Increase In Maximum Cystometric Capacity Research Articles

Intradetrusor Injections of Onabotulinum Toxin-A in Children With Urinary Incontinence due to Neurogenic Detrusor Overactivity Refractory to Antimuscarinic Treatment.

PurposeThis was a prospective single-arm study to assess the efficacy and safety of intradetrusor injections of onabotulinum toxin-A in children with urinary incontinence associated with neurogenic detrusor overactivity due to myelomeningocele. All patients had failed the first-line treatment of a combination of oral antimuscarinics and intermittent catheterization.Materials and MethodsThe study group consisted of 31 children with myelomeningocele with a mean age of 7.95 years (range, 5-3 years) who were followed up for a mean of 29 weeks. The amount of onabotulinum toxin A injected was 10 U/kg with a maximal dose of 300 U. There were 20 to 30 injection sites with rigid cystoscopic guidance under general anesthesia.ResultsThirty of 31 patients reported dryness between intermittent catheterization intervals. The mean reduction in maximum detrusor pressure and the mean increase in maximum cystometric capacity from baseline were 53% and 51.5%, respectively, 6 weeks after injection. We found a 324% increase in mean bladder compliance and a 57% increase in mean intermittent catheterization volumes. The mean duration of efficacy was 28 weeks with a single injection and 36 weeks for repeated injections (minimum, 16 weeks; maximum, 52 weeks). The mean time interval between repeated onabotulinum toxin-A injections was 7 months (maximum, 13 months). Intradetrusor injections of onabotulinum toxin-A were well tolerated.ConclusionsOnabotulinum toxin-A injections into the bladder wall provide a significant symptomatic and urodynamic improvement in children with neurogenic detrusor overactivity due to myelomeningocele who are on intermittent catheterization. The treatment seems to be safe and very well tolerated.

Onabotulinumtoxin-A intradetrusorial injections modulate bladder expression of NGF, TrkA, p75 and TRPV1 in patients with detrusor overactivity

How onabotulinumtoxinA (onab/A) injected in the detrusor muscle improves detrusor overactivity (DO) is still a matter of debate. Nerve growth factor (NGF) seems to play a role in determining urgency and DO. Recent studies showed that NGF decreases in patients with DO who respond to onab/A treatment. We investigated onab/A-induced changes on gene expression of NGF, TRPV1, TrkA and p75 in bladder wall tissue of patients affected by neurogenic and idiopathic DO. Twenty-five patients (18 with neurogenic DO and 7 with idiopathic DO) received onab/A injections into the detrusor muscle. Urodynamic studies and cystoscopies with sampling of the bladder wall were performed before and 1 month after onab/A injections. Onab/A-induced changes in urodynamic variables (first volume and maximum pressure of uninhibited detrusor contractions and maximum cystometric capacity) and NGF, TRPV1, TRKA, p75 gene expression by means of quantitative Real Time-Polymerase Chain Reaction. NGF protein levels were assessed in tissue homogenates by enzyme-linked immunosorbent assay. Onab/A significantly improved urodynamic findings (as shown by the increase in maximum cystometric capacity), decreased the bladder tissue levels of NGF protein and significantly increased NGF, TrkA, p75 and TRPV1 gene expression independently from the etiology of DO. No significant correlation has been found between NGF down-regulation and the increase in MCC. Correlations between NGF gene expression and NGF receptors’ gene expression were influenced by onab/A dosages. In the short time follow-up, onab/A decreases NGF protein levels and increases NGF and associated receptors’ gene expression possibly by inhibiting NGF release. Further studies with longer follow-up will clarify time course of onab/A-induced modifications in NGF expression.

Videourodynamic changes of botulinum toxin A in patients with neurogenic bladder dysfunction (NBD) and idiopathic detrusor overactivity (IDO) refractory to drug treatment

To document the videourodynamic changes and the efficacy and safety profile of botulinum toxin A (BoNT-A, Dysport(®)) in neurogenic bladder dysfunction (NBD) including neurogenic detrusor overactivity, low-compliance and break-low-compliance and idiopathic detrusor overactivity (IDO), in patients refractory to drug treatment. Sixty-four patients with NBD and 170 patients with IDO were treated between 2002 and 2007. Diagnostic approach included medical history, bladder diary, standardised questionnaire rating quality of life, sonography, videourodynamic and temporary sacral nerve block. All patients received BoNT-A-injection under local anaesthesia. Patients with NBD received 500 mouse units (MU) and patients with IDO received 250MU BoNT-A, injected into ten sites including the trigonum. Patients were followed up 6weeks after injection. For NBD, 58/64 (91%) patients achieved satisfactory continence during the day as well as significant reduction in incontinence episodes and improvement in quality of life. For IDO, 158/170 (93%) were responders with regard to urgency and urge incontinence. Urodynamical changes included significant improvement in the following parameters in both groups: increase in maximum cystometric capacity and decrease in detrusor pressure. BoNT-A was well tolerated; no drug-related side effects were documented. No de novo vesicoureteral reflux was induced. Long-term follow-up revealed a mean duration effect of BoNT-A of 5.7months in NBD and 4.9months in IDO. BoNT-A is highly effective in NBD as well as in IDO suggesting that this is a good treatment option for patients with detrusor overactivity. Furthermore, intratrigonal injection is safe and not associated with vesicoureteral reflux.

Urodynamic Assessment of Poor Responders After Botulinum Toxin-A Treatment for Overactive Bladder

Botulinum toxin-A (BTX-A) is effective in treating overactive bladder (OAB) refractory to anticholinergics. Most patients have improvements in symptoms, urodynamic parameters, and quality of life, and a poor response is uncommon. The aim of this study was to determine whether poor responders could be predicted from preoperative urodynamic parameters. Data were collected prospectively from 33 OAB patients with idiopathic detrusor overactivity. All patients underwent intradetrusor injections of 200 U BTX-A. Response to treatment was assessed by patient perception, OAB symptoms, and quality of life data. Urodynamics were conducted at baseline and 4, 12, and 24 weeks postinjection. We performed statistical analysis using the Wilcoxon matched pairs, Mann-Whitney, two-sample, and paired t-tests. Receiver operator characteristic (ROC) curves were plotted for relevant parameters. Five patients had a poor response to treatment. Significant increases in maximum cystometric capacity (MCC), reflex detrusor volume (RDV), and bladder compliance with decreases in maximum detrusor pressures (MDP) on filling were observed in the responders over 24 weeks. Minimal urodynamic benefit was observed in the poor responders group over the same period. When comparing the two groups, baseline MDP in poor responders was 138.0 +/- 30.7 compared with 74.4 +/- 32.6 in the responders (P = 0.0028). ROC analysis suggested that a pretreatment MDP greater than 110 may have predictive value (AUC, 0.946; sensitivity, 0.86; specificity, 1.0) for a poor response to treatment. Very high MDP greater than 110 may predict a poor response to treatment with 200 U of BTX-A. Higher doses may be necessary in these patients.

Duloxetine compared with placebo for treating women with symptoms of overactive bladder

To evaluate duloxetine (a serotonin-noradrenaline reuptake inhibitor) in women with symptoms of overactive bladder (OAB), as it has been shown to increase the bladder capacity in an animal model. In all, 306 women (aged 21-84 years) were recruited and randomly assigned to placebo (153) or duloxetine (80-mg/day for 4 weeks increased to 120-mg/day for 8 weeks; 153). Symptoms of OAB were defined as bothersome urinary urgency and/or urge urinary incontinence (UI) for > or =3 months. Participants were also required to have a mean daytime voiding interval (VI) of < or=2 h and urodynamic observations of either detrusor overactivity (DOA) or urgency which limited bladder capacity to <400 mL, both with no stress UI (SUI). The primary efficacy analysis compared the treatment effects on mean change from baseline to endpoint in the mean number of voiding episodes (VE)/24 h. The secondary efficacy analyses compared the treatment effects on the number of UI episodes (IE)/24 h, in the Incontinence Quality of Life questionnaire (I-QOL) score, and on the mean daytime VI. Safety was assessed with vital signs, adverse event reporting, routine laboratory testing, electrocardiogram, and the measurement of postvoid residual urine volumes (PVR). Patients randomized to duloxetine had significant improvements over those randomized to placebo for decreases in VE and IE, for increases in the daytime VI, and for improvements in I-QOL scores at both doses of duloxetine. Urodynamic studies showed no significant increases in maximum cystometric capacity or in the volume threshold for DOA. The most common treatment-emergent adverse events with duloxetine (nausea, 31%; dry mouth, 16%; dizziness, 14%; constipation, 14%; insomnia, 13%; and fatigue, 11%) were the same as those reported by women with SUI and were significantly more common with duloxetine than placebo. Laboratory assessments, vital signs and electrocardiograms were stable relative to baseline, with no relevant differences detected between groups. There was a significant difference in the change in PVR with duloxetine (<5 mL mean increase) but no patient reported hesitancy or retention. In this trial, duloxetine was better than placebo for treating women with 'wet' and 'dry' symptoms of OAB associated with DOA or a bladder capacity of <400 mL.

Trospium chloride in patients with neurogenic detrusor overactivity: Is dose titration of benefit to the patients?

To determine whether dose titration based on therapeutic response is superior to standard dosing of oral trospium chloride in patients with neurogenic detrusor overactivity and, moreover, to investigate the possible underlying causes of differences in efficacy at equal doses in some patients. Using a double-blind approach, two groups (standard dose and adjustable dose) with a total of 80 patients were treated with trospium chloride coated tablets for a period of 3 - 5 weeks. Treatment duration and daily doses varied depending on change ofurodynamic parameters defined as therapeutic response. In Week 1, both groups started on 45 mg/day (3 x 15 mg). In the adjustable dose group, it was permissible to increase the daily dose to 90 or 135 mg/day depending on the urodynamic treatment response. In contrast, doses remained unchanged in the standard dose group although a need for dose adjustment had been recognized under the double-blind conditions. Therapeutic response was defined as improvement of at least two of the following three urodynamic parameters: bladder compliance 2 20 ml/cmH20, maximum cystometric capacity > 250 ml and maximum detrusor pressure < 40 cmH20. Changes in individual urodynamic parameters were defined as secondary efficacy variables. Primary and secondary parameters were assessed by comparing baseline values with those at the end of treatment. Therapeutic response was analyzed by using the Fisher-Yates test, and the Mann-Whitney U-test was used for secondary parameters. Trospium plasma concentration was measured to assess patient's compliance and as a tool to elucidate possible factors influencing treatment efficacy. Safety and tolerability were evaluated based on withdrawal rates and adverse events. Both dose groups had comparable baseline characteristics. Therapeutic response was achieved in 58% of patients in the adjustable dose group (ADG) and in 72% of those in the standard dose group (SDG, p -0.23). Clinically relevant increases in maximum cystometric capacity and bladder compliance were observed, and there was a clear decrease in detrusor pressure. After Day 7, the daily dose was increased in 52.8% of all patients in the adjustable dose group and (seemingly) in 32.5% of those of the standard dose group. Further dose escalation after Day 14 was assessed as necessary in 15% of the standard dose group and 22% of the adjustable dose group. The main changes in urodynamic parameters occurred during the first 7 days of treatment, but in some patients it takes a longer time. No statistically significant differences between plasma trospium chloride levels in the two dose groups were observed at any time, but increase of plasma concentration with higher doses became obvious when patients were differentiated to individual dose stages. In both groups, the most common treatment-related adverse event was dry mouth (ADG 35%, SDG 37%), which never led to discontinuation of treatment. Rates of other adverse events such as dry skin, dysopia, increased heart rate and gastrointestinal disorders were much lower. Generally, in patients with neurogenic detrusor overactivity daily doses of 45 mg trospium chloride can be considered as being the standard dose, and dose adjustment, e.g. due to increased body weight, might usually not be necessary. However, increased daily doses of up to 135 mg appear to be safe when prescribed in individual patients less responsive to the drug.

Urodynamics-Based Evidence for the Beneficial Effect of Imipramine on Valve Bladders in Children

In an era, in which valve bladder is recognised as perhaps the single most important determinant of long-term outcome in patients with posterior urethral valves (PUV), an insight into the etiopathogenesis and management of valve bladders is warranted. The present study was designed to evaluate bladder dysfunction in PUV and to assess the response to imipramine in these patients, both subjectively and objectively, by serial urodynamic studies (UDS). From 1998-2001, 30 patients with PUV who had documented bladder dysfunction on UDS were studied. Patients with non-compliant or unstable bladders were treated with imipramine (1.5 - 2 mg/kg). All the patients in the present study were 5 years or older and hence old enough to be toilet trained. Assessment of continence and side effects of the drug was done after 3 months and repeat UDS were done at 3-6 months, 1 and 2 years. On the basis of initial treatment, the patients were divided into 2 groups; a fulguration group (n = 10, 33.3 %) and a vesicostomy group (n = 20, 66.6 %). Symptomatic voiding dysfunction was present in 27 of the 30 patients (90 %). Two patterns of urodynamic abnormalities were noted in the present study; 1) unstable bladders with single or multiple uninhibited contractions (18/30 patients, 60 %), and 2) small capacity, hypocompliant, hypertonic bladder (12/30 patients, 40 %). Post imipramine therapy significant symptomatic improvement was noted in 16/30 patients. On serial UDS, there was a 18-20 % increase in maximum cystometric capacity (MCC) and 30-35 % increase in pressure specific bladder volume (PSBV) following one year of imipramine therapy in 16/30 patients and 11/30 patients, respectively. 4 patients failed to show any improvement in MCC and PSBV with imipramine, they had been initially diverted with vesicostomy and later required augmentation cystoplasty. Unstable bladders and those with marginal bladder capacity and compliance showed the best response to imipramine therapy. Fibrotic, small capacity, hypertonic bladders are less responsive to imipramine. However, a trial of imipramine therapy is still warranted in these patients, as only 4/12 (33.3 %) patients with fibrotic hypertonic bladders failed to show any response and ultimately required augmentation cystoplasty. Imipramine qualifies as an effective and cheap drug for valve bladders.

Intravesical Oxybutynin Chloride and Clean Intermittent Catheterisation in Patients with Neurogenic Vesical Dysfunction and Decreased Bladder Capacity

Oral administration of oxybutynin chloride is effective in increasing bladder capacity in patients with neurogenic bladder dysfunction who are practising clean intermittent catheterisation, but it is often associated with systemic side effects. The effect of intravesical instillation of oxybutynin chloride was studied in 14 patients who were practising clean intermittent catheterisation and in whom the maximum cystometric capacity was < 250 ml and/or vesical compliance < 5. A 5-mg tablet of oxybutynin chloride was crushed and suspended in 10 ml of boiled and cooled water and instilled into the bladder after emptying it completely; this was carried out thrice daily either by the patient or by his carer. During follow-up (6-12 months) no local or systemic side effects were observed and patient compliance was excellent in 12 patients, who showed an increase in maximum cystometric capacity and vesical compliance. One patient could not retain the drug intravesically because of reflex detrusor contraction and he was excluded from the study. One patient was lost to follow-up. The results suggest that the intravesical instillation of oxybutynin chloride is safe and effective in the treatment of selected patients with neurogenic bladder dysfunction whose bladder capacity is small and who are practising clean intermittent catheterisation.

Urodynamic Studies in Acupuncture for Women with Frequency, Urgency and Dysuria

Urodynamic measurements were performed before and after acupuncture at 2 different points in 52 women who presented with frequency, urgency and dysuria. Measurements included cystometry, anal sphincter electromyography, urethral pressure profilometry and uroflowmetry.The results of this study showed a significant increase in maximum cystometric capacity and a decrease in peak urinary flow rate after acupuncture at the Sp. 6 point, which has traditionally been used for the treatment of urinary problems. During acupuncture at the Sp. 6 point there were periodic increases in intraurethral pressure at the distal urethra, which were measured with a microtip transducer. Acupuncture-induced detrusor inhibition and external sphincteric contractions were demonstrated.Clinically symptomatic improvement was noted in 22 of the 26 patients who were treated by acupuncture at the Sp. 6 point. Our studies indicated that acupuncture could be used as a simple and effective method to treat female patients with frequency, urgency and dysuria.

Oxybutynin Versus Propantheline in Patients with Multiple Sclerosis and Detrusor Hyperreflexia

Hyperreflexia is the most common urological finding in patients with multiple sclerosis. A prospective randomized study was done to compare the effectiveness of 2 commonly used drugs, oxybutynin and propantheline. Of the 34 patients entered into the trial 19 were treated with oxybutynin and 15 with propantheline. The urological symptoms (frequency, nocturia, hesitancy, urgency and urge incontinence) were graded according to severity from 0 to 3. Patients with urinary infection were excluded. Urodynamic examination, consisting of cystometrography and electromyography, was performed in all patients before treatment. Both groups of patients had comparable neurological, urological and urodynamic status before treatment. In 4 patients (21 per cent) treated with oxybutynin and in 4 (27 per cent) treated with propantheline side effects were so severe that the treatment had to be discontinued. Symptomatic response to oxybutynin was good in 10 patients (67 per cent), fair in 2 (13 per cent) and poor in 3 (20 per cent). Propantheline produced good symptomatic results in 4 patients (36 per cent), fair in 1 (9 per cent) and poor in 6 (55 per cent). The mean increase in maximum cystometric capacity on cystometrography was significantly larger in the oxybutynin group than in the propantheline group (144 ± 115 versus 35 ± 101). Our results indicate that oxybutynin is more effective than propantheline in the treatment of detrusor hyperreflexia in patients with multiple sclerosis.