The Maximal Urethral Pressure at Rest and during Normal Bladder Filling Is Only Determined by the Activity of the Urethral Smooth Musculature in the Female.

The aim of this opinion paper is to determine the entities that define the maximal urethral pressure (MUP) during rest and during bladder filling that is needed to guarantee continence in females. For the development of this opinion, the literature was searched for via the Pubmed database and historic sources. Animal studies indicate that the maximal urethral pressure is determined by the smooth muscle activity in the mid-urethra. Additionally, during increased smooth muscle tone development, the largest sympathetic responses are found in the middle part of the urethra. This could be confirmed in human studies that are unable to find striated EMG activity in this area. Moreover, the external urethral striated sphincter is situated at the distal urethra, which is not the area with the highest pressure. The external urethral sphincter only provides additional urethral pressure in situations of exertion and physical activity. From a physics point of view, the phasic pressure of the external striated sphincter at the distal urethra cannot be added to the tonic pressure generated by the smooth muscle in the mid-urethra. The assertion that mid-urethral pressure is the result of different pressure forces around the urethra, including that of the external striated sphincter, is not supported by basic research evidence combined with physical calculation and should therefore be considered a misconception in the field of functional urology.

Comparing two types of botulinum-A toxin detrusor injections in patients with severe neurogenic detrusor overactivity: a case-control study.

OBJECTIVE: To compare the efficacy of two types of botulinum toxin type A (BTX-A; Dysport, Ipsen Ltd, Slough, UK) or Botox (Allergan Inc., Irvine, CA, USA) and examine the possible dose-effect relation for Dysport in those patients, as multifocal detrusor injections with BTX-A are effective for severe neurogenic detrusor overactivity in adults. PATIENTS AND METHODS: This was an open-label, observational case-control study comparing Dysport and Botox, and the dose-effect relation for Dysport. The patients included were treated with either Dysport (cases; 500, 750, or 1000 IU), or with Botox (controls: 300 IU, and exceptionally 200 or 400 IU). The continence volume (primary), mean and maximum catheterized volume, and antimuscarinic use were assessed, and cystometric variables measured were overactivity volume (primary), detrusor compliance, and cystometric capacity. All variables were assessed at baseline, 3 and 9 months after treatment, and results analysed using analysis of variance (paired) t-tests, chi-square tests and regression analysis. RESULTS: There were 28 cases and 28 matched controls; their demographic characteristics, bladder management, and baseline values were comparable between the groups. At 3 months there was a significant improvement in cystometric variables and continence volume in both groups, but in mean catheterized volume and reduced use of antimuscarinics in cases only. At 9 months there was no significant improvement over baseline except for the continence volume in the cases. There were no significant differences in results between the groups except for the continence volume at 3 months (459 mL after Dysport and 396 mL after Botox; P=0.015). There was no dose-related response for Dysport at 3.8 months of follow-up. The interval between injections (9.5, 14.5 and 16.1 months for Dysport 500, 750, and 1000 IU; 10.1 months for Botox) was not significant. There were nine non-responders in the Dysport group and seven in the Botox group; the patient characteristics and baseline data were comparable to those of the responders. There was transient hypoasthenia in one of the responders (750 IU Dysport). CONCLUSIONS: A single treatment session with either Dysport or Botox in a setting combined with antimuscarinics might improve the patient's condition for up to a year. There was no clear dose-related effect for Dysport in adults.

Treatment of neurogenic detrusor overactivity with botulinum toxin A: the first seven years.

INTRODUCTION: This retrospective study describes the results of botulinum toxin A detrusor injections following a fixed protocol in 216 patients with untreatable neurogenic detrusor overactivity and incontinence. A comparison is made between the two preparations currently available, and the efficacy of multiple treatments is studied. PATIENTS AND METHODS: Botox 300 MU (mouse units) or Dysport 750 MU were injected into the detrusor wall in 365 sessions in 216 patients. The average age of the 144 men and 72 women was 32.3 years. Patients were investigated before treatment and at 6 weeks and 6 months after treatment. Maximal detrusor pressure, detrusor compliance, reflex volume and cystometric capacity were recorded. Use of anticholinergics and patient satisfaction were ascertained from questionnaires. Appropriate statistics were applied. RESULTS: All urodynamic parameters improved. The use of anticholinergics decreased substantially. No differences were noted between the two preparations. The incontinence situation improved markedly. The effect of the treatment was noted after about 2 weeks and lasted for about 9 months. CONCLUSIONS: Botulinum toxin A treatment in neurogenic detrusor overactivity patients is effective, long-lasting and repeatable. The treatment is minimally invasive and might be considered as an alternative to high-dosage anticholinergic medication.

EAU guidelines on neurogenic lower urinary tract dysfunction.

CONTEXT: Most patients with neurogenic lower urinary tract dysfunction (NLUTD) require life-long care to maintain their quality of life (QoL) and to maximise life expectancy. OBJECTIVE: To provide a summary of the 2008 version of the European Association of Urology (EAU) guidelines on NLUTD and to assess the effectiveness of currently available diagnostic tools, particularly ultrasound imaging and urodynamics. EVIDENCE ACQUISITION: The recommendations provided in the 2008 EAU guidelines on NLUTD are based on a review of the literature, using online searches of Medline and other source documents published between 2004 and 2007. A level of evidence and/or a grade of recommendation have been assigned to the guidelines where possible. EVIDENCE SYNTHESIS: NLUTD encompasses a wide spectrum of pathologies, and patients often require life-long, intensive medical care to maximise their life-expectancy and to maintain their QoL. Treatment must be tailored to the needs of the individual patient and, in many cases, involves a multidisciplinary team of experts. Timely diagnosis and treatment are essential if irreversible deterioration of both the upper and lower urinary tracts are to be avoided. Therapeutic decisions are made on the basis of a comprehensive medical assessment, including urodynamics to identify the type of dysfunction. Advances in investigative technologies have facilitated the noninvasive and conservative management of patients who have NLUTD. CONCLUSIONS: The diagnosis and treatment of NLUTD, which is a highly specialised and complex field involving both urology and medicine, requires up-to-date expert advice to be readily available. The current guidelines are designed to fulfil this need.

Propiverine compared to oxybutynin in neurogenic detrusor overactivity--results of a randomized, double-blind, multicenter clinical study.

OBJECTIVES: To compare the efficacy and tolerability of propiverine and oxybutynin in patients with neurogenic detrusor overactivity. METHODS: Patients were eligible, if at least 18 years of age and suffering from neurogenic detrusor overactivity. Eligibility also required a maximum cystometric capacity less than 300 ml. After a one-week run-in period, propiverine 15 mg t.i.d. or oxybutynin 5mg t.i.d. were administered for 21 days. As primary efficacy outcomes urodynamic parameters were assessed. As tolerability outcome the percentage of patients with newly manifesting anticholinergic adverse events was taken. RESULTS: 131 patients were recruited at 20 study centers. The maximum cystometric capacity (ml) was increased significantly in the propiverine group from 198 (+/-110) to 309 (+/-166), and in the oxybutynin group from 164 (+/-64) to 298 (+/-125). Similarly, maximum detrusor pressure during the filling phase (cm H(2)O) was lowered significantly in the propiverine group from 56.8 (+/-36.2) to 37.8 (+/-31.6), and in the oxybutynin group from 68.6 (+/-34.5) to 43.1 (+/-29.2). No significant differences resulted between treatment groups. Anticholinergic adverse events were reported less frequently in the propiverine compared to the oxybutynin group (63.0% versus 77.8%). Dryness of the mouth, the most frequent adverse event, was reported significantly less (47.1% versus 67.2%; p=0.02) in the propiverine compared to the oxybutynin group. CONCLUSION: Propiverine and oxybutynin are equally effective in increasing bladder capacity and lowering bladder pressure in patients with neurogenic detrusor overactivity. The trend for better tolerability of propiverine compared to oxybutynin achieved significance for dryness of the mouth.

Efficacy, tolerability and safety of propiverine hydrochloride in children and adolescents with congenital or traumatic neurogenic detrusor overactivity--a retrospective study.

OBJECTIVES: Anticholinergic treatment combined with intermittent catheterisation is the cornerstone of the conservative treatment strategy in children with neurogenic detrusor overactivity, which in most cases is due to congenital causes. Efficacy, tolerability and safety of propiverine hydrochloride were evaluated retrospectively in these children. METHODS: At four specialized outpatient clinics, all children's records were scrutinized for first-line propiverine hydrochloride treatment, or second- or third-line treatment after failure of a non-selective alpha-blocker (phenoxybenzamine) and/or other anticholinergics (oxybutynin, trospium chloride). The primary efficacy outcomes were urodynamic parameters, with clinical symptoms as secondary outcomes. Statistical analysis was performed by paired t-tests (significance level p < 0.05). RESULTS: Altogether 74 children and adolescents (40 boys, 34 girls; age range 11 months-19 years) were treated with propiverine hydrochloride (average duration 2 years and approximately 4 months; individual dose range 5-75 mg). The primary efficacy outcome parameters improved significantly: maximum cystometric capacity 161.2 [standard deviation (SD) 97.3] to 252.2 ml (SD 117.2), p < 0.001; maximum detrusor pressure 43.8 (SD 39.2) to 27.1 cm H(2)O (SD 26.4), p = 0.002; bladder compliance 7.6 (SD 6.4) to 17.0 ml/cm H(2)O (SD 16.2), p < 0.001. Phasic detrusor overactivity was abolished by 63%; incontinence resolved by 54%. One patient spontaneously reported a typical anticholinergic adverse event, which resolved after dose reduction. No safety concerns were documented. CONCLUSIONS: Propiverine hydrochloride is effective in neurogenic detrusor overactivity in children and adolescents, even in some of those cases unresponsive to other anticholinergics. The low incidence rate (<1.5%) of adverse events evidences a favourable risk-benefit profile of propiverine hydrochloride, considering in particular the total documented treatment and surveillance period of 171 patient years and nine months.

Success of repeat detrusor injections of botulinum a toxin in patients with severe neurogenic detrusor overactivity and incontinence.

OBJECTIVES: Detrusor injections with botulinum toxin type A are an effective treatment for neurogenic detrusor overactivity, lasting for 9-12 months. When the patients develop botulinum resistance, subsequent injections might be less effective. Repeat injections in patients with severe neurogenic detrusor overactivity and incontinence were studied. METHODS: Patients received Botox (300 UI) or Dysport (750 UI) injections. Clinical variables: satisfaction, anticholinergics use, mean and maximum bladder capacity, continence volume. Cystometric parameters: compliance, cystometric capacity, reflex volume. STATISTICS: Anova, chi2-tests; t-tests and paired t-tests (p=0.05). RESULTS: Forty-three men and 23 women (mean age 38.3 years; mean duration of lesion 9.2 years) were included. The interval between subsequent injections (on average 9-11 months) did not change significantly (p=0.5594). The satisfaction was high and anticholinergics use decreased substantially (p=0.0000). Significant improvements were found in clinical parameters and in cystometric capacity, for compliance only at the second treatment. The incidence of reflex contractions was significantly reduced. Four patients had transient adverse events after Dysport. CONCLUSIONS: Repeat injections with botulinum toxin type A are as effective as the first one. The cause for repeat treatment is relapse of overactive bladder symptoms.

An empirical treatment algorithm for incontinent children.

PURPOSE: Successful response rates of monotherapeutic strategies in urge incontinent children are limited. We evaluate whether adjuvant treatment improves outcomes. MATERIALS AND METHODS: Incontinent children were evaluated according to International Consultation on Incontinence standards. Propiverine (0.4 mg/kg) was applied 2 times daily for 4 weeks (treatment period 1) before reevaluation. Primary outcome was achievement of continence and secondary outcome was improvement of functional bladder capacity. In partial responders an alternative adjuvant treatment was initiated for another 12 weeks (treatment period 2). RESULTS: Of 70 enrolled patients 29 achieved continence (responders) and 35 responded partially and were assigned to adjuvant treatment, which consisted of selective alpha-blocker for functional bladder outflow obstruction (6), desmopressin for excessive nocturnal urine production (19) and biofeedback for increased pelvic floor activity during micturition (10). Only 6 nonresponders (9%) were assigned to specialized management. After treatment 2, 20 of the 35 partial responders achieved continence, thus avoiding specialized management. CONCLUSIONS: Propiverine monotherapy for incontinent children is effective. However, applying adjuvant treatment modalities to partial responders increases overall efficacy rates.

European experience of 200 cases treated with botulinum-A toxin injections into the detrusor muscle for urinary incontinence due to neurogenic detrusor overactivity.

OBJECTIVES: To present a comprehensive experience with botulinum-A toxin (BTA) injected into the detrusor muscle in patients with spinal cord injuries/diseases causing neurogenic incontinence. METHODS: Ten European medical centers provided the results of 231 patients with neurogenic detrusor overactivity who were treated with BTA. 300 units of Botox (Allergan Inc.) were injected cystoscopically into the detrusor muscle at 30 different locations, while sparing the trigonum. Urinary continence status, concomitant anticholinergic medication use and patient satisfaction were recorded. Key urodynamic parameters (reflex volume, maximum detrusor pressure during voiding, detrusor compliance and maximum cystometric bladder capacity) at baseline and at the first and second urodynamic follow-up examinations were analyzed. RESULTS: By the time of the initial (mean 12 weeks after injection) as well as at the second urodynamic follow-up examinations (mean 36 weeks after injection), the mean cystometric bladder capacity (p < 0.0001) and the mean reflex volume (p < 0.01) increased significantly, while the mean voiding pressure (p < 0.0001) decreased significantly. The mean bladder compliance had increased significantly (p < 0.0001) by the first follow-up examination and non-significantly by the time of the second follow-up. No injection related complications or toxin related side effects were reported. The patients considerably reduced or even stopped taking anticholinergic drugs without recurrence of reflex incontinence and were satisfied with the treatment. CONCLUSIONS: This retrospective European multicenter study presents the most extensive experience to date with BTA injections into the detrusor muscle to treat neurogenic incontinence due to detrusor overactivity and confirms that this new treatment is safe and valuable. Significant improvement of bladder function corresponds with continence and the subjective satisfaction indicated by the treated patients.

Tamsulosin: efficacy and safety in patients with neurogenic lower urinary tract dysfunction due to suprasacral spinal cord injury.

PURPOSE: We evaluated the efficacy and safety of tamsulosin in patients with neurogenic lower urinary tract dysfunction secondary to suprasacral spinal cord lesions in a 4-week randomized controlled trial (RCT) followed by a 1-year, open label, long-term study. MATERIALS AND METHODS: A total of 263 patients were randomized to 4-week double-blind therapy with placebo, or 0.4 or 0.8 mg tamsulosin once daily. Of these, 244 patients completed the RCT, 186 continued long-term tamsulosin therapy (0.4 or 0.8 mg once daily) and 134 completed 1-year treatment. The primary efficacy parameter was maximum urethral pressure (MUP). RESULTS: Although the mean decrease in MUP at 4 weeks in the RCT did not reach statistical significance over the placebo, it was more pronounced with 0.4 (-12.2 cm H2O or -10%) and 0.8 mg (-9.6 cm H2O or -9%) tamsulosin than placebo (-6.5 cm H2O or -3%). In the long-term study there was a statistically significant mean decrease in MUP (-18.0 cm H2O, p <0.001 or -15%) from baseline to end point. In the long-term study tamsulosin also decreased maximum urethral closure pressure, improved several cystometry parameters related to bladder storage and emptying, and increased to a statistically significantly degree, from baseline to end point, mean voided volume based on the micturition diary. There was statistically significant improvement for the International Prostate Symptom Score Quality of Life, as well as several questions about symptoms related to urinary leakage, and 1 question on bladder emptying and frequency, bother and severity of symptoms of autonomic dysreflexia. Finally, 71% of patients improved according to investigators (44% slightly and 27% much improved). Both doses were effective and well tolerated. CONCLUSIONS: Long-term tamsulosin treatment (0.4 and 0.8 mg once daily) seems to be effective and well tolerated in patients with neurogenic lower urinary tract dysfunction. The results suggest that it improves bladder storage and emptying, and decreases symptoms of autonomic dysreflexia.