management. In children with NDO, conservative medical treatment combined with CIC is feasible and provides an improved pattern of bladder function, which could help avoid bladder surgery.

Intravesical oxybutynin protects the vesical wall against functional and smooth muscle changes in rabbits with detrusor overactivity

The aim of this study was to evaluate the protective effect of intravesical oxybutynin on the bladder wall of rabbits with detrusor overactivity and partial bladder outlet obstruction (PBOO). Forty-five North Folk male rabbits were randomly distributed into GI, used as control (n = 15), GII-PBOO (n = 14), and GIII-PBOO + intravesical oxybutynin (n = 15). Connective tissue and elastic fibers were quantified as volumetric density on picrosirius red and Weigert's Fuchsin-Resorcin-stained sections, respectively. In T2, bladder weight was significantly higher in animals in GII and GIII. Smooth muscle bundle diameter was increased by 42% in GII compared with GI (p < 0.02).Elastic fibers were significantly higher in GII and GIII as compared with control group. Collagen concentration in GIII and GII was significantly lower than G1 (p < 0.025). Intravesical oxybutynin protected against structural and functional detrusor modifications of the partially obstructed bladder.

Efficacy of Combined Oral-Intravesical Oxybutynin Hydrochloride Treatment for Patients with Overactive Detrusors and Indwelling Urethral Catheters

The purpose of this article is to investigate the efficacy of intravesical oxybutynin hydrochloride (OH) to treat patients with overactive detrusors who are unresponsive to oral anticholinergic therapy alone. Twenty-five patients who were treated with oral OH for overactive detrusor (but who did not respond to treatment and were using indwelling urethral catheters) were given intravesical OH without changing oral treatment. Pre- and posttreatment bladder capacities were compared in urodynamic studies. The study showed that positive clinical results can be achieved with combined oral and intravesical OH treatments in patients with overactive detrusors who had indwelling urethral catheters because of severely reduced bladder capacity. However, a significant number of patients discontinued this treatment because of infection and difficulty in performing the procedure. Clinicians and rehabilitation nurses should provide education and support to eliminate these problems. In addition, the development of single-use standard sterile OH preparations for intravesical applications may increase the efficacy of the method.

The effect of intravesical oxybutynin on the ice water test and on electrical perception thresholds in patients with neurogenic detrusor overactivity

The C-fiber-mediated bladder-cooling reflex and the determination of the current perception thresholds (CPTs) permit to investigate afferent LUT pathways. They have both been proposed to detect and differentiate neurologic bladder dysfunction. This study evaluates, prospectively, the effect of oxybutynin, an antimuscarinic with direct antispasmodic effect on smooth muscle, on repeated ice water test (IWT) and CPTs in patients with a known incomplete neurogenic bladder. Patients with a known incomplete lesion of the bladder innervation, detrusor overactivity during cystometric bladder filling and a continuous positive response to repeated IWT were included. After the initial tests, 30 mg intravesical oxybutynin (1 mg/ml) was instilled and left in the bladder for 15 min. Afterwards CPTs and IWT were re-assessed. After the drug application, the bladder-cooling reflex could not be initiated, even after three instillations, in 16/17 patients. The bladder CPT increased from 29.7 +/- 11.3 to 39.1 +/- 15.7 mA after oxybutynin (P = 0.001). No difference was found in CPT of the left forearm (P = 0.208). Intravesical oxybutynin blocks the bladder-cooling reflex and increases but does not block CPT sensation in the bladder in most patients with incomplete neurogenic lesion and detrusor overactivity. These results help explain the clinical effect of intravesical oxybutynin in neurogenic patients. They also indicate that a pharmacological local influence on C-fiber-related activity can give different clinical effects.

Protective action of intravesical oxybutynin on bladder ultrastructure in rabbits with detrusor overactivity

To evaluate the protective effect of intravesical oxybutynin on the ultrastructure of rabbits with detrusor overactivity (DO). Seventeen North Folk male rabbits were distributed into three groups: GI (n = 5) used as control, GII (n = 5), and GIII (n = 5) with DO. One animal from GII and one from GIII were excluded because they did not develop DO. In GIII, the animals were treated with daily intravesical application of 0.5 mg/Kg of oxybutynin for 30 days. Bladder weight was significantly higher in animals from GII and GIII as compared to GI. After 30 days, cystometric study revealed that vesical capacity was significantly decreased in GII and GIII. Detrusor pressure was significantly higher in GII. Electron microscopy showed increase of intercellular space, cell junctions and caveolae areas asymmetries, mitochondria and cellular degeneration in GII, while in GIII, these alterations have improved after a 30-day treatment. Animals treated with intravesical oxybutynin presented ultrastructural aspect similar to normal.

Intravesical Oxybutynin for Children With Poorly Compliant Neurogenic Bladder: A Systematic Review

Children with neurogenic bladder and poor bladder compliance are usually treated with bladder catheterization and oral anticholinergic medication. They may become nonresponders to the drug or present with severe side effects. We evaluated the effectiveness and tolerability of intravesical oxybutynin in children with poorly compliant neurogenic bladder. We conducted a search of MEDLINE, EMBASE, CINAHL, SciELO, dissertations/theses in ProQuest, LILACS, the Cochrane Library, protocol registries and the gray literature. Two reviewers independently assessed study quality and extracted data. Eight studies (2 prospective, 6 retrospective) assessed the effectiveness and side effects of intravesical oxybutynin in children with neurogenic bladder. A total of 297 children started treatment, of whom 22% (66 patients) discontinued therapy, with 9% (28) quitting due to systemic side effects. Mean change in bladder compliance (primary outcome) was reported in only 2 studies (+7.4 and +7.5 ml/cm H(2)O). The pooled mean change in pressure at maximum bladder capacity was -16.4 cm H(2)O (95% CI -22.8 to -10.0). Incontinence improved significantly in most studies, with "dry and improved" rates ranging from 61% to 83%. The funnel plot of pressure at maximum bladder capacity suggested no publication bias. Adjunctive intravesical oxybutynin therapy increased mean maximum bladder capacity and decreased bladder pressure in children with neurogenic bladder. However, identified studies offered a low level of evidence, with most being poorly reported retrospective case series with potential biases. Although the incidence of side effects was lower with the intravesical route, side effects are still possible and should be discussed with patients and families. The evidence available is insufficient to recommend this therapy. Research of more sound study design such as a randomized controlled trial should be conducted to assess the efficacy and side effects of intravesical oxybutynin in children.

The neurogenic bladder: medical treatment

Neurogenic bladder sphincter dysfunction (NBSD) can cause severe and irreversible renal damage and bladder-wall destruction years before incontinence becomes an issue. Therefore, the first step in adequate management is to recognize early the bladder at risk for upper- and lower-tract deterioration and to start adequate medical treatment proactively. Clean intermittent catheterization combined with anticholinergics (oral or intravesical) is the standard therapy for NBSD. Early institution of such treatment can prevent both renal damage and secondary bladder-wall changes, thereby potentially improving long-term outcomes. In children with severe side effects or with insufficient suppression of detrusor overactivity despite maximal dosage of oral oxybutynin, intravesical instillation is an effective alternative. Intravesical instillation eliminates systemic side effects by reducing the first-pass metabolism and, compared with oral oxybutynin, intravesical oxybutynin is a more potent and long-acting detrusor suppressor. There is growing evidence that with early adequate treatment, kidneys are saved and normal bladder growth can be achieved in children so they will no longer need surgical bladder augmentation to achieve safe urinary continence in adolescence and adulthood.