NeonatalAbs,nenceSyndromeHowWeGotHereandWhereWeAreGoing
KathrynZiegler,DO,FAAPNewbornSpecialCareAssociates
AbingtonJeffersonHealth
Disclosures
• Ihavenofinancialdisclosures• Wewilldiscusstheuseofmorphineininfantswhichisanofflabeluse
Objec,ves
• Discusstheincidence/epidemiologyofopioiduse
• Discusstheincidence/epidemiologyofNeonatalAbs,nenceSyndrome
• DiscusstreatmentstrategiesforNeonatalAbs,nenceSyndrome
• DiscussQualityImprovementEffortsforNeonatalAbs,nenceSyndrome
Opioids
• Natural,endogenousandsynthe,c• BindµreceptorsinCNS– Supraspinalanalgesia– Seda,on,euphoria,miosis,respiratorydepressionanddecreasedGImo,lity
– Prolongedusecausesphysicalandpsychologicaldependence
Opioids
• Natural– Morphine(extractedfromopium)
• Synthe,c– Codeine,heroin,hydromorphone,fentanyl,methadone
• Endogenous– Enkephalins,endorphins,endomorphins
TheProblem
• Overdosedeathrateincreasedby137%since2000– 200%increasedindeathfromopioidoverdose
• Americansconsume80%ofglobalopioidsupply– 99%ofhydrocodonesupply
• Heroinoverdoseshavetripledinlast4years– Pastmisuseofprescrip,onopioidsclearlylinked
Manchinka,,etal
IncreasingDeathfromOpioids• Sex:
• Males(7.6%)• Females(4.7%)
• Age• 25-34yearolds(10.5%)• 35-44yearolds(8.7%)• 55-64yearolds(5.7%)• ≥65yearolds(7.7%)
• Race• White,nonhispanic(8%)• Black,nonhispanic(8.2%)
• Geography• Northeast(8.8%)• Midwest(9.6%)• South(6.9%)
Rudd,R.A.etal
IncreasesinDrugandOpioidOverdoseDeaths—UnitedStates,2000–2014
AmericanJournalofTransplantaConVolume16,Issue4,pages1323-1327,22MAR2016DOI:10.1111/ajt.13776hgp://onlinelibrary.wiley.com/doi/10.1111/ajt.13776/full#ajt13776-fig-0002
TheProblem
1986Publica,onthatopioidscanbeusedin
peoplewithoutcancer
andpain
1996AmericanPain
SocietyTradmarkspainasthe5thVS
1996
PurduePharmareleasesoxycon,n
1998VA/JCHAO
makepain5thVS
1998Federa,onofStateMedicalBoards-Drscan
safelyRxnarco,cs
TheProblem
2001JCHAOissuesstandardsurging
hospitalstoregularlyaskpa,entsabout
pain
2001JCHAO
publishesguidetoaddressphysician
concernsaboutaddic,onandtolerance
2007Purdue
Pharmapleadsguiltyto
misbrandingofoxycon,n
2012259
millionopioidRxwrigen$9billion
2013Opioiddeathssurpasscaraccidentsas
leadingcauseofaccidentaldeath
TheProblem
• Pregnantwomendonotescapethereachofopioidaddic,on– 4.5%ofpregnantwomenreportusingillicitdrugs
• InfantsborntowomenonopioidsareatriskofNeonatalAbs,nenceSyndrome(NAS)
• 300%increaseinNAS(2000-2013)– 1.5à6cases/1000hospitalbirths
hgps://www.cdc.gov/mmwr/volumes/65/wr/mm6531a2.htm
TheProblem
• Pennsylvaniabythenumbers(2000-2015)– Neonatalstaysrelatedtosubstanceabuse
• é250%(6.5à19.6/1000neonatalstays)
– Neonatalabs,nencesyndrome• é870%(1.6à16/1000neonatalstays)
– Cost• 28,000days• $20million
NeonatalAbs,nenceSyndrome
• Constella,onofsymptomsseenininfantswhoareexposedtoopiatesinutero
• Somevaria,oninonsetandseverityofsymptoms– Timingofmostrecentdrugusepriortodelivery– Maternalmetabolism– Placentalmetabolism– Infantmetabolism/excre,on– Concomitantuseofotherdrugs/substances
NeonatalAbs,nenceSyndrome
• 55-94%ofinfantsexposedinuteroexhibitsymptoms
• Seldomeffectsinfants<34weeksgesta,on
OpioiduseinPregnancy
• Opioidsaresmall,lipophilic,lowmolecularweight– Crossplacentalandbloodbrainbarriers
• Detoxifica,onassociatedwithincreasedriskoffetaldistressandloss
NeonatalAbs,nenceSyndrome
• CNSsymptoms– Con,nuousand/orhigh-pitchedcrying– Difficultysleeping– Hyperac,veMoroReflex– Tremors– Hypertonicity– Skinexcoria,on– Generalizedconvulsions/seizures
NeonatalAbs,nenceSyndrome
• AutonomicSymptoms– Temperatureeleva,on– Sneezing/nasalstuffiness– Mogledskin– Tachypnea– Swea,ng– Yawning
NeonatalAbs,nenceSyndrome
• Gastrointes,nalsymptoms– Feedingdifficul,es
• Unabletoorganizetofeed• Bi,ngnipple• Lackofcoordina,on
– Frequentwatery/loosestools• Leadstoskinbreakdown
– Regurgita,on– Excessivesucking– Failuretothrive
NeonatalAbs,nenceSyndrome
Substance OnsetofSymptoms
Heroin Birth–3days
Methadone/buprenorphine
Birth–7days(subacutesignsupto6months)
Benzodiazapene Hours-2weeks
NonNarco,cSubstanceExposure
• Cocaine– Nowithdrawal
• NEC,abrup,on,fetaldistressandIUGR
• Alcohol– Hyperac,vity,tremors,poorsuck,hyperphagia– Sxatbirth
• Caffeine– Jigeriness,bradycardia,vomi,ng,tachypnea– Sxatbirthandfor1-7days
NonNarco,cSubstanceExposure
• Barbiturates– Similartoopioids– Sxatbirthupto14days
• SSRI’s– Irritability,tremors,poorsuck,feedingdifficul,es,hypertonia,fever,hypoglycemia,seizures
– Sxhourstodays
NonNarco,cSubstanceExposure
• Benzodiazapene– Similartoopioids
• Hypo/hypertonia• Poorsuck• Hypothermia• Apnea• Tremors• Vomi,ng• Tachypnea
– Onsethourstoweeks
Differen,alDiagnosis
• Sepsis– meningi,s
• Electrolyteabnormality• Hematologicirregulari,es• Perinatalasphyxia• Intracranialpathology
Diagnosis
• History,history,history– Maternalmedical,familyandsocialhistory– Pregnancyhistory– Birthhistory
• Labs– Cbc,bmp,+/-bloodculture(ifillappearing)– Urine/meconiumdrugscreens
• Risk/benefitevalua,on– RarelyLPifhistoryc/wNAS
Drugtes,ng
• IdeallyUDSfrommotheronadmission• InfantUDS(preferablyfirstvoid)• InfantMeconiumdrugscreen– Reflectsexposurefrom20weeksGA– Collectfirsttwosamples
• Infanthair• Umbilicalcord,ssue
Assessment
• FinneganScoring– DevelopedbyDr.LoregaFinneganin1975– Providesquan,ta,veassessmentofNAS– PredominanttoolusedinUnitedStates– Usedfortermneonates<3weeksofage
UsingtheFinneganScore
• Beginscoringwheninfantsshowsignsofwithdrawal– Scoreq3-4hours,auerfeedswheninfantatbest
• Start“treatment”when3scores≥24or2scores≥24oronescoreof≥14
Treatment
• Nonpharmacologic– Swaddling– Holding,rocking,swaying– Quiet,dark,nons,mula,ngenvironment– Encourageroomingin
• Extendedfamily
BreasxeedingandNAS?
• YES!!!– Ifmotherisinatreatmentprogram– UDSisposi,veonlyformethadone/buprenorphine
• AssociatedwithlesssevereNASthatpresentslaterandislesssevere
• Lessfrequentlyrequirespharmacologicinterven,on
BreasxeedingandNAS
• Smallamountsmethadone/buprenorphinesecretedintobreastmilk
• Longtermneurodevelopmentalinforma,onnotavailable
• Notenoughdatatodiscouragebreasxeeding• Frankdiscussionwithmotheraboutslowweaning
PharmacologicTreatment
• 83%ofcliniciansintheUnitedStatesuseanopioidasthedrugoffirstchoice– MorphineorMethadone
• Phenobarbitalismosttypicalsecond-linedrugifopiatedoesnotcontrolsymptoms
• Clonidineasadjunc,vetherapyalsoanop,on• Alsoconsiderusingmethadone
QualityImprovement
• Recentlymul,plestudieshavesurfacedlookingatthecareofNAS
• FocusondecreasedLOS– Decreasedcost
• Standardiza,onoftreatments• NASEduca,on• RoomingIn
NASatAbingtonHospital
• AbingtonHospital– 8milesnorthofPhiladelphia– Approximately5000deliveries/year– 34bed;Level3bNICU
• Increasingopioidexposedinfants• NAStaskforceformedin2014
NASatAbingtonHospital
• PreData– June2013-June2015– 101infantswithposi,veUDS/MDS– 36infantsrequiredtreatmentwithmorphine– LOSwithNAS22.4days– LOSwithoutNAS4.1days
37
9
2
25
25
17
82
Methadone
Cocaine
PCP
Oxycodone
Opiates
MJ
Benzo's
Barbituartes
AbingtonHospital-Posi,veDrugScreen
FutureDirec,ons
• YaleNewHavenChildren’sHospital• Standardiza,onofnonpharmacologic
care• Parentaleduca,on• NovelAssessmentApproach• Morphineprn• BypassingtheNICU
• NovelApproachtoNAS• Func,onalAssessment• Abilitytoeat• BFeffec,velyortake>1oz/feed
• Abilitytosleep• Undisturbed>1hour
• Abilitytobeconsoled• Within10minutes
• NovelapproachtoTreatment• Ifonscheduledmorphine• 10%weanTID
• Auermaximumnonpharmacologicinterven,ons• 1doseofmorphinegiven(0.05mg/kg)• Reassesed3hourslater• Ea,ng,sleepingandconsolingwell• Nofurtherdoses
• 55infantspreimplementa,on• 44infantspostimplementa,on– LOS:22.4à5.9days– PharmacologicTx:98%à14%– Costs:$44,000à$10,000– Noreadmissions,noadverseevents
Summary
• Opioidaddic,oniscurrentlyanepidemic• Pregnantwomencanbeaddicted• NeonatalAbs,nenceSyndrome–treatmenthasbeenstablethroughtheyears
• Breastfeedwhenable• AssessmentchangehasnoADRs• Nonpharmacologictreatmentisfeasible
Acknowledgements
• NASTaskForceatAbingtonHospitalJeffersonHealth
• MoiraWinstanley,NNP-BC• AndrewLoh,MD
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