Apnea Article

7/27/2019 Apnea Article

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Obstructive sleep apnoea (OSA) impactsnegatively the health and well being of tens ofmillionsofindividualsworldwide.Thisdisorderisanindependentriskfactorforhypertension,heartfailure,myocardialinfarction,strokeandarrhythmias,whereseverityofsleepapnoeatypicallypredictsrisk.OSAmay also impair cognitive function, mood, diabeticcontrol, and potentially liver and renal function.Unfortunately,OSAisfrequentlyachallengingchronicdisorderforwhichthemosteffectivetherapiesrequire

considerableeffortandcommitmentfromthepatient.Du to sigicat halth cosqucs of utratdsleep apnoea, like quality of life and the long-termcommitmentrequiredbythepatient,anindividualizedad xibl tratmt pla must b dvlopd basdupo th disas svrit, th idividual, spcictreatmentgoals,theoverallhealthriskforsleepapnoea

Treatmentofobstructivesleepapnoea

SigridVeasey

Center for Sleep & Respiratory Neurobiology & Department of Medicine, University of Pennsylvania School of

Medicine, Philadelphia, PA, USA

ReceivedOctober16,2008

Obstructive sleep apnoea (OSA) is a prevalent disorder with signicant co-morbidities. Presently only

rarely, treatments for obstructive sleep apnoea are curative. More typically, this is a disease that requires

lifelong intervention and commitment from both the patients and healthcare providers. In light of the

commitments, there is no uniform approach to treating sleep apnoea. Rather, approach to treatment

of OSA should be governed by disease severity, symptoms and health risk and by which approach will

work best for in a specic patient. It is equally important to identify and treat contributors to obstructive

sleep apnoea severity, including obesity and endocrine disorders. In this sense, treating the patient with

obstructive sleep apnoea requires a long-term partnership between patient and sleep medicine healthcare

providers. With a strong partnership, obstructive sleep apnoea may be effectively treated in growing

numbers of patients.

Key wordsCPAP-obesity-OSA-sleepiness-treatment

morbidities,andthelikelihoodofitssuccess.This,intur, rquirs xtsiv commuicatio withi a strogcollaborationbetweenphysicianandpatienttodevelopth most ffctiv idividual tratmt pla. Th rsttwostepsinmanaginganindividualpatientwithOSAaretodecidewhattotreatandthenhowtotreat.Closecollaborativefollowupisrequiredtodeterminehoweffectivelythetreatmentplanisworking.Large-scalestudiesfocusingonindividualswithmildtomoderate

diseasecanprovidethemuchneededinsightintohowbesttomanagethemajorityof individualswithmild-moderateOSA.

Deciding what to treat

The treatment goal should be to normalize theapoa hpopoa idx (AHI), but ormalizig alllvls of AHI i all substs of patits ma ot rsult

236

Idia J Md Rs 131, Fbruar 2010, pp 236-244

Review Article


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i improvd halth outcoms. Morovr, bcaus thtreatmentrequiresasubstantialeffortonthepatientspart, it is of utmost importac to dcid rst xactlwhatshouldbetreated.

AHI: I cosidrig th AHI, arlir studis strogl

support tratig svr obstructiv slp apoa (AHI>30events/h)1-8. I this subst of patits, tratig OSAeffectivelyhasbeenshowntoimprovebothsubjectiveand objective sleepiness9,10, oxgatio3,8, someaspects of cognitive function3,10-12, hypertension13,sigicat cardiovascular vts ad mortalit, moodandqualityoflife3,14. Rct studis show xtrmlhigh independent odds ratios for cardiovascularmortalityinOSA1,2,wheretreatingOSAeffectivelydramaticallynegatesthemorbidityandmortalityrisksassociatedwithOSA 1. Thus, i all patits with AHIsof30/horhigher,thereissubstantialevidencefromcarefully designed randomized controlled trials tosupport th importac of tratig th AHI i svrOSA. Howvr, this group rprsts 15-20 pr ctof all individuals with obstructive sleep apnoea.Th vast majorit of patits must b xamid igratr dpth to approximat how sigicatl OSAmightimpactonhealthorqualityoflife.TheTablesummarizes components of the treatment decision

process to provide individualized assessment of therisks ad bts of tratig mild to modrat OSA.

Sleepiness/fatigue:Sleepinessandfatigueare,perhaps,the most common presenting symptoms or signsin OSA15. One of the challengeswith treatingOSAsleepinessisthatsleepinessinthegeneralpopulationis high (>15%) ad thus, umrous atiologis forsleepiness/fatiguemaybepresentinagivenindividual

with OSA16.A thorough sleep history and physicalxam is sstial to dtct othr xabl sourcs ofslpiss/fatigu to xclud isufcit slp tim,poor sleep hygiene, other primary sleep disorders,medication,illnessandconditions.Whenothercauseshave been addressed, it is reasonable to treat anyindividualwithsleepinessforOSA,includingmildandmodrat. A rct mta-aalsis xamid th ffctsofcontinuouspositiveairwaypressure(CPAP)onmild-modrat OSA dd with a AHI btw 5 ad30/h17. Sv cotrolld studis qualid for thisaalsis. Subjctiv slpiss was sigicatl

rducd with tratig mild-modrat OSA. I cotrast,the effects on objective measures, the multiple sleeplatency test and the maintenance ofwakefulness testwr ot sigicatl improvd with ffctivl tratigOSA17.Oneofthemajorhealthrisksofsleepiness/fatigueis drows drivig rlatd motor vhicl accidts. Mildslp apoa (AHI 6-15/h) icrass th risk of motorvhicl accidts with a odds ratio 2.6 with th 95pr ct codc itrval btw 1.7-3.9 18.Evenmoreimportant,therateofpersonalinjuryishigherforallmotorvehiclecrasheswheretheatfaultdriverhasmildOSA19.CPAPreducesmotorvehiclecrashratesin

idividuals with a AHI >10/h19

.WhetherCPAPtherapyreduces motor vehicle accidents in individuals withmildsleepapnoearemainscontroversial20,butbecausetreatingsleepapnoeaimprovessleepiness,thedecisiontotreatmildsleepapnoeashouldbebasedonsleepiness,

at least for now. Thus, individuals with OSA andsleepiness,drowsinessorinattentivenesswhiledrivingshould rst b carfull assssd for all pottial caussofsleepiness,thentreatedforreversiblenon-OSAcausesof slpiss ad rassssd. If slpiss prsists, vindividualswithmildormoderateOSAshouldbetreatedat leastshort term todeterminewhether treatedOSA

lessens drowsiness anddrowsy or inattentive driving.It is importat to udrstad that ths assssmts ofdrowsiness,fatigueandmotorvehiclecrashriskarenotxact. So that if thr is a doubt, tratmt should btried.Atthesametime,anumberofpatientswillhaveresidualsleepinessdespitetherapyandthis,too,mustbefurtheraddressed.

Whether mild or moderate OSA contributes toneurobehaviouralimpairments,beyondsleepinessand

Table. Issus to addrss to optimiz obstructiv slp apoa

therapy

Apnoea/hypopnoea index:Doesthe patienthavesevereOSA

(>30apnoeas/hypopnoesa/h?

Sleepiness, fatigue, mood and cognitive function: Are there

other causes of sleepiness/fatigue in the patient? Does the

sleepinessorfatigueimposerisk(drivingorworkrelated)or

impactnegativelyoftheindividualsqualityoflife?

Obesity and overall health status:Doesobesitycontributetothe

svrit of OSA i this idividual? If so, what aspcts should

beaddressed:caloricintake,nutritionalcontentand/or activity

lvl/xrcis?

Underlying endocrine disorders: Does the clinical history

ad phsical xamiatio suggst hpothroidism, Cushigs

syndrome or acromegaly as a potential contributor to OSAseverity?

Use of medications that may worsen sleep disordered breathing:

Dos th patit us alcohol, sdativs, muscl rlaxats,

narcoticsortestosteronesupplementation?

Associated disorders: Cardiovascular - Are there additional

cardiovascularrisk factors in thisindividualwhich represent

th highst risk ad th most importat to targt rst?

Hprglcamic cotrol- Dos th patit hav diabts or

borderlinediabetes?

VeASey: TReATMenT OF OSA 237


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vigilance,remainscontroversial,butthereareseveralstudiessupportinga link.ChervinsgrouphasshownthatcognitiveimpairmentisevidentinchildrenwithmildOSA21.ThattreatingOSAinchildrenimprovescognitiveperformancefurthersupportsthisconcept 22.Similarly,treatingOSAinindividualswithAlzheimers

diseasealsoimprovescognitiveperformance23.VarianceincognitiveperformanceinadultswithoutAlzheimers

is sufcitl high ad to dat studis of ths groupsofOSAsubjectshavenotbeenadequatelypoweredtodetermine treatmenteffect.There areseveral studiesi adults to suggst that oxhamoglobi dsaturatiotimemaybeanimportantvariableindeterminingriskforcognitivedysfunctionfromOSA24,25.

Obesity:ObesityisthemajorriskfactorforOSAandthisconditionisamajorhealthcrisisinmanydeveloped

countries26.Addressing obesity should be a priorityfor every sleep medicine health care provider, anddevelopinganeffective realisticweightlossplan foroverweightandobesepatientswithOSAshouldbeacorrsto i vr tratmt pla. Obsit is ddb a bod mass idx > 30 kg/m2 and overweightis dd as a bod mass idx 25-30 kg/m2. Theprevalence and severityofOSArise in parallelwith

th bod mass idx27.Anincreaseofbodyweightby10 pr ct ovr tim icrass th AHI, o avrag,by30percent28. O th othr sid, a 10-15 pr ctrductio i bod wight ca rduc th AHI b 50percent29,30.Withtoofewpatientseffectivelytreatedtoormaliz th AHI, wight loss should b cosidrd

as an important complementary treatment for OSA.Thus, vr ffort to lowr wight ad rduc th AHIfor the untreated hours of disease should be made,particularlybecause thiseffort is likely to lessen the

severityofmanyOSA co-morbidities.The frontlineweightmanagementprogrammeshouldincludecurrentdietassessment,historyofpreviouslyusedweightlossstrategies,educationabout targetdailycaloricintake,ad xrcis capacit ad xpctd caloric loss fromspcic xrcis davours. For patits who havobesityco-morbidities,includingOSA,andhavefaileddietarybehaviouralmanagementprogrammes,bariatric

surgerymaybeconsidered.Theseproceduresincludegastric rstrictio with or without itstial bpass. Igeneral the surgeries result inanoverall60percentloss of xcss bod wight with substatial rductiosi th AHI i most patits ad a rsolutio of OSAin>80per centofpatients over time31. I summar,in all overweight and obesepatientswithOSA, theimportanceofweightlossshouldbeemphasizedand

discussedcarefullyuponeachpatientvisit,andevery

patient should understand how clinically importantweight loss istoreduceOSAandits co-morbidities.Fiall, it is critical to cov th importac of ahealthy diet for all familymembers, particularly thechildren,asitisfareasiertomaintainweightthanto

loseweight.

Endocrine disorders: There are several endocrineconditionsthatmaypresentasOSAandatthesametimemaycontributetoOSAanditssymptomatology.Thus,allinitialevaluationsofpatientsshouldincludeconsiderationofwhetherthepatienthasclinicalsignsand symptoms of hypothyroidism, acromegalyor Cushings syndrome. Of these conditions,hpothroidism is th most commo (2% of adults),and its presentation can have considerable overlap

withOSAsymptoms:fatigue,weightgain,myalgias,memory loss, decreasedlibido,and depressedmood.Signs and symptoms that may also be present inhpothroidism but ar ot xpctd i ucomplicatdOSA include hoarseness, facial swelling, weakness,coarse dry hair or skin, hair loss, cold intolerance,non-pitting oedema, low pulse pressure and

hporxia with dlad rlaxatio. I th slpclinictheprevalenceofsubclinicalhypothyroidismis

approximatl 11 pr ct32-34.Asacommonoccurrencewith OSA symptomatology overlap there remains acontroversywhether all patients should be screenedfor hpothroidism. Clarl if a of th mor spcichypothyroidism signs or symptoms are present then

orderingabloodthyroidstimulatinghormoneandfreethroxi 4 (TSH ad FT4) ar warratd. It is importattounderstandthatsubclinicalhypothyroidismcanbe

idtid b blood work with a ormal phsical xam35.Treatingclinicalhypothyroidismcanresultinmarkedimprovmts i th AHI, particularl if th TSH isveryhigh35-39,andtreatingsubclinicalhypothyroidismappars to improv slpiss mor so tha AHI40.Oneimportant consideration in treating newly diagnosedOSA and hypothyroidism may be the timing ofthrapis. It is widl accptd that rapid rplacmtofthyroidhormonecanresultincardiovascularstress

includingischaemiainuntreatedOSApatients 36. It isthrfor rcommdd to trat OSA rst with CPAPand tobegin thyroid replacement therapy only afterCPAPiseffectivelyalleviatingapnoeicevents 36.Whenthepatientiseuthyroid,carefulreassessmentofOSAis dd ovr th xt ar, as th AHI ma fall adtheoptimalpressuremaychangeasupperairwaysofttissuesrecede.

238 InDIAn J MeD ReS, FeBRUARy 2010


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Acromgal is dd as xcssiv growthhormo. OSA is xtrml commo i patitswith acromgal (>50%)41,42, but this is a xtrmlucommo cliical coditio (1 i 25,000 idividuals,or 0.0%). Patits with acromgal ma hav bothcentral and obstructive sleep-disordered breathing

events. Grunstein and collegues41 discovered thatpatientswith centralsleep apnoeaeventshavehighergrowthhormonelevelsandinsulin-likegrowthfactor-1levels,suggestingalinkbetweengrowthhormoneand

sleep-state dependent respiratory control. Treatmentwitha long-acting somatostatin analogue,octreotideimprovs th AHI whthr of ot growth hormolevelsnormalize.

Cushings disease is the least common of the

docri disordrs that ma iuc OSA43. Theprvalc of Cushigs sdrom is 1 i 500,00044.Like hypothyroidism there is some overlap insmptomatolg ad sigs. Faturs suggstiv ofCushingssyndromeincludeafatpadorpalpablehumpo th mid uppr back, facial ushig, thi fragil ski,slowlyhealingskin,acneinolderindividuals,boneloss,ad trucal purpl or pik stria. It is uclar whthrtreatment of Cushings improves sleep apnoea, butbecausetreatment isassociatedwithlossofheadand

necksofttissue,itislikelythatOSAwouldimprovewithtreatmentofCushings.

Medications that may worsen OSA: As the lists ofavailablenonprescriptionandprescriptionmedications

rapidl xpad, so dos th list of mdicatios that caworsen OSA. Alcohol, a frequently self-prescribedmind altering substance has been shown to clearly

icras AHI45-50. Patients should be diagnosed andtreatedforOSAontheirpresentalcoholconsumption.Howvr, alcohol us should b discouragd ad whalcohol igstio has chagd sigicatl, th OSAsvrit ad tratmt should b rassssd. numroussedatingmedicationsworsenOSAand/orcausecentralsleep apnoea, particularly clonazepam, quetiapine,methadone, lorazepam, diazepam51-55. Testosterone

supplementation or replacement therapy is alsoassociatd with icrasig th AHI ad icrasigth svrit of oxhamoglobi dsaturatios56-58.Oneofthenewermedicationsinrheumatoidarthritis,iximab, a chimric moocloal atibod to TnF-,hasbeensuggestedtoworsenOSA,inacasestudy59.numrous mdicatios promot wight gai, butmany of thesemedications are used to treat seriousmedicalconditionsandthuscarefuldiscussionwiththe

patientsotherphysiciansis essential todecideupon

whthr a mdicatio ca b rplacd. Bcaus thmajority ofmedications have not been assessed foreffectsonOSA,it ispossiblethat recentmedicationchangesinagivenpatientmaycontributetoworseningof smptoms. It is importat to udrstad th ratioalforeachmedicationandtodiscusswiththephysician

who prescribed any medication that may worsenOSA,theneedforthemedicationandwhetherthereare alternativemedicationswithout effects onOSA.Whenthemedicationisclinicallyneeded,asleepstudyshouldbeperformedonthesteadydosefollowedby

reassessmentofOSAtreatmentplans.

Disorders and medical conditions that may beworsened by OSA:TherewillbepatientswithmildtomoderateOSAwhodonothavesleepiness,fatigueorcognitiveimpairments,andthequestionthencomes-doanyofthesepatientsneedtreatment?Presently,this

questionisincompletelyansweredbyclinicalresearch,butsnoringandmildOSAcanincreasebloodpressure,andbothconditionsareassociatedwitha10-foldriskincarotidarteryatherosclerosis60. Mild-modrat OSAis a idpdt risk factor for tp II diabts61,andCPAP therapy can improve glycaemic control andinsulinresistance62-65. Fibromalgia is associatd withOSAandthereisacasereportofmarkedimprovement

withtreatmentforOSA 66. Furthr, carfull cotrolld,double-blindedclinicaltrialsareneededtodeterminehowaggressivelytotreatpatientswithmild-moderateOSA who have no neurobehavioural symptoms buthavehypertension,atherosclerosisand/ordiabetes.

Deciding how to treat OSA

I additio to addrssig wight loss i ovrwightandobesepatientsandmedicationsandillnessesthatmight xacrbat OSA i all patits, substs of patitswillhaveeithersevereOSAwithorwithoutsymptomsor mild-moderate OSA with symptoms or diseaseinteractionsforwhichstudiessupporttheconceptthat

lowrig th AHI could improv outcoms. Thr arnowidelyaccepteduniversallyeffectivetherapiesforOSA.Treatments that havebeenproven effective tolowr th AHI i substs of patits iclud positiv

airway pressure (PAP) therapy, including continuousPAP (CPAP), positional therapy, oral appliancesdesignedtoadvancethemandible,severalupperairwaysurgicalprocedures,andmedications.

Positive airway pressure therapy:Ofalloftheavailabletreatmentoptions,theonethatrequiresthemosteffortfrom the patient, PAP, is the most effective therapyforOSA.PAPtherapy,predominantlyCPAP,hasbeen



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show to rduc th AHI to


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cognition.Clearly,largerstudiesinpatientswithOSAandnocognitiveimpairmentshouldnowbeperformedassessingtheeffectsacrossmultipledosesandacrossseveralnights/dose.

Treating residual daytime sleepiness: As mentioned

earliernotallsleepinessinOSAisdirectlyrelatedtoOSA. Thus, it is imperative to identify and addressall potentially reversible causes of sleepiness in

each individual presenting with OSA and sleepinessor fatigue. Once CPAP therapy has been initiated,a xt stp is to dtrmi whthr PAP is ffctivin alleviating all sleep-disordered breathing and iswornfor allsleep.Santamaria andcolleagues82havepublishd a xcllt follow up tratmt pla toensureoptimizationofCPAPtherapy,includingtreating

isufcit slp ad othr slp disordrs, dprssio,nasalsymptoms,dryness,desensitizationtoPAPandvricatio of corrct prssurs ad optimal mask.When all of these causes and conditions have beenfullyaddressedandsleepinesspersists,itisreasonableto use stimulant therapy to increase vigilance andalertness,butitisessentialtounderstandandtoconveyto th patit that modail caot substitut for CPAPor a oral appliac. A rct stud xamid thffct of modail aftr CPAP withdrawal o drivigperformance95. As xpctd drivig prformac aftrCPAP withdrawal dtrioratd. Howvr, modail didnotrescuetheimpairedperformance95. I rgular CPAPusrs modail dos improv objctiv ad subjctivsleepiness96,andeffectsappeartoendure97. Armodail,

th R-atiomr of modail, appars quall ffctivinimprovingresidualsleepinessinCPAP-treatedOSA

ad has a much logr half-lif (10-15 h), t dosnotappeartointerferewithnighttimesleep98. Bcausof theincreasedcardiovascularrisks inpatientswithOSA, use of amphetamine-based stimulants with apotential added risk for cardiovascular morbidities99should b discouragd. I summar, stimulat thraphasaplace in treatingselectpatientswith refractorysleepinesswhoarebeingtreatedsuccessfullyforOSAbut only after carefully addressing other causes andensuringoptimaluseofPAPtherapy.

Conclusions

OSA is a complicatd disordr with sigicatmorbidities affectingmultiple organ systems.At thesametime,formostindividualswithOSA,thisisalife-

log illss that rquirs sigicat ffort o th partofboththesleepmedicinehealthcaredeliveryteamand the patient. Additionally, the treatment optionsandassessmentofeffectivenessarecomplicated,with

outcomes rapidlyupdated.Consequently, specialized

treatmentcenterswillplayimportantrolesinensuringxcllt halth car dlivr for patits with OSA.Every patient must have a treatment plan designedspcicall i cosidratio of that idividualsunderlying illnesses, OSA severity, and treatment

targets.This treatment plan should be developed incollaborationwiththepatientasarealistic,achievableplan.Thepatientmustbecontinuallyfollowedas thedisease, its co-morbidities as well as our treatmentoptionsarerapidlyevolving.

Acknowledgment

This work is supportd i part b nIH HL 080492.

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Reprint requests: Dr Sigrid Vas, Uivrsit of Pslvaia, Traslatioal Rsarch Bldg, Room 2115

125 S. 31st St, Philadlphia, PA 19104, USA e-mail:[email protected]


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