Evaluation of 3 Methods of Bladder Irrigation to Treat Bacteriuria in Persons With Neurogenic Bladder

Abstract

Background/Objective: We conducted a randomized, double-blind comparison of twice daily bladder irrigation using 1 of 3 different solutions in community-residing persons with neurogenic bladder who used indwelling catheters to evaluate efficacy in treatment of bacteriuria.

Methods: Eighty-nine persons with bacteriuria were randomized to irrigate their bladders twice daily for 8 weeks with 30 mL of (a) sterile saline, (b) acetic acid, or (c) neomycin-polymyxin solution. Urinalysis, cultures, and antimicrobial susceptibility tests were performed at baseline and weeks 2, 4, and 8 to determine the extent to which each of the solutions affected numbers and types of bacteria, urinary pH, urinary leukocytes, and generation of antimicrobial-resistant organisms.

Results: Bladder irrigation was well tolerated with the exception of 3 participants who had bladder spasms. None of the 3 irrigants had a detectable effect on the degree of bacteriuria or pyuria in 52 persons who completed the study protocol. A significant increase in urinary pH occurred in all 3 groups. No significant development of resistance to oral antimicrobials beyond what was observed at baseline was detected.

Conclusions: Bladder irrigation was generally well tolerated for 8 weeks. No advantages were detected for neomycin-polymyxin or acetic acid over saline in terms of reducing the urinary bacterial load and inflammation. We cannot recommend bladder irrigation as a means of treatment for bacteriuria in persons with neurogenic bladder.     

The rationale for bladder washouts in children with neurogenic bladder

Children with a neurogenic bladder are at risk of developing recurrent urinary tract infections and long-term kidney failure. Due to an altered lower urinary tract, children may be overtreated for simple bacteriuria or undertreated for a potentially severe urinary tract infection. This group of patients represent high users of healthcare, and are at risk of colonization and development of antibiotic resistance. Bladder washouts with non-antibiotic electrochemically activated solutions are a potential new prophylactic option for patients with bladder dysfunction when clean intermittent catheterization has resulted in chronic bacteriuria.     

Effect of cranberry extract on bacteriuria and pyuria in persons with neurogenic bladder secondary to spinal cord injury

OBJECTIVE: To determine whether antibacterial effects of cranberry extract will reduce or eliminate bacteriuria and pyuria in persons with spinal cord injury (SCI). DESIGN: Randomized, double-blind, placebo-controlled study. PARTICIPANTS: Participants were people with SCI residing in the community who were 1 year or longer postinjury with neurogenic bladder managed by intermittent catheterization or external collection device and a baseline urine culture demonstrating at least 10(5) colonies per milliliter of bacteria. METHODS: Each participant ingested 2 g of concentrated cranberry juice or placebo in capsule form daily for 6 months. Baseline urinalysis and cultures were performed at the time of the initial clinic visit and monthly for 6 months. Microbiologic data were evaluated using analysis of variance with repeated measures. RESULTS: Twenty-six persons received cranberry extract and 22 persons received placebo. There were no differences or trends detected between participants and controls with respect to number of urine specimens with bacterial counts of at least 10(4) colonies per milliliter, types and numbers of different bacterial species, numbers of urinary leukocytes, urinary pH, or episodes of symptomatic urinary tract infection. CONCLUSION: Cranberry extract taken in capsule form did not reduce bacteriuria and pyuria in persons with SCI and cannot be recommended as a means to treat these conditions.     

Simplified bladder training augments the effectiveness of tolterodine in patients with an overactive bladder

OBJECTIVES: To compare the efficacy of tolterodine plus simplified bladder training (BT) with tolterodine alone in patients with an overactive bladder. PATIENTS AND METHODS: In a multicentre, single-blind study at 51 Scandinavian centres, 505 patients aged >or= 18 years with symptoms of urinary frequency (>or= 8 micturitions/24 h) and urgency, with or without urge incontinence, were randomized to oral treatment with either tolterodine 2 mg twice daily plus simplified BT or tolterodine alone. Changes in voiding diary variables were evaluated after 2, 12 and 24 weeks of treatment. The patients' perceptions of their bladder symptoms and tolerability (adverse events) were also determined. RESULTS: In all, 501 patients (75% women) were evaluable on an intention-to-treat basis (244 on tolterodine + BT and 257 on tolterodine alone). Tolterodine significantly reduced the voiding frequency and increased the volume voided per void at all sample times; these effects were significantly increased by adding BT. At the end of the study the median percentage reduction in voiding frequency was greater with tolterodine + BT than with tolterodine alone (33% vs 25%, P < 0.001), while the median percentage increase in volume voided per void was 31% with tolterodine + BT and 20% with tolterodine alone (P < 0.001). There was a median of 81% fewer incontinence episodes than at baseline with tolterodine alone, which was not significantly different from that with tolterodine + BT (- 87%). The two groups had comparable median percentage reductions in urgency episodes. Some 76% of patients on tolterodine + BT reported an improvement in their bladder symptoms relative to baseline, compared with 71% on tolterodine alone. Tolterodine was well tolerated; the most common adverse event was mild dry mouth. CONCLUSION: Tolterodine 2 mg twice daily is an effective and well tolerated treatment for an overactive bladder, the effectiveness of which can be augmented by a simplified BT regimen.     

Efficacy of antimicrobial-impregnated bladder catheters in reducing catheter-associated bacteriuria: a prospective, randomized, multicenter clinical trial

Objectives. To examine the efficacy of bladder catheters impregnated with minocycline and rifampin in reducing catheter-associated bacteriuria.Methods. A prospective, randomized clinical trial was conducted at five academic medical centers. Patients undergoing radical prostatectomy were randomized to receive intraoperatively either regular silicone bladder catheters (control catheters) or silicone bladder catheters impregnated with minocycline and rifampin (antimicrobial-impregnated catheters). Catheters remained in place for a mean of 2 weeks. Urine cultures were obtained at about 3, 7, and 14 days after catheter insertion. Bacteriuria was defined as the growth of organism(s) in urine at a concentration of 10⁴ colony-forming units per milliliter or greater.Results. Kaplan-Meier analysis demonstrated that it took significantly longer for patients (n = 56) who received the antimicrobial-impregnated catheters to develop bacteriuria than those (n = 68) who received the control catheters (P = 0.006 by the log-rank test). Patients who received the antimicrobial-impregnated catheters had significantly lower rates of bacteriuria than those in the control group both at day 7 (15.2% versus 39.7%) and at day 14 (58.5% versus 83.5%) after catheter insertion. Patients who received the antimicrobial-impregnated catheters had significantly lower rates of gram-positive bacteriuria than the control group (7.1% versus 38.2%; P <0.001) but similar rates of gram-negative bacteriuria (46.4% versus 47.1%) and candiduria (3.6% versus 2.9%). The antimicrobial-impregnated catheters provided zones of inhibition against Enterococcus faecalis and Escherichia coli, both at baseline and on removal.Conclusions. Bladder catheters impregnated with minocycline and rifampin significantly reduced the rate of gram-positive catheter-associated bacteriuria up to 2 weeks after catheter insertion.     

Genital nerve stimulation is tolerable and effective for bladder inhibition in sensate individuals with incomplete SCI

Background: Neurogenic detrusor overactivity after spinal cord injury (SCI) causes urinary incontinence and reduces bladder capacity. Surface electrical genital nerve stimulation (GNS) acutely inhibits reflex bladder contractions. The stimulation amplitude selected for GNS is typically twice the amplitude that is required to evoke the pudendal-anal reflex. There is concern about the ability of persons with sensation to comfortably tolerate effective levels of GNS. The objective of this work is to determine if persons with incomplete SCI are able to tolerate acute GNS for bladder inhibition.

Methods: Twenty-four subjects with neurogenic detrusor overactivity, SCI, and pelvic sensation were enrolled in this case series. The setting was the Spinal Cord Injury Service of a Veterans Affairs Medical Center. Primary outcome measures were sensation threshold and tolerable stimulation amplitude; secondary outcome measures were bladder capacity and bladder contraction inhibition.

Results: GNS was tolerable up to 30±16?mA (range 8?mA to ≥60?mA) at amplitudes greater than twice the pudendal-anal (PA) reflex threshold, which was 8±5?mA (range 4?mA to 20?mA). Twelve subjects tolerated GNS at greater than twice the PA, six tolerated 1–1.5 times the PA, and five had no identifiable PA. GNS at tolerable amplitudes inhibited reflexive bladder contractions or increased bladder capacity 135±109?mL (n=23). GNS did not cause autonomic dysreflexia or intolerable spasticity.

Conclusions: GNS is tolerable at amplitudes that effectively inhibit neurogenic detrusor overactivity in individuals with pelvic sensation. GNS therefore is a tool with potential clinical applications for persons with preserved sensation.     

Usefulness of the bladder assist device (BLAD)

We investigated the effectiveness of the Bladder Assist Device on urinary tract infection of patients with indwelling catheters. The patients, except for those with cord bladder and vesicoureteral reflux, could urinate intermittently under the BLAD system. Irrigation of the bladder using BLAD made urine clear and decreased urinary bacteria. Because of intermittent urination in patients who had been using the BLAD system for two weeks, the urine became somewhat clear and the number of bacteria decreased. Combination of bladder irrigation and intermittent urination using this system may inhibit urinary tract infection of an indwelling catheter. BLAD is considered to be a useful device for patients with continuous indwelling catheters.     

Long-term urodynamics followup of bladder augmentation for neurogenic bladder

PURPOSE: Augmentation enterocystoplasty is well tolerated by patients with neurogenic bladder in whom conservative therapy has failed. However, few studies exist on long-term urodynamic evaluation of these patients. We assessed the clinical and urodynamic outcomes of patients with neurogenic bladder treated with augmentation enterocystoplasty with at least 4 years of followup. MATERIALS AND METHODS: A total of 26 patients with neurogenic voiding dysfunction underwent augmentation enterocystoplasty alone or in conjunction with various continence or antireflux techniques. Clinical outcomes regarding incontinence, medications, catheterization schedule, subsequent interventions, bowel function and patient satisfaction were addressed. Urodynamic evaluation was performed to assess the long-term durability of bladder augmentation. RESULTS: Mean followup was 8.0 years (range 4 to 13). All but 1 patient (96%) in our series had near or complete resolution of urinary incontinence. Mean total bladder capacity +/- SD increased from 201 +/- 106 to 615 +/- 204 ml. (p <0.001) and mean maximum detrusor pressure decreased from 81 +/- 43 to 20 +/- 12 cm. H O (p <0.01). Mean interval between catheterizations was 5 hours, with volumes ranging from 314 to 743 ml. Only 2 patients (8%) needed a low dose of oxybutynin postoperatively to maintain continence consistently. Of the 26 patients 23 (88%) reported no significant change in bowel function and nearly all patients expressed extreme satisfaction with urological management. A subsequent urological procedure was required in 12 patients (46%) at a mean of 4.4 years after initial surgery.(2)CONCLUSIONS: Bladder augmentation provides durable clinical and urodynamic improvement for patients with neurogenic bladder dysfunction refractory to conservative therapy. Furthermore, there is a high level of patient satisfaction with bladder augmentation.     

Escherichia coli colonizing the neurogenic bladder are similar to widespread clones causing disease in patients with normal bladder function

Study design:Clonal typing of neurogenic clones.Objective:To determine whether neurogenic clones carried over weeks in the urine of asymptomatic children with neurogenic bladder were similar to known uropathogenic clones associated with disease.Setting:Michigan State University; VA Medical Center, Minneapolis, MN, USA.Methods:Escherichia coli isolates from the urine of 15 children previously followed were typed by multilocus sequence typing and compared to 2 human pyelonephritis genome strains, 29 pediatric or adult symptomatic urinary tract infection strains, 15 pediatric asymptomatic bacteriuria strains, 6 animal urinary tract infection strains and a neonatal meningitis-septicemia prototype K1 strain. Phylotypes and virulence genotypes were determined using PCR.Results:Twenty-nine E. coli isolates were classified into 15 clones. Six of 15 clones were the same sequence type or a close relative to a clone that caused disease in a human or animal. These clones were considered uropathogens. The remaining nine clones were not closely related to a clone that caused disease and were considered commensal clones. Uropathogens were predominantly group B2, exhibited more virulence genes and were carried for more weeks in the neurogenic bladder compared to commensal clones. Nine of 15 children carried one or more uropathogenic clones; 4 children carried one or more commensal clones and 2 children carried both uropathogenic and commensal clones.Conclusion:Children with neurogenic bladder most commonly carried commensal clones. Uropathogenic clones were associated with prolonged carriage, however, carriage was not associated with symptomatic disease or deterioration of the upper urinary tract.Spinal Cord (2008) 46, 633-638; doi:10.1038/sc.2008.60; published online 17 June 2008.     

Present status on bladder replacement--colon bladder replacement]

Bladder replacement using a detubularized right colonic segment was successfully performed on 22 male patients with bladder cancer after radical cystectomy. There were 10 early postoperative complications and one of them required reoperation. Urodynamic studies, performed on 16 patients, showed a low pressure reservoir at a large capacity without any involuntary spikes in every case. Of the 16 patients, 4 were nocturnally enuretic and 1 was partially continent. The other 11 patients (68.8%) were totally continent and voiding well, except one who was on intermittent self-catheterization. The incidence of urinary reservoir infections in patients treated with colon bladder replacement was investigated in 18 patients. The incidence rate of bacteriuria was 5.6% and the positive rate of pyuria was 27.8%. The detection rate of bacteriuria and pyuria was significantly low in patients after colon bladder replacement. These findings indicate that colon bladder replacement can be an ideal option for selected patients with bladder cancer.     

Safety of gentamicin bladder irrigations in complex urological cases

PURPOSE: Recurrent urinary tract infections are common in complex pediatric urological cases, particularly those requiring clean intermittent catheterization. At our institution gentamicin bladder irrigations have been used for antimicrobial prophylaxis and to treat symptomatic bacteriuria, particularly when the infection does not involve the upper urinary tract. The purpose of this study was to assess the safety of this therapy. MATERIALS AND METHODS: A retrospective study was performed of all children treated with gentamicin bladder irrigations from 1999 to 2004. The dose was 14 mg gentamicin in 30 ml saline instilled via catheter once or twice daily. Serum creatinine and random gentamicin levels were obtained according to a protocol based on risk of gentamicin toxicity. Patient demographics, laboratory results and outcomes were abstracted from the medical records. RESULTS: A total of 80 patients (38 males and 42 females) were identified. Median patient age was 10 years and median duration of treatment was 90 days. No patient had detectable serum gentamicin levels greater than 0.4 mg/dl. Small increases in serum creatinine were seen in 3 patients, all of whom had chronic renal insufficiency. A total of 21 patients (26%) had breakthrough UTIs, of which 5 (24%) were gentamicin resistant. No adverse events were documented. CONCLUSIONS: Gentamicin bladder irrigations are a helpful adjunct in the management of complex pediatric urological cases involving recurrent symptomatic bacteriuria. We no longer require intensive laboratory monitoring of low risk patients at our institution.     

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.     

Botulinum toxin type a is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month study

PURPOSE: We determined the safety and efficacy of each of 2 doses of botulinum toxin type A (BTX-A) (200 or 300 U BOTOX) injected into the detrusor for urinary incontinence caused by neurogenic detrusor overactivity of predominantly spinal cord origin. MATERIALS AND METHODS: A total of 59 patients with urinary incontinence caused by neurogenic detrusor overactivity (due to spinal cord injury in 53 and multiple sclerosis in 6) requiring clean intermittent self-catheterization were randomized to receive a single dose into the detrusor of BTX-A (200 U or 300 U) or placebo. Changes in daily frequency of urinary incontinence episodes were monitored via a patient bladder diary during 24 weeks. Key urodynamic assessments (maximum cystometric capacity, reflex detrusor volume and maximum detrusor pressure during bladder contraction) were used to provide objective measures of the treatment effect on bladder function. The impact of treatment on quality of life was assessed using the Incontinence Quality of Life questionnaire. RESULTS: There were significant posttreatment decreases in incontinence episodes from baseline in the 2 BTX-A groups (p 相似文献   

Follow-up of patients treated for urinary bladder calculi

Fifty patients were followed-up for an average of 3 years after treatment for urinary bladder calculi. In 10 of these (20%) altogether 20 metabolic or endocrine diagnoses were revealed at follow-up: hypercalcaemia, 8; hyperuricosaemia, 4; high parathormone, 3; hyperuricosuria, 2; hypercalciuria, 2: hyperoxaluria, 1. About half of the patients also had other diagnoses, dominated by outflow obstruction at the prostatic level, followed by neurogenic bladder disorder. Fifteen had developed new bladder calculi. Urography revealed upper tract calculi in 12 patients, but 11 of these were free from metabolic disorder. Significant bacteriuria was common (24%). Our conclusion is that a follow-up is to be recommended after treatment of bladder calculi. It should include cystoscopy and screening for endocrine/metabolic disorders.     

Bacteriuria management and urological evaluation of patients with spina bifida and neurogenic bladder: a multicenter survey

PURPOSE: We assessed how groups at spina bifida clinics evaluate and manage the urinary tract in patients with spina bifida, neurogenic bladder and bacteriuria. MATERIALS AND METHODS: A survey was mailed to all 169 clinics listed by the Spina Bifida Association of America. Survey items addressed baseline and surveillance evaluation, criteria used to assess urinary tract health and approaches to treatment in patients with spina bifida and neurogenic bladder. RESULTS: Of the 169 clinics personnel at 59 (35%) responded to the survey. Almost half of the respondents had an established protocol or standard of care. At most clinics the use of ultrasound (93%), voiding cystourethrograms (85%) and urodynamic testing (76%) was supported but not renal isotopic studies (14%) or excretory urograms (2%) for baseline evaluation. At all clinics ultrasound was supported for routine surveillance but there was no consensus for other imaging modalities. Assessment of clinic approaches to the evaluation and management of bacteriuria demonstrated variable results, although at most clinics fever, flank pain, dysuria, and changes in urinary pattern were identified as being consistent with true infection. Groups at clinics following their protocol or standard of care showed no significant differences in their approach compared to those at clinics lacking a protocol or standard of care. CONCLUSIONS: No consensus exists for the evaluation and management of bacteriuria in patients with spina bifida and neurogenic bladder at clinics specializing in the care of such patients, even at those with established standards of care. A clear need exists for an established, national set of evidence based guidelines to assist medical decision making in this high risk population and, thus, improve care.     

Functional improvement in spinal cord injury-induced neurogenic bladder by bladder augmentation using bladder acellular matrix graft in the rat

Spinal cord injury (SCI) rostral to the lumbosacral level causes bladder hyperreflexia and detrusor-sphincter dyssynergia (DSD), which are accompanied by bladder hypertrophy. We hypothesize that bladder augmentation using a bladder acellular matrix graft (BAMG) can improve the function of SCI-mediated neurogenic bladder. In female rats (n = 35), SCI was induced by transection of the spinal cord at the lower thoracic level. Eight weeks following spinalization, bladder augmentation using BAMG was performed after hemicystectomy of the hypertrophic bladder. Cystometrography was performed at 8 weeks after spinalization and again at 8 weeks after augmentation. Several urodynamic parameters were measured and the grafted bladder was histologically evaluated. Thirty one rats were alive 8 weeks after spinalization. Twenty two (71%) rats developed hyperreflexic bladders and nine (29%) rats had underactive bladders before bladder augmentation. Twenty six rats survived until 8 weeks after augmentation. Urodynamic parameters showed improvement in some bladder functions in both hyperreflexic and underactive bladders after augmentation. In addition, bladder compliance was increased in hyperreflexic bladders and decreased in underactive bladders. Bladder augmentation decreased bladder capacity in high-capacity rats and increased it in low-capacity rats. Histological evaluation showed complete regeneration of BAMG in SCI-induced neurogenic bladder at 8 weeks after augmentation. This is the first report suggesting that the voiding function in SCI-induced neurogenic bladder can be improved by augmentation using BAMG. Improved voiding function was accompanied by histological regeneration of BAMG.     

Time-dependent effects of castration on the bladder function and histological changes in the bladder and blood vessels

We examined the effect of androgens on bladder blood flow （BBF）, bladder function and histological changes in castrated male rats. Male Wistar rats were classified into unoperated group （control group）, groups castrated at the age of 8weeks （group 8wPC） and groups castrated at the age of 4weeks （group 4wPC）. Each rat was used at the age of 20weeks. BBF was measured using fluorescent microspheres. Bladder cystometry was performed without anesthesia or restraint; the bladder was first irrigated with saline and then with 0.25% acetic acid （AA） solution. Maximum voiding pressure and voiding interval were measured. The bladder and lilac artery were histologically examined for differences in smooth muscle and quantity of collagen fiber to analyze the effect of castration on the smooth muscle content. No differences were noted in BBF following castration. The voiding intervals for all groups were shortened （P 〈 0.001） following AA irrigation. No significant difference was noted in the maximum voiding pressure. Histological changes were observed in bladder and lilac artery. Smooth muscle/collagen ratio at the bladder was lower in groups 8wPC and 4wPC compared to the control group （P 〈 0.01）, while that at the lilac artery was decreased in group 4wPC compared to the control group （P〈 0.001）. In conclusion, our findings indicate that castration does not alter BBF, but leads to histological changes in the bladder as well as its associated blood vessels.     

Nerve growth factor combined with vascular endothelial growth factor enhances regeneration of bladder acellular matrix graft in spinal cord injury-induced neurogenic rat bladder

OBJECTIVE

To determine the combined effects of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) on regeneration of the bladder acellular matrix graft (BAMG) in spinal cord injury (SCI)‐mediated neurogenic bladder in rats.

MATERIALS AND METHODS

In all, 40 female Sprague‐Dawley rats were used. At 8 weeks after spinalization surgery (neurogenic bladder), they were divided into five groups consisting of untreated controls and those whose bladders were injected with either no growth factor, NGF (2 µg/rat), VEGF (2 µg/rat) or both at partial BAMG replacement surgery. After 8 weeks, bladder function was assessed by urodynamic studies and the bladders were harvested for histological examination. Smooth muscle induction, collagen and nerve fibre regeneration were assessed immunohistochemically using antibodies to smooth muscle actin (α‐actin), Masson’s trichrome and protein gene product 9.5, respectively.

RESULTS

Bladder capacity and compliance were significantly increased in all BAMG groups 8 weeks after surgery compared with that before bladder replacement surgery. Bladder capacity and compliance were much higher in the VEGF and NGF combined group than in the control, or NGF and VEGF alone groups. There was no significant difference in the residual volume ratio among all groups.

CONCLUSIONS

This is the first report showing that NGF has a significant synergistic effect on the development, differentiation and functional restoration of the BAMG when administered with VEGF in neurogenic bladder. Our results indicate that NGF may be a useful cytokine for enhancing the regeneration of a functional bladder following acellular matrix grafting in a neurogenic rat model.     

Tolterodine in the treatment of overactive bladder: analysis of the pooled phase II efficacy and safety data

OBJECTIVES: To summarize the efficacy and safety of tolterodine from the pooled data of four multicenter, randomized, double-blind, placebo-controlled, dose-ranging, parallel-group Phase II studies in patients with urodynamically proved overactive bladder (detrusor instability or detrusor hyperreflexia) and to analyze the concentration-effect relation. METHODS: After a 1-week run-in period to establish baseline values, 319 patients were randomized to receive placebo or tolterodine 0.5, 1, 2, or 4 mg twice daily. Micturition diary and urodynamic variables and subjective urinary symptoms were assessed after 2 weeks of treatment. Patients were classified as "extensive" or "poor" metabolizers of tolterodine on the basis of serum levels of tolterodine. RESULTS: A per-protocol analysis of efficacy in 262 patients showed dose-related improvements in micturition diary and urodynamic variables. A dosage of 4 mg twice daily was, however, associated with an increase in residual urinary volume. The incidence of adverse events (mainly mild or moderate antimuscarinic effects) was comparable between placebo and tolterodine dosages of 2 mg twice daily. No serious drug-related adverse events were observed, and tolterodine had no clinically significant impact on electrocardiographic or laboratory findings. Changes in urodynamic variables were found to be related to the sum of unbound serum concentrations of tolterodine and its major active 5-hydroxymethyl metabolite. In poor and extensive metabolizers of tolterodine, exposure to the sum of these active moieties was similar, and the efficacy and safety profiles were comparable. CONCLUSIONS: The results of this pooled data analysis indicate that tolterodine offers an effective treatment for patients with urinary symptoms attributable to overactive bladder. The optimal dosage is 1 to 2 mg twice daily, irrespective of metabolic phenotype.     

Effects of contraceptive pills and intrauterine devices on urinary bladder

The incidence of bacteriuria and cystoscopic changes in women on oral contraceptives or users of IUD (intrauterine devices) were evaluated compared with a control group. Subjects with bacteriuria accounted for 40.5 per cent of pill users, 20 per cent of women fitted with IUD, and 16 per cent of the control group. Bladder trabeculations were found in 50.5 per cent of the pill group, 8.7 per cent of the IUD group, and 8 per cent of the controls. Congested bladder trigone was observed in 24.6 per cent of women fitted with an IUD. The mode of action of ovarian hormones and their possible side effects on the bladder are discussed. The relation of IUD to pelvic inflammatory disease and its effect on the urinary bladder are evaluated.