25/10/2015 Diabeticketoacidosisandhyperosmolarhyperglycemicstateinadults:Treatment
http://www.uptodate.com/contents/diabeticketoacidosisandhyperosmolarhyperglycemicstateinadultstreatment?topicKey=ENDO%2F1795&elapsedTim 1/24
OfficialreprintfromUpToDate www.uptodate.com2015UpToDate
AuthorsAbbasEKitabchi,PhD,MD,FACP,MACEIrlBHirsch,MDMichaelEmmett,MD
SectionEditorDavidMNathan,MD
DeputyEditorJeanEMulder,MD
Diabeticketoacidosisandhyperosmolarhyperglycemicstateinadults:Treatment
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.Literaturereviewcurrentthrough:Sep2015.|Thistopiclastupdated:Oct17,2014.
INTRODUCTIONDiabeticketoacidosis(DKA)andhyperosmolarhyperglycemicstate(HHS,alsoknownashyperosmotichyperglycemicnonketoticstate[HHNK])aretwoofthemostseriousacutecomplicationsofdiabetes.Theyarepartofthespectrumofhyperglycemiaandeachrepresentsanextremeinthespectrum.
ThetreatmentofDKAandHHSinadultswillbereviewedhere.Theepidemiology,pathogenesis,clinicalfeatures,evaluation,anddiagnosisofthesedisordersarediscussedseparately.DKAinchildrenisalsoreviewedseparately.
DEFINITIONSDiabeticketoacidosis(DKA)andhyperosmolarhyperglycemicstate(HHS)differclinicallyaccordingtothepresenceofketoacidosisand,usually,thedegreeofhyperglycemia[13].ThedefinitionsproposedbytheAmericanDiabetesAssociation(ADA)forDKAandHHSareshowninthetable(table1)[1].
SignificantoverlapbetweenDKAandHHSoccursinmorethanonethirdofpatients[7].ThetypicaltotalbodydeficitsofwaterandelectrolytesinDKAandHHSarecomparedinthetable(table2).(See"Diabeticketoacidosisandhyperosmolarhyperglycemicstateinadults:Clinicalfeatures,evaluation,anddiagnosis",sectionon'Diagnosticcriteria'.)
TREATMENT
OverviewandprotocolsThetreatmentofdiabeticketoacidosis(DKA)andhyperosmolarhyperglycemicstate(HHS)issimilar,includingcorrectionofthefluidandelectrolyteabnormalitiesthataretypicallypresent(hyperosmolality,hypovolemia,metabolicacidosis[inDKA],andpotassiumdepletion)andtheadministrationofinsulin[1,810].
ThefirststepinthetreatmentofDKAorHHSisinfusionofisotonicsalinetoexpandextracellularvolumeand
(See"Diabeticketoacidosisandhyperosmolarhyperglycemicstateinadults:Epidemiologyandpathogenesis".)
(See"Diabeticketoacidosisandhyperosmolarhyperglycemicstateinadults:Clinicalfeatures,evaluation,anddiagnosis".)
(See"Clinicalfeaturesanddiagnosisofdiabeticketoacidosisinchildren".)
(See"Treatmentandcomplicationsofdiabeticketoacidosisinchildren".)
InDKA,metabolicacidosisisoftenthemajorfinding,whiletheserumglucoseconcentrationisgenerallybelow800mg/dL(44.4mmol/L)andoftenapproximately350to500mg/dL(19.4to27.8mmol/L)[13].However,serumglucoseconcentrationsmayexceed900mg/dL(50mmol/L)inpatientswithDKAwhoarecomatose[3,4].
InHHS,thereislittleornoketoacidaccumulation,theserumglucoseconcentrationfrequentlyexceeds1000mg/dL(56mmol/L),theplasmaosmolalitymayreach380mosmol/kg,andneurologicabnormalitiesarefrequentlypresent(includingcomain25to50percentofcases)[1,2,5,6].
25/10/2015 Diabeticketoacidosisandhyperosmolarhyperglycemicstateinadults:Treatment
http://www.uptodate.com/contents/diabeticketoacidosisandhyperosmolarhyperglycemicstateinadultstreatment?topicKey=ENDO%2F1795&elapsedTim 2/24
stabilizecardiovascularstatus(table3).Thisalsoincreasesinsulinresponsivenessbyloweringtheplasmaosmolality,reducingvasoconstrictionandimprovingperfusion,andreducingstresshormonelevels[11,12].Thenextstepiscorrectionofthepotassiumdeficit.Thechoiceoffluidreplacementmaybeinfluencedbythepotassiumdeficit.Potassiumrepletionaffectsthesalinesolutionthatisgiven,sincepotassiumisasosmoticallyactiveassodium.(See'Potassiumreplacement'below.)
Lowdoseintravenous(IV)insulinshouldbeadministeredtoallpatientswithmoderatetosevereDKAwhohaveaserumpotassium3.3mEq/L.Iftheserumpotassiumislessthan3.3mEq/L,insulintherapyshouldbedelayeduntilpotassiumreplacementhasbegunandtheserumpotassiumconcentrationhasincreased.Thedelayisnecessarybecauseinsulinwillworsenthehypokalemiabydrivingpotassiumintothecells,andthiscouldtriggercardiacarrhythmias.(See'Intravenousregularinsulin'below.)
Therapyrequiresfrequentclinicalandlaboratorymonitoringandtheidentificationandtreatmentofanyprecipitatingevents,includinginfection.(See'Monitoring'below.)
OurapproachoutlinedbelowispredominantlybaseduponclinicalexperienceandislargelyinagreementwiththeAmericanDiabetesAssociation(ADA)consensusalgorithmsforthetreatmentofDKA(algorithm1)andHHS(algorithm2)andtheJointBritishDiabetesSocietiesguidelineforthemanagementofDKA[1,13,14].
FluidreplacementInpatientswithDKAorHHS,werecommendvigorousIVelectrolyteandfluidreplacementtocorrectbothhypovolemiaandhyperosmolality.
Fluidrepletionisusuallyinitiatedwithisotonicsaline(0.9percentsodiumchloride).Theoptimalrateofisotonicsalineinfusionisdependentupontheclinicalstateofthepatient.Isotonicsalineshouldbeinfusedasquicklyaspossibleinpatientswithhypovolemicshock.(See"Treatmentofseverehypovolemiaorhypovolemicshockinadults".)
Inhypovolemicpatientswithoutshock(andwithoutheartfailure),isotonicsalineisinfusedatarateof15to20mL/kgleanbodyweightperhour(about1000mL/hourinanaveragesizedperson),forthefirstcouplehours,withamaximumof
25/10/2015 Diabeticketoacidosisandhyperosmolarhyperglycemicstateinadults:Treatment
http://www.uptodate.com/contents/diabeticketoacidosisandhyperosmolarhyperglycemicstateinadultstreatment?topicKey=ENDO%2F1795&elapsedTim 3/24
mEq/L.
WhenpotassiumsaltsareaddedtoIVfluids,theyhavethesameosmoticeffectassodiumsalts,andthisshouldbeconsideredwhendeterminingthepotentialeffectsofIVfluidinfusiononchangesinosmolality.Asanexample,40mEqofKCladdedto1Loffluidgenerates80mOsmol/Lofelectrolyteosmolality.Theadditionof40mEqofpotassiumto1Lofonehalfisotonicsalinecreatesasolutionwithanosmolalityof234mOsmol/L(77mEqsodiumchloride[NaCl]and40mEqKCl),whichisessentiallythreequartersisotonicsaline.(Theosmolalityofisotonicsalineis285to308mOsmol/L).If40mEqofKClisaddedtoisotonicsaline,thefinalosmolalitywillbeabout388mOsmol/L.However,KCLwillnothavenearlythesameextracellularfluid(ECF)expansioneffectbecausemostwillshiftintocellsveryrapidly.(See"Maintenanceandreplacementfluidtherapyinadults",sectionon'Choiceofreplacementfluid'.)
AlmostallpatientswithDKAorHHShaveasubstantialpotassiumdeficit,mainlyduetourinarylossesrelatedtotheglucoseosmoticdiuresisandtosecondaryhyperaldosteronism.Despitethetotalbodypotassiumdeficit,theserumpotassiumconcentrationisusuallynormalor,inaboutonethirdofcases,elevatedatpresentationdueprimarilytoinsulindeficiencyandhyperosmolality,bothofwhichresultinpotassiummovementoutofthecells[22].Thechangeinpotassiumdistributionisrapidlyreversedwiththeadministrationofinsulin,resultinginanoftendramaticfallintheserumpotassiumconcentration,despitepotassiumreplacement[19,20].However,cautionisnecessaryifrenalfunctionremainsdepressedand/orurineoutputdoesnotincreasetoalevel>50mL/hour.CarefulmonitoringoftheserumpotassiumisessentialforthemanagementofbothDKAandHHS.(See'Monitoring'belowand"Diabeticketoacidosisandhyperosmolarhyperglycemicstateinadults:Epidemiologyandpathogenesis",sectionon'Potassium'.)
InsulinWerecommendtreatmentwithlowdoseIVinsulininallpatientswithmoderatetosevereDKAorHHSwhohaveaserumpotassium3.3mEq/L.Theonlyindicationfordelayinginsulintherapyisaserumpotassiumbelow3.3mEq/L,sinceinsulinwillworsenthehypokalemiabydrivingpotassiumintothecells.Patientswithaninitialserumpotassiumbelow3.3mEq/Lshouldreceiveaggressivefluidandpotassiumreplacementpriortotreatmentwithinsulin.Insulintherapyshouldbedelayeduntiltheserumpotassiumisabove3.3mEq/Ltoavoidpossiblearrhythmias,cardiacarrest,andrespiratorymuscleweakness[1,19,20].(See'Potassiumreplacement'above.)
IVregularinsulinandrapidactinginsulinanalogsareequallyeffectiveintreatingDKA[23].Duetocostconsiderations,weprefertreatmentwithregularinsulin,ratherthanrapidactinginsulinanalogs.ChoiceofIVinsulinshouldbebaseduponinstitutionalpreferences,clinicianexperience,andcostconcerns.(See'Intravenousregularinsulin'belowand'Intravenousinsulinanalogs'below.)
Insulintherapylowerstheserumglucoseconcentration(primarilybydecreasinghepaticglucoseproductionratherthanenhancingperipheralutilization[24]),diminishesketoneproduction(byreducingbothlipolysisandglucagon
Iftheinitialserumpotassiumisbelow3.3mEq/L,IVpotassiumchloride(KCl20to40mEq/hour,whichusuallyrequires20to40mEq/Laddedtosaline)shouldbegiven.Thechoiceofreplacementfluid(isotonicoronehalfisotonicsaline)dependsuponthestateofhydration,correctedsodiumconcentration,doseofKCl,bloodpressure,andaclinicalassessmentofoverallvolumestatus.Potassiumrepletionismosturgentinpatientswithmassivepotassiumdeficitswhoarehypokalemicpriortotherapy[1921].Suchpatientsrequireaggressivepotassiumreplacement(40mEq/hour,withadditionalsupplementationbaseduponhourlyserumpotassiummeasurements)tomaintaintheserumpotassiumconcentrationwithinthenormalrangeof4to5mEq/L.
Iftheinitialserumpotassiumisbetween3.3and5.3mEq/L,IVKCl(20to30mEq)isaddedtoeachliterofIVreplacementfluidandcontinueduntiltheserumpotassium(K)concentrationhasincreasedtothe4.0to5.0mEq/Lrange.
Iftheserumpotassiumconcentrationisinitiallygreaterthan5.3mEq/L,thenpotassiumreplacementshouldbedelayeduntilitsconcentrationhasfallenbelowthislevel.
25/10/2015 Diabeticketoacidosisandhyperosmolarhyperglycemicstateinadults:Treatment
http://www.uptodate.com/contents/diabeticketoacidosisandhyperosmolarhyperglycemicstateinadultstreatment?topicKey=ENDO%2F1795&elapsedTim 4/24
secretion),andmayaugmentketoneutilization.Theantilipolyticactionofinsulinrequiresamuchlowerdosethanthatrequiredtoreducetheserumglucoseconcentration.Therefore,iftheadministereddoseofinsulinisreducingtheglucoseconcentration,itshouldbemorethanenoughtostopketonegeneration[9,24,25].(See"Diabeticketoacidosisandhyperosmolarhyperglycemicstateinadults:Epidemiologyandpathogenesis",sectionon'Pathogenesis'.)
