Account for high flow rate-low detrusor pressure voids in female: Contribution of VBN model

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ORIGINAL ARTICLE

Account for high flow rate-low detrusor pressure voids in female: Contribution of VBN model

Analyse des mictions avec grand débit et faible pression (qp) chez la femme : contribution du modèle VBN

F.A. Valentini

, B.G. Marti , G. Robain , P.P. Nelson

SorbonneUniversité,HôpitalRothschild,75012Paris,France

Received14August2019;accepted18October2019 Availableonline14November2019

KEYWORDS Highflowrate-low detrusorpressure voids;

Urethralelasticity;

Female;

VBNmodel.

Summary

Introduction.—Nomograms using the VBN model of womenmicturition allowed evaluating detrusorcontractility(k)andurethralobstruction(U)frompressure-flow(PFs)recordings.While themodelworkedformostofthepatients,anintriguingresult,negativeUvaluewasobserved forpatients with highflow-lowdetrusorpressure(Qp voids).Toexplain thatcondition,our hypothesiswasaweakurethralresistancetodilatationorincreasedexpansibility(URD).

Methods.—Theareaofferedtothefluidateachpointoftheurethra(itsdilatation)isafunction ofthetimedependingdifferencebetweeninsideandoutsidepressures.IntheVBNmodel,this functionissigmoid-like,thesameforallwomen.ForQpvoids,Qrecordedwasmorehigherthan itwouldbewiththerecordedpressure(VBNanalysis).So,modelingallowedcomputingabnor- mallyincreasedurethralwallexpansibility(URD)whoseconsequencewouldbeanincreased flow.

Results.—Among 222non-neurologicwomenreferredfor investigationofvariouslower uri- narytractsymptoms,27 (meanage66.3±11.4y)hadQpvoid:Qmax=27±6mL/s; pdet.Qmax

=7.5±4.7cmH2O.MeanURDvaluewas.36±.67.IntroductionofURDinamodeledanalysisof urodynamictracesledtoagoodfittingbetweenrecordedandcomputedtracesforthe27Qp.

∗Correspondingauthorat:Servicedemédecinephysiqueetderéadaptation,hôpitalRothschild,5,rueSanterre,Paris,75012,France.

E-mailaddress:favalentini@gmail.com(F.A.Valentini).

https://doi.org/10.1016/j.purol.2019.10.003

1166-7087/©2019ElsevierMassonSAS.Allrightsreserved.

Conclusion.—Mathematical modelingofmicturition allowsproposingan explanationofthe unexpectedobservationsofQpvoids.Theywouldbeduetoabnormalurethralwallelasticity.

Despitemajorchallengesmeasurementofthiselasticitywouldbethenextstep.

Levelofevidence.—3.

©2019ElsevierMassonSAS.Allrightsreserved.

MOTSCLÉS Mictionsavecgrand débitetbasse pressiondudétrusor; Élasticitéurétrale; Femme;

VBNmodèle

Résumé

Introduction.—DesnomogrammesobtenusenutilisantlemodèledemictionVBNpermettent d’évaluer la contractilité du detrusor (k) et l’obstruction urétrale (U)à partir des enreg- istrementsd’instantanésmictionnelschezlafemme.Alorsquelemodèledonnedesrésultats cohérentpourlaplupartdespatientes,unrésultat étonnant,unevaleur négativedeU,est observélorsdemictionsàgranddébitetfaiblepression(mictionsQp).Pourexpliquercette condition,notrehypothèseétaitunefaiblerésistanceurétraleàladilatationouexpansibilité augmentée(URD).

Méthodes.—Lasurfacedesectiondelaveinefluideenchaquepointdel’urètre(sadilatation) estunefonctiondeladifférenceentrepressionsinterneetexterne.DanslemodèleVBN,cette fonctionestassimilableàunesigmoïde,identiquepourtouteslesfemmes.Lorsdesmictions Qp,ledébitenregistréestplusélevéqu’ilneseraitétantdonnélapressiondudétrusor(VBN analyse).Lamodélisationpermetdecalculerl’expansibilitéanormaledel’urètre(URD)dont laconséquenceestuneaugmentationdudébit.

Résultats.—Parmi 222 patientes non neurologiques évaluées pour divers troubles du bas appareil urinaire, 27 (âge moyen 66,3±11,4 ans) présentaient une miction Qp : Qmax=27±6mL/s;pdet.Qmax=7,5±4,7cmH2O.Lavaleurmoyennedel’URDétait0,36±0,67.

L’introduction de l’URDdans le modèleVBN permettait unebonne restitution des courbes enregistréespourles27Qp.

Conclusion.—Lamodélisationmathématiquedelamictionpermetdeproposeruneexplication àl’observationdesmictionsQp.Celles-cirésulteraientd’uneélasticitéanormaledel’urètre.

Malgrédenombreuses difficultésde réalisation,l’étapesuivante devrait êtrela mesure de l’élasticitéurétrale.

Niveaudepreuve.— 3.

©2019ElsevierMassonSAS.Tousdroitsr´eserv´es.

Introduction

Duringnormal voiding theurethra shouldopen and dilate easilyfollowingthedetrusorcontraction,i.e.anincreasein detrusorpressure.Insomewomen,anunexpectedobserved condition isa high flow rateconcomitant withaverylow detrusorpressure(Qpvoid).Ifrepetitiveforsuccessivevoids thatpatternisacharacteristicofagivenpatient.

Whateverthedefinitionofurethralresistance,suchflows implyaweak‘‘urethralresistance’’whichdependsonthe lawofurethralelasticity.Conditionforweakurethralresis- tance is a highly expansible urethra. Observation of low detrusor pressure implies noexternal compression of the urethra.

That particular condition has been little investigated androughhypothesishavebeenproposedwithoutscientific proofandnumericaljustification.Apresumedmechanismis completepelvicfloorrelaxation.However,duringanormal void,forcespossiblyaffectingtheurethralflowincludenot only pelvic floor muscle relaxation but also urethral wall

elasticity,sphincters tone, and possible abdominalstrain- ing.

High flow-low pressure voidings are currently, without conclusive evidence, associated to stress urinary inconti- nence [1,2]. Some attempts to explain that phenomenon havebeen made involving either themechanism of open- ingoftheurethra[3],oraurethraldysfunction[4].Noneof theseproposalsexplainsthehighflowrate.

Urethracomprisesfromthecentertotheperiphery:the mucosa,thesub-mucosa (longitudinally arrangedcollagen fibers witha rich vascular plexus), the smooth muscle in alooseconnectivetissuematrixandathickstriatedmus- clewhichencirclestheinnerurethrallayers[5].IntheVBN knowledgemathematicalmodelofmicturition[6],urethrais describedasanelastictubepartlysurroundedbyacontrac- tilesheath(sphincter);therewasonlyadifferenceinthe anatomicaldescriptionoftheurethrabetweengenders,ure- thralelasticity(standard)beingassumedthesame.

Anomogramallowingevaluationofdetrusorcontractility (VBNparameterk)andurethralobstruction(anatomicalor

‘‘urethralresistance’’)(VBNurethralparameterU)froma pressureflow study(PFs) hasbeen established [7,8].But, whenappliedtohighflowrate-lowdetrusorpressurevoids thenomogram leadstointriguingresults suchasnegative value of Uparameter. So, Qpvoids areclearly due toan abnormallyweak‘‘urethralresistance’’.

Buttheintuitivenotionof‘‘urethralresistance’’cannot beusedinaquantitativemanner:itwouldbeinconsistent withgenerallawsofhydrodynamics.Duringvoiding,theflow rateisdeterminedbyagoverningzonelocatedat thesite of the main sonic transition which may be deduced from pressure-flowstudies[9]andwhichisinmostofcasesthe meatus. If the meatus governs the flow, as it is the out theabdominalcompartment,theactivepressureisthesum ofthe vesicalpressureandof an about3cmH2O altitude component.

Ourpurposewastosearchforacontributionoftheure- thra which would be related tothe urethral elasticity to explainQpvoids.

Study design, materials and methods

IntheVBNknowledgemathematicalmodel[6]acompres- sive obstruction was described by the VBN parameter U in woman. The law of urethral elasticity describes the cross—sectionoftheurethra(A)vs.thedifferencebetween insideandoutsidepressure(p).Itis asigmoid-likefunc- tionwithamaximumbenddA/dp≈2[6];hypothesiswas ahomogenousbehavioralongtheurethra.Similarlawshave beenproposed[9,10].

Unegativevalues,foundduringVBNanalysisofQpvoids, would correspond to a negative obstruction which would makenosense.IfUwasnegative,itwascertainthatthe urethrawasmoredilatablethanusual.IfUwasslightlypos- itive,itwasunclearwhetherpropertiesoftheurethrawere normalornot.

Ourhypothesis wasthat the primarymechanism resul- tinginaQpvoidwasanabnormallyincreasedurethralwall expansibility,with an amplitude inversely proportional to thedensityofurethralelasticfibersbylengthunit.

Adjustmentoftheurethralmodelwasthenperformedin ordertodealwiththesenegativevalues;moreexpansible urethrawasthendescribedintheVBNmodel[6]bymulti- plyingthestandardelasticitybyaparametercalledurethral resistancetodilatation (URD)whomvalue waslowerthan oneinaQpvoid.Alowvalueofthisparameterwillhavethe effectof increasingthe flow.Boundary conditionwasURD

=1whenUapproachedzero.

Retrospectively urodynamic recordings of a population non-neurologic women, without symptom suggestive of obstruction(i.e.nohesitancy,strainingtovoid,doublevoid- ing,slowstream...), nohistory of prioranti-incontinence surgeryandreferredforinvestigationofvariousloweruri- narytractsymptoms(LUTS)wereanalyzedfor researchof high flow/low pressure (Qp) voiding pattern to test that hypothesis.

Each urodynamicsessionwasperformed usingaurody- namicunitfromLaborie(MississaugaCanada).Urodynamic testswerecarriedoutaccordingtotheInternationalConti- nenceSocietyGoodUrodynamicPractices[11].Urodynamic studyincludedoneFFinprivatecondition(sittingposition) followedbyonecystometry(triplelumenurethralcatheter

7Fallowingfor urethralpressurerecording)andintubated flow(IF)insittingposition.Bladderwasfilledwithsalineat room-temperatureatamediumfillingrateof50mL/min.

Exclusioncriteriawerevoidedvolume<100mL,prolapse ofgrade≥2,abdominalstraininghigherthan5cmH2Odur- ingthevoidingphaseandurodynamicdiagnosisofdetrusor underactivity[12].

Statistical analysis

Dataarepresentedasmean±SDandrange.Statisticalanal- ysiswasperformedusingSAS,version5.0(SASInstitute,Inc., Cary,NC).Allstatisticalresultswereconsideredsignificant atP<0.05.

Results

Fromurodynamicrecordingsof222non-neurogenicwomen investigated for various lower urinary tract symptoms and no obstruction, 27 (12.1%) women exhibited a high flow/lowdetrusorpressure(Qp)voidingpatternduringtheir PFsstudy(Qmax=27±6mL.s⁻¹;pdet.Qmax=7.5±4.7cmH2O);

mean value of U was −9.0±6.2cm H2O while a positive value(19.4±14.2cmH2O)wasobservedfortheotherpart ofthepopulation.

MeanageoftheQppopulationwas66.3±11.4y[42—88 y];predominanturinarycomplaintwasstressurinaryincon- tinence(9),mixedincontinence(9),frequency(5),urgency (2) and recurrent urinary tractinfection (2). Urodynamic diagnoses were detrusorhyperactivity withimpaired con- tractility(5),intrinsicsphincterdeficiency(11),voidingwith onlyrelaxationoftheurethra(9)and‘‘normal’’(2).Ofnote, thoseurodynamicstudieswerecarriedoutwitha7Frtriple lumencatheterallowingforurethralpressurerecording.

Bladder voidingefficiency (BVE)was>90%, no abdomi- nal straining wasobserved during the intubated flow and abdominalpressurekeptaconstantvalueduringvoid.

EvaluationofdetrusorcontractilityfortheQppopulation wask=.29±.14whilek=.49±.25fortheotherpartofthe population.

Forthe sub-populationwithhigh Qmaxand lowpdet.Qmax

themeanURDvalue was.36±.67.IntroducingURDinthe VBNcomputationsallowedagoodfittingbetweenrecorded andcomputedtraces.

An example is given in the Fig. 1 where a signifi- cant recording was analyzed with VBN model; data are Qmax=18mL.s⁻¹,pdet.Qmax=7cmH2O(ratioQ/P=2.6).Inthe right traces, theVBN model is roughly appliedtoanalyze urodynamictraces(standardurethralelasticity,URD=1.0).

Oneobservestheabsenceoffittingbetweenrecordedcurves (flow in red, detrusor pressure in fuchsia) and computed curves(flowinblue,detrusorpressureingrey).Agoodfit- tingisobtainedwithintroductionofanincreasedurethral elasticityconstantallalongvoiding(URD=0.15).

Thiswomanwas42yearsold,withcomplaintofmixed urinaryincontinenceandurodynamicdiagnosis ofintrinsic sphincter deficiency (maximum urethral closure pressure 35cmH2O).

Figure1. Analysisofurodynamictracesofanexampleofhighflow-lowpressurevoid(Qp).Flowcurve:redrecorded,bluecomputed;

detrusorpressurecurve:fuchsiarecorded,greycomputed.Right:RoughanalysisofurodynamictraceswiththeVBNmodelwithstandard urethralexpansibility.Absenceoffittingbetweenrecordedandcomputedcurvesofflowanddetrusorpressure.Left:Goodfittingbetween recordedandcomputedcurvesobtainedwithintroductionofanincreasedurethralexpansibilityinthecomputation.

Discussion

Todate,nosatisfactoryexplanationhadbeenproposedfor voidingswithconcomitanthighmaximumflowrateandlow detrusorpressure (Qp). Ourhypothesis is that changesin urethral elasticity would be only a change in the density of elastic fibers; sothe law of urethral elasticity for one fiberistheusualone.Asecondhypothesisisachangeinthe histologicalstructureoftheurethralwall(urethralepithe- lium, vasculature and smooth muscle) and would imply a differentlawofelasticity(changeinmaximumbend,notin thedensityoffibers).Mathematicalmodelingallowstesting differentlawsofurethralelasticity.

Aremarkableresultisthegoodrestitutionofurodynamic recordingsapplyingthefirsthypothesiswithintroductionof alowurethralresistancetodilatationandthenewparam- eterURD.

Studying thesecondhypothesis, thelack ofsufficiently precise data on the histological structure of the urethral wall during the life span prevents confirmation or denial ofthathypothesis.Effectofageinghasbeendescribedby Carlileetal.[13]inwomenofagerange[19—88yearold]:

decreaseintherelativevolumeofstriatedmuscleandblood vesselsandan increase in therelativevolumeof connec- tivetissue.Thechanges inthevolumeofthemusclebulk havebeencloselyrelatedtostressurinaryincontinence[5].

Thatsecond approachdoesnotallowagoodrestitutionof urodynamicrecordings.

Other hypothesestoexplainQpvoidsarerelatedtoan underactivedetrusororstressurinaryincontinence.

Hypothesis thatan underactivedetrusorwouldonly be thecauseisnotsatisfactoryasthisconditionisassociated withlow flow rate.In ourstudy,women withurodynamic diagnosisofdetrusorunderactivityhavebeenexcluded.

Hypothesisofarelationship withstressurinaryinconti- nenceisnotverifiedasinthestudiedpopulationonly9(33%) patientscomplainedofstressurinaryincontinenceandonly 11 (41%) were diagnosed as intrinsic sphincter deficiency withouturodynamicstressincontinence[14].

Tobediscussed,hypothesistestingofpelvicfloorrelax- ation would need imaging, difficult to implement during

voiding.Notethatsuchrelaxationisequivalenttotheopen- ingofasphincterwhiletheQpconditionappearsonlywhen thesphincterisfullyopened.

OurfindingsareconsistentwiththeconclusionofDJGrif- fiths[9]:‘‘mechanicalpropertiesoftheflowgoverningzone duringmicturitionmaybededucedfromPFs’’.

In the absence of obstruction, the sonic transition in women is located at the meatus (outside of the abdomi- nalcompartment)[9],sothedrivingpressureisthebladder pressureplus an altitudecomponent, whichis due tothe differenceinheightbetweenthebladderandtheurethral meatuswhentheurethraiswell-supported.Thatlastcom- ponentcannotbenegligibleinQpvoidsbecausethedetrusor pressureis verylow.Ifthesonictransitionremains atthe meatus,variationsin flow cannot due tolocalchanges in urethralwallelasticity.Modeling allowsan explanationof thisintriguinghighflow/lowpressurevoidingphenomenon, which involves abnormal elasticity of the urethral wall.

Direct measurement of urethral wall elasticity would be desirable but seem technically difficult. Ultrasound shear waveelastography(SWE)couldperhapsbeausefulmethod [15].

Mainlimitationsofthisstudyareitsretrospectivedesign andthesmallstudiedpopulation.Otherlimitationsaretodo nottakeintoaccountthemechanicalbehaviorofthediffer- entlayersoftheurethra.Thisassumptionresultsfromthe lackofsufficientlyprecisedataonthehistologicalstructure oftheurethralwallduringthelifespan.

Another limitation is the assumption that elasticity is nottimedependent;thatistoneglecthysteresiswhilewe knowthatbladderelasticityshowhysteresiswhichexplains thedifferencebetween quickandslowfilling.It hasbeen observedbyurethralpressurereflectometry[4]aurethral hysteresis:forthesamecrosssectionA,thepressureislower attheendofvoidingthanatitsbeginning.

To summarize,VBN model analysisallowsproposing an explanationofvoidingswithhighflowrateandlowdetrusor pressureinwomen.

Further studies would be quantification of density of elasticfibersin theurethra oridentification of aurethral componentresponsibleforthisabnormalbehavior.

Astudy withalargerpopulationwould eliminatesome assumptionsandguidethemanagementofthepatients.

Conclusion

Mathematicalmodelingof micturitionallowsproposing an explanationforvoidingswithhighflowrateandlowdetrusor pressureinwomenwhichwouldbeanincreasedexpansibil- ityofurethralwall.Futurestudieswillfocusonhistological urethralwallchangestopossiblyconfirmthesemodifications inurethralelasticity.

Appendix A. Supplementary data

Supplementary data associated with this article can be found, in the online version, at https://doi.

org/10.1016/j.purol.2019.10.003.

Disclosure of interest

Theauthorsdeclarethattheyhavenocompetinginterest.

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