Bladder contractility and urethral resistance relation: What does a pressure flow study tell us?

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1 International Journal of Urology (212) 19, doi: /j x Review Articleiju_2947 Bladder contractility and urethral resistance relation: What does a pressure flow study tell us? Noritoshi Sekido Department of Urology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Abbreviations & Acronyms A = cross-sectional area AG nomogram = Abrams Griffiths nomogram AG number = Abrams Griffiths number BCI = bladder contractility index BOO = bladder outlet obstruction BOR = bladder output relation BPE = benign prostatic enlargement BPO = benign prostatic obstruction DAMPF = detrusor-adjusted mean passive urethral resistance relation DESD = detrusor external sphincter dyssynergia FCZ = flow rate controlling zone ICS = International Continence Society LPURR = linearized passive urethral resistance relation LUTS = lower urinary tract symptoms NB = neurogenic bladder P = pressure Pabd = abdominal pressure Pdet = detrusor pressure Pdet.iso = isovolumetric detrusor pressure during isovolumetric contraction Pdet.min.void = minimum voiding pressure PFS = pressure flow study PIP = projected isovolumetric pressure Pmuo = minimum urethral opening pressure POP = pelvic organ prolapse PURR = passive urethral resistance relation PV = prostate volume Pves = intravesical pressure Q = flow rate Qmax = maximum flow rate R = urethral energy loss UD = underactive detrusor UDS = urodynamic studies URA = group-specific resistance factor URR = urethral resistance relation vdet = velocity of shortening of the bladder circumference vest = maximum possible detrusor contraction velocity WF = Watts factor WFmax = point of the maximum value of Watts factor Correspondence: Noritoshi Sekido M.D., Department of Urology, Faculty of Medicine, University of Tsukuba, Tennodai, Tsukuba, Ibaraki , Japan. nsekido@md.tsukuba.ac.jp Received 19 September 211; accepted 5 December 211. Online publication 1 January 212 Abstract: Hydrodynamic analysis of a pressure flow study is the only reliable method to determine the presence or absence of a bladder outlet obstruction, especially benign prostatic obstruction. To interpret the results of pressure flow study in benign prostatic obstruction, understanding the outlines of the basic theory about evaluation of the relationship between bladder contractility and urethral resistance relation is of paramount importance. In contrast, hydrodynamic analysis of pressure flow study in conditions other than benign prostatic obstruction is complicated by the limits of theories about the hydrodynamics of the lower urinary tract. In this review, the proposed hydrodynamic theories about the relationship between bladder contractility and urethral resistance relation are outlined. Then, problems encountered in the application of hydrodynamic analysis of pressure flow study to diseases other than benign prostatic obstruction are discussed. Key words: bladder contractility, pressure flow study, urethral resistance relation. Introduction It is believed that a PFS is the most reliable functional examination to determine the presence or absence of a BOO, especially BPO. 1 However, there are many arguments about the applicability of nomograms and other indicators, which were developed for BPO, to diseases other than BPO. 2 Educational programs and certificate systems have been established in several countries, because UDS including PFS are recognized as sophisticated functional examinations that demand high expertise. 3 5 However, all urologists should know at least the basic theoretical aspects of PFS in order to interpret the results of PFS properly. Therefore, the present review outlines the relationship between bladder contractility and urethral resistance in order to help physicians understand PFS. Basic considerations for carrying out PFS When carrying out PFS, the procedure should follow the guidelines in Good urodynamic practice 6 and Standardization of terminology of lower urinary tract function: pressureflow studies of voiding, urethral resistance, and urethral obstruction 7 that were proposed by the ICS. Because PFS examines the dynamic phase of the micturition cycle, obtaining correct and interpretable data is essential for proper analysis of the relationship between pressure and flow. There are several points that should be emphasized: 1 Strict adherence to the ICS standards for zero pressure and reference height is recommended. 6 Zero pressure is the surrounding atmospheric pressure, and is the value recorded when a transducer is open to the environment. 6 The reference height, which is the level at which the transducers must be placed so that all urodynamic pressures have the same hydrostatic component, is defined as the upper edge of the symphysis pubis. 6 2 Because Pdet (Pves minus Pabd) is used for the analysis of PFS, the correct measurement of Pabd, as well as Pves, is quite important. 8 Quality control techniques, such as The Japanese Urological Association

2 Pressure flow study and hydrodynamics having the patient cough immediately before and after voiding, are mandatory to confirm the precise measurements of Pves and Pabd. 6 3 When reading the Qmax graphically, the line should be smoothed to a continuous curve, and the smoothed curve, whether smoothed electronically or manually, should be reported. 6 Such a smoothed, clinically meaningful Qmax will be different from (lower than) the peak value in the flow rate recording by electronic instruments currently available. 6 4 Pmuo, which is very important for diagnosing BPO, is a conceptual value, and it differs from opening pressure or closing pressure. In ICS terminology, Pmuo corresponds to the minimum voiding pressure (Pdet.min-.void) measured at the end of voiding. 9 An important issue is how to decide the end of voiding point. It is reasonable to cut off the last few milliliters (approximately 5 1 ml) accumulating in the flowmeter at a very low flow rate (e.g. less than 2 ml/s), usually 5 1 s before flow finally ceases, because this volume is more likely to originate from the draining of the distal urethra than from flow through the prostatic obstruction. 7,1,11 This point should be always confirmed on an original PFS trace. Hydrodynamic aspects of bladder and urethra Hydrodynamically, the bladder is an energy source. The urethra (relaxed bladder outlet) is an energy convertor, namely, the urethra splits the energy that is provided by the bladder into pressure and flow. 1 PFS is an examination that estimates the hydrodynamic properties of the bladder and urethra (outlet) during voiding based on the measurements of just two parameters: P and Q. Interestingly, degradation of the energy in the human urethra as a result of frictional energy loss was estimated to be up to 7% in men and up to 5% in women. 12,13 The female urethra is shorter in length, larger in diameter and has fewer changes of direction/shape than the male urethra. Consequently, less energy is extracted in the female urethra than in the long, narrow and convoluted male urethra. 12 Bladder contractility Bladder contractility consists of contractile strength (amplitude) and contractile duration (endurance or sustainment). 14 Generally speaking, bladder contractility is usually evaluated by contractile strength, because the utility of measuring the contraction duration is not well validated. 15 It has been supposed that an increased postvoid residual urine volume reflects an impairment of bladder contraction endurance. 14 Therefore, in the present review, bladder contractility indicates contractile strength. Pdet becomes equivalent to bladder contractility only when a bladder contracts while no flow occurs, the so-called isovolumetric contraction (Pdet.iso). 16 In fact, most noninvasive PFS reported in the literature apply this principle. 17 As mentioned previously, because the urethra converts the energy into P and Q, Pdet is not equivalent to bladder contractility when flow occurs. In other words, primarily the urethra, not the bladder, determines Pdet. Bladder contractility cannot be evaluated by measurement of only Pdet, so that the BOR, in which bladder contractility is defined by Pdet.iso and the maximum possible flow rate, is utilized for representing bladder contractility (Fig. 1a, and see Appendix 1 1). 16,18 2 An important point is that according to BOR, low Pdet results when urethral energy conversion is good (low pressure high flow) and high Pdet occurs when urethral energy conversion is bad (high pressure low flow). 21 BOR continuously changes as bladder volume decreases during voiding. 2 Evaluation of BOR itself in a given patient is inconvenient, because BOR cannot be superimposed on a pressure flow plot (PQ plot) that does not include simultaneous information about bladder volume. Actually, BOR is converted to WF, which is used as an index of bladder contractility (Fig. 1b, and see Appendix 1 2). 22 The WFmax or the point of the value at Qmax (WF at Qmax) is utilized to estimate bladder contractility. 16,23 Also, an estimation of Pdet.iso is possible, because WF multiplied by 1 is almost equivalent to Pdet.iso. 16 Drawbacks of WF are that the calculation is complicated and reproducibility is poor. 22 Thus, the simpler and easier method for evaluation of Pdet.iso is practical. The utility of a continuous stop flow or mechanical stop flow test in PFS has been reported. 23,24 However, it is more practical if Pdet.iso can be obtained without interruption of the urinary flow. In this regard, a PIP that is an estimate of Pdet.iso can be obtained by extrapolating an actual value of Pdet into the pressure axis if the slope and curvature of the BOR are already known (see Appendix 1 3). 24 In BPO patients, the PIP is called the BCI (cmh 2O). A BCI of 1 15 cmh 2O is considered to be normal contractility, less than 1 cmh 2O to be weak contractility (less than 5 cmh 2O to be very weak contractility), and greater than 15 cmh 2O to be strong contractility. 11,25 In contrast, in elderly women with urgency urinary incontinence, the PIP of 3 75 cmh 2O is considered to be normal (typical) contractility, less than 3 cmh 2O to be weak contractility, and greater than 75 cmh 2O to be strong contractility. It should be emphasized that the validity of application of PIP to patients with other diseases/conditions remains unknown. 23 Urethral resistance relation Originally, the urethra was considered to be a rigid tube and urinary flow was considered to be turbulent flow, so that energy loss (urethral resistance factor) was used to describe the outlet conditions. 13, The Japanese Urological Association 217

3 N SEKIDO (a) Isovolumetric detrusor pressure Detrusor pressure URR V3 V2 V1 BORs Flow rate Maximum possible flow rate (b) 5 WF maximum = 15.3 μw/mm Volume = 53 ml Q 25 ml/s pves 1 cmh 2 O μw/mm pabd 1 cmh 2 O pdet 1 cmh 2 O Bladder Volume Fig. 1 (a) BOR as the bladder empties from V1 to V3. Note that Pdet.iso gradually increases as bladder volume decreases. URR is simultaneously described. Modified from: Griffiths DJ. The course of micturition. In: Griffiths DJ (ed.). Urodynamics. Adam Hilger Ltd., Bristol, 198; (b) WF. A 58-year-old male with reduced bladder sensation of unknown etiology showed almost normal PFS. WF increases towards the end of micturition (WFmax = 15.3 mw/mm 2 at bladder volume of 53 ml, i.e. after he voided approximately 7 ml of urine). At present, the urethra is considered to be a collapsible/ distensible tube. Consequently, the outlet conditions are expressed not by energy loss, but by the URR. 3 When assessing URR, the hypothetical model requires the optimal outflow condition in which the urethra completely relaxes during voiding, namely, the FCZ completely opens and relaxes during voiding. 31 This means that that URR is analyzed in a portion of the low pressure side in the PQ plot, usually the portion after Pdet.qmax. 31 This part of URR is called the PURR, with emphasis on the relaxed state of the urethra. 31 In a rigid pipe that has a constant diameter, the A determines Q. 31 In contrast, in a collapsible/distensible tube, Pmuo, which is the lowest pressure required to unfold the urethral lumen and keep it open, is consumed and is not converted to fluid flow velocity (Fig. 2). 1,31 An important point is that in the collapsible/distensible tube model, FCZ (usually at the pelvic floor level) controls the relationship The Japanese Urological Association

4 Pressure flow study and hydrodynamics Flow rate (ml/sec) * Pmuo 1 Normal Pmuo 2 Constrictive obstruction Detrusor pressure (cmh 2 O) Compressive obstruction Fig. 2 URR. Dashed curve (*) represents URR in a rigid pipe where primarily the A of the tube determines URR. Three solid curves represent URR in collapsible/distensible tube where Pmuo, as well as the A of FCZ, is an important determinant for URR. If the A is reduced (e.g. urethral stricture), the curve becomes flatter (constrictive obstruction). If Pmuo is elevated from Pmuo 1 to Pmuo 2 (e.g. BPO), the curve is shifted toward the high pressure (compressive obstruction). Because Pmuo determines the detrusor contraction strength necessary to initiate and maintain voiding, a compressive obstruction is more prone to promote retention or significant residual urine than a constrictive obstruction, even with the same Pdet.qmax (arrowhead). Modified from: Schäfer W. Principles and clinical application of advanced urodynamic analysis of voiding function. Urol. Clin. North Am. 199; 17: between P and Q. 1,3,31 Although A and Pmuo are variable throughout the full length of the tube, A and Pmuo only at the FCZ represent the hydrodynamic properties of the tube 1,3,31 (see Appendix 1 4). Schäfer assumed that this model applied well to the female urethra, and fairly well to the male urethra. 31 The male urethra is much longer than the female urethra. However, the increase in relevant frictional losses in the male urethra is of real importance only when URR is controlled by an A not far from the meatus. 31 Actually FCZ is in the region of the pelvic floor, where the highest static opening pressure is needed to unfold the urethral lumen. 31 The differences in URR between females and males are probably derived from differences in the elasticity and A of FCZ or differences in the tonus of a periurethral striated muscle and pelvic floor muscle. 31 PURR is calculated electronically using the software of modern UDS equipment and is represented graphically. It is emphasized that in this model, the type of obstruction is divided into compressive obstruction, in which Pmuo increases, and constrictive obstruction, in which A FCZ decreases, with Pmuo being almost unchanged (Fig. 2). 1,31 Patients with a constrictive obstruction without an obvious increase in Pmuo, such as a urethral stricture, tend to have insignificant residual urine, even if Qmax is quite low. 1 In contrast, patients with a compressive obstruction, such as BPO, are prone to have significant residual urine. 1 Normal PFS parameters in men and women There is a lack of normal values of PFS parameters in men and women. In 37 healthy males between the ages of 18 and 4 years, the following normal values were reported: 32 Pdet.qmax (cmh 2O) and Qmax (ml/s; median, range): 51 (27 83) and 25 (14 48), respectively; mean AG number, mean URA and mean BCI (cmh 2O, 2SD): , , and 18 6, respectively. Upper limits were also proposed: 32 AG number, 4 cmh 2O; Schäfer grade, II; URA, 21 cmh 2O. In 24 healthy females, the normal values are shown in Table Interestingly, approximately 3 4% of women need abdominal straining to void. 34,35 Importantly, a concomitant increase in Pdet of at least 15 cmh 2O develops in all women. 35 Although almost all flow patterns are abnormal, abdominal straining increases Qmax if the urethra is completely relaxed and if FCZ is not under the influence of abdominal pressure. 34,36 The significance of abdominal straining is unclear. It might be a test-induced artifact, especially in young female patients. 35 In contrast, if initiation of the micturition reflex is combined with bladder contraction and urethral relaxation before slow and not strong abdominal straining, it probably has little negative influence on lower urinary tract function, especially in middle-aged women in whom straining is part of the usual voiding pattern. 35 The involvement of abdominal straining in voiding makes the evaluation of bladder contractility in female patients more complicated than in male patients. PFS in male BOO BPE is a common condition in elderly males. There is a significant, but at best modest, correlation between PV measured by transrectal ultrasonography and obstruction defined by PFS, and the correlation coefficient (r) is approximately The incidences of unobstructed on PFS are 32%, 3% and 1% in PV less than 4 ml, 4 to 6 ml, and more than 6 ml, respectively. 37 Up to now, PFS remains the only objective means of establishing or ruling out obstruction. The reason why so many diagnostic indicators of male BOO (primarily BPO) have been proposed is that interpretation of a raw PFS trace seems to be neither easy nor straightforward. In his article, Spångberg described the fol- 212 The Japanese Urological Association 219

5 N SEKIDO Table 1 Normal values of PFS parameters in women Age (years) Pdet.qmax (cmh 2O) 29 (29 42) 26 (23 39) 24 (18 31) Qmax (ml/s) 23 (2 27) 25 (22 37) 18 (16 24) PIP5 (cmh 2O) 153 (129 17) 149 ( ) 123 (12 14) PIP1 (cmh 2O) 53 (49 68) 58 (47 76) 43 (4 5) Pdet.iso (cmh 2O) 49 (37 72) 35 (29 46) 44 (33 53) Note that the Pdet.iso estimated by PIP5 is much larger than that estimated by PIP1, which is almost identical to Pdet.iso by the stop flow test. Data presented are medians (interquartile range). lowing:... the slope and curvature of the pressure/flow plot eyeballed when diagnosing obstruction. This method may be working well as long as a person experienced in interpreting pressure/flow plots like Dr Griffiths....Unfortunately, every urodynamic unit does not have a Dr Griffiths and we therefore believe it is important to use a better defined analytic procedure With regard to the diagnosis of male BOO, the AG nomogram formerly was, and the ICS nomogram currently is, popular. 42 In contrast, for the detailed analysis of BOO, the Schäfer nomogram is used to grade BOO in terms of Pmuo, 1,24 whereas the Chess classification 43 and Spångberg nomogram 41 analyze BOO in terms of both Pmuo and slope. Continuous variables including the AG number (or bladder outlet obstruction index, BOOI), 7,25 DAMPF from a Schäfer nomogram, 11 and URA 44 have been also proposed. Among these, the AG nomogram/ics nomogram, Schäfer nomogram, AG number and URA are frequently used for analysis of PFS in male BOO patients. Although PFS is useful to diagnose obstruction, there are many controversies about its ability to predict outcomes of prostatectomy. It is believed that the higher the obstruction grade, the better the outcome. 45,46 Javle et al. showed that prostatectomy resulted in unsuccessful subjective and objective outcomes in 18% of BOO patients, 6% of equivocal patients and 1% of unobstructed patients. 47 Weak bladder contractility, equivocal or absent obstruction, and detrusor overactivity are considered to be ominous signs on PFS. However, recently, prostatectomy has provided beneficial effects in selected patients with weak detrusor contractility and/or insignificant obstruction The short- and longterm satisfaction rate after prostatectomy in patients with weak contractility is approximately 65%. 49,5 The reductions in symptoms and bother in the equivocal or unobstructed patients occur in approximately 7% of those reductions in the obstructed patients. 51 Although detrusor overactivity per se might not be a definitive negative predictive factor, the success rate of prostatectomy is 29% in equivocal obstruction with detrusor overactivity and 2% in detrusor overactivity with weak contractility without BOO. 52,53 Seki et al. also showed a positive and consistent correlation between the baseline degree of detrusor contractility and the improvement in overactive bladder-related symptoms. 54 AG nomogram, AG number and ICS nomogram When PQ plots from 117 clinical BPO patients were divided into three categories, namely pattern A: mean slope <2 cmh 2O/(mL/s) and Pmuo <4 cmh 2O; pattern B: mean slope >2; and pattern C: mean slope <2 and Pmuo >4, 21 (18%), 85 (73%), and 6 (5%) of the BPO patients were classified as A, B and C, respectively. 42 When categories B and C were considered to be obstructed, 78% of clinical BPO patients had urodynamic obstruction. 42 Based on these results, an AG nomogram (Fig. 3a) was constructed with three categories: obstructed, equivocal and unobstructed. 55 Diagnosis of a given patient was based on the site of Pdet.qmax of the patient on a nomogram. When classified as equivocal, a given patient is considered obstructed if Pmuo > 4 or slope > 2, and unobstructed if Pmuo < 4 and slope < The popular indicator AG number is a kind of projected Pmuo. AG number ( BOOI)= Pdet. qmax 2 Qmax AG numbers of >4, 15 4 and less than <15 are considered to be obstructed, equivocal and unobstructed, respectively. 55 An ICS nomogram (Fig. 3b) was constructed based on this classification of AG numbers, although AG numbers >4, 2 4 and <2 are considered to be obstructed, equivocal and unobstructed, respectively, in an ICS nomogram. 7 The AG number is a continuous variable and enables quantitative comparison before and after treatment of BPO. 11 However, the hydrodynamically meaningful minimally important difference in the AG number remains unknown. Schäfer nomogram Schäfer first proposed three categories in terms of Pmuo; namely, unobstructed, obstructed and severely obstructed, The Japanese Urological Association

6 Pressure flow study and hydrodynamics Detrusor pressure (cmh2o) (a) 1 8 Obstructed 6 Equivocal * 4 ** a 2 b *** Unobstructed Detrusor pressure (cmh2o) (b) 1 8 AG > AG 2 4 AG < Flow rate (ml/sec) Flow rate (ml/sec) (c) (d) 2 N ST Flow rate (ml/sec) W A 5 O I II III IV V VW B VI Detrusor pressure (cmh2o) Detrusor pressure (cmh 2 O) Flow rate (ml/sec) Fig. 3 (a) AG nomogram. Slope (cmh 2O/(mL/s)) is a b, where a corresponds to Pdet.qmax Pmuo and b corresponds to Qmax. When classified as equivocal, a given patient is considered obstructed if Pmuo >4 (*) or slope >2 (**), and unobstructed if Pmuo <4 and slope <2 (***). Modified from: Lim CS, Abrams P. The Abrams-Griffiths nomogram. World J. Urol. 1995; 13: According to Figure 2, line (**) would represent constrictive obstruction, and line (*) would represent compressive obstruction. (b) ICS nomogram. Note that this nomogram is almost identical to an AG nomogram because the difference is only in the dashed line that is divided between equivocal and unobstructed regions in AG nomogram. Modified from: Griffiths DJ, Hofner K, van Mastrigt R, Rollema HJ, Spångberg A, Gleason D. Standardization of terminology of lower urinary tract function: pressure-flow studies of voiding, urethral resistance, and urethral obstruction. Neurourol. Urodyn. 1997; 16: 1 18 and Abrams P. Bladder outlet obstruction index, bladder contractility index and bladder voiding efficiency: three simple indices to define bladder voiding function. BJU Int. 1999; 84: (c) Schäfer nomogram. Numbers VI represent grades of obstruction. ST, strong contractility; N, normal contractility; W, weak contractility; VW, very weak contractility. Modified from: Schäfer W. Principles and clinical application of advanced urodynamic analysis of voiding function. Urol. Clin. North Am. 199; 17: Note that the Schäfer nomogram is different from the AG nomogram, ICS nomogram, and URA in the vertical axis because Q is considered as a function of P. (d) URA. An asterisk represents a moment of voiding (usually at Pdet.qmax) when Pdet = 1 cmh 2O and Q is 5 ml/s. This point lies on the curve for URA = 6 cmh 2O, which is therefore the value of the urethral resistance at this moment. Modified from: Griffiths D, van Mastright R, Bosch R. Quantification of urethral resistance and bladder function during voiding, with special reference to the effects of prostate size reduction on urethral obstruction due to benign prostatic hyperplasia. Neurourol. Urodyn. 1989; 8: which resembles the AG nomogram. 56 However, he realized that this classification did not catch minor urodynamic changes that were caused by medical therapy. Next, Schäfer proposed a simple and more practical method to express PURR as a straight line (LPURR) in which a straight line linking Pdet.qmax and Pmuo is drawn on the PQ plot. 1,21 LPURR is a method that represents the hydrodynamic properties of the urethra by two factors: thea of FCZ (slope of the line), and the distensibility of FCZ (Pmuo, position of the line), and is independent of both inherent detrusor strength and the volume voided. 11,31,57 Then, he developed the Schäfer nomogram with LPURR based on analysis of PURR from more than 2 voidings. 1,11 As seen in Figure 3c, Q is the dependent variable on the vertical axis, because Schäfer claims that Q depends on Pdet. 11 In a Schäfer nomogram, the type of BPE obstruction is proposed to be primarily compressive obstruction, and the degree of obstruction is divided into seven categories (grades) depending on Pmuo (cmh 2O): <2 () and 2 3 (I), unobstructed; 3 5 (II III, each width is 1), minimally to moderately obstructed; The Japanese Urological Association 221

7 N SEKIDO (IV V, each width is 25); and >1 (VI), moderately to severely obstructed. 1,11 The range of each grade was determined based on the intra-individual variability measured in three to ten voidings by more than 1 men before and after transurethral resection. 1 A Pmuo less than approximately 25 cmh 2O, which represents a lack of obstruction, is commonly found in asymptomatic patients or those whose symptoms cannot be further reduced by prostatectomy. 1,56 Patients with BPE are distributed with 2% each in grades I, II, III, IV and V VI, respectively. 11 In addition, the reason why the boundary lines become progressively flatter as the obstruction grade rises is that the constrictive factor seems to make a more significant contribution to the higher obstruction grades. 1 The existence of a BPE-specific obstruction type allows Pmuo to be estimated by projecting a parallel line to the boundary lines from the Pdet.qmax point to the intersection with the pressure axis, as for the AG number or URA. 11 So, like the AG nomogram, the grade of a given patient is determined based on a single point of the Pdet.qmax site of the patient on the Schäfer nomogram. Furthermore, it is necessary to evaluate the full LPURR line for quality control, as well as Pdet.qmax. 11 Line A in Figure 3c shows that this patient meets the typical BPEspecific obstruction conditions well. 1,11 In contrast, if the full LPURR line of a given patient crosses the boundary line(s) (line B in Fig. 3c), the reasons for this, such as the possibility of disagreement between the hydrodynamic model and the condition of a given patient or the possibility of low quality PFS data, should be thoroughly investigated before a definitive diagnosis is made. 11 Schäfer proposed that the full PURR line should be used for clinical decisionmaking in an individual patient or for evaluation of small changes after medical therapy. 11 Furthermore, the position of the LPURR line characterizes the outlet conditions, while the peak of the line indicates detrusor contraction strength. 31 Therefore, using the Pdet.qmax point makes it possible to evaluate bladder contractility concomitantly with the grade of obstruction when BCI lines are superimposed on the nomogram. 1 The Schäfer nomogram with BCI lines allows us to interpret the PQ plot with respect to detrusor contractility and outlet conditions. Rosier et al. analyzed WF of 242 men with LUTS, and proposed a lower limit level of WF (W/m 2) for each grade: 4, 5.5; I, 6.8; II, 8.; III, 9.3; IV, 1.5; V, 11.8; and VI, 13. More than half of the patients who were classified with a weak detrusor on the Schäfer nomogram had good bladder contractility on WF. 58 This suggests that bladder contractility should not be evaluated solely by BCI when patients are classified with a weak detrusor on the Schäfer nomogram. 58 Group-specific urethral resistance factor In a group of patients where the hydrodynamic model was applicable, the slope of PURR showed a statistically significant positive correlation with Pmuo (Spearman s rank correlation coefficient:.58). 44 Then, PURR is estimated from an instantaneous Pdet and Q, so that the projected (estimated) Pmuo (URA, Fig. 3d, see Appendix 1 5) can be obtained. Usually, the point of Pdet.qmax is used to calculate URA. URA is applicable to both adult men and women, because PURR is applicable to both sexes. 31,44 In contrast, URA is not applicable to children, because the hydrodynamic model for children might be different from adults. 44 Thus, URA is considered to be a group-specific resistance factor. A URA of more than 21 or 29 cmh 2O is regarded as evidence of significant obstruction, but URA is somewhat inappropriate for diagnosing obstruction because intraindividual variability is significant. 32,44 URA is used for comparison among groups of adult patients or for evaluation of changes as a result of some interventions. 44 A high quality PFS is a powerful tool in the diagnosis and grading of BPO. This examination can be mastered much more easily than UDS for neurogenic or pediatric patients, so that it is generally included in conventional UDS, rather than advanced UDS. 4 Actually, it seems that PFS for BPO is not always as invasive or troublesome in trained hands as expected. 45 The agreements between the results of a Schäfer nomogram (/I: unobstructed, II: equivocal, III-: obstructed) and URA (<21: unobstructed, 21 29: equivocal, <29: obstructed), between ICS nomogram and URA, and between Schäfer and ICS nomograms, are 78%, 82% and 94%, respectively. 59 The difference in URA from Schäfer or ICS nomograms is most evident in patients with relatively low pressure (approximately Pdet.qmax less than 6 cmh 2O) and low flow (approximately Qmax less than 1 ml/s). 59 In addition, URA exceeds Pmuo by PURR in 96% of the patients with Qmax less than 6 ml/s, because constrictive obstruction probably plays a more significant role in very poor flow. 6 Although its clinical implications remain inconclusive, the advantage of a Schäfer nomogram is that it not only defines bladder outlet obstruction, but also classifies its severity, which might be helpful in choosing and monitoring treatment. 61 Furthermore, if one draws a LPURR line, one can differentiate the types of obstruction: compressive (line A in Fig. 3c) versus constrictive (line B in Fig. 3c). In terms of detecting a treatment effect, URA tends to be particularly sensitive in detecting a moderate change in BOO, but the differences between URA and Pdet.qmax, Pmuo or AG numbers in this regard are not statistically significant. 62 Although LPURR seems to be too coarse to identify a moderate change in BOO, recent studies about the effects of an alpha-blocker show that LPURR can detect a change resulting from the drug URA tends to be less able to detect a large change in BOO after prostatectomy, whereas AG numbers or LPURR tends to be more sensitive in this regard than Pdet.qmax or Pmuo. 62 A continuous scale, such as AG number and URA, simplifies statistical comparisons The Japanese Urological Association

8 Pressure flow study and hydrodynamics PFS in female BOO Although PURR is very applicable to the female urethra, 31 the analysis of PFS data is complicated by the wide range of conditions or diseases that cause female BOO. Akikwala et al. reported the etiologies of 4 urodynamically proven BOO patients: POP, 25%; anti-incontinence surgery, 25%; dysfunctional voiding, 1%; bladder neck stenosis, 7%; urethral stricture, 7%; urethral diverticulum, 2.5%; and idiopathic causes, 22.5%. 65 Because of the wide variety of etiologies, the site of obstruction, as well as the presence or absence of a urodynamic obstruction, should be investigated, and in this regard, video-uds is considered to be the most useful examination. 66 In contrast to male BOO, urodynamic criteria for diagnosis of female BOO are not well established. It is suggested that a Pdet.qmax >2 25 cmh 2O and Qmax <12 15 ml/s warrants the diagnosis of female BOO. 67 Recently, in some of the literature about PFS for POP, nomograms for BPO or BCI in men have been used to analyze PFS parameters for women. 68,69 However, BCI might largely overestimate Pdet.iso in female patients. 24 It is urgently necessary to investigate whether nomograms or indicators for male BOO can be applied to female patients. PFS in neurogenic bladder A principal indication of UDS is as a functional evaluation of patients with NB. However, the utility of hydrodynamic analysis of PFS in patients with NB as carried out in BPO patients remains to be determined. 7 Significant inconsistency exists between the actual voiding phase in NB that causes DESD or non-relaxing urethral sphincter and the theoretical model of voiding through a collapsible/ distensible tube on the assumption of an optimal (relaxed) outlet condition. Furthermore, it should be remembered that PURR is derived from PFS data after Pdet.qmax, whereas DESD or a non-relaxing urethral sphincter presents continuously or sporadically during voiding. In patients with various neurological diseases, Sakakibara et al. reported that 57% of DESD cases and 8% of non-desd cases had an AG number greater than 4 (P <.5), and that the mean AG numbers were 46.4 and 17.1 in DESD and non-desd cases, respectively (P <.1). 71 In several clinical trials of alpha-blockers, PFS parameters were selected as one of the end-points, and significant decreases in Pdet.qmax and R (see Appendix 1 6) were found Uchiyama et al. carried out UDS in patients with Parkinson s disease before and after receiving a single dose of levo-dopa and found that both WFmax and AG number were significantly increased. 75 Although PFS in NB might play roles in diagnosing BOO or evaluating pharmacotherapy, the number of patients and reported trials are so small that further studies are required. NB often causes detrusor hypo-/acontractility or impairment of voluntary initiation of bladder contraction, so that Pabd significantly contributes to voiding as a compensatory mechanism (Fig. 4). However, a valid method of analyzing voiding with abdominal straining on PFS remains unknown. 76,77 Furthermore, whether Pdet is a representative parameter in such cases also remains to be determined. In conclusion, at present, careful observation of raw pressure flow traces, not a simple use of nomograms and/or indicators for BPO, is of the utmost importance to lead physicians to precise urodynamic answers to urodynamic questions. PFS in underactive detrusor PFS is expected to diagnose definitively UD, because PFS is able to determine bladder contractility (Fig. 4). According to the definition of the ICS, UD is considered to be a decrease in strength and/or duration. 9 However, the ICS does not propose standardized evaluation methods or reference values. BCI and DAMPF were developed for adult men, but these indexes have not been validated in women. 78 Expert opinion proposed that a WFmax smaller than 7 W/m 2 is evidence of bladder hypocontractility, but this threshold value has not been validated. 78 Watanabe et al. reported that residual urine volumes were significantly larger in diabetes mellitus patients with LUTS and WFmax smaller than 8 W/m Therefore, a threshold value of WF smaller than approximately 7 W/m 2 might be considered to be one of the indicators of UD. Cucchi et al. calculated the vest with estimated Pdet.iso (WFmax multiplied by 1) and estimated the maximum possible flow rate. 8 They proposed that UD was evident when Pdet.iso and/or vest were lower than the 25th percentile of distribution of the controls. 8 According to them, Pdet.iso and vest were 81 cmh 2O versus 54 cmh 2O (P =.1) and 23. mm/s versus 5.7 mm/s (P =.1), respectively, in controls and UD patients with a residual urine rate of more than 67%. 8 Furthermore, impairment of the shortening velocity preceded impairment of contraction strength, and was more serious than impairment of contraction strength. 8,81 In those studies, UD was defined as WFmax less than 12 mw/mm 2 and BCI less than 1 cmh 2O for males, and for postmenopausal females, both Qmax and Qave below the lower limits on a Liverpool nomogram, Pdet.qmax less than 2 cmh 2O, residual urine volume more than 5 ml and WFmax less than 5 mw/mm 2. 81,82 Conclusions PFS is an established tool for diagnosis and grading of BPO. However, established diagnostic algorithms for other clinical conditions have not been determined. Therefore, when making a diagnosis, it is necessary to examine the actual PFS trace thoroughly, combined with a careful review of the other clinical findings. In conclusion, high-quality PFS and 212 The Japanese Urological Association 223

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