nomograms allowing evaluation detrusor contractility in women

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ORIGINAL ARTICLE

Usefulness of an algebraic ﬁtting of

nomograms allowing evaluation detrusor contractility in women

Intérêt du lissage algébrique des nomogammes permettant l’évaluation de la contractilité du detrusor de la femme

F.A. Valentini

^a^,^d^,∗

, B.G. Marti

^b

, P.P. Nelson

^b

, P.E. Zimmern

^c

, G. Robain

^a

aHôpitalRothschild,médecinephysiqueetderéadaptation,5,rueSanterre,75012Paris, France

bHôpitalSaint-Antoine,75012Paris,France

cUniversityofTexasSouthwestern,Dallas,TX75390,USA

dUniversitéPierre-et-Marie-Curie,4,placeJussieu,75005Paris,France

Received29April2016;accepted21June2016 Availableonline15July2016

KEYWORDS Detrusor contractility;

Nomograms;

Bladderoutlet obstruction;

Women

Summary

Aims.—NomogramsbasedonValentini-Besson-Nelson(VBN)modelimplyingonly3measure- ments(ﬁllingbladdervolume,maximumﬂow-rate[Qmax]anddetrusorpressureatQmax)were recentlydevelopedtoevaluatedetrusorcontractility(k)andurethralobstruction(U)inwomen.

Astheiralgebraicﬁttingleadstofastevaluations(Excel^®software),ouraimswereapplications topopulationsofnon-neurologicwomenwithoutandwithbladderoutletobstruction(BOO).

Methods.—Thesoftwarewas appliedto measurementsobtainedduring pressureflowstud- ies.Hiddenhypothesisofnomogramswerenosignificantcontributionofabdominalpressure betweenonsetofflowandQmaxandstandardnervousexcitationsuntilQmax.Studiedpopula- tionswere202womenwithoutsymptomsuggestiveofobstructionand125womenwithproven anatomicalurethralobstructionwhounderwenturodynamicstudy.

Results.—Fornon-obstructedwomen,agoodagreementwasfoundbetweenthevaluesofk andUobtainedusingnomogramsoracompleteVBNanalysisoftherecordedcurves.Whatever theobstructivestatus,therewasagoodcorrelationbetweenthevalueofkandU.Evolution withageingwassimilarwithhighervaluesofkandUintheBOOgroup.Curvesk(age)andU(age) gavecoefﬁcientsallowinganageadjustment.Thehighkvalueinthedetrusoroveractive(DO) groupwasconsistentwithasimilareffecttothatofBOOonthedetrusor.

∗Correspondingauthor.HôpitalRothschild,médecinephysiqueetderéadaptation,5,rueSanterre,75012Paris,France.

E-mailaddresses:francoise.valentini@rth.aphp.fr,favalentini@gmail.com(F.A.Valentini).

http://dx.doi.org/10.1016/j.purol.2016.06.010

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Conclusion.—Evaluation of detrusor contractility (k) and urethral obstruction (U) can be obtainedfromthepoint ofQmax duringpressure-ﬂowstudy.Evolutionwithageingissimilar with(highervalues)orwithoutBOO.DOalsoinducesanincreaseddetrusorcontractility.

Levelofevidence.—4.

MOTSCLÉS Contractilitédu detrusor; Nomogrammes; Obstruction sous-vésicale; Femme

Résumé

Introduction.—DesnomogrammesdéduitsdumodèleValentini-Besson-Nelson(VBN)permet- tentd’évaluerlacontractilitédudetrusor(k)etl’obstructionurétrale(U)chezlafemme.Leur lissagealgébriquepermetuneévaluationtrèsrapide(sousExcel^®)àpartirdesdonnéesd’un instantanémictionnelàl’instantdudébitmaximum (Qmax).Notrebutétait l’applicationde cetteméthodeàdesfemmesnon-neurologiques.

Méthodes.—Deuxpopulationsontétéétudiées:202patientessanssymptômeobstructifet 125patientesayantuneobstructionurétraleanatomiquedocumentée.Lesconditionsrequises étaientl’absencedepressionabdominalesigniﬁcativeetdesexcitationsnerveusesstandards entreledébutdudébitetl’atteinteduQmax.

Résultats.—Chezlespatientesnon-obstruées,onretrouvaitunebonnecorrespondanceentre lesvaleursdeketUobtenuesparutilisationdesnomogrammesetcellesobtenuesparanalyse VBNdel’ensembledescourbes.Quelquesoitlestatutobstructif,ontrouvaitunebonnecor- rélationentrelesvaleursdeketU.L’effetduvieillissementétaitsemblabledansles2groupes avecdesvaleurssigniﬁcativementplusélevéesdeketUdanslegroupeobstrué.Lescourbes k(âge)etU(âge)donnentdescoefﬁcientspermettantunecorrectiond’âge.Hyperactivitédu detrusoretobstructionurétraleconduisentàdesvaleursélevéesdek.

Conclusion.—Contractilitédudetrusor(k)etobstructionurétrale(U)peuventêtreévaluées àpartirdupointdeQmaxpendantunIM.L’obstructionanatomiqueconduitàdesvaleursplus élevéesmais l’évolution avec levieillissement est comparable. L’hyperactivité du detrusor entraîneelleaussiuneaugmentationdelacontractilitédudetrusor.

Niveaudepreuve.— 4.

Introduction

Detrusorcontractilityandurethralobstruction(anatomical or‘‘urethralresistance’’)arethedrivingfactorsofthevoid- ingprocess.Thesemechanicalparametersarerespectively namedkandUintheVBNmathematicalmodelofmicturi- tion[1,2].

In aprevious study,k andU have been evaluatedin a populationofnon-neurologic,non-obstructedwomenfrom theVBN analysis of thewhole set of urodynamic tracings recordedduringapressure-ﬂowstudy(PFs)[3].Inwomen, unlike in men, the impact of bladder outlet obstruction (BOO)onbladdercontractilityhasbeenlittlediscussed.

Recently, VBN-based nomograms have been developed [4]tofollowwomenatriskofobstructionovertime.They allowevaluating k andU froma PFs recording usingonly three measurements: filling volume (Vini), maximum flow rate(Qmax) anddetrusorpressureat Qmax (pdet.Qmax).More algebraicfittingofthesenomogramshaveallowedtocarry outausablesoftwareinExcel^® orinanysimplehandheld.

Thus,itisnolongernecessary toextrapolatebetweenthe referencecurvesofnomogramstoobtainthevaluesofkand U.UsingtheExcel^® software,valuesareobtainedinstanta- neouslyfromthethreemeasurementslistedabove.

Ouraimswere:

• tocompare thevaluesofk andUobtainedfromnomo- gramsandcompleteVBNanalysis;

• to apply the nomograms to data of large cohorts of non-neurogenicwomentestedurodynamicallyinorderto analyzetheeffectofanatomicalurethralobstructionon detrusorcontractility;

• toproposeacorrectionoftheeffectofageinginorderto separatetheeffectofageingfromaspeciﬁceffectofa lowerurinarytractdysfunction(LUTD)onthemechanical parameters.

Materials and methods

ThisstudywasconductedinaccordancewiththeDeclaration of Helsinki. Urodynamic datawere obtained from 2large databasesfrom2institutions.

Non-obstructed group

The ﬁrstsample (non-obstructedgroup)comprisedwomen without symptom suggestive of obstruction (i.e. no

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hesitancy,strainingtovoid,doublevoiding,slowstream...), nohistory of prioranti-incontinence surgery andreferred for evaluation of LUTD. After urodynamic session, urody- namicdiagnosisallowedcategorizationasnormal(N),phasic orterminaldetrusoroveractivity(PDOorTDO),urodynam- ics stress urinary incontinence (USI), intrinsic sphincteric deﬁciency(ISD)orhypertonicurethra(urethralpressureat rest>(110—age)+20%)).Forthatsample, accordingtothe localpracticeofEthicsCommittee,thereisnoformalInsti- tutional Review Boardapproval requiredfor retrospective studies.

Obstructed group

The second sample (obstructed group) comprised women with anatomically proven BOO. BOO diagnosis was based onhistory,presentingsymptoms,examﬁndings,andsiteof obstructionconﬁrmedonlateralvoidingcystogram.Forthat sample, thestudy wasapproved by thelocal Institutional ReviewBoard.

Methods

CriteriaforinclusionwerePFstracingsprovidingmaximum flowrateQmaxanddetrusorpressureatQmax(pdet.Qmax)with- outsignificantcontributionofabdominalpressurebetween onsetofflowandQmax(<3cmH2O(firstsample)and<10cm H2O (second sample)), a Qmax>2mL/s, an initial bladder volume(Vini)>100mL,andanon-interruptedflow.

Criteriaforexclusionwereneurologicaldisease,diabetes mellitusand,intheﬁrstsamplegrade>2prolapse.

Allpatientswereevaluatedusingmedicalhistory,review ofmedications,bladderdiaryforatleast48hincludingvoid- ingtimesandvoidedvolumesbothdayandnight,physical examination,anddipstickurinalysis.

Urodynamic sessions for sub-population (1) were per- formed using the Dorado^® unit from Laborie. Cystometry wasperformedwiththepatientintheseatedpositionwith a7-Ftriple-lumenurethralcatheterperfusedwithsalineat roomtemperature usinga ﬁllingrate of 50mL/min. Pres- sure transducers were zeroed to atmospheric pressure at the upper edge of the symphysis pubis. Rectal pressure wasrecordedusingapuncturedintrarectalballooncatheter

ﬁlledwith2mLof saline accordingto thereportof Good UrodynamicPracticeguidelines[5].

Urodynamic sessions for sub-population (2) were per- formedusingtheAquarius^® unitfromLaborie.Cystometry wasperformedwiththepatientintheseatedpositionwith a6-Fdouble-lumenurethralcatheterperfusedwithsaline atroomtemperatureusingaﬁllingrateof50mL/min.Pres- sure transducers were zeroed to atmospheric pressure at theupperedgeofthesymphysispubis.Rectalpressurewas recordedusingarectalballoon.

Deﬁnitions givenin the standardization of terminology oflowerurinarytractfunction(ICS[6],itsFrenchadapta- tion[7] andICS/IUGA jointreport for female pelvicﬂoor dysfunction[8])wereusedtoclassifyurodynamicdiagnosis.

StandardvaluesofVBNparameterswerek=1.0(without unit)andU=0(unitcmH2O).

Statistical analysis

Dataarepresentedasmean±SDandrange.Analysisofvari- ance(ANOVA),ttest,andthechi-squaretestwereusedas appropriate.Allstatistical resultswereconsidered signiﬁ- cantatP<0.05.Statistical analyseswereperformedusing SAS,version5.0(SASInstitute,Inc.,Cary,NC).

Results

Analysis using nomograms vs. VBN analysis of the whole recordings

Thenon-obstructedgroupcomprised202women,(meanage 58.1±17.2y;range[20—90y]).Inaprevious study[3],for partofthatgroup (125women),anassessment ofparam- eters(k andU)fromurodynamictracingsrecordedduring PFshadbeencarriedout.Asecondaryanalysisofdatausing nomogramsallowedcomparisonbetweenVBNanalysisand VBNnomograms.

Bland-Altman plots [9] showed a good agreement betweenthetwomethodsforevaluationofkandU(Fig.1).

So, the point of Qmax was eligible for evaluation of the mechanicalparameters.

Figure1. Bland-AltmanplotsforcomparisonofvaluesfoundfordetrusorcontractilitykandurethralobstructionUusing2different methods:VBNanalysisofthewholerecordedcurvesduringPFsandnomograms.

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Table1 CorrelationskandUvs.ageinthe2studiedpopulations.FortheBOOpopulation,thenumberofagegroups arereduced,duetothesmallnumberofwomenyoungerthan30y(N=4)andolderthan80y(N=3).

Age(y) <30 30—39 40—49 50—59 60—69 70—79 >80

NowithoutBOO 8 16 26 40 37 46 29

k .64±.33 .63±24 .63±.29 .54±.22 .43±.24 .37±.18 .30±.17 U(cmH2O) 22.6±20.4 22.2±18.3 22.6±19.8 16.1±13.8 13.9±10.8 10.2±10.5 8.4±8.6

NowithBOO 13 17 36 38 21

k .87±.16 .89±.59 .71±.46 .64±.30 .54±.35

U(cmH2O) 37.6±13.0 37.6±31.9 29.4±23.9 27.6±16.9 23.1±20.0

Correlation k(U)

TheVBNparameterskandUwereidentiﬁedinthe2pop- ulationsusingthenomogramsfromVini,Qmax and pdet.Qmax

recordedduringPFs.

Non-obstructed group

In the non-obstructed group, the mean value and range wererespectively0.49±0.25,range[0.02—1.20]forkand 17.0±15.2cmH2Orange[1.2—73.9cmH2O]forU.

Therewasasigniﬁcantcorrelation(P<.0001)betweenk andU:k=.245+.014*U(R²=.747).

Obstructed group

Intheobstructedgroup(N=125),(meanage57.7±12.7y;

range [21—87y]), the mean value and range were respectively 0.67±0.41, range [0.15—2.61] for k and 28.4±21.9cmH2Orange[1.2—135.0cmH2O]forU.

Therewasasigniﬁcantcorrelation(P<.0001)betweenk andU:k=.192+.017*U(R²=.840).

Correlation k and U vs. age

MeanvalueofkandUwassigniﬁcantlyhigheraccordingwith agestratiﬁcationin theobstructedgroup(comparingnon- obstructedvs.obstructed:P<.0001foreachparameter).

Inthe2populations,valueofkandUremainedconstant until menopausal age, and then decreased regularlywith advancingage(Table1andFig.2).

Attempt to correct the effect of ageing in various clinical conditions

As the decreaseof k and U was roughly linear after 50y (Fig.2),decreasecoefﬁcients(slopeofstraightlinebetween 50and80y)werecalculated.Inthenon-obstructedgroup theyweredk/dt=−0.009/yanddU/dt=−0.47/y,andinthe obstructedgroupdk/dt=−0.011/yanddU/dt=−0.48/y.

Aﬁrstresultwasthattheslopesweresimilarwhatever theobstructivestatus.

Inthenon-obstructedgroupwomenwerecategorizedas normal (No=18), phasic or terminal detrusor overactivity (71 PDOand71TDO), urodynamicstress incontinence(15 USI),intrinsicsphinctericdeﬁciency(17ISD)orhypertonic urethra(No=10).

Meanageinthenon-obstructedgroupwas58.1±17.2y not so far from mean age in the obstructed group (57.0±13.0y).Anattemptwasmadetocompareallclinical conditionsofnon-obstructedsubgroupswiththeobstructed one. Thus, age adjusted value of k and U (<kadj> and

<Uadj>)werecomputedusingtheslopesofthecurvesk(age) andU(age)forthegroupswhoseagedifferedsigniﬁcantly fromthemeanage:PDO,TDO,ISDandhypertonicurethra (Tables2and3).

Figure2. ChangesinvalueofkandUwithageinginthenon-obstructedand theBOOpopulations.Square:non-obstructedwomen.

Triangle:BOOwomen.

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Table2 MeanvaluesofkandUvs.urodynamicdiagnosisandanatomicalobstruction.

NormalUD Phasic DO (PDO)

Terminal DO (TDO)

USI ISD IHUP Allnon-

obstructed

AllBOO

Number 18 71 71 15 17 10 202 125

Age(y) 59.0±16.0 53.4±17.3 66.1±14.6 59.0±15.0 68.0±15.0 45.0±16.0 58.1±.17.2 57.0±13.0 k .47±24 .56±.30 .52±.30 .39±.14 .38±.14 .48±.20 .48±.20 .68±.40

Pvs.PDO n.s. — n.s. 0.0183 0.0060 n.s. — —

Pvs.TDO n.s. n.s. — n.s. 0.0317 n.s. — —

U 17.3±15.0 20±16.0 21±19.0 8.8±7.7 8.3±6.8 15.0±13.0 15.6±.14.0 28.5±22.0

Pvs.PDO n.s. — n.s. 0.0090 0.0048 n.s. —

pvs.TDO n.s. n.s. — 0.0289 0.0172 n.s. — —

Withageadjustmentthevalueofdetrusorcontractility intheTDOgroupbecameclosertothevalueobservedinthe obstructedgroup.InbothDOgroups,detrusorcontractility ishigherthaninthegroupwithnormalUD.

Discussion

Thefirstnomogramstoevaluatedetrusorcontractilityand urethralobstructionhavebeenrecentlyproposed[4]tofol- lowwomen atrisk ofobstruction over time.Inthisstudy, these nomograms (and the associated software obtained fromalgebraicfittingoftheirequations)areappliedtotwo differentpopulations,onewithoutsymptomsofobstruction butwithlowerurinarytractsymptoms,andtheotherwith provenBOO(obstruction aftersling placement,stage3—4 cystocele,meatalstrictureordistalurethralfibrosis).Toour knowledge,thereisnocomparisonofdetrusorcontractility betweensuchpopulations.

Theﬁrstissuewastotestthenomogramsvs.themodeled analysisofthewholerecordingsduringPFs.

An interesting ﬁnding is that nomograms, which imply attentiontothepointofQmax,andmodeledanalysisofthe whole curves of ﬂow and detrusor pressure, give a good agreementbetweenvalueofdetrusorcontractilityandure- thralobstruction.

Nomograms allow no-consuming time evaluation de detrusorcontractility; ﬁttingequations [4]arerecalledin AppendixA,theExcel^® associatedsoftwareisavailableon request.Sotheeasetouseandusefulnessofthealgebraic ﬁttingofnomogramsaredemonstrated.

Some conditions are supposed: negligible abdominal straining and standard nervous excitations (detrusor and

Table3 Ageadjustedvalueofthemechanicalparam- eters (<kadj> and <Uadj>) for the groups whose age differedsigniﬁcantlyfromthemeanage(58.5y)ofnon- obstructedandobstructedpopulations.

PDO TDO ISD IHUP

<kadj> .52 .59 .47 .47

<Uadj> 17.6 24.6 13.2 11.2

Inthenon-obstructedgroupvs. obstructedgroup,references values are respectively 0.48 and 0.68 for k, and 15.6 and 28.5cmH2OforU.

sphincter) until the flow reaches Qmax. In this study, the firstcondition isfulfilled,thesecond oneis moredifficult toassertbutcanbeassumedsatisfiedinabsenceofbreak intheascendinglimboftheflowcurve.

ThesecondissuewastoevaluatetheimpactofBOOon detrusorcontractility.Are BOOandageingconcomitant or concurrent?

The consequence of BOOis an increaseddetrusorcon- tractilitytocompensatefortheurethralobstruction.

Whateverthe obstructive status,detrusor contractility remainsconstantuntilmenopauseageandthendecreases rapidly. An interesting ﬁnding is that the curves k(age) andU(age)fornon-obstructedandobstructedpopulations areroughly translated. There is also a strong correlation betweenkandU,whichimpliesanadjustmentofthedetru- sorcontractilitytothe‘‘urethralresistance’’.

Thethirdissuewastoseparatetheeffectofageingfrom thespeciﬁc effectofsome LUTD.Thechangesin detrusor contractility have led us to bring a great interest to the effectofDOandBOOonthismechanicalparameter.

Detrusorcontractilityisgreaterinwomenwithdetrusor overactivitycomparedwithotherclinicalconditions.Similar observationshavebeenreportedbyCucchi[10]inmenwith

‘‘unstablebladder’’,withandwithoutBOOandbyCucchi etal.[11] in women.Pﬁsterer etal. [12]studied women withorwithoutDOandfoundsameresults.

For PDO, the speciﬁc effect of DO is weak compared to that observed in the TDO population, (older than the PDO one). An interesting ﬁnding is that with the ‘‘age- adjustment’’, the value of the detrusor contractility of unobstructedwomen withTDO becomescloser tothat of women with BOO. In the PDO population, younger than thewholepopulation,‘‘age-adjustment’’keepsavalueof the detrusorcontractility higher than the value observed in all the other urodynamic diagnosis groups. So, DO has the same consequence on detrusorcontractility than BOO.

In thesub-groupsISD and IHUP, theeffectof ageing is preponderant;age-adjustmentgives valuescloseto those ofwomenwithnormalUD.

Thestudyhaslimitations,itisaretrospectivestudyandit impliessomeconditionsonabdominalstrainingandnervous excitationsuntilthetimeofQmax.

Toourknowledge,thisstudyistheﬁrstquantitativeeval- uationusingnomogramsoftheeffectofBOOandageingon thedetrusorcontractilityandfortheﬁrsttimeanattempt tonormalizetheeffectofageing.

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Conclusion

Algebraic ﬁtting of nomograms allows a quick evaluation detrusorcontractility(k)andurethralobstruction(U)from thepointof Qmaxin PFs.Thesetwoparametersareeasily computedfromsimplesoftwareinExcel^®.Astrongcorrela- tionwasnotedbetweendetrusorcontractilityandurethral obstruction consistent withan adaptive process whatever thestatusofurethralobstruction.

Afterageadjustment,DO(phasicorterminal)appearsto producehigherdetrusorcontractility andtheeffectofDO looksliketheeffectofBOOofthedetrusor.

Author’s contributions

F.A. Valentini: project development, manuscript writ- ing/editing,datacollection,computations.

B.G. Marti: project development, manuscript writ- ing/editing.

P.P.Nelson:projectdevelopment,manuscriptwriting,computations.

P.E. Zimmern: project development, manuscript editing, datacollection.

G.Robain:datacollection.

Disclosure of interest

Theauthorsdeclarethattheyhavenocompetinginterest.

Appendix A. Supplementary data

Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.purol.2016.06.010.Theexcelsoftwarecanbe obtainedonrequesttotheaddressfavalentini@gmail.com

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