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Urodynamics and Benign Prostatic Hyperplasia Alexis E. Te, MD Associate Professor of Urology Director of the Brady Prostate Center and Urodynamic Laboratory Weill Medical College of Cornell University New York, New York, USA NOTE: The following slides are to be used for medical education purposes only. Copyright belongs to Prous Science and Prous Science is not responsible for any modification or change made by the users to these slides.

Urodynamics Important role in understanding LUTS Defines and documents voiding pathophysiology causing symptoms LUTS subclassified as either irritative or obstructive, or storage or emptying

Lower Urinary Tract Symptoms Obstructive Hesitancy (LUTS) Associated with BPH Weak stream Straining to pass urine Prolonged micturition Feeling of incomplete bladder emptying Urinary retention Irritative Urgency Frequency Nocturia Urge incontinence Kirby, R.S. et al. Benign prostatic hyperplasia. Health Press, 1995. 1

BPH and Bladder Outlet Obstruction Enlarged prostate causes urinary outflow obstruction Rational treatment to improve symptoms for decades Increased Outlet Resistance Increased Work Load Muscle Hypertrophy Detrusor Overactivity Poor Compliance Decreased Volume Increased Tone Neural/Receptor Issue Increased Tone/ Response Muscle Decompensation Incomplete Emptying Retention Overstretched Muscle Endstage Muscle Dysfunction

BPH and Bladder Outlet Obstruction Bladder outlet obstruction is a urodynamic defined condition Can only be defined by urodynamics Detrusor overactivity is also a urodynamic detected activity Similar symptoms and its irritative presence has a significant impact on quality of life

Pressure-Flow UDS Remain Best Method Documenting urodynamic pathology Differentiate prostatic obstruction versus bladder dysfunction Some caveats: Correlation of symptoms and UDS findings are complex and multifactorial Direct relationship of symptoms severity to UDS not well established Management not significantly altered by UDS Urodynamics not routine in clinical guidelines fpr BPH management Useful tool prior to interventional surgical therapy Document bladder function Assess bladder function Confirm diagnosis

BPH, Progression and Bladder Outlet Obstruction Natural history evaluated in the placebo-controlled arm of multiple randomized placebo-controlled studies Untreated urodynamic documented obstruction not well studied and data lacking Poor correlation of symptoms with age, prostate size and urodynamic parameters i.e., uroflow, post-void residual and detrusor pressure Influence of obstruction inferred from insight into urinary retention and surgery outcomes End result of bladder outlet obstruction Ball et al. Br J Urol 1981, 53: 613-16 Andersen et al. Scand J Urol Nephrol 1980, 14: 23-7 Barry et al. J Urol 1993, 150: 351-8 Barry et al. J Urol 1992, 148: 1549-57 Barry et al. J Urol 1992, 148: 1558-63 Boyarsky et al. Trans Am Assoc Genito-Urin Surg 1977, 68: 29 Bruskewitz et al. J Urol 1986, 136: 613-5 Schafer et al. World J Urol 1989, 6: 198-203 Simonsen et al. Urol Res 1987, 15: 355-8

Natural History of BPH Jacobsen et al. - The natural history of benign prostatic hyperplasia 2,000 randomly selected men aged 40-79 in Olmstead county, Minnesota Men with symptomatic BPH Incidence of urinary retention was dramatically increased with age and symptoms. Retention was 7/1000 person-years of follow-up Over 70 years old, 1 in 10 chance of retention within 5 years Greater risk if they had urinary symptoms Risk factors include: Age greater than 70 years AUA symptom index of 8 or greater Prostatic size greater than 30 g Peak urinary flow rate (Qmax) of <12 3.9-fold unadjusted or 2.1-fold adjusted relative risk of urinary retention Jacobsen et al. J Urol 1997, 158(2): 481-7

Can UDS Assist in Treatment Selection and Severity Assessment of BPH? Wasson et al. - Outcome of watchful waiting or TURP in a prospective multicenter trial Follow-up of 2.8 years, TURP superior to watchful waiting in regard to treatment failures and in eradicating moderate to severe LUTS Wasson et al. N Engl J Med 1995, 332(2): 75-9

BPH and Urodynamics Relation between voiding symptoms and bladder function and outlet obstruction is not simple Voiding symptoms are not directly diagnostic of inherent detrusor dysfunction and/or outlet obstruction Silent obstructive uropathy can occur without significant voiding symptoms Symptoms may not be prostate specific May represent other nonprostatic etiologies such as impaired bladder contractility, detrusor instability, sensory urgency, urethral strictures and vesical neck obstruction. 25-50% of men undergoing urodynamic investigation for prostatism symptoms do not have urodynamic evidence of obstruction Abrams et al. J Urol 1979, 121: 640-2 Abrams et al. Br J Urol 1979, 51: 129-34 Blaivas et al. Urol Clin North Am 1990, 17: 543-52 Coolsaet et al. Neurourol Urodyn 1986, 5: 435 Jensen et al. Scand J Urol Nephrol 1988, 114 (Suppl): 72-7 Dean et al. J Urol 1991, 145: 79A Hellstrom et al. Scand J Urol Nephrol 1986, 20: 187-92

UDS Differential Diagnosis of BPH Kaplan et al. 2500 consecutive men with symptomatic BPH with video UDS February 1982 to July 1994 787 evaluable patients 39% prostatic obstruction and detrusor instability 23% isolated prostatic obstruction 64% had prostatic obstruction with 63% of them having detrusor instability 54% had detrusor instability and 23% as sole diagnosis Impaired detrusor contractility 17% with 6% as their only diagnosis 0.4% had sensory urgency Kaplan SA, Bowers DA, Te AE, Olsson CA. J Urol 1996, 155: 1305-8.

Why the Poor Correlation Between Symptoms and UDS Findings? Differences in technique, equipment, operator interpretation, patient population and patient cooperation Controls or normal standards are lacking Standards developed by consensus panels (ICS) and not by studies Donovan et al. J Urol 1994, 151: 294A Kirchner-Hermanns et al. J Urol 1994, 151: 295A Griffiths et al.neurourol Urodyn 1997, 16: 521-32

UDS Still Useful Because: Only objective studies to provide understanding of bladder function and outlet obstruction Able to diagnose etiology of irritative and obstructive voiding symptoms, incontinence, urinary retention and the development of bladder outlet obstruction Greatest utility in elucidating voiding dysfunctional processes associated with neurological disease such as spina bifida, multiple sclerosis, diabetes, and others in the face of BPH Can potentially provide objective measurement of success in outcomes of BPH treatments Abrams et al. Neurourol Urodyn 1988, 7: 403-27 Griffiths et al. Neurourol Urodyn 1983, 2:27 Kaplan et al. J Chronic Dis 1974, 27: 387-404 Kaplan & Te Probl Urol 1992, 6: 659-68 McConnell et al. AHCPR Publication 94-0582. Rockville: AHCPR, PHS, US Department of Health and Human Services, 1994 Abrams et al. J Urol 1977, 117: 70-1 Ball et al. J Urol 1982, 128: 538-40 Kelly et al. J Urol 1989, 142: 1507-9 Scott et al. South Med J 1967, 60(2): 948-52

Cystometry Two types, filling CMG and voiding CMG CMG refers to a filling CMG and can be performed with either a gas or liquid medium Majority of studies utilize a liquid medium Two-lumen catheter One lumen to fill the bladder and the other to measure intravesical pressure Assess bladder capacity, involuntary detrusor contractions (IDC), bladder compliance and contraction pressures Diagnosis of bladder outlet obstruction can not be made 60% of men with symptoms of prostatism have IDC Postoperatively the incidence is 25-30% IDC may be associated with higher treatment failures Not recommended by the AUA BPH guidelines Jensen et al. Scand J Urol Nephrol 1988, 114(Suppl): 78-83 Cucchi et al. J Urol 1994; 51: 1342-4 Jensen et al. Urologe [A] 1990; 29: 1-4

Multichannel Urodynamics and Video Multichannel Urodynamics Multichannel urodynamics are synchronous pressureflow studies Best to define bladder outlet obstruction in men Simultaneous fluoroscopic video allows for visualization of location of obstruction (PO vs. VNO) Diagnose impaired contractility, detrusor instability and sensory urgency Clarify diagnosis with associated underlying neurological or postoperative surgical condition Detect diverticula as well as vesicoureteral reflux on VCUG Kaplan Sa, Te AE et al. J Urol 1994, 152: 2063-5 George et al. Br J Urol 1986, 58: 290-5 Glemain et al. Eur Urol 1993, 24: 12-17 Neal et al. Br J Urol 1987, 60: 560-6

VCUG: VNO vs. PO

Technical Utility of Multichannel UDS Principal role is to analyze the act of micturition Examines the detrusor function as measured by its generation of pressure in relation to its outlet resistance as defined by its flow: Bladder outlet obstruction is elevated, voiding pressure with low peak urinary flow Impaired detrusor function is reduced, bladder pressure or contractility function identified as low voiding pressure in the presence of diminished flow ( low pressure, low flow ) Can distinguish whether low urinary flow is secondary to obstruction and to impaired contractility Identify obstruction in normal urinary flow with high detrusor contraction pressure Measurement of capacity, filling pressure, parameters of a contraction and detect uninhibited contractions Identify detrusor sphincter synergy, anatomical function Assess and clarify bladder function in the neurological patient Provide pretherapeutic assessment of bladder function that enables one to infer outcome prediction better Objective physiological tool with which to study patients with BPH Andersen et al. Scand J Urol Nephrol 1982, 16: 25-30 Hald et al. Prostate 1989, 2(Suppl): 69-77 Haylen et al. Br J Urol 1989, 64: 30-8 Jensen et al. Neurourol Urodyn 1989, 8: 545 Grino et al. J Urol 1993,149: 339-41

Multichannel UDS Simultaneous synchronous real-time measurements Double lumen urethral catheter into bladder Measures total vesical pressure Rectal catheter Measures abdominal pressure Uroflometry Measures urinary flow rate Detrusor pressure is calculated Total vesical pressure abdominal pressure Other aspects: EMG monitoring Pelvic floor or sphincter activity VCUG imaging Griffiths et al.neurourol Urodyn 1997,16: 521-32. Reprinted with permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc

Multichannel UDS of BOO

Quantitative Analytical Investigation of Prostatic Obstruction with UDS No standard well instituted Many urodynamic philosophies and operator preference in analytical studies Variations include catheter size, employment of suprapubic access, techniques of zeroing and type of EMG probe Basic concepts of diagnosis are the same

History of Quantitative Obstruction Model Analysis Early efforts emphasized theories based on rigid tube physics Utilized a urethral resistance factor based on rigid tube hydrodynamic theory If the calculated factor exceeded a certain value, obstruction would be diagnosed However, not clinically applicable since urethra is not a rigid tube Approach abandoned by the International Continence Society Standardization Committee Griffiths et al. Urol Int 1975; 30: 28

Resistance Factors and Models Attempts to quantify resistance on advanced theoretical hydrodynamics Involved biophysical models and advanced analytical procedures Advance mathematical definitions of bladder outlet obstruction by calculating resistance coefficients Required a focus on techniques to assess the power of detrusor contractility

Assessing Power Griffiths describes a method to assess quantitatively the strength of detrusor contractions during any voiding where flow rate, detrusor pressure and residual urine are measured Mathematically extrapolate a single point from the Hill curves, i.e., force versus contraction velocity Parameters assessed include power [the product of detrusor pressure (Pdet) and flow rate] and work (power integrated over time) Griffiths developed WF, a factor dependent on detrusor pressure, uroflow, speed of detrusor contraction and bladder volume which uses two adjustable parameters isovolumetric pressure and detrusor shortening velocity which are volume independent Griffiths et al. Urol Int 1975, 30: 28 Griffiths et al. Med Biol Eng 1971, 7: 201-15 Griffiths et al. Med Biol Eng 1971, 9: 589-96 Griffiths et al. Br J Urol 1973, 45: 497-507

Models Used to Define Obstruction and Assess Resistance Utilizing the complex relationship between pressure, flow and outlet resistance during the dynamic function of voiding Multiple biophysical models and advanced quantitative analytical techniques have been developed to study this complex relationship These elegant models have sought to characterize and simplify this complex relationship to a quantitative value of comparison

Methods of Quantitative Assessment of Bladder Outlet Obstruction (adapted from ICS standardization committee 1997) Method Aim Number of p/q points Assumed shape of URR Number of parameters Number of grade severity or continuous Abrams-Griffiths nomogram diagnosis 1 n/a n/a 3 Spangberg nomogram diagnosis 1 n/a n/a 3 URA linpurr resistance 1 curved 1 continuous Schafer PURR resistance 1 linear 1 7 CHESS resistance Many curved 2 continuous OBI58 resistance Many linear 1 continuous Spangbergetal. resistance Many linear or curved 3 continuous + 3 categories DAMPF resistance 2 linear 1 continuous A/G number resistance 1 linear 1 continuous Abrams et al. Br J Urol 1997, 51: 129-34 Spangberg et al. Neurourol Urodyn 1997, 10: 139-67 Griffiths et al. Neurourol Urodyn 1997, 8: 17-27 Rollema et al. J Urol 148:111-6 Schafer W. Urol Clin N Am 17: 553-66 Schafer W. In: Hinman F Jr (ed) Benign prostatic hypertrophy. New York: SpringerVerlag, 470-96 Hofner et al. World J Urol 1995, 13: 59-64 Kranse et al. J Urol 1991, 145: 261A. Schafer W. World J Urol 1995, 13: 47-58. Lim et al. World J Urol 1995, 13: 34-39.

Schafer s Model and Nomogram Describes the urethra as a distensible tube with a flowcontrolling zone in its proximal urethra Relationship between detrusor pressure and flow rate is described by the tube s distensibility and the size of the flowcontrolling zone PURR, the passive urethral resistance relationship, a graphical description From this graphical description, an index quantifying obstruction is derived, termed the LPURR, the linear passive urethral resistance relation LPURR is derived by looking up the position of a line segment that connects the point Qmax, p(qmax) with the point of lowest pressure during flow in a nomogram Schafer et al. Neurourol Urodyn 1988, 7: 219-21 Schafer et al. World J Urol 1989, 6: 198-203 Schafer et al. Urol Clin North Am 1990, 17: 553-66

A Pressure Flow Plot ( ICS Standardization Committee 1997 ) Griffiths et al.neurourol Urodyn 1997,16: 521-32. Reprinted with permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc

Abrams-Griffith Nomogram In the 1970s, Griffiths et al. introduced their urethral resistance relation, a graphical concept that analyzed the relationship between detrusor pressure and flow during voiding to define the lowest resistance when the bladder outlet was passive or relaxed Evolved to a pressure-flow nomogram in 1979 by Abrams and Griffiths with group-specific urethral resistance quantified Classified as obstructed, equivocal or unobstructed, and was modified by the International Continence Society in a provisional recommendation for standardization in 1997 Abrams-Griffiths (AG) nomogram were similarly confirmed by Rollema and van Mastrigt in 1992. Griffiths et al. Med Biol Eng 1971, 7: 201-15 Griffiths et al. Med Biol Eng 1971, 9: 589-96 Griffiths et al Br J Urol 1973, 45: 497-507 Rollema et al. J Urol 1992, 148: 111-16 Abrams et al. Br J Urol 1979, 51:129-34 Griffiths et al. Neurourol Urodyn 1989, 8:17-27 Lim et al. World J Urol 1995, 13:34-9 Griffiths et al. Neurourol Urodyn 1997, 16:521-32

ICS Provisional Modified Abrams-Griffith Nomogram Defining Bladder Outlet Obstruction Griffiths et al.neurourol Urodyn 1997,16: 521-32. Reprinted with permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc

Computer Modeling Van Mastrigt and Rollema developed a computer program, CLIM Analyze detrusor pressure, flow rate signals during voiding and isometric detrusor pressure increase just before flow starts U/L, the maximum extrapolated rate of increase of isometric pressure, as well as URA can be calculated OBI, another quantification of urethral resistance can be calculated OBI is the parameter that fits the lowest part of a pressure-flow rate relation with an orthogonal polynomial Spangberg et al. described a model based on computer analysis of pressure-flow data Model describes the flow-controlling zone in the urethra as it distends with increasing urethral pressure and calculates a urethral pressure/area relationship quantity Sarky and Blaivas described a series of computer-generated parameters that added a time factor to the pressure-flow curve Rollema HJ et al. Neurourol Urodyn 1991, 10: 71-6 Rollema HJ et al. Urol Int 1991, 1(Suppl): 52-4 Kranse M et al. J Urol 1991, 145: 261A Spangberg et al. Neurourol Urodyn 1990, 9: 123-38 Terio et al. Med Biol Eng Comput 1989, 27: 314-21 Sarky et al. Neurourol Urodyn 1988, 7: 221-22 Sarky et al. Neurourol Urodyn 1988, 7: 223

Consensus Standards by the International Continence Society Provide a simple and reproducible method with high validity of diagnosing obstruction as well as a sensitive and reproducible method with high validity of measuring urethral resistance and changes in resistance Provisional recommendations for obstruction assessment so as to standardize an approach to evaluation One provisional diagnostic classification utilized classifications from calculated values to classify obstruction: if (Pdet, Qmax 2Qmax) > 40, the pressure-flow study is obstructed; if (Pdet, Qmax 2Qmax) < 20, the pressure-flow study is unobstructed; if in between, then the study is equivocal Modified Abrams-Griffith nomogram incorporating a compromise of various models resulted in a provisional ICS method of defining obstruction that was developed in 1997 Griffiths et al.neurourol Urodyn 1997, 16:521-532

Clinical Application of UDS Studies Jensen et al. and BPH Treatments Utilization of obstructive parameters Lowered failure rate after surgery from as high as 20% to 8% and increased the exclusion from surgery from 5% to 9%. BOO parameters (catheterized flow of less than 12 ml/s and a peak detrusor pressure of more than 45 cm H2O) However, no long-term follow-up pressure-flow analyses in symptomatic patients with prostatism who are left untreated, or those who are treated either surgically or pharmacologically have been studied in a randomized, placebo controlled long-term study Jensen et al. Neurourol Urodyn 1983, 2: 117

Clinical Application of UDS Studies and BPH Treatments Abrams et al. Examined 152 men who underwent prostatectomy for BPH based on urodynamic testing 86% of patients improved, on the basis of Qmax and a decrease in voiding pressure Subjectively, 88% of patients had improvement in their symptoms In an earlier study, inclusion of urodynamic testing in the operative criteria lowered the postoperative failure from 28% to 12% However, 28% is a higher surgical failure rate than that reported by others Abrams et al Urol 1979, 121: 640-2 McConnell et al. AHCPR Publication 94-0582. Rockville: AHCPR, PHS, US Dept of HHS, 1994

Clinical Application of UDS Studies and BPH Treatments Kuo and Tsai Examined 50 patients with UDS and by a general symptom analysis before and after prostatectomy Subjective outcome analysis was divided into good, fair and worse Examined selected preoperative UDS parameters such as different levels of Qmax, and those with high-pressure obstruction, low-pressure obstruction and low-pressure/no obstruction (LPNOB) Concluded prostatectomy best for Qmax less than 15 ml/s and those with high-pressure obstruction Poor outcome noted in patients with a Qmax greater than 15 ml/s and those classified as LPNOB Since failure rate is this high, does this identify a population with flows greater than 15 ml/s who would benefit from multichannel urodynamic testing to identify them as LPNOB? Kuo HC, Tsai TC. Taiwan I Hsueh Hui Tsa Chih 1988, 87: 323-30

Detrusor Overactivty, OAB and BPH Treatments Involuntary detrusor contraction (or detrusor overactivity) is a urodynamic entity that been recognized as important, especially with the recent trend to treat and monitor irritative symptom concurrent with BPH The prognostic significance of its presence preoperatively and its risk for persistence postoperatively has impact, especially if the goal of treatment is to improve symptom score Currently, the presence of involuntary detrusor contractions on a urodynamic assessment does not have good predictive value for its presence postoperatively

Prostatectomy and OAB Olsson et al. Examined 129 consecutive men, after prostatectomy Mean age 72 years with voiding symptoms after prostatectomy Urodynamic findings were retrospectively analyzed with respect to symptoms, uroflow and synchronous video pressure-flow cystometry Obstruction was found in 38% of patients Impaired contractility in 25% Intrinsic sphincter deficiency in 8% 80 patients without neurological disorders Involuntary bladder contractions were detected in 50% 49 patients with neurological disorders Involuntary bladder contractions were detected in 76%. Highlights significance of involuntary detrusor contractions as a potential cause of treatment failure after prostatectomy Olsson et al. J Urol 1994, 151: 326A

Involuntary Detrusor Contractions and OAB in BPH

Evaluation of Risk of Retention Prevention to decrease the morbidities of BPH progression have been highlighted as goals for pharmaceutical and interventional therapies Can UDS identify those at highest risk and those not at risk? Roehrborn et al. Eur Urol 2000, 37(5): 528 McNeill SA et al. Urology 2001, 57(3): 459

Evaluation of Risk of Retention Te et al. Analyzed urodynamic parameters to predict the risk of urinary retention in men with BOO Retrospectively analyzed UDS of 944 consecutive men evaluated for LUTS 290 (30.7%) were diagnosed with BOO BOO=Pdet@Qmax> 45 cm H2O and Qmax < 12 ml/sec Categorized into two groups Group A (n=133): men with no history of retention Group B (n=157): men with a history of retention Total prostate volume (PV), AUA Symptom Score (Sx), PSA and UDS parameters: Pmax, Pdet@Qmax, detrusor contraction length (DCL) and Qmax were analyzed. Te AE et al. J Urol 2001, 165(5): 267.

Evaluation of Risk of Retention Group A Group B P value Pmax 58.9 ±18.9cm H2O 93.8±27.9 cm H2O <0.001* DCL 126.5±69.1 sec. 147.6 ±78.7sec. <0.018* Qmax 8.5±2.6ml/sec. 4.2±2.1ml/sec. <0.05* PV 34±11.2 cc. 43.4±17.5 cc. <0.001* Sx 14.2±8.6 16.5±9.7 0.09 Statistical significance was demonstrated between group A and group B with regards to Pmax, DCL, Qmax and PV Symptom severity was not significant Te AE et al. J Urol 2001, 165(5): 267

Evaluation of Risk of Retention ROC revealed that Pmax @ 70 cm H2O had sensitivity and specificity of 73.9% and 82%, respectively, and an 82.8% and 72.8% positive and negative predictive value for urinary retention DCL @ 100 sec had a sensitivity of 70% and specificity of 44% to predict retention Novel nomogram created combining Pmax and DCL for PV >30 to maximized the sensitivity of predicting retention to 90% Suggest urodynamic pressure flow studies predict retention risk in men with BOO and the utility of urodynamics in BPH management Te AE et al. J Urol 2001, 165(5): 267

Summary Urodynamics is our best research tool to study detrusor and bladder outlet physiology Bladder outlet and detrusor interactions impact upon patient symptoms, response to therapy, and ultimate progression to complications This pathophysiology still requires further investigation and UDS provide objectivity to the study and treatment of BPH Since there are many different therapeutic options available for symptomatic BPH, and now more accurately described as lower urinary tract symptoms or LUTS, each therapy needs to find its appropriate indication based on its underlying urodynamic etiology Ultimately, urodynamic parameters that distinguish patient characteristics to allow guideline recommendations based on fact rather than the subjective assessments of both patients and urologists is a goal still to be attained