Neonatal Narcotic Abstinence Syndrome: A National .1 Neonatal Narcotic Abstinence Syndrome: A National

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NeonatalNarcoticAbstinenceSyndrome:ANationalEpidemic

Moira Crowley, MDAssistant Professor, PediatricsNeonatal Faculty, NAS ProjectPerinatal Quality Collaborative

Ohio Childrens Hospitals Neonatal Research Consortium

Objectives

Describe the opioid epidemic in the United States as well as on a local level

Review the mechanism of action of opiates and what causes withdrawal symptoms

Describe current treatment strategies for NAS and outcomes

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NEONATALABSTINENCESYNDROME:SCOPEOFTHEPROBLEM

Pain 1995:studiesshowed

cancerpatientspainwasundertreated.

1995:AmericanPainAssociationissuedguidelinesonpainmanagement.

1999:USVeteransAffairsDeptadoptedandspreadphysicianeducation

2000:JointCommissiononHospitalAccreditation:PainistheFifthVitalSign

PrescriptionDrugUseOntheRise

NarcoticprescriptionsinU.Sincreased6foldfrom19972006

Nowaccountformoreoverdosedeathsthancocaineandheroincombined

Moredeathsthancaraccidents In2010,enoughopiatepainrelieverswereprescribedtomedicateeveryAmericanadultwithastandardpaintreatmentdoseof5mghydrocodoneq4hrfor1month

CDC.gov

MMWR, July 2, 2013

DeathsfromNarcoticOverdosesinYoungWomen

Date of download: 11/6/2012 Copyright 2012 American Medical Association. All rights reserved.

From: Neonatal Abstinence Syndrome and Associated Health Care Expenditures: United States, 2000-2009

JAMA. 2012;307(18):1934-1940. doi:10.1001/jama.2012.3951

Date of download: 11/6/2012 Copyright 2012 American Medical Association. All rights reserved.

From: Neonatal Abstinence Syndrome and Associated Health Care Expenditures: United States, 2000-2009

JAMA. 2012;307(18):1934-1940. doi:10.1001/jama.2012.3951

This represents1 infant born per hour in the US with sings of drug withdrawal

EpidemicofUnintentionalDrugOverdosesinOhio19792008

NarcoticprescriptionsinOhioincreased6foldfrom1997to2006

OpiateRelatedAdmissionstoTreatmentCenters 2001

EpidemicisSpreading 2005

EpidemicisSpreading 2007

EpidemicisSpreading2009

EpidemicisSpreading2011

NewbornHospitalizationsforNASInOhio

WhatDoseIllicitSubstanceUseLookLikeinGeorgia?

~7%Georgiaresidentsusedillicitdrugsinpastmonth

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SubstanceAbuseTreatmentAdmissions,2005

17Source:ONDCP,GeorgiaDrugControlUpdate

NonmedicalUseofPrescribedOpiates

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NeonatalAbstinenceSyndrome

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NeonatalAbstinenceSyndrome(NAS)

Awithdrawalsyndromeexperiencedbydrugexposedneonates

Usuallyreferstosymptomsfromopiateexposure Otherdrugsimplicated

Benzodiazepines,SSRIs,Cocaine,Amphetamines,Alcohol

Affects55%94%ofexposedneonates

Diagnosis UniversalscreeningofALLpregnantwomen Testingofurine,meconium,hairorumbilicalcordsamples

Urinemayhavefastestturnaroundbutonlyreflectsrecentexposure(

PresentationofOpioidWithdrawal

TimingWhichopioidabused

Maybedelayeduntil7ormoredays LastusebymomNettransferacrossplacenta InfantmetabolismPolysubstanceuse

OpioidreceptorsconcentratedwithinCNSandGItract

SpecificSigns CNS irritability

Inconsolable, hyperactive reflexes, poor sleep, seizures

Autonomic over reactivity Sneezing, temperature instability, sniffles

Gastrointestinal Dysfunction Loose stools, emesis/reflux

OriginofNASAssessmentToolsFinneganLP,ConnaughtonJFJr,KronRE,EmichJP.Neonatalabstinencesyndrome:

Assessmentandmanagement.AddictDis.1975;2(1):141158.

Circa1975

IDsymptomsfortoolfromliteratureandclinicalexperience

Symptomsrankedbypathologicalsignificance

Initialtoolcomposedof32weighteditems

ImpactofTool Decreasedneedforpharmacologicalmanagement(30%versus46%)comparedtonoscoringsystem

Decreaseddurationoftreatment(6versus8days)

Reducedhospitalstayby25%

ModifiedFinneganTool 1986ModificationstoOriginalFinnegan

21originalitems

Reorganizedinto3categories:

CNS,GIandmetabolic

SamescoringprocessandcutoffpointsforRXtreatment

ValidationStudies

Nonefound

UsedbysignificantmajorityofNICUs

Howmanyothermodifiedtoolsareoutthere?

PharmacologyofNAS

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WhatDoOpioidsDo? Opiatereceptors(,,)

Allfoundinbrain alsoinGItract

Activationofreceptormodulatesneurotransmitterrelease: Norepinephrine

Acutely inhibits release at synaptic terminals Rate of release over time increases towards

normal with chronic use Also:Serotoninacetylcholine,dopamineandsubstanceP

ClinicalManifestationsofOpioidUse

Analgesia Drowsiness Respiratory depression Decreased GI motility, nausea and vomiting Use tolerance, physiologic dependence,

addiction

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WhatHappensWhenExposureEnds?

Abrupt discontinuation supranormal norepinephrine release Autonomic and behavioral signs associated

with NAS

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PharmacologicTreatmentofNAS

RelievemoderatetoseveresymptomsofNAS Finneganscores>8

Nonpharmacologictherapyexhausted Humanelybutlowestpossibleexposure

Neuronalapoptosis

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CurrentNeonatalStrategies Firstline:opiate generallymorphine Methadone:?Concernforpharmacokinetics,andarrhythmia?

Osborn, et al Cochrane Database, 2010

Mayturnouttobebetterdrug ReportsoflongQTsyndrome Ifchoosethisdrug,recommendbabiesbeonCRmonitor.

Methadone

Buprenorphine Partialopioidagonist,sublingualtablet 2smallrandomizedopenlabeltrials,Kraftetal2008and2011 Buprenorphinevs.tinctureofopium

Nodifference Buprenorphine(higherdose)vs.morphine

Decreasedtreatmentdaysandhospitalstay

Limitedsafetydata,varyingserumconcentrations

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SecondLine Whenmaxopiatedosereached

Opiate + Pheno Opiate aloneTime Score> 8(%) 10% 15%Duration Hosp (d) 35 21 76 22Max Dose 4.7 16.8Costs ($US1000) 33.3 17.9 69.2 19.7

Osborn, Cochrane Review, 2010

Phenobarbital

Long-acting barbiturate CNS depression Enhancement of inhibitory neurotransmitter -

aminobutyric acid Polypharmacy

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Clonidine

Centraladrenergicreceptoragonist Actsatparasympatheticreceptorsinmidbrainandmedulla inhibitsympatheticoutflowbydecreasingcentralcatecholaminerelease Decreasesvasomotortoneandheartrate

Abruptdiscontinuation hypertensionandsympatheticoveractivity(tachycardia,agitation,sweating)

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Clonidine,cont.KaplanMeiercurveeffectofclonidineondaysofDTOtherapy

EffectofclonidineonamountofDTOneededtocontrolNAS

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From:Agthe,etalPediatrics,May2009

KnowledgeGaps Sizeofepidemic Optimaltreatmentstrategies,includingdrug,dose,safety,sideeffectsduetodifferencesinneonatalmetabolism

ImpactofpolysubstanceuseonseverityofNAS Differencesinoutcomefordifferentmaternaltreatmentstrategies

Safetyoftreatmentasoutpatient Longtermoutcomesofchildrenexposedtonarcoticsinutero

OhioChildrensHospitalNASConsortium

OrganizedinJan2012 CharteredbyGovKasichtoworktogethertoimprovecareofchildren

NeoInauguralProject:NAS launchedSept2012

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Descriptors:553neonates(2012 2013)

Mean RangeMaternal Age, y 26.7 y 17-44Maternal RaceWhite, Non-Hispanic ( %)

92%

Single 84%Insurance,

PublicNone

80%10%

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PerinatalDescriptorsN= 553

Prenatal Care 89%

Pregnancy Complications

85%

Sexually Transmitted Disease

7%

HIV 0

Hep C 25.9%

Hep B 1.0%

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MaternalOpiateExposures

Source: IllegalPrescribed

Unknown

46%34%20%

0

50

100

150

200

250

300

Opiate Short ActingHeroin Methadone>1 Opiate

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InfantTreatmentCharacteristicSymptoms Started (hours; Mean)

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Treatment Length (days; Mean)

18.5

Hospital Stay (days; Mean) 22.2

Number of Drugs Used (Mean) 1.5

Drugs usedMorphineMethadone

50%49%

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010

2030

4050

60

Day

s

A B C D E FCENTERS

TreatmentStay

DifferencesbySite

0

50

100

150

200

250

300

350N

umbe

r with

Co-

Expo

sure

TobaccoMarijuanaCocaineAlcoholAmphetamine

PolyExposures

MultipleSimultaneousWithdrawals

82% Exposed to tobacco Average cotinine level by cord analysis 135

ng Maximum = 270 Average US Adult Smoker= 100 ng

10% Exposed to SSRI or Benzodiazepine Known withdrawal syndromes

010

2030

4050

Day

s

A B C D E FCENTERS

MorphineMethadone

DifferencesbyDrug

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OhioPotentiallyBetterProtocolNon-Pharmacologic

Swaddle, Comfort, MBM or 22 Calorie

Initiate NAS score 9 q3h two timesDrug: Morphine/ Methadone0.05 mg/kg PO

Escalate If 12, increase doseStabilize No increase for 48 hrsWean 10% of max dose daily

Discharge 48 hours off drug

01020

30405060

7080

1 2 3 4 5 6 7 8 9 10 11 12 13

Consecutive Patients

Trea

tmen

t Day

sImpactofProtocol

New Protocol

HowCanWeSpreadWhatWeveLearned?

OPQC January 2014 started the NAS project

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WhoIsOPQC? OhioDepartmentofJob&FamilyServices OhioDepartmentofHealth VitalStats OhioMedicaid OhioACOGAAP Peds +OB +Quality Improvement Leaders OPQCCentral

SecureCentralDeidentifiedDataProcessing

S