Original Paper Urol Int 1992:48:42-47
Division o f Urology. Stanford University School o f Medicine, Calif., USA
Pharmacologic T reatment of Detrusor Incontinence with Thiphenamil HCI
KeyWords
Abstract
Urodynamics Bladder Isometrics Continence Stability
A controlled double-blind crossover study is reported in which quantitative urodynamic data and qualitative information are combined to evaluate the treatment o f detrusor incontinence using thiphenamil HCI in patients with detrusor instability. Patients placed on the treatment protocol were randomized to placebo or thiphenamil 400 mg q.i.d. Two weeks o f thiphenamil HCI or placebo administration were followed by 1 week o f washout followed by a cross-over to an additional 2 weeks o f placebo or thiphenamil HCI administration. O f the 23 patients 7 dropped out at various stages o f the study. The mean age o f patients studied was 44 ± 14 years old. Throughout the study, patients were asked to complete a formalized diary card of the amount and time o f voiding and the incidence o f incontinence. Three urodynamics stud ies were done in the following sequence: pretreatment, postwashout, and posttreatment. Parameters o f bladder capacity, sensations, stability and pressure/flow were obtained. In addition, resting urethral closure pressures were recorded. The results show that the fre quency o f incontinence, which was based on the patients’ responses, decreased significantly (0.01 < p < 0.025). There was an insignificant decrease in the number o f voidings and increase in the amount voided each time. Patients on thiphenamil reported that their pads were significantly drier from baseline (p = 0.01). In response to questions comparing prob lems caused by urine loss during baseline and thiphenamil treatment, analysis shows a signif icant decrease o f problems due to loss o f urine (p = 0.01) when the patient was taking the drug compared to the placebo. Evaluation o f urodynamic parameters shows a significant reduc tion in detrusor voiding pressure from 46.1 ± 25.3 to 31.9 ± 14.1 (p = 0.05). N o significant changes were observed in the flow rate, capacity, urethral resting or opening pressure or blad der work. Residual volume during urodynamics was lower on thiphenamil HCI but this dif ference was marginally significant. It is concluded that patients reported that thiphenamil HCI produced a significant decrease in their frequency and amount o f incontinence. This conclusion is based on the documentation available in the diary cards and questionnaire. The urodynamic studies do not, as a whole, reflect an objective numerical improvement in many o f the parameters considered.
Introduction
The majority of patients complaining of urinary incon tinence have an unstable bladder during filling and do not have stress incontinence [1-3]. In addition, a large per
Received: December 24. 1990 Accepted: January 29. 1991
centage of patients [3] with stress urinary incontinence also have detrusor instability. These patients are best treated pharmacologically since the success rate of surgi cal intervention in detrusor incontinence is low [4-8]. As a consequence, the search for pharmacologic agents that
C.E. Constantinou. PhD Division o f Urology. S-287. Stanford University Medical Center. 300 Pasteur Drive Stanford. C*A 94305-5118 (U SA)
© 1992 S. Karger AG. Basel 0042-1138/92/0481-0042 $2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 10:21:35 AM
C.E. Constantinou
Methods Patients A total o f 23 women were enrolled in this study which was carried out with institutional approval for protection o f human subjects in research. Patients referred for consideration in this protocol had a prior physical examination and history at which time stress urinary incontinence was excluded as a cause o f incontinence. Patients likely to get pregnant, those suffering from heart disease, interstitial cysti tis, congenital anomalies, urinary tract infections and diabetes were excluded.
Drug Protocol The order o f thiphenamil HC1 or placebo administration was ran domized. Patients starting with thiphenamil HC1 during the first 2 weeks had placebo during the concluding 2 weeks. Similarly, patients starting with placebo during the first 2 weeks concluded with thi phenamil HCI during the last 2 weeks. The order in which placebo or thiphenamil HCI was administered made no difference in patient evaluation. The 2 weeks o f thiphenamil HCI or placebo administra tion were followed by 1 week o f washout, subsequently followed by an additional 2 weeks o f placebo or thiphenamil HCI. With this scheme, patients were randomized to placebo/thiphenamil HCI 400 mg q.i.d. O f the 23 patients who started in this protocol, 7 dropped out at various stages o f the study. The mean age o f patients evaluated was 44 ± 14 years old. The patients were asked to keep a diary o f their continence status, which was used to subjectively evaluate their progress through the study.
Subjective Evaluation o f incontinence Patients documented the frequency o f voiding, amount voided, and frequency o f incontinence on diary cards. A two-sample t test was performed to test the significance o f the data changes provided from the diary. In addition to the diary cards, a questionnaire was used to charac terize incontinence and voiding habits. The data were analyzed using the McNemar’s test: twosamplc tests for binomial proportions for matched-pair data performed for the yes/no questions. The other questions based on a ranking scale were analyzed using the Wilcoxon Rank Sum test. Subjective evaluation data arc given as mean and standard error. Numerical results from urodynamics were computed using the paired t test available through SPSS software package. Val ues given arc mean ± standard deviations, median and range for the urodynamics data.
Urodynamic Pool Pretreatment, postwashout, and posttreatment urodynamic eval uations incorporating the following specific tests were then per formed: (a) catheter-free urine flow rate, (b) resting urethral pressure profile, (c) filling cystometrogram (CMG), and (d) pressure/flow study during voiding. The profile was obtained with the patient in the supine position while the CMG was obtained with the patient sitting on a commode. Specificially. each test consists o f the follow ing. (a) Catheter-free flow was obtained upon the patient’s arrival in the urodynamics laboratory before any invasive monitoring. Sub jects were instructed to arrive with a full bladder. Prior to catheter ization. each patient voided on a commode outfitted with a DISA 14F5 urine flow meter. Residual urine was measured after uroflowmetry. (b) The resting urethral pressure profile. The empty bladder was filled with 100 ml o f saline. A dual microtip transducer was passed with two pressure sensors located 5 cm from the tip o f the catheter. These sensors were located diametrically opposite each other (thereby recording anterior and posterior closure). The trans ducers were pulled externally from the bladder at a rate o f 1.0 mm/s, using a mechanical stepper motor puller, (c) Filling (CMG). A dou ble-lumen 10-french catheter was passed into the bladder via the ure thra. One lumen was used to fill the bladder and the other was con nected to a pressure transducer to measure intravesical pressure [P(vcs)l- Intra-abdominal pressure [P (abd)l was measured using a pres sure sensor attached to a water-filled balloon catheter and passed into the rectum. Detrusor pressure [P(det)] was estimated by subtraction of P(ab
Division o f Urology. Stanford University School o f Medicine, Calif., USA
Pharmacologic T reatment of Detrusor Incontinence with Thiphenamil HCI
KeyWords
Abstract
Urodynamics Bladder Isometrics Continence Stability
A controlled double-blind crossover study is reported in which quantitative urodynamic data and qualitative information are combined to evaluate the treatment o f detrusor incontinence using thiphenamil HCI in patients with detrusor instability. Patients placed on the treatment protocol were randomized to placebo or thiphenamil 400 mg q.i.d. Two weeks o f thiphenamil HCI or placebo administration were followed by 1 week o f washout followed by a cross-over to an additional 2 weeks o f placebo or thiphenamil HCI administration. O f the 23 patients 7 dropped out at various stages o f the study. The mean age o f patients studied was 44 ± 14 years old. Throughout the study, patients were asked to complete a formalized diary card of the amount and time o f voiding and the incidence o f incontinence. Three urodynamics stud ies were done in the following sequence: pretreatment, postwashout, and posttreatment. Parameters o f bladder capacity, sensations, stability and pressure/flow were obtained. In addition, resting urethral closure pressures were recorded. The results show that the fre quency o f incontinence, which was based on the patients’ responses, decreased significantly (0.01 < p < 0.025). There was an insignificant decrease in the number o f voidings and increase in the amount voided each time. Patients on thiphenamil reported that their pads were significantly drier from baseline (p = 0.01). In response to questions comparing prob lems caused by urine loss during baseline and thiphenamil treatment, analysis shows a signif icant decrease o f problems due to loss o f urine (p = 0.01) when the patient was taking the drug compared to the placebo. Evaluation o f urodynamic parameters shows a significant reduc tion in detrusor voiding pressure from 46.1 ± 25.3 to 31.9 ± 14.1 (p = 0.05). N o significant changes were observed in the flow rate, capacity, urethral resting or opening pressure or blad der work. Residual volume during urodynamics was lower on thiphenamil HCI but this dif ference was marginally significant. It is concluded that patients reported that thiphenamil HCI produced a significant decrease in their frequency and amount o f incontinence. This conclusion is based on the documentation available in the diary cards and questionnaire. The urodynamic studies do not, as a whole, reflect an objective numerical improvement in many o f the parameters considered.
Introduction
The majority of patients complaining of urinary incon tinence have an unstable bladder during filling and do not have stress incontinence [1-3]. In addition, a large per
Received: December 24. 1990 Accepted: January 29. 1991
centage of patients [3] with stress urinary incontinence also have detrusor instability. These patients are best treated pharmacologically since the success rate of surgi cal intervention in detrusor incontinence is low [4-8]. As a consequence, the search for pharmacologic agents that
C.E. Constantinou. PhD Division o f Urology. S-287. Stanford University Medical Center. 300 Pasteur Drive Stanford. C*A 94305-5118 (U SA)
© 1992 S. Karger AG. Basel 0042-1138/92/0481-0042 $2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 10:21:35 AM
C.E. Constantinou
Methods Patients A total o f 23 women were enrolled in this study which was carried out with institutional approval for protection o f human subjects in research. Patients referred for consideration in this protocol had a prior physical examination and history at which time stress urinary incontinence was excluded as a cause o f incontinence. Patients likely to get pregnant, those suffering from heart disease, interstitial cysti tis, congenital anomalies, urinary tract infections and diabetes were excluded.
Drug Protocol The order o f thiphenamil HC1 or placebo administration was ran domized. Patients starting with thiphenamil HC1 during the first 2 weeks had placebo during the concluding 2 weeks. Similarly, patients starting with placebo during the first 2 weeks concluded with thi phenamil HCI during the last 2 weeks. The order in which placebo or thiphenamil HCI was administered made no difference in patient evaluation. The 2 weeks o f thiphenamil HCI or placebo administra tion were followed by 1 week o f washout, subsequently followed by an additional 2 weeks o f placebo or thiphenamil HCI. With this scheme, patients were randomized to placebo/thiphenamil HCI 400 mg q.i.d. O f the 23 patients who started in this protocol, 7 dropped out at various stages o f the study. The mean age o f patients evaluated was 44 ± 14 years old. The patients were asked to keep a diary o f their continence status, which was used to subjectively evaluate their progress through the study.
Subjective Evaluation o f incontinence Patients documented the frequency o f voiding, amount voided, and frequency o f incontinence on diary cards. A two-sample t test was performed to test the significance o f the data changes provided from the diary. In addition to the diary cards, a questionnaire was used to charac terize incontinence and voiding habits. The data were analyzed using the McNemar’s test: twosamplc tests for binomial proportions for matched-pair data performed for the yes/no questions. The other questions based on a ranking scale were analyzed using the Wilcoxon Rank Sum test. Subjective evaluation data arc given as mean and standard error. Numerical results from urodynamics were computed using the paired t test available through SPSS software package. Val ues given arc mean ± standard deviations, median and range for the urodynamics data.
Urodynamic Pool Pretreatment, postwashout, and posttreatment urodynamic eval uations incorporating the following specific tests were then per formed: (a) catheter-free urine flow rate, (b) resting urethral pressure profile, (c) filling cystometrogram (CMG), and (d) pressure/flow study during voiding. The profile was obtained with the patient in the supine position while the CMG was obtained with the patient sitting on a commode. Specificially. each test consists o f the follow ing. (a) Catheter-free flow was obtained upon the patient’s arrival in the urodynamics laboratory before any invasive monitoring. Sub jects were instructed to arrive with a full bladder. Prior to catheter ization. each patient voided on a commode outfitted with a DISA 14F5 urine flow meter. Residual urine was measured after uroflowmetry. (b) The resting urethral pressure profile. The empty bladder was filled with 100 ml o f saline. A dual microtip transducer was passed with two pressure sensors located 5 cm from the tip o f the catheter. These sensors were located diametrically opposite each other (thereby recording anterior and posterior closure). The trans ducers were pulled externally from the bladder at a rate o f 1.0 mm/s, using a mechanical stepper motor puller, (c) Filling (CMG). A dou ble-lumen 10-french catheter was passed into the bladder via the ure thra. One lumen was used to fill the bladder and the other was con nected to a pressure transducer to measure intravesical pressure [P(vcs)l- Intra-abdominal pressure [P (abd)l was measured using a pres sure sensor attached to a water-filled balloon catheter and passed into the rectum. Detrusor pressure [P(det)] was estimated by subtraction of P(ab
