A rational combination of intravesical and systemic agents for the treatment of interstitial cystitis

OBJECTIVE: Interstitial cystitis is a condition with a poorly understood etiology and, consequently, various treatment options have been described in the literature, with a less than optimal outcome. The aim of this study was to examine the role of a combination of intravesical hydrocortisone and heparin, together with oral bladder sedatives and systemic triamcinolone, for the treatment of interstitial cystitis. MATERIAL AND METHODS: A total of 26 patients who were diagnosed as having interstitial cystitis were treated with weekly intravesical hydrocortisone (200 mg) and heparin (25,000 IU) in physiological saline for 6 weeks. In addition, they were given oral bladder sedatives such as oxybutynin or tolterodine. Ulcerative, refractory and recurrent cases were treated with intramuscular triamcinolone (40 mg) weekly for 6 weeks. RESULTS: All patients experienced an improvement in symptoms within 48 h of their first intravesical instillation. While 19 patients (73%) experienced almost complete pain relief, five of the remaining seven patients improved with intramuscular triamcinolone. Frequency reduced from a mean of 23.2 to 10.9 voids per day and was acceptable in 21 patients (80%). Six patients (23%) had a relapse of symptoms in the form of pain and were treated satisfactorily by means of intramuscular triamcinolone. The mean duration of follow-up was 18.3 months. CONCLUSION: A combination of intravesical hydrocortisone and heparin, along with oral bladder sedatives and systemic steroids, has been used with encouraging results in a small group of patients with interstitial cystitis.     

Clinical efficacy of oxybutynin on sensory urgency as compared with that on motor urgency.

OBJECTIVE: Anticholinergic drug is widely accepted as an effective medication for frequency, urgency and urge incontinence related to detrusor overactivity (motor urgency). In order to elucidate whether anticholinergic drug is also effective for these symptoms related to bladder hypersensitivity (sensory urgency), clinical efficacy of oxybutynin on sensory urgency was compared with that on motor urgency. METHOD: Twenty-four patients with sensory urgency, and 53 patients with motor urgency were treated with oxybutynin (6 mg/day) for 4 weeks and subjective and objective efficacies were evaluated. Subjective parameters were quantified with urge score (grade 0-3) and daily numbers of voiding and incontinence. Objective efficacies were evaluated with pre-/ postcomparison of cystometric parameters. RESULTS: Excellent or good overall efficacy was obtained in 62.5% (15/24) of the sensory urgency group and 60.4% (32/53) of the motor urgency group. There was no statistical difference between these two groups. Objective cystometric parameters, bladder volume at first sensation and maximum cystometric capacity, statistically improved after the treatment in both groups. CONCLUSION: The results suggest that oxybutynin works as well on sensory urgency as it does on motor urgency.     

Effect of intravesical Resiniferatoxin (RTX) on lower urinary tract symptoms, urodynamic parameters, and quality of life of patients with urodynamic increased bladder sensation

OBJECTIVES: Intravesical resiniferatoxin (RTX) has been used with variable efficacy in the treatment of detrusor overactivity (DO). Patients with interstitial cystitis (IC) failed to benefit from this treatment, but a single placebo-controlled study in patients with non-IC painful bladders showed that RTX was effective in the short-term. We investigated the efficacy of intravesical RTX in patients with urgency and frequency due to increased bladder sensation. METHODS: Patients with intractable urgency and frequency, with or without urgency incontinence or bladder pain/discomfort, and with no urodynamic evidence of DO were recruited. After a single intravesical instillation of 100ml 50 nM RTX solution, patients were followed at 1, 3, and 6 mo for changes in urodynamics, bladder diary, the King's Health Questionnaire (KHQ), and degree of bladder pain. RESULTS: Fifteen patients (mean age, 52.5 yr) were treated. RTX significantly improved maximum cystometric capacity, volume at first desire to void, mean micturition volume, 24-h frequency, and daytime frequency for up to 6 mo after treatment. The overall KHQ score improved at all time points, with sustained improvements in the Symptom Severity, Incontinence Impact, and Personal Relationships domains. A >50% decrease in pain was reported by five of seven patients with painful bladders at 1 mo, but only one of seven at 6 mo. CONCLUSIONS: In our small open-label study, a single administration of intravesical RTX in patients with frequency and urgency due to increased bladder sensation significantly improved lower urinary tract symptoms, urodynamic parameters, and quality of life for up to 6 mo.     

Randomized, double-blind, multicenter trial on treatment of frequency, urgency and incontinence related to detrusor hyperactivity: oxybutynin versus propantheline versus placebo

Clinical efficacy and adverse effects of oxybutynin and propantheline in the treatment of symptoms related to detrusor hyperactivity were studied in a randomized, controlled, double-blind multicenter trial. Of 169 patients entered into the study 154 were evaluable for statistical analysis. Mean grade of improvement (visual analogue scale) was significantly higher with oxybutynin (58.2%) versus propantheline (44.7%) and placebo (43.4%). Mean bladder volume at first involuntary cystometric contraction was significantly increased with oxybutynin (+57.0 ml.) versus placebo (-9.7 ml.). Mean maximum cystometric bladder capacity was also significantly increased with oxybutynin (+80.1 ml.) versus placebo (+22.5 ml.). Rate of inquired possible adverse effects was significantly higher for oxybutynin (63%) versus propantheline (44%) and placebo (33%). However, only 5 patients dropped out of the study because of adverse effects (oxybutynin 2 and propantheline 3). No serious or lasting adverse effects were encountered with dryness of the mouth being the major complaint. Oxybutynin has statistically significant effects on subjective symptoms and objective urodynamic parameters in patients with detrusor hyperactivity compared to propantheline.     

Intravesical hyaluronic acid for interstitial cystitis/painful bladder syndrome: A comparative randomized assessment of different regimens

Objectives: To compare the clinical effectiveness of different regimens of intravesical hyaluronic acid instillation for patients with interstitial cystitis/painful bladder syndrome. Methods: A total of 60 patients (age 16–77 years) diagnosed with interstitial cystitis/painful bladder syndrome were enrolled in this prospective, randomized study. A total of 30 patients were assigned to receive four weekly intravesical instillations of 40 mg of hyaluronic acid followed by five monthly instillations (hyaluronic acid‐9 group). Another 30 patients received 12 intravesical instillations of 40 mg hyaluronic acid every 2 weeks (hyaluronic acid‐12 group). Symptomatic changes after hyaluronic acid treatments were assessed using Interstitial Cystitis Symptom and Problem Indexes, pain visual analog scale, functional bladder capacity, frequency and nocturia in voiding diary, maximum flow rate, voided volume, postvoid residual volume, and Quality of Life Index at 1, 3 and 6 months. Results: Of the 60 patients, 59 were evaluable at the end of the study. The Interstitial Cystitis Symptom Index, Interstitial Cystitis Problem Index and total score, pain visual analog scale, functional bladder capacity, maximum flow rate, and Quality of Life Index improved significantly after 6 months in both groups. The frequency and voided volume improved significantly only in the hyaluronic acid‐12 group. However, patients with moderate and marked improvement were clinically similar in both groups. The measured variables did not differ between the two groups over the course of the study. Conclusion: No significant difference was noted in the therapeutic effect between two hyaluronic acid instillation regimens for treatment of interstitial cystitis/painful bladder syndrome patients. Both groups showed significant improvement in symptom scores and Quality of Life Index.     

Does the potassium stimulation test predict cystometric,cystoscopic outcome in interstitial cystitis?

PURPOSE: We establish the relationship among symptom duration, cystometric and cystoscopic findings and potassium stimulation test in patients with interstitial cystitis. MATERIALS AND METHODS: A retrospective chart review was performed of 189 patients treated at an ambulatory clinic between 1992 and 1998. Urodynamic parameters, potassium stimulation test results and subjective response to treatment were evaluated. Fisher's exact test was used for statistical analysis. RESULTS: Of the 189 patients diagnosed with interstitial cystitis 173 (92%) were female and 16 (8%) were male. The potassium stimulation test was positive in 105 (83%) patients, negative in 16 (13%) and equivocal in 6 (4%). A cystometrogram and potassium stimulation test were done in 118 patients. Bladder capacity averaged 259 ml. in patients with tests potassium positive and negative, while average bladder volume at first sensation to void was 85 ml. and 148 ml. in those with negative and positive tests, respectively. Among the 102 patients with a positive potassium stimulation test 52 had normal cystoscopic findings. CONCLUSIONS: The potassium stimulation test is not correlated with either bladder capacity or cystoscopic findings.     

Menstrual cycle affects bladder pain sensation in subjects with interstitial cystitis

PURPOSE: Using psychophysical methods we compared the effect of the menstrual cycle on bladder sensation in subjects with the diagnosis of interstitial cystitis (IC) and in controls. MATERIALS AND METHODS: Female participants with normal menstrual cycles, including 7 with IC and 8 healthy controls, were recruited into this study. They completed daily diaries related to bladder pain and other body pain, and tracked daily micturition frequency. In a subset formal psychophysical testing of thermal and ischemic pain was performed at 2 times of the menstrual cycle, corresponding to the luteal and follicular phases. Cystometrograms were performed at the same time. RESULTS: Subjects with IC had higher pain scores and frequency than controls throughout the entire menstrual cycle. Pain scores were highest in the perimenstrual period in subjects with IC and controls. Micturition frequency was highest in the perimenstrual period in subjects with IC. Cystometric evaluation of a first need to void and the evocation of bladder pain demonstrated that lower intravesical volume and pressure were necessary to evoke bladder pain during the follicular period than during the luteal period in subjects with IC, although there was no effect on the first need to void. CONCLUSIONS: These findings are consistent with clinical lore that suggests a perimenstrual flare in pain in subjects with IC. To our knowledge it also demonstrates for the first time a menstrual cycle effect on bladder sensory function in subjects with IC. This suggests a potential role of gonadal hormones on bladder sensory processing and, therefore, a potential role for hormonal modulation as a therapeutic modality in this patient population.     

A double-blind, randomized controlled trial of cystometry using saline versus 0.3 M potassium chloride infusion in women with overactive bladder syndrome

AIM: To evaluate the effect of 0.3 M potassium chloride on cystometric parameters by comparing it with normal saline as a filling solution in women with overactive bladder (OAB). PATIENTS AND METHODS: Twenty-three women with significant OAB symptoms underwent consecutive cystometrograms (CMGs) using 0.9% normal saline (NS) and 0.3 M potassium chloride (KCl), the order of which was randomized for each patient. Individual CMGs were performed by separate investigators and both patients and investigators were blinded to the order in which each solution was given and to the results of the other CMG. RESULTS: Regardless of the nature of the filling solution, the order in which the CMGs were performed had little influence on either first desire to void (FDV, mean 83.5 ml vs. 117.8 ml for first and second CMGs respectively, P = 0.10) or on maximum cystometric capacity (Cmax, mean 265.0 ml vs. 264.4 ml, P = 0.98). KCl produced a significant (24%) reduction in mean Cmax compared to NS (mean 228.6 ml vs. 300.8 ml, P = 0.001), irrespective of the order of infusion. CONCLUSION: This comparative study using 0.3 M KCl versus NS as filling solutions suggests that intravesical potassium may not simply act on urothelial sensory nerve endings; it may also stimulate detrusor muscle contraction. These findings may influence the interpretation of the potassium sensitivity test in patients with OAB symptoms, particularly in those suspected of having interstitial cystitis.     

Efficacy and safety of oxybutynin in children with detrusor hyperreflexia secondary to neurogenic bladder dysfunction

PURPOSE: We evaluated the efficacy and safety of oxybutynin in children with detrusor hyperreflexia due to neurological conditions. MATERIALS AND METHODS: Study 1--A prospective, open label trial of 3 formulations of oxybutynin (tablets, syrup and extended release tablets) was conducted for 24 weeks in children 6 to 15 years old with detrusor hyperreflexia who used oxybutynin and clean intermittent catheterization. The effect of treatment on average urine volume per catheterization and on secondary urodynamic outcomes was evaluated. Study 2--The efficacy and safety of oxybutynin syrup were evaluated urodynamically in an open label study of children 1 to 5 years old with detrusor hyperreflexia who used oxybutynin and clean intermittent catheterization. RESULTS: Study 1--Mean urine volume per catheterization (+/- SEM) increased by 25.5 +/- 5.9 ml (p <0.001). Maximal cystometric capacity increased by 75.4 +/- 9.8 ml (p <0.001). Mean detrusor and intravesical pressures were significantly decreased by -9.2 +/- 2.3 (p < or =0.001) and -7.5 +/- 2.5 cm H2O (p <0.004), respectively, at week 24. Of 61 children with uninhibited detrusor contractions 15 cm H2O or greater at baseline 34 did not have them at week 24 (p <0.001). Improvements in bladder function were consistent across all oxybutynin formulations. Study 2--Mean maximal cystometric capacity increased significantly by 71.5 +/- 21.99 ml (p = 0.005). At study end only 12.5% of patients had uninhibited detrusor contractions 15 cm H2O or greater compared with 68.8% at baseline (p = 0.004). Oxybutynin was well tolerated in both studies. There were no serious treatment related adverse events. CONCLUSIONS: All 3 formulations of oxybutynin are safe and effective in children with neurogenic bladder dysfunction.     

Bladder stretch alters urinary heparin-binding epidermal growth factor and antiproliferative factor in patients with interstitial cystitis

PURPOSE: The etiology of interstitial cystitis is unknown. Urine from patients with interstitial cystitis has been shown to inhibit urothelial proliferation through a putative antiproliferative factor and to contain decreased levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) compared to controls. Stretch of detrusor smooth muscle cells is known to stimulate HB-EGF production. Because bladder hydrodistention sometimes alleviates the symptoms of interstitial cystitis, we determined whether the stretch stimulus of hydrodistention alters antiproliferative factor activity and/or HB-EGF in interstitial cystitis urine specimens. MATERIALS AND METHODS: Urine was collected immediately before, and 2 to 4 hours and 2 weeks after hydrodistention from 15 patients with symptoms and cystoscopic findings compatible with interstitial cystitis and 13 controls. Hydrodistention was performed with the subject under general or regional anesthesia and bladders were distended to 80 cm. water 3 times. Urinary HB-EGF was measured by enzyme-linked immunosorbent assay and urinary antiproliferative factor activity was determined by measuring 3H-thymidine uptake by normal human bladder urothelial cells. RESULTS: Hydrodistention significantly increased urinary HB-EGF in patients with interstitial cystitis toward normal control values (before distention p = 0.003, 2 weeks after distention p = 0.67). Urine antiproliferative factor activity decreased significantly after hydrodistention in patients with interstitial cystitis. However, antiproliferative factor activity in interstitial cystitis and control specimens was still statistically different 2 weeks after distention (before distention p = 0.0000004, 2 weeks after distention p = 0.04). CONCLUSIONS: Bladder stretch increased HB-EGF and conversely reduced antiproliferative factor activity in urine from patients with interstitial cystitis but not controls up to 2 weeks after distention. These results provide additional evidence for the possible role of antiproliferative factor and decreased HB-EGF in the pathophysiology of interstitial cystitis. To our knowledge this is also the first human study to show that in vivo bladder stretch can alter urinary factors that regulate cell growth.     

Pilot study of sequential oral antibiotics for the treatment of interstitial cystitis

PURPOSE: Interstitial cystitis is a chronic disease of unknown etiology characterized by bladder pain, urgency and frequency. Although a single microbe has not been implicated as a cause of interstitial cystitis, several groups noted various organisms in the urine of some women with interstitial cystitis and some patients reported that antibiotics decrease symptoms. Consequently we performed a prospective, randomized, double-blinded, placebo controlled pilot study of sequential oral antibiotics. MATERIALS AND METHODS: We randomized 50 patients with interstitial cystitis to receive 18 weeks of placebo or antibiotics, including rifampin plus a sequence of doxycycline, erythromycin, metronidazole, clindamycin, amoxicillin and ciprofloxacin for 3 weeks each. RESULTS: Intent to treat analysis demonstrated that 12 of 25 patients (48%) in the antibiotic and 6 of 25 (24%) in the placebo group reported overall improvement (p = 0.14), while 10 and 5, respectively, noticed improvement in pain and urgency (p = 0.22). In the antibiotic group 20 participants (80%) had adverse effects compared with 10 (40%) in the placebo group (p = 0.009). CONCLUSIONS: Our findings suggest that these antibiotics alone or in combination may sometimes be associated with decreased symptoms in some patients but they do not represent a major advance in therapy for interstitial cystitis.     

A clinical study on subjective sensations during bladder filling

Subjective sensations during the tonic phase of a bladder filling during cystometry were determined in 649 patients with incontinence and/or micturition problems of neurogenic and non-neurogenic origin. In this study 354 patients perceived three distinct sensations: a ‘first sensation of filling’ at 40% of bladder capacity, a ‘first desire to void’ at 75% of bladder capacity and a ‘strong desire to void’ at maximum cystometric capacity; 184 patients had one or two different sensations. Volume seemed more important than intravesical pressure in eliciting the sensations. In the distinction by the patient between the three consecutive sensations, both changes in intensity of volume perception and the existence of a specific neurological pathway for each sensation might play a role. Sensations appeared earlier during filling when asymtomatic urinary tract infection was present. These data give additional information about the subjective proprioception of bladder filling.     

The effect of chronic inflammatory condition of the bladder and estrogen replacement therapy on bladder functions and histology in surgically menopause and chronic cystitis induced rats

AIMS: We investigated the effect of chronic inflammatory condition of the bladder and estrogen replacement therapy on bladder function and histological changes in surgically menopause and chronic cystitis induced rats. METHODS: The study included 36 female Sprague-Dawley rats, divided into five groups. After bilateral ovariectomy, chronic cystitis was induced by intravesical instillation of HCl, and then group 1 (n = 8) received nasal estrogen, and group 2 (n = 8) received oral estrogen replacement therapy. Group 3 (n = 7) underwent ovariectomy and chronic cystitis, but no replacement therapy. Group 4 (n = 7) had only ovariectomy. Group 5 (n = 6) was taken as sham group. The rats were sacrificed after 60 days, and cystometric study and histological findings were compared among the groups. RESULTS: The mean maximal bladder capacity and compliance revealed significant decreases in group 3 and 4 compared with group 5, and significant increases in group 1 and 2 compared with group 3. Histological findings showed significant increases in the mast cells and leukocyte infiltration of group 3 and 4 compared with group 5, and significant decreases in the mast cells and leukocyte infiltration of group 1 and 2 compared with group 3. CONCLUSIONS: This experimental menopause and chronic cystitis model showed that bladder function and histology might deteriorate much more with chronic cystitis in postmenopausal period. This is the first study in the literature to report that chronic inflammatory bladder occurring after menopause can be improved by estrogen replacement therapy.     

Clinical and urodynamic experience with intravesical hyaluronic acid in painful bladder syndrome associated with interstitial cystitis

Introductionfew studies have been carried out on therapeutic options in patients with painful bladder syndrome associated with interstitial cystitis. The aim is to verify the safety and effectiveness of treatment with sodium hyaluronate through intravesical instillation in patients with painful bladder syndrome.Materials and methodsa series of 18 female patients is presented, with a mean age of 51 years and prior diagnosis of painful bladder syndrome, who were treated by means of the weekly infusion of an intravesical solution of 40 mg of sodium hyaluronate in sterile solution, over a period of eight weeks. The patients were examined clinically and urodynamically prior to their inclusion in the study and eight months after the instillations had concluded.Resultsthere was a statistically significant improvement in the urodynamic parameters and in the symptoms measured quantitatively by means of the questionnaire “Pelvic Pain and Urgency/Frequency” between the baseline situation and after the vesical instillation of sodium hyaluronate in patients with painful bladder syndrome. There was no toxicity arising from the treatment, given that no adverse effects were recorded in relation to it.Conclusionthe clinical use of intravesical hyaluronic acid in patients with painful bladder syndrome possibly associated with interstitial cystitis has been demonstrated. The clinical improvement is also associated both with increased bladder capacity and improved bladder sensitivity. Tolerance was excellent. Clinical tests that more profoundly evaluate the therapeutic potential of this drug in this type of patients are required.     

Intravesical electromotive administration of oxybutynin in patients with detrusor hyperreflexia unresponsive to standard anticholinergic regimens

PURPOSE: About 15% to 20% of patients with detrusor hyperreflexia do not benefit from oral oxybutynin regimens, frequently because of unpleasant side effects. Several reports indicate that intravesical oxybutynin is effective in many of these patients but there are some who still fail to respond. MATERIALS AND METHODS: A select group of 10 adults with detrusor hyperreflexia unresponsive to standard oral and intravesical oxybutynin regimens were treated at weekly intervals with 5 mg. oxybutynin orally, or 5 mg. oxybutynin in 100 ml. intravesically for 60 minutes of passive diffusion and for 30 minutes with 5 mA. electrical current. Each treatment (plus oral placebo and 2 intravesical controls) was associated with an 8-hour, full urodynamic monitoring session, and periodic blood and bladder content sampling. RESULTS: There was no significant objective improvement with oral or intravesical passive diffusion oxybutynin. Conversely there was significant improvement in 5 of 6 objective urodynamic measurements with intravesical electromotive oxybutynin. Plasma profiles were a single peak and decay following oral oxybutynin and 2 distinct peaks with intravesical passive diffusion and electromotive oxybutynin. Area under the curve for intravesical passive diffusion were 709 ng. per 8 hours versus oral 1,485 (p <0.05) versus intravesical electromotive 2,781 (p <0.001). Bladder content samples confirmed oxybutynin absorption. Oral oxybutynin caused anticholinergic side effects in 7 of 10 patients. There were no side effects with intravesical passive diffusion or electromotive administrations. CONCLUSIONS: Accelerated intravesical administration results in greater bioavailability and increased objective benefits without side effects in previously unresponsive patients compared with oral and intravesical passive diffusion oxybutynin administration.     

Lack of effect following repeated in vivo exposure of the rabbit urinary bladder to urine from interstitial cystitis patients at low infusion volumes

We reported previously that substances in interstitial cystitis urine, when infused into the rabbit bladder, induce changes that resemble bladders of interstitial cystitis (IC) patients. Here we report our investigation of the effect of additional molecular weight subfractions of IC urine and lower infusion volume in this rabbit bladder bioassay. Urine was pooled from symptomatic IC patients, asymptomatic IC patients (in remission), and normal volunteers. Two fractions of 20× concentrated urine were obtained for each of the 3 groups: a 10–100-kD fraction and a fraction > 100 kD but <0.22 μm. Six rabbits per group were infused twice per week with 6 ml of 1 of these 6 urine fractions or saline as a control. After 6 weeks, each rabbit was cystoscoped before and after hydrodistension, bladder capacity and urea permeability were determined, and the bladder was removed for histologic examination. A questionnaire revealed a significant difference (P < 0.01) regarding voiding symptom severity between symptomatic IC patients and both normal volunteers and IC patients in remission. There was no statistically significant difference among groups of rabbits in cystoscopic bladder appearance, bladder capacity, urea permeability, or bladder histology. If a urine-borne factor is in part responsible for IC symptoms, the rabbit bladder must be filled with urine to near capacity to be able to detect a difference between IC and normal urine in this rabbit bladder bioassay. Neurourol. Urodynam. 17:147–152, 1998. © 1998 Wiley-Liss, Inc.     

Blood flow,pressure and compliance in the male human bladder

PURPOSE: The regulation of human bladder blood flow during filling is poorly understood. We characterized changes in bladder blood flow with filling and examined the relationship of bladder compliance and blood flow. MATERIALS AND METHODS: A total of 17 awake male patients underwent saline cystometry followed by cystoscopy while under local anesthesia, during which a laser Doppler flow probe was placed into the posterior bladder wall detrusor. Systemic blood pressure, bladder blood flow and intravesical pressure were measured with the bladder empty and filled to 25%, 50%, 75% and 100% of awake maximum cystometric capacity as well as immediately after bladder drainage. RESULTS: Mean bladder blood flow was lowest in the empty bladder and increased with bladder filling. A mean peak flow plus or minus standard error of 7.6 +/- 1.1 ml. per minute per 100 gm. tissue was observed at volumes greater than 75% but less than 100% of maximum cystometric capacity. At 100% maximum cystometric capacity mean intravesical pressure increased by 73% from 25.2 to 43.5 cm. water and bladder blood flow decreased by 36%. Rapid bladder drainage was associated with a rebound in mean bladder blood flow to approximately 1.6 times baseline. Bladder compliance calculated for the whole filling curve positively correlated with bladder blood flow (p = 0.025), that is low compliance was associated with low blood flow. CONCLUSIONS: Human bladder blood flow tends to increase with increasing volume and pressure, and depends largely on local regulation. At capacity bladder blood flow is significantly decreased. Immediately after bladder drainage there is a rebound in blood flow, allowing reperfusion to occur. Decreased bladder blood flow and decreased bladder wall compliance correlated strongly, suggesting that ischemia may lead to structural changes in the bladder wall.     

Efficacy and safety of tolterodine in people with neurogenic detrusor overactivity

OBJECTIVE: To compare tolterodine with oxybutynin and placebo in people with neurogenic detrusor overactivity. DESIGN: Prospective, randomized, double-blind, crossover trial plus open-label comparative stage. PARTICIPANTS: Ten participants with neurogenic detrusor overactivity due to spinal cord injury or multiple sclerosis who used intermittent catheterization. METHODS: Bladder capacity on cystometrogram, a 10-day record of catheterization volumes, number of incontinent episodes per day, and perceived dry mouth using a visual analog scale (VAS) were measured for the following: (a) a blinded comparison: tolterodine, 2 mg twice daily, vs placebo, twice daily; and (b) an unblinded comparison: oxybutynin vs tolterodine, each at self-selected doses (SSDs). RESULTS: Tolterodine, 2 mg twice daily, was superior to placebo in enhancing catheterization volumes (P < 0.0005) and reducing incontinence (P < 0.001), but was comparable with placebo in cystometric bladder capacity. Efficacy of tolterodine SSD was comparable with oxybutynin SSD with regard to catheterization volumes, degree of incontinence, and cystometric bladder capacity. The side effect profile (dry mouth) was comparable between tolterodine, 2 mg twice daily, and placebo, but differed significantly when comparing tolterodine SSD with oxybutynin SSD (P < 0.05). CONCLUSION: Tolterodine, when used at SSDs, is comparable with oxybutynin at SSDs in enhancing bladder volume and improving continence, but with less dry mouth. Tolterodine at the recommended dosage of 2 mg twice daily improves incontinence and bladder volumes compared with placebo, and without significant dry mouth. Larger doses of tolterodine may be needed to achieve best effect in this population, but further studies are required.     

Psychophysical evidence of hypersensitivity in subjects with interstitial cystitis

PURPOSE: We quantified differences in somatic and visceral sensation in healthy subjects and subjects with interstitial cystitis (IC). MATERIALS AND METHODS: A total of 13 subjects with IC and 13 healthy subjects answered psychological questionnaires and underwent psychophysical testing of thermal and pressure thresholds for sensation as well as the ischemic forearm test of pain tolerance. A subset of subjects also underwent bladder sensory testing with the determination of 3 consecutive cystometrograms. Ratings of intensity and unpleasantness were determined. RESULTS: Subjects with IC were significantly more sensitive to deep tissue measures of sensation related to pressure, ischemia and bladder than healthy subjects. Cutaneous thermal pain measures were similar in the 2 groups. Psychological measures indicated higher reactivity in subjects with IC. CONCLUSIONS: Similar to other visceral pain disorders, such as irritable bowel syndrome, hypersensitivity to somatic stimuli was noted in subjects with IC. This suggests altered central mechanisms in the processing of sensory events from the bladder.     

The effect of intravesical sodium nitroprusside on idiopathic detrusor overactivity

Although nitric oxide (NO) plays an important role in the urethra and outlet region of the bladder, the role of this inhibitory neurotransmitter in the human detrusor remains unclear. We conducted a prospective, randomised, open study on 31 patients with urodynamically proven idiopathic detrusor overactivity in order to examine the effects of intravesical administration of the NO donor sodium nitroprusside (SNP) on detrusor overactivity. Thirty-one consecutive patients (14 male, 17 female; mean age 53.0±2.7 years) with idiopathic detrusor overactivity diagnosed by pressure-flow analysis were included in this study. The patients were randomised into two groups. Cystometries were performed with normal saline in the control group (n=10) and with 7.2 mM SNP solution (2.16 mg/ml) in the study group (n=21). We urodynamically investigated sensation, maximal cystometric capacity, compliance, instability index, amplitude and frequency of involuntary contractions. No statistically significant differences was found between the first (pressure-flow) and second (saline or SNP cystometry) urodynamic values in the control and study groups (P>0.05). We have demonstrated that SNP does not have any effect on uninhibited bladder contractions. These results suggest that the intravesical administration of SNP is not an effective treatment for detrusor overactivity.