Is a sequence of tests during urethral pressure profi lometry correlated with symptoms assessment in women ?

ARTICLE INFO _________________________________________________________ ___________________ IBJU | STANDARDIZED URETHRAL PROFILOMETRY IN WOMEN AND SYMPTOMS ASSESSMENT 810 of tests. UPP is always performed by the same two nurses and the tests always performed following the same sequence. If it is not observed any alteration of the MUCP value at rest, we search for a correlation between the patient complaints and MUCP value changes following dynamic tests. Is the MUCP value at rest reproducible during a session whatever the patient complaints are? Do the changes in MUCP values during different dynamic tests provide information on the lower urinary tract dysfunction? The aim of this retrospective study was to try to give an answer to these questions. MATERIALS AND METHODS Population The studied population consisted of 140 consecutive women without neurological disease or/and pelvic organ prolapse of grade > 2 (mean age 56.8 ± 15.5 years [21-90 years]) referred for evaluation of lower urinary tract dysfunction (June 2007 to March 2009). Each woman completed a 3-day frequency-volume chart and the ICIQ-UI-SF before the urodynamic testing; this allowed a stratifi cation of the population in four groups according with the symptoms: continent, with stress incontinence, urge incontinence, or mixed incontinence. The continent women complained of urgency or pain. Stress incontinence is defi ned as involuntary leakage of urine following effort or exertion, including sneezing or coughing; urge incontinence is defi ned as the involuntary leakage accompanied by or immediately preceded by urgency, and mixed incontinence as the involuntary leakage associated with stress and urge conditions (12). A second stratifi cation was made according to age: less than 45 years old (before menopause), 45 to 65 years old (menopausal transition) and above 65 years old (long term menopause). In France, the mean age for menopause is 50 years. This study was conducted in accordance with the Declaration of Helsinki. According to the local practice of our Ethics Committee, there is no formal Institutional Review Board approval required for retrospective studies performed with the usual procedure of investigation. Urodynamic session A urodynamic session included the following tests: 1) free urofl owmetry at arrival; 2) UPP with empty bladder (supine position) before fi lling cystometry and pressure fl ow study (seating); 3) UPP bladder fi lled with 250 mL (or less, in cases of detrusor overactivity, at normal desire to void) with saline at room temperature (supine position except for standing recording) and 4) free urofl owmetry. Cystometry (fi lling rate 50 mL/min.) and UPP were performed using a 7F triple lumen water perfusion catheter. Pressures were zeroed to atmosphere with the transducers placed at the level of the upper edge of the pubic symphysis. All urodynamic studies were performed using a Dorado® unit from Laborie and conducted by two nurses who applied our protocol. Urodynamic testing was performed according with Good Urodynamic Practices (13) and, during cystometry, women were asked to cough during fi lling at 100 mL intervals to ensure that pressure signals responded equally. Urethral protocol: For UPP the puller speed was set to 1 mm/s except for standing recording when the catheter was pulled manually (14). The distal eye-hole was kept in the lateral position and the catheter position observed during the test to avoid change in orientation. The sequence of test was: (1) UPP at rest; (2) Kegel manoeuvre at MUCP; (3) UPP with 3 to 5 successive coughs (stress profi le); (4) VLPP; (5) UPP before 10 successive strong coughs and (5’) after (fatigability test), then (6) UPP was recorded in standing position. Recordings All MUCP values were reviewed independently by 2 investigators. Good agreement occurred in up to 88% of the fi les. In the remaining 12%, an additional interpretation was made jointly to reach a single conclusion. Comparisons MUCP value at rest (empty bladder) (P1) was compared with (P0), (P3), (P5), (P5’) and (P6) according with the continence status in the whole population and in the age groups. The relevant MUCP value (P3) was the value obtained after maIBJU | STANDARDIZED URETHRAL PROFILOMETRY IN WOMEN AND SYMPTOMS ASSESSMENT 811 nual smoothing of the stress profi le in order to exclude the spikes due to cough efforts. Statistical analysis The numerical data are described by means and standard deviation and categorical data as percentages. The Wilcoxon signed rank test was used for comparison of related samples, analysis of variance and the Chi 2 test to compare unrelated samples. Statistical analysis was performed using SAS, version 5.0 (SAS Institute, Inc., Cary, NC). All statistical results were considered signifi cant at p < 0.05. Reproducibility The Bland-Altman plot (15) (difference vs. mean plot) was used to show the agreement between the two measurements of MUCP during resting profi le (empty bladder).


INTRODUCTION
Controversies about the role of urethral pressure profi lometry (UPP) in clinical practice (1)(2)(3) are mainly based on the reproducibility of the measurements and on the lack of standardization (4).
Other main controversies are related to the predictive value of the preoperative maximum urethral closure pressure (MUCP) and the success of the surgery of stress incontinence (5)(6)(7)(8)(9) and the postoperative quality of life (10).Conversely, De Lancey (11) found that MUCP was the most characteristic parameter of stress incontinence.
In our urodynamic laboratory, we have defi ned a strict protocol for UPP which is routinely applied in order to rule out many causes of variability.It consists of a well-defi ned sequence of tests.UPP is always performed by the same two nurses and the tests always performed following the same sequence.If it is not observed any alteration of the MUCP value at rest, we search for a correlation between the patient complaints and MUCP value changes following dynamic tests.
Is the MUCP value at rest reproducible during a session whatever the patient complaints are?Do the changes in MUCP values during different dynamic tests provide information on the lower urinary tract dysfunction?The aim of this retrospective study was to try to give an answer to these questions.

Population
The studied population consisted of 140 consecutive women without neurological disease or/and pelvic organ prolapse of grade > 2 (mean age 56.8 ± 15.5 years [21-90 years]) referred for evaluation of lower urinary tract dysfunction (June 2007 to March 2009).Each woman completed a 3-day frequency-volume chart and the ICIQ-UI-SF before the urodynamic testing; this allowed a stratifi cation of the population in four groups according with the symptoms: continent, with stress incontinence, urge incontinence, or mixed incontinence.The continent women complained of urgency or pain.
Stress incontinence is defi ned as involuntary leakage of urine following effort or exertion, including sneezing or coughing; urge incontinence is defi ned as the involuntary leakage accompanied by or immediately preceded by urgency, and mixed incontinence as the involuntary leakage associated with stress and urge conditions (12).A second stratifi cation was made according to age: less than 45 years old (before menopause), 45 to 65 years old (menopausal transition) and above 65 years old (long term menopause).In France, the mean age for menopause is 50 years.
This study was conducted in accordance with the Declaration of Helsinki.According to the local practice of our Ethics Committee, there is no formal Institutional Review Board approval required for retrospective studies performed with the usual procedure of investigation.

Urodynamic session
A urodynamic session included the following tests: 1) free urofl owmetry at arrival; 2) UPP with empty bladder (supine position) before fi lling cystometry and pressure fl ow study (seating); 3) UPP bladder fi lled with 250 mL (or less, in cases of detrusor overactivity, at normal desire to void) with saline at room temperature (supine position except for standing recording) and 4) free urofl owmetry.Cystometry (fi lling rate 50 mL/min.)and UPP were performed using a 7F triple lumen water perfusion catheter.Pressures were zeroed to atmosphere with the transducers placed at the level of the upper edge of the pubic symphysis.All urodynamic studies were performed using a Dorado® unit from Laborie and conducted by two nurses who applied our protocol.
Urodynamic testing was performed according with Good Urodynamic Practices (13) and, during cystometry, women were asked to cough during fi lling at 100 mL intervals to ensure that pressure signals responded equally.
Urethral protocol: For UPP the puller speed was set to 1 mm/s except for standing recording when the catheter was pulled manually (14).The distal eye-hole was kept in the lateral position and the catheter position observed during the test to avoid change in orientation.The sequence of test was: (1) UPP at rest; (2) Kegel manoeuvre at MUCP; (3) UPP with 3 to 5 successive coughs (stress profi le); (4) VLPP; (5) UPP before 10 successive strong coughs and (5') after (fatigability test), then (6) UPP was recorded in standing position.

Recordings
All MUCP values were reviewed independently by 2 investigators.Good agreement occurred in up to 88% of the fi les.In the remaining 12%, an additional interpretation was made jointly to reach a single conclusion.

Comparisons
MUCP value at rest (empty bladder) (P1) was compared with (P0), (P3), (P5), (P5') and (P6) according with the continence status in the whole population and in the age groups.The relevant MUCP value (P3) was the value obtained after ma-nual smoothing of the stress profi le in order to exclude the spikes due to cough efforts.

Statistical analysis
The numerical data are described by means and standard deviation and categorical data as percentages.The Wilcoxon signed rank test was used for comparison of related samples, analysis of variance and the Chi 2 test to compare unrelated samples.Statistical analysis was performed using SAS, version 5.0 (SAS Institute, Inc., Cary, NC).All statistical results were considered significant at p < 0.05.

Reproducibility
The Bland-Altman plot (15) (difference vs. mean plot) was used to show the agreement between the two measurements of MUCP during resting profi le (empty bladder).

RESULTS
Demographic data showed that there was no signifi cant difference in age and in percentage of menopause between the 4 symptoms groups; previous pelvic surgery was more frequent in the groups with urge or mixed incontinence (Table -1).There was no signifi cant difference neither in subjective symptoms appraisal in incontinent groups nor in VLPP between stress and mixed incontinence groups (Table -1).The motive for referring was not signifi cantly different in the 3 age-groups.

Analysis of all subjects (Table-2)
Whatever the continence status, there was a good reproducibility during a session of the resting MUCP (empty bladder) (P1 and P5) (t-test and Bland-Altman plots, Figure -1).
In incontinent women, MUCP with fi lled bladder (P1) decreased signifi cantly when compared to MUCP with empty bladder (P0).MUCP of stress profi le (P3), after fatigability test (P5') and standing (P6) were signifi cantly lower than MUCP at rest in women with stress or mixed incontinence.We observed no difference between MUCP values during dynamic testing (P3, P5'and P6) and the resting value (P1) in women with urge incontinence.
In continent women, only two signifi cant decreases of MUCP were observed: during the stress profi le (p = 0.0012) and after the fatigability test (p = 0.0005).

Analysis per age-group (Tables 3, 4 and 5)
In all continence sub-groups, as in the whole population, there was no signifi cant difference between the MUCP measurements (P1 and P5) at rest (empty bladder).
In the young group (Table -3), MUCP decreased signifi cantly during the stress profi le in the SUI sub-group (p = 0.0028) and after the fatigability test for women with SUI (p = 0.0277) or mixed incontinence (p = 0.0330) (that last type of incontinence implying a stress component).There was a good reproducibility of MUCP during all tests for both continent and urge incontinence subgroups.
In the middle age group (Table-4), changes in MUCP were signifi cant with fi lled bladder (P1) vs. empty bladder (P0) except in the continent subgroup, during stress profi le (P3) in all subgroups, after fatigability (P5') in the SUI and mixed incontinence subgroup, and only in the SUI group in standing position (P6).
In the oldest group (Table -5) with SUI, the change in MUCP was signifi cant with fi lled bladder (P1) vs. empty bladder (P0) (p = 0.0374) and during the stress profi le (P3) (p = 0.0103).Changes in MUCP were observed in all tests for the mixed incontinence subgroup but only with empty bladder (P0) (p = 0.0054) and standing (P6) (p = 0.0015) in the urge subgroup.In the continent subgroup, MUCP decreased only after fatigability test (P5').

DISCUSSION
MUCP is a specifi c aspect of UPP.The main criticism addressed to it is that it is not an absolute measure of the urethral pressure, since it is an evaluation of the sphincter at rest, that does not provide information about the bladder neck or proximal urethra, that can be variable due to involuntary muscular contractions (irritant effect of the catheter), that the pressure varies with size and type of catheter, rate of perfusion, bladder volume and patient position (4), and that there is a wide variation in MUCP among individuals of similar age (16).
In relation to the causes of urinary incontinence in women, we must underline two urethral components: urethral hypermobility and intrinsic sphincter defi ciency.It has been demonstrated that women with MUCP in the lowest quartile are likely to experience failure of mid urethral sling surgery (17) and that MUCP  40 cm H 2 0 is a risk factor affecting cure after transobturator tape procedure (5).
The conclusion of the ICS standardisation report on urethral pressure measurement (18) is that "the clinical utility of urethral pressure measurement is unclear" and that "there is no doubt that the urethral pressure is of signifi cant importance for the continence mechanism".
Our study searched for the reproducibility of the MUCP value at rest, after fi lling the bladder, during a UPP session and tried to assess if different static and dynamic tests during that UPP session were correlated with the patient complaint.
During the UPP session, there was no signifi cant change of MUCP value with fi lled bladder (P1 and P5) whatever the age and the complaint.That fi rst result allowed us to use a complex UPP session and to search for a correlation between the change in MUCP value and the symptoms evoked before urodynamics.
Comparisons of MUCP value between full and empty bladder are still controversial: "some studies report lower mean MUCP with a full bladder, but others show no difference or even an increase in MUCP with bladder fi lling" (4).Most of these studies are limited to a comparison between "normal" and stress incontinent women without reference to the menopause status.In our population, MUCP value with empty bladder (P0) was almost always higher than MUCP with fi lled bladder (P1).However, the difference was only signifi cant in incontinent women and, looking at age-groups, only in middle age and oldest subgroups.That variation can be explained by an impairment, occurring early with ageing, of both the sphincteric unit and the support system in women with stress or mixed incontinence; in women with urge incontinence that decrease can be the consequence of a voiding-like refl ex mediated by changes in intercellular electrical coupling and localized contractions of smooth muscle due to the stretching of small portions of the bladder wall (19)(20).
When we look at the specifi c condition of stress incontinence, resting MUCP value is known to tend to be lower than in continent women and decreases as a function of age (11)(12)(13)(14)(15)(16), but there is no absolute cut-off value with suffi cient sensitivity and specifi city for that diagnosis and the association between MUCP and the severity of incontinence (1,21,22).In our population, MUCP values at rest (P1) tend to be lower in stress incontinent women except in the middle age group where women with mixed incontinence (which however implies a stress component) have lower MUCP.
When analyzing the results of the dynamic tests, we notice some differences.In standing position, looking at the whole population, a signifi cant decrease of MUCP (P6) was only observed in women with stress or mixed incontinence which could be related to a defi ciency of both intrinsic sphincter and peri-urethral muscles.In relation to the age groups, some differences appeared: the MUCP decreased only in women with SUI in the middle age and in women with mixed or urge incontinence in the oldest age.The previous assumption remains valid while the unexpected result for the oldest SUI group could be the consequence of a very low resting MUCP value.MUCP value remained unchanged in the continent group; that last result differs from the conclusion of Henriksson et al. (23) and Dörfl inger et al. (24) but agrees with the conclusion of Lose (25).
In the whole population, MUCP decreased during the stress profi le (P3) except in women with urge incontinence.In relation to age groups, that decrease occured always in SUI women, in all women in the middle age group and in women with stress or mixed incontinence in the oldest group.The decrease of MUCP during stress profi le (P3) could be related to a urethral hypermobility as it has been demonstrated by Schick et al. (26).The difference between the middle age and the oldest group could be the consequence of a more rigid urethra due to oestrogen defi ciency or pelvic surgery or both.
In the whole population, a MUCP decrease after the fatigability test (P5') was observed in the same groups as during stress profi le (all except urge incontinence).In young and middle-age groups, a signifi cant MUCP decrease was observed in women with SUI or mixed incontinence (stress component).In the oldest group, the non signifi cant decrease of MUCP resulted from the lower resting value of MUCP as for standing position.The decrease of MUCP following repeated cough efforts (fatigability test) has been described in women with stress urinary incontinence (14) with the hypothesis of an increased fatigue of the peri-urethral muscles.In the whole population, we fi nded a similar decrease not only in women with stress incontinence but also in women with mixed incontinence due to the stress component.
Thus, this study showed that there was a good reproducibility of MUCP value at rest when a rigorous protocol of testing was applied.What can we conclude about a correlation between the patient complaints and the MUCP value change?In a fi rst approach (i.e. the whole population) decrease of MUCP during dynamic testing was related to stress or mixed incontinence.Interestingly, that results must be cautiously analysed according to the age groups.In the youngest group (non menopausal women), the sequence of tests revealed the stress component of incontinence.In the middle--age group (peri-menopausal women) the sphincter behaviour was modifi ed by the hormonal status and the fatigability test appeared to be the only dynamic test allowing to discriminate urge from stress.In the oldest group (long-term menopause), the low resting value of MUCP seemed to conceal most of the results of dynamic testing.
At last, a negative result (no MUCP decrease) during the fatigability test was observed wha-tever the age of women with urge incontinence complaint.
Criticism to our protocol could be that it is time consuming or that it can be exhausting.But in fact, our protocol only takes about 10 min.and women do not complain of tiredness.
Limitations of this fi rst study include the fact that this is a retrospective study and the stratifi cations of the population according with age (rough hormonal status) and symptoms (continence status) were not accurate; it would be completed by the approach of MUCP value changes according with the urodynamic diagnosis.

CONCLUSIONS
When a strict protocol is applied, MUCP at rest has a good reproducibility during a urethral profi lometry session.Bladder fi lling induces a decrease in MUCP value in incontinent women whatever the type of incontinence in middle age and old age.
However, if a complex sequence of tests during urethral pressure profi lometry remains discussed in peri-and long-term menopause women, it allows specifying the stress component of incontinence in non menopausal women and the urgency component in all incontinent women.

Table 2 -Maximum Urethral Closure Pressure (MUCP) value during Urethral Pressure Profi lometry in the whole population. Comparison between the value at rest (bladder fi lled) (P1) and the value during other tests: P0 bladder empty, P3 during stress profi le, P5 before 10 cough efforts, P5' after these cough efforts, and P6 in standing position. P0 to P5': supine position. MUCP values are given as mean ± standard deviation. In P1 value and MUCP values signifi cantly different of P1.
Abbreviations: MUCP, Maximum Urethral Closure Pressure; SUI, stress urinary incontinence; Inc,incontinence; n.s., non signifi cant.

Table 3 -Maximum Urethral Closure Pressure (MUCP) value during Urethral Pressure Profi lometry in young age group (< 45 years). Comparison between the value at rest (bladder fi lled) (P1) and the value during other tests: P0 bladder empty, P3 during stress profi le, P5 before 10 cough efforts, P5' after these cough efforts, and P6 in standing position. P0 to P5': supine position. MUCP values are given as mean ± standard deviation. In P1 value and MUCP values signifi cantly different of P1.
Abbreviations: MUCP, Maximum Urethral Closure Pressure; SUI, stress urinary incontinence; Inc,incontinence; n.s., non signifi cant.

Table 5 -Maximum Urethral Closure Pressure (MUCP) value during Urethral Pressure Profi lometry in oldest age group (> 65 years). Comparison between the value at rest (bladder fi lled) (P1) and the value during other tests: P0 bladder empty, P3 during stress profi le, P5 before 10 cough efforts, P5' after these cough efforts, and P6 in standing position. P0 to P5': supine position. MUCP values are given as mean ± standard deviation. In P1 value and MUCP values signifi cantly different of P1.
Abbreviations: MUCP, Maximum Urethral Closure Pressure; SUI, stress urinary incontinence; Inc,incontinence; n.s., non signifi cant.