www.revportpneumol.org
ORIGINAL
ARTICLE
Titration
with
automatic
continuous
positive
airway
pressure
in
obstructive
sleep
apnea
C.
Dias
a,∗,
L.
Sousa
a,
L.
Batata
a,
R.
Reis
b,
F.
Teixeira
a,
J.
Moita
a,
J.
Moutinho
dos
Santos
aaSleepMedicineCenter---CentroHospitalareUniversitáriodeCoimbra,Coimbra,Portugal
bPulmonologyDepartment---CentroHospitalardoPorto,CentrodeMedicinadoSono---HospitalCufPorto,Porto,Portugal
Received26September2016;accepted3April2017
KEYWORDS Obstructivesleep apnea; Continuouspositive airwaypressure; Titration autotitrationpositive airwaypressure Abstract
Backgroundandobjective: Autotitratingpositiveairwaypressure(APAP)isanaccepted titra-tion method todeterminethe optimalpositive airwaypressure (PAP),for thetreatment of obstructivesleepapnea(OSA).TherequireddurationofAPAPmonitoringtodetermineafixed continuouspositiveairwaypressurelevelstillremainstobeestablished.Weaimedtoevaluate the variationinPAP level,delivered by APAPdevices,atdifferentperiodsoftreatment,to determinetheAPAPtreatmentdurationrequiredtoreachaneffectiveandstablePAPlevel. Methods:Across-sectionalstudyof62patientsnewlydiagnosedwithOSAwereevaluatedafter 3monthsofAPAPtherapy.APAPdatacorrespondingtothefirstday(D1),firstweek(W1),seventh week(W7)andtwelfthweek(W12)underAPAPtherapywascollected.Fortheanalysisofthe pressurebehaviour,thedifferenceofP95thpressurelevelbetweenW12andW7(PW12---W7), W12andW1(PW12---W1)andW12andD1(PW12---D1)wascalculated.
Results:TherewasahighcorrelationinP95thpressurelevelbetweenD1andW12(r=0.771; p>0.0001), W1andW12(r=0.817;p>0.0001),andW7andW12(r=0.926;p>0.0001).This correlationprogressivelyincreasedwithAPAPuse.Asignificancedifferencewasfoundin con-cordancebetweenPW12---W7andPW12---D1(p=0.046)withinthepressurerange±2cmH2O. HowevertherewasnosignificantdifferenceinconcordancebetweenPW12---W7andPW12---W1. Conclusions: OneweekofAPAPtherapyseemssufficienttodetermineaneffectiveandstable PAPlevel,withinthepressurerange±2cmH2O.
©2017SociedadePortuguesadePneumologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan openaccessarticleundertheCCBY-NC-NDlicense( http://creativecommons.org/licenses/by-nc-nd/4.0/).
∗Correspondingauthor.
E-mailaddress:catarinadias1@gmail.com(C.Dias).
http://dx.doi.org/10.1016/j.rppnen.2017.04.002
2173-5115/©2017SociedadePortuguesadePneumologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
Obstructive sleep apnea syndrome (OSAS) is a common disorderaffectingatleast2%---4%ofadultpopulation.1
Con-tinuous positive airway pressure (CPAP) is considered the treatment of choice of OSAS. There are several methods used to determine the pressure level for CPAP therapy, namely,afull-nightmanualtitrationinasleeplaboratory, a split-night diagnostic titrationand certain autotitrating positiveairwaypressure (APAP)devices.A full-night man-ualtitrationinasleeplaboratoryisconsideredthebest,1as
itallowsdirectobservationforconducting pressure selec-tion,beingabletoadjustthe fitof themask,eliminating leaks and helping the patient adapt to CPAP.1,2 However,
therearesomelimitationsassociatedwiththispractice;the costsand time involved in repeatpolysomnography (PSG) duetoincompletetitrations,laboratoryversus home envi-ronmentandlimited‘‘one-night’’sampling.2,3APAPdevices
areabletodetect theairflow andpressureinthecircuit, aswellastheoccurrenceofrespiratoryevents.Itis possi-bletodeterminetheappropriatepressurethroughthedata obtainedfromAPAPtrackingsystemsregistration,with sim-ilaradherenceandoutcomes,anditismorecost-effective, comparedtomanuallaboratoryCPAPtitration.2,4Many
cli-niciansprescribeCPAPbasedonautomatictitrationrather than manual titration. However, the required duration of APAPmonitoringtodetermineafixedCPAPlevelstillremains tobeestablished.2,5
Theaimofthisstudywastoevaluatethevariationin pos-itiveairwaypressure(PAP)levelofAPAPdevicesatdifferent periods of treatment, up until 12 weeks, in CPAP-naïve patients with obstructive sleep apnea (OSA), in order to determine theAPAP treatment timerequired toreach an effectiveandstablePAPlevel.
Methods
Subjectsandstudydesign
We carriedout a cross-sectional study that included con-secutiveadultpatientswithnewlydiagnosedOSAfollowed in the Sleep Medicine Centre --- Centro Hospitalar e Uni-versitário de Coimbra, during a two-month period, from March 2014. Recruited patients initiated APAP therapy and were evaluated in consultation with a sleep physi-cian at 3 months. Information concerning gender, age, initialbodymassindex(BMI),neckcircumference(NC), ini-tial and follow-up Epworth Sleepiness Scale (ESS) score, apnea---hypopnea index (AHI) and APAP data (downloaded duringtheclinicalconsult)wascollected.
DiagnosisofOSAwasobtainedwithalevel3sleepstudy device (Alice PDx, Embletta X100, Nox T3 or Stardust II) atthepatient’shomewithunattendedrecording.The fol-lowingmorning sleepstudies weremanuallyscored by an experienced sleeptechnician according tothe criteria of theAmericanAcademyofSleepMedicine,6andAPAPtherapy
wasimmediatelyprescribedbyasleepphysicianifcriteria for treatment were present, namely: AHI≥30 events per hour;AHI≥15eventsperhourwithassociatedsymptomsor cardiovascularcomorbiditiesandAHI=5---15eventsperhour
withsignificantandintolerablesymptomsnotexplainedby otherfactors.1
Patientswereexcluded if any of thefollowing criteria werepresent:previoususeofPAPdevice,previous pharyn-gealOSAsurgery,chronicnasalobstruction,hypoventilation disorders, a predominance of centralevents, malignancy, cognitivedisabilityandincompletemedicaldata.
APAP
and
adherence
data
TheAPAP deviceswereS8AutoSpiritIITMandS9AutoSetTM
(Resmed,NorthRyde,Australia),withnoseandfacemasks optimized for the facial structure and comfort of the patient.Deviceswerechosenrandomly.Heatedhumidifiers wereprescribedwhennecessary,onlyafterthebeginningof treatment.APAPdatacollectedincluded:airleaksat95th percentile(P95th),airpressuredelivered(P95th),residual AHI and adherence data from thefirst day (D1), the first week(W1),theseventhweek(W7)andtwelfthweek(W12) underAPAPtherapy.Thetitrationpressurelevelassumedto beeffectiveintreatingthemajorityofeventswasdefined asthe95thpercentilepressurelevel,whichmeansthat sub-jectsspent95%oftherecordingtimebelowthispressure. Fortheanalysisofthepressurebehaviour,thedifferenceof theP95thpressurelevelbetweenW12andW7(PW12---W7), W12andW1(PW12---W1)andW12andD1(PW12---D1)were calculated.
AdherencedataincludedpercentageofdaysofAPAPuse, percentageofdaysofAPAPuseofmorethan4handmedian ofhoursofuseperdaysofuse.Onlyadherentpatients(use >4h/night70%ofthenights)7,8withaleaklowerthan0.3L/s
andanAHI<5/hatthelastevaluationwereconsideredfor thepressurebehaviouranalysis.
Initialanalysiscomparedthesamplecharacteristicsand therapyparametersbetweenthetwogroups,accordingto the device used,in order toexclude any significant bias, asboth detect flow limitationbut aredrivenby different therapy algorithms. Secondarily,an analysis of the whole samplewasperformed.
Analysis
Continuous variables were expressed as mean±standard deviation.Frequencyandpercentagewereusedfor categor-icaldata.TheANOVAtestwasusedforcomparisonofmeans inpairedsamples.Pearson’scorrelationcoefficientwasused to evaluate the relation between P95th pressure level at W12andtheotherperiods.TheKendalltestwasusedto ana-lyzetheconcordancebetweenPW12---W7andPW12---W1and betweenPW12---W7andPW12---D1,withinthepressurerange of ±2cmH2O (as during asplit-night CPAP titrationstudy,
the AmericanAcademy ofSleep Medicinerecommends an increaseby2or2.5cmH2Owithanintervalnoshorterthan
5min to eliminate obstructive respiratory events, rather than an increase by at least 1cmH2O, given the shorter
CPAP titration duration).9 Results were considered
signifi-cantat apleveloflessthan0.05.Statistical analysiswas performed withStatistical PackagefortheSocial Sciences (SPSS)version22.0.
Table1 ClinicalcharacteristicsandadherencedataofAPAPtherapyofstudypopulation,group1andgroup2.
Studypopulation(n=62) Group1(n=37) Group2(n=25) pvalue(group1vs.group2)
Agemean,years 63±12 65.1±10.2 60.3±14.3 0.114
Gender(male/female) 62(53/9) 34/3 19/5 0.081
BMImean,kg/m2 32.28±5.27 31.7±4.9 33.1±5.8 0.304
Neckcircumference,meancm 43.2±4 43±4.2 43.4±3.7 0.82 ESSscore(atthediagnosis) 13±6 13.7±5.4 12.8±6 0.551 AHI/h(atthediagnosis) 40.2±22.76 44.5±20.81 33.8±24.43 0.071
ESSscoreatW12 7±4.1 7.5±3.9 7.2±5 0.772 ResidualAHI/h D1 5.3±6 4.9±4.2 5.9±8 0.522 W1 4.1±3.8 4.1±3.3 4.1±4.5 0.999 W7 3.2±2.7 3.6±2.8 2.6±2.4 0.151 W12 3±2.5 3.3±2.5 2.5±2.5 0.182 Leak,L/s D1 12.9±7.5 13.6±7.5 12.43±7.4 0.187 W1 12.7±7.2 13.26±7.2 12±7.2 0.210 W7 12.8±7.8 13.25±7.8 12.14±7.9 0.140 W12 13.7±8.1 14.29±8.1 13±8.2 0.167
Percentageofnightsuse>4h 97±3.8 97.4±3.8 96.5±3.8 0.382
Medianuse,h/night 6.9±0.9 7.1±0.95 6.9±0.85 0.182
Dataarepresentedasmeanvalues±standarddeviation.Group1---deviceS8AutoSpiritIITM;group2---deviceS9AutoSetTM;BMIbody
massindex;ESSEpworthSleepinessScale,AHIapnea---hypopneaindex.D1firstdayunderAPAP;W1firstweekunderAPAP;W7seventh weekunderAPAP;W12twelfthweekunderAPAPtherapy.
Results
Outofatotal110patientswithOSAandAPAPtherapy,62 wereincluded, according totheselection criteria. Of the 62patients,38(61.2%)receivedS8AutoSpiritIITM(group1) and24(38.7%)receivedS9AutoSetTM(group2).Descriptive summary statistics,outcome and APAP adherence did not differbetweengroups,inaccordancewiththedeviceused (Table1).RelativelytotheOSAseverity,12(19.4%)patients had a mild OSA, 17 (27.4%) a moderate and 33 (53.2%) a severeOSA.Therewasnosignificantweightchangeduring follow-up(datanotshown).
The APAP devices were programmed with a mean lower and upper pressure set to 5.8±1.13cmH2O and
14.2±1.1cmH2O, respectively.There werenodifferences
in the objective complianceof APAP therapy or leak lev-els between groups. When assessing the effectiveness of thetreatment,therewerenodifferencesbetweengroups. Bothmentionedanimprovementinthedaytimesleepiness, estimatedwithESS.ThemeanresidualAHIwas≤5/hafter APAPtherapyinitiation,withoutdifferencesbetweengroups (Table1).Theapnea---hypopneaindexreachednormal lev-elsatW12in54patients,withameanvalue2.23±1.1/hin thesepatients(datanotshown).
Astherewerenodifferencesingeneralfeatures, objec-tive compliance and effectiveness of treatment in both devicegroups,theanalysisofpressurebehaviourwas per-formedconsideringthestudypopulation,butonlyincluding thepatientswitharesidualAHI<5/hatthelastevaluation (n=54).Nosignificantdifferenceswerefoundbetweenthe meanvaluesofairpressuredeliveredat P95thatthefour periods(Table2).
The concordance rates, within the range ±2cmH2O,
betweentheP95thpressurelevelatW12andD1,W12and W1,W12andW7were92.6%,94.4%and100%,respectively (Table 3).Withinthis range,asignificance differencewas found in concordance between PW12---W7 and PW12---D1 (p=0.046;Table4),howevertherewasnosignificant differ-enceinconcordancebetweenPW12---W7andPW12---W1.
Discussion
Inthisstudy,weanalyzedthevariationinPAPlevelofAPAP devicesatfourdifferentperiodsof treatment,upuntil12 weeks,inaCPAP-naïvepopulationwithOSA.Wecompared, correlatedandevaluatedtheconcordanceinpressurelevels betweentheseperiods.
There was no significant difference in concordance betweenthedifferenceofP95thpressurelevelatthe12th weekandat the7thweek andbetween thedifferenceof P95thpressure level at the 12thweek and thefirst week oftreatment, withinthepressure range±2cmH2O. A
sig-nificancedifferencewasfoundinconcordancebetweenthe differenceofP95thpressurelevelatthe12thweekandat the7thweekandbetweenthedifferenceofP95thpressure levelatthe12thweekandthefirstdayoftreatment.This resultsuggeststhatoneweekofAPAPtherapyissufficient todetermineatherapeuticCPAPlevelrequirement.
Literatureconcerningthescopeofthisstudyislimited; nonethelessmanycliniciansprescribefixedCPAP basedon APAPmonitoring.Currently,therearedevicesinthemarket designedtoobtainthismeasureautomatically,changingthe APAPmodetoCPAPmode afteraperiodof time. Further-more,insomesettingsandcountries,theuseofCPAPover
Table2 ComparisonofP95thpressurelevelsreachedatthefourperiods.
MeanofP95thpressurelevel(cmH2O) Studypopulation(n=54) pvalue
P95thD1 11.27±1.53 0.407
P95thW1 11.12±1.53
P95thW7 11.32±1.66
P95thW12 11.18±1.62
P95th95percentile.TherewasahighcorrelationinP95thpressurelevelbetweenD1andW12(r=0.771;p>0.0001),W1 andW12
(r=0.817;p>0.0001),andW7andW12(r=0.926;p>0.0001).ThiscorrelationprogressivelyincreasedwithAPAPuse.
Table3 Concordanceineffectivepressurelevels.
ConcordancewithP95thpressurelevelatW12(n)
D1 W1 W7
Concordanceintherange±2cmH2O 92.6%(50) 94.4%(51) 100%(54)
P95th95percentile.
Table4 Comparisonofeffectivelevelpressureconcordance. ConcordancebetweenP W12---W7andPW12---W1 (n)
pvalue ConcordancebetweenP W12---W7andPW12---D1 (n)
pvalue
Concordanceintherange±2cmH2O 94.4%(51) 0.083 92.6%(50) 0.046a PW12---W7differencebetweentheP95thpressureatW12andW7;PW12---W1differencebetweentheP95thpressureatW12andW1;P W12---D1differencebetweentheP95thpressureatW12andD1.
aStatisticallysignificantresult.
APAPismorefrequentfordifferentreasons---cost,comfort, efficacy,etc.However,theEPAPchosenfortheCPAPmodeis frequentlyperformedusingtheautomaticalgorithmofAPAP devicesandnotwithanovernightPSG,duetothegreater costanddifficultlaboratory access.Therefore,knowledge aboutthetimeneeded foran APAPdevice toestablish an effective andstable fixed EPAPis extremely important in ordernottoextendtheperiod withtheAPAP device ina meaninglesswaynortocurtailtheperiodbeforeaneffective EPAPmeasureisobtained.
Various studies analyzed the pressure behaviour with APAP therapy,in patients withOSA. However,tothe best of our knowledge, an APAP monitoring with the aim of determiningstabilizationofthepressurelevelhasnotbeen performed.Choi10compared2weeksofauto-adjusted
titra-tionandtitrationusingapredictiveequationwithfullnight standardtitration,withnosignificantdifferencein concord-ancebetweenauto-adjustingtitrationandtitrationusingan equation comparedto manual titration, withinthe range ±1cmH2O.Damianietal.5analyzedthetitration
effective-nessoftwoAPAPdevices,duringonenightwitheachdevice (two consecutive nights), with agreement between the medianpressurelevel,confirmedwithportablemonitoring inlaboratoryandwithfixedCPAPattheAPAPrecommended pressures(thirdandfourthnights).Bachouretal.11triedto
findtheoptimalAPAPtrialduration;patientsreceivedAPAP duringa5-daytrialathome.Nodifferencewasfoundinthe pressurevariabilityindexbetweenthe5days.Luo etal.12
reportedthatCPAPfromautomatictitration(3---5nights)was
significantlyhigherthanthepressureobtainedfrommanual titration.Althoughthesestudieshavedifferentaims,some resultsmaybecomparedtoourfindings.Itisworthnoting theshortdurationofhomeunattendedtitration(1nightto2 weeks)whichdoesnotprovidesufficienttimetoobtain sig-nificantdifferencesintherapeuticpressurelevel.Adelayed effectofCPAPhasbeendescribed.13Series14quantifiedthe
changesintherequiredleveltwoweeksafterasleepstudy andafter2,8and20monthsofCPAPtherapy.Theeffective CPAP level progressivelydecreased withtime,with signif-icantdifferencesbetweenthefirstthreeevaluations.This delayedeffectofCPAPcouldbeattributedtoan improve-mentinupperairwaymorphology,15and/ortothecorrection
ofsleepfragmentation.16Therequiredpressuretoeliminate
obstructiverespiratoryeventsvariesoveranightdepending onfactorslikealcohol, hypnoticagentuse,bodyposition, nasalobstructionandsleepstate.2,17Additionally,pressure
requirements may vary over time due to weight change, differentmedicalconditionandresolutionofupperairway oedemacausedbyrepetitiveapnea.18,19
Basedonthesestatements,ourstudyconsideredalonger periodofAPAPtherapy,comparedtopreviousstudies. Addi-tionally,threeevaluationperiodscorrespondedtothemean pressurevaluesofthreeseparateweeks(W1,W7andW12), allowinganaveragepressureoverthecourseofthenight, for seven consecutive nights in three different weeks.As far aswe know, thereis noliterature about the required duration ofAPAP monitoring required toprescribe afixed pressure, and our study, after a follow-up of 12 weeks,
showedthatoneweekofAPAPtherapyseemssufficientto determineaneffectiveandstablefixedpressurelevel.
Alimitationof thisstudyis therelativelysmallsample size.
Conclusion
Inconclusion,oneweekofAPAPtherapyseemssufficientto determineaneffectiveandstablePAPlevel,withinthe pres-surerange±2cmH2O.Futurestudies,withalargernumber
ofpatients,arenecessarytocorroboratethesefindings.
Ethical
responsibilities
Protection of human and animal subjects.The authors declarethatnoexperimentswereperformedonhumansor animalsforthisstudy.
Confidentialityofdata.Theauthorsdeclarethatnopatient dataappearinthisarticle.
Right to privacy and informed consent.The authors declarethatnopatientdataappearinthisarticle.
Conflicts
of
interest
Theauthorshavenoconflictsofinteresttodeclare.
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