Is the Bladder a Reliable Witness for Predicting Detrusor Overactivity?

Voiding Dysfunction Is the Bladder a Reliable Witness for Predicting Detrusor Overactivity? H. Hashim* and P. Abrams From the Bristol Urological Institute, Southmead Hospital, Westbury-on-Trym, Bristol, United Kingdom

Purpose: We determined how well the symptoms of OAB syndrome correlate with urodynamic DO using International Continence Society definitions. Materials and Methods: The study included adult males and females 18 years or older who attended a tertiary referral center for urodynamics from February 2002 to February 2004. Patients were selected based on OAB syndrome symptoms (urgency, urgency urinary incontinence and frequency). The percent of patients who had symptoms alone or in combination and DO was calculated. Results: There was a better correlation in results between OAB symptoms and the urodynamic diagnosis of DO in men than in women. Of men 69% and 44% of women with urgency (OAB dry) had DO, while 90% of men and 58% of women with urgency and urgency urinary incontinence (OAB wet) had DO. Stress urinary incontinence seems to have accounted for the decreased rates in women since 87% of women with urgency urinary incontinence also had the symptom of stress urinary incontinence. The ICS definition does not specify what constitutes abnormal voiding frequency. Analysis of results showed that increasing voiding frequency did not have any effect on increasing the accuracy of diagnosis of DO except in women with 10 or more daytime micturition episodes. Conclusions: The bladder is a better and more reliable witness in men than in women with a greater correlation between OAB symptoms and urodynamic DO, more so in the OAB wet than in OAB dry patients. Key Words: bladder, sex characteristics, urodynamics, urinary incontinence

well OAB syndrome symptoms predict urodynamic DO using the new definitions of OAB and OAB symptoms in men and women from the same population group. To our knowledge this is the first and largest study to evaluate this association using the new definition.

he standardization subcommittee of the ICS in its latest report (February 2002) defined OAB syndrome1 as urgency with or without urge incontinence, usually with frequency and nocturia, if there is no proven infection or other obvious pathological condition. OAB is also known as the urgency syndrome or urgency-frequency syndrome. These symptom combinations are suggestive of urodynamically demonstrable DO and almost all treatments for OAB assume this causation. OAB is a symptomatic diagnosis, while DO is an urodynamic observation defined by involuntary detrusor contractions during the filling phase, which may be spontaneous or provoked.1 A previous study in male patients has shown that 75% with urgency incontinence but only 44% with frequency and urgency had DO.2 In another study of female patients 54.2% with OAB symptoms had DO.3 These studies were done before the new ICS report was published and, thus, they were based on older definitions of urgency (strong desire to void accompanied by fear of leakage or fear of pain) and urge urinary incontinence (involuntary loss of urine associated with a strong desire to void). They included male or female patients but not male and female patients. According to the new definition OAB symptoms are suggestive of DO, although the definition does not specify the actual correlation between OAB and DO. We defined how

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MATERIALS AND METHODS All UDS were done at a specialist referral center performing about 20 to 25 UDS tests weekly in male and female children and adults who undergo standard, video or ambulatory UDS. All patients are sent a 7-day frequency/volume chart, which must be completed before attending for the UDS test. Those on antimuscarinics are instructed to stop ingesting them 1 week prior to attending for the test, thus, providing a washout period and avoiding any interference with test results. An 8Fr filling catheter beside an epidural catheter or a 6Fr double lumen catheter is used to measure vesical pressure. There is no evidence that 1 technique is superior to the other. However, using a double lumen catheter allows bladder filling and refilling. The 2 catheter technique is less expensive and seems to provide more accurate measurement of urethral pressure profiles, which is routinely done in all of our patients. During voiding the filling catheter is removed and the epidural catheter is kept in the bladder to measure vesical pressure. Abdominal pressure is measured with a rectal catheter using a 6Fr manometer tubing covered with a finger stall from a nonsterile surgical rubber glove to prevent blockage by feces. A cut is made in the finger stall and the tube is inserted into the rectum to a distance approximately 10 cm from the anal mar-

Submitted for publication April 5, 2005. * Correspondence: Bristol Urological Institute, Southmead Hospital, Westbury-on-Trym, Bristol, BS10 5NB, United Kingdom (telephone: ⫹44 117 959 5690; FAX: ⫹44 117 950 2229; e-mail: [email protected]).

0022-5347/06/1751-0191/0 THE JOURNAL OF UROLOGY® Copyright © 2006 by AMERICAN UROLOGICAL ASSOCIATION

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Vol. 175, 191-195, January 2006 Printed in U.S.A. DOI:10.1016/S0022-5347(05)00067-4

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gin. Filling is done in men while standing and women while sitting at a rate of 50 ml per minute using normal saline solution at room temperature for standard UDS and iodine based contrast medium for video UDS. All UDS information, including patient demographics, medical history, examination, urinalysis, urine free flow rate, post-void residual volume, results of the filling and voiding phases, and bladder capacity, are entered during the test onto the hospital medical database. For study purposes the UDS database was converted into Microsoft® Access to make it easily accessible and more usable. All UDS investigations were done according to the ICS good urodynamics practices protocol.4 All investigators have obtained a certificate in UDS following attendance at the Certificate in Urodynamics course. Inclusion criteria were male and female adults 18 years or older with at least 1 OAB symptom from February 2002 to February 2004 (see Appendix). Patients who reported only UUI and no urgency were assumed to have urgency by definition. Patients with frequency alone or nocturia alone were not considered to have OAB. Patient traces were examined to see if DO was present. Data were first analyzed by looking at patients with all 4 symptoms of OAB. The definition of F that was used was 7 or greater micturition episodes, which was an arbitrary number since the definition of OAB does not specify a threshold number of micturitions. Data were further analyzed using different cutoff points for frequency, namely 8 or greater, 9 or greater, or 10 or greater, to see if that made any difference to the predictability of DO from OAB symptoms. Nocturia, which has a multifactorial etiology, was excluded from this subsequent analysis. Fisher’s exact and the chi-square test were used to determine p values. It was desirable to discover which of the predictor variables (urgency, UUI, frequency and nocturia) are significant predictors of DO in men and women in the presence of the other variables. A logistic regression modeling selection process was done with DO as the outcome variable and the 4 symptoms as possible predictor variables. Combining the 3 predictor variables urgency, UUI and nocturia into a model gave the OR and CI of each variable, allowing for the influence of the other 2 variables. In women further analysis was done to see if OAB wet women also had stress incontinence. RESULTS A total of 1,809 patients underwent urodynamics in the specified period, including 474 men with a median age of 61 years (mean 59) and 1,335 women with a median age of 53

Flowchart shows patients with and without OAB and DO

TABLE 1. Urgency, UUI and nocturia vs effect of other 2 predictor variables in men and women Symptom Men: Urgency UUI Nocturia Women: Urgency UUI Nocturia

OR

95% CI

p Value

2.75 2.06 2.32

1.56–4.85 1.14–3.72 1.31–4.11

⬍0.001 0.016 0.004

9.03 1.73 1.49

4.90–16.64 1.11–2.70 1.09–2.04

⬍0.001 0.015 0.012

years (mean 53). Of these patients only 1,415 had complete storage symptom data entries available in the database of urgency, UUI, frequency and nocturia. When nocturia was excluded from analysis, 1457 of the 1,809 patients (80%) were included in the study because they had complete storage symptoms data entries available in the database of urgency, UUI and frequency. The other 352 patients had 1 or more missing data on the database and, thus, they were excluded from analysis. Of the 1,457 patients 1,076 had OAB symptoms and 381 had no OAB symptoms (see figure). Further data analysis was done to examine men and women separately. When nocturia was included in the analysis of men, a higher significant percent with urgency had DO than those without urgency (78.6% vs 46.5%, p ⬍0.001), a higher significant percent with UUI had DO than those without UUI (84.2% vs 59.8%, p ⬍0.001), a higher significant percent with frequency had DO than those without frequency (75.1% vs 64.9%, p ⫽ 0.033) and a higher significant percent with nocturia had DO than those without nocturia (74.1% vs 51.5%, p ⬍0.001). These results were for symptoms occurring alone or in combination with each other. Similar results were obtained in women. A higher significant percent with urgency had DO than those without urgency (58.2% vs 8.2%, p ⬍0.001), a higher significant percent with UUI had DO than those without UUI (59.8% vs 17.9%, p ⬍0.001), a higher significant percent with frequency had DO than those without frequency (49.6% vs 42.2%, p ⬍0.018) and a higher significant percent with nocturia had DO than those without nocturia (50.7% vs 34.1%, p ⬍0.001). In men and women it was found that urgency, UUI and nocturia were significant predictor variables of DO in the presence of each other but once urgency, UUI and nocturia were included in a model. Adding frequency as a fourth predictor did not significantly improve the model prediction of DO (table 1). Therefore, the final DO model included only urgency, UUI and nocturia as predictors. Further analysis was done to assess whether increasing frequency made a difference to the diagnostic value and association between OAB and DO in men and women (table 2). Nocturia was excluded from this analysis since it was already shown that it is an important predictor of DO. Of men with urgency alone 69% had DO, which seemed to increase with additional symptoms. In men for all of the daytime frequencies of 7 or greater, 8 or greater, 9 or greater and 10 or greater it was found that a significantly higher percent who were OAB dry and OAB wet had DO compared to those with no OAB symptoms or frequency alone (p ⬍0.05 and ⬍0.01, respectively). It was also found that there was a significant difference between having DO and not having DO when frequency was used as a predictor variable. How-

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TABLE 2. Men and women with DO who had OAB symptoms with different voiding frequencies, excluding nocturia ⬍ % DO Men (No. voids)

⬍ % DO Women (No. voids)

Storage Symptoms

7 or Greater

8 or Greater

9 or Greater

10 or Greater

7 or Greater

8 or Greater

9 or Greater

10 or Greater

No OAB symptoms F only Urgency only Urgency & F Urgency & UUI Urgency, F & UUI

39 58 69 72 90 82

43 58 71 71 85 84

46 59 70 72 81 88

45 63 69 76 82 89

31 28 44 46 58 61

31 27 51 43 56 64

30 27 49 43 57 66

29 33 47 45 58 67

ever, the model with only urgency and UUI as predictors was not significantly improved by also including frequency as a predictor. Thus, the best model had only urgency and UUI as predictor variables (table 3). In women 44% of those with urgency alone had DO and it also increased gradually with additional symptoms. For all daytime frequencies it was found that a significantly higher percent of patients who were OAB wet had DO compared to those with no OAB. Unlike men, when frequency was used as a single predictor variable of DO in women, it was only when frequency was 9 or greater and 10 or greater that a significant difference was observed (p ⫽ 0.031 and 0.007, respectively). There appeared to be a trend toward more significant p values when frequency was the single variable predicting DO since the cutoff increased and it was a better predictor of DO when higher cutoff values (10 rather than 7) were used. Also, in females when the cutoff was 10, frequency remained in the best model found to predict DO along with urgency and UUI, whereas for lower cutoffs this was not the case (table 3). When women with stress incontinence were excluded from analysis, between 19% and 30% with frequency alone had DO and, thus, frequency remained a poor predictor of DO.

TABLE 3. Single OAB symptom, excluding nocturia as DO predictor in presence of other 2 variables in men and women Frequency (symptom)

OR

95% CI

p Value

2.19 2.67

1.23–3.89 1.54–4.61

0.008 ⬍0.001

2.19 2.67

1.23–3.89 1.54–4.61

0.008 ⬍0.001

2.19 2.67

1.23–3.89 1.54–4.61

0.008 ⬍0.001

2.19 2.67

1.23–3.89 1.54–4.61

0.008 ⬍0.001

1.83 1.95

1.18–2.84 1.20–3.18

0.007 0.007

1.74 2.04

1.12–2.70 1.25–3.32

0.013 0.004

1.74 2.04

1.12–2.70 1.25–3.32

0.013 0.004

1.79 1.94 1.34

1.15–2.78 1.19–3.17 1.00–1.79

0.010 0.008 0.048

Men 7 or Greater: UUI Urgency 8 or Greater: UUI Urgency 9 or Greater: UUI Urgency 10 or Greater: UUI Urgency

Women 7 or Greater: UUI Urgency 8 or Greater: UUI Urgency 9 or Greater: UUI Urgency 10 or Greater: UUI Urgency F

Overall it was found that 82% of men with OAB had DO (sensitivity) and 82% with DO had OAB (positive predictive value), while 58% of women with OAB had DO (sensitivity) and 85% with DO had OAB (positive predictive value). Also, 87% of women who were OAB wet had SUI symptoms with 52% having USI. Therefore, 13% of women who had UUI had no SUI symptoms but 2% had USI. Of women who had UUI and DO 86% also had SUI with 46% having USI. Of women who had UUI and DO 14% had no symptoms of SUI but 2% had USI. DISCUSSION The ICS definition of frequency does not specify the actual number of voiding frequencies that should be included for OAB symptoms. Previous studies have shown that normal daytime voiding frequency is between 6 and 8 depending on age5 and voiding frequencies greater than 8 become bothersome.6 During the initial analysis of this study we used 7 or greater daytime voiding frequency episodes for the analysis. We subsequently used 8 or greater, 9 or greater and 10 or greater to see if that improved the diagnosis of DO and determine if a cutoff point for frequency could be used for the definition of OAB. In men and women when symptoms were used in combination, only urgency, UUI and nocturia significantly increased the prediction of DO and frequency did not add any further significant information. This was evident when all 4 OAB symptoms were used at a micturition frequency of 7 or greater. Similar findings were also demonstrated by a selfreported mail questionnaire in women, which showed that frequency is univariately weakly predictive of DO but not significant in a multivariate model with urgency, incontinence and nocturia.7 This may seem to be contradicting the results obtained when nocturia was included in the analysis, which showed that frequency was a significant predictor of DO as a single entity at all levels. However, the reason for the difference is that there were fewer patients diluted over more categories when nocturia was included, resulting in fewer patients per category. Overall frequency alone is a poor predictor of DO in patients with OAB but a better one in men than women. The study also showed that about 90% of men but only 58% of women who were OAB wet had DO at an F of 7 or greater. The result in men was higher than previously reported in the literature, while that in women was only slightly higher. This may partly be due to the referral pattern at our center with more patients with OAB being referred for urodynamics. The difference between the proportions in men and women was also present at higher frequency cutoff points and in different combinations with UUI. Why is there a

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difference between men and women? The reason for this appears to be that mixed incontinence complicates matters in women. Women often experience SUI and UUI (mixed incontinence), making it difficult to differentiate the 2 conditions, while men rarely experience SUI. This study also raises the issue of the reproducibility of symptoms in UDS since about 40% of men and 30% of women with no OAB symptoms had DO on UDS, which may have been because urgency is experienced differently by different patients and, thus, their symptoms are conveyed in different ways. There is a great need for a validated urgency scale that measures urgency rather than bladder sensation, which the current urgency scales measure.8 Also, in patients with OAB symptoms a negative UDS result may be due to failure to reproduce symptoms. Therefore, it is important to inquire about the reproduction of symptoms during UDS and correlate this with findings during the test. From a clinical and practical point of view the most important point before urodynamics is to enquire about, and treat the most bothersome patient symptom. UDS should be done only if it is going to change patient treatment since treatment is initiated on a symptomatic diagnosis in most patients with OAB or help differentiate the etiology of voiding dysfunction, or

if it is done after failed conservative/medical treatment.9 If standard UDS fails to reproduce symptoms, referral for ambulatory UDS may be considered when available. The most important question that this study raises is whether the definition of OAB should be revised to exclude frequency or whether it should include an actual frequency value, ie 10 or greater. This question must to be answered by epidemiological studies that include men and women. CONCLUSIONS To our knowledge this study is the first and largest one to evaluate the correlation between OAB symptoms and urodynamic DO since the publication of the new definition of OAB. It is also the first to involve men and women investigated at the same department serving urology and gynecology. The definition of OAB based on urgency is the best one that we currently have for predicting patients with DO and it is a better predictor in men than in women. Frequency seems to be a poor predictor of DO and it does not add any diagnostic value in patients with symptoms of urgency, UUI and nocturia. This observation would probably need to be verified by epidemiological studies involving men and women.

APPENDIX Definition of OAB Symptoms Symptom

Definition

Urgency UUI Increased F Nocturia

The The The The

complaint complaint complaint complaint

of a sudden compelling desire to pass urine, which is difficult to defer (OAB dry) of involuntary leakage accompanied by or immediately preceded by urgency (OAB wet) by the patient who considers that he/she voids too often by day that the individual has to wake at night 1 or more times to void

Abbreviations and Acronyms DO F ICS OAB SUI UDS USI UUI

⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽ ⫽

detrusor overactivity daytime frequency International Continence Society overactive bladder stress urinary incontinence urodynamics urodynamic stress incontinence urge urinary incontinence

REFERENCES 1. Abrams, P., Cardozo, L., Fall, M., Griffiths, D., Rosier, P., Ulmsten, U. et al: The standardisation of terminology of lower urinary tract function: report from the Standardisation Subcommittee of the International Continence Society. Neurourol Urodyn, 21: 167, 2002 2. Hyman, M. J., Groutz, A. and Blaivas, J. G.: Detrusor instability in men: correlation of lower urinary tract symptoms with urodynamic findings. J Urol, 166: 550, 2001 3. Digesu, G. A., Khullar, V., Cardozo, L. and Salvatore, S.: Overactive bladder symptoms: do we need urodynamics? Neurourol Urodyn, 22: 105, 2003 4. Schafer, W., Abrams, P., Liao, L., Mattiasson, A., Pesce, F., Spangberg, A. et al: Good urodynamic practices: uroflowmetry, filling cystometry, and pressure-flow studies. Neurourol Urodyn, 21: 261, 2002 5. Van Haarst, E. P., Heldeweg, E. A., Newling, D. W. and Schlatmann, T. J.: The 24-h frequency-volume chart in adults reporting no voiding complaints: defining reference values and analysing variables. BJU Int, 93: 1257, 2004

6. Swithinbank, L. and Abrams, P.: Lower urinary tract symptoms in community-dwelling women: defining diurnal and nocturnal frequency and ‘the incontinence case’. BJU Int, suppl., 88: 18, 2001 7. Matharu, G., Donaldson, M. M. K., McGrother, C. W. and Matthews, R. J.: Relationship between urinary symptoms reported in a postal questionnaire and urodynamic diagnosis. Neurourol Urodyn, 24: 100, 2005 8. Chapple, C. R., Artibani, W., Cardozo, L. D., Castro-Diaz, D., Craggs, M., Haab, F. et al: The role of urinary urgency and its measurement in the overactive bladder symptom syndrome: current concepts and future prospects. BJU Int, 95: 335, 2005 9. Colli, E., Artibani, W., Goka, J., Parazzini, F. and Wein, A. J.: Are urodynamic tests useful tools for the initial conservative management of non-neurogenic urinary incontinence? A review of the literature. Eur Urol, 43: 63, 2003

EDITORIAL COMMENT These authors present a robust review of urodynamic findings in patients referred to their specialty clinic who would meet the new definition of OAB, as defined by the ICS in 2002. As the authors mention, prior studies demonstrated that conventional urodynamic testing is neither sensitive nor specific with respect to cystometric detrusor overactivity and the subjective symptoms of overactive bladder. The authors examined each of the components of OAB (urgency, and urge incontinence) and their correlation with demonstrable detrusor overactivity in a univariate and multivariate manner. They conclude that urinary frequency, except

OVERACTIVE BLADDER SYNDROME AND URODYNAMIC DETRUSOR OVERACTIVITY when severe, does not correlate with DO as well as urgency and urge incontinence. Although few, there are some limitations to the study, primarily related to the specialized nature of their practice. Are these referred patients with refractory disease and would the prevalence of detrusor overactivity in a community practice be less? While the comments regarding correlations between urinary frequency and DO are certainly founded, the elimination of urinary frequency from the definition of OAB is not. This will be a

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valuable reference correlating the subjective and objective parameters of OAB. Erin T. Bird Division of Urology Department of Surgery Scott and White Hospital Texas A and M Health Science Center Temple, Texas