Transcript Neonatal Abstinence Syndrome - South Dakota Perinatal Association

Neonatal
Abstinence
Syndrome
Lauritz Meyer, MD
September 11, 2015
SDPA Conference
Disclosure
• I have no financial relationships to disclose.
Objectives
• Describe the incidence of Neonatal Abstinence
Syndrome in the United States
• Identify common symptoms of Neonatal
Abstinence Syndrome
• Familiarize with scoring systems for Neonatal
Abstinence Syndrome
• Identify treatment strategies for Neonatal
Abstinence Syndrome
Neonatal Abstinence
Syndrome
• Defined as a group of clinical signs and symptoms
in a neonate resulting from prolonged exposure to
illicit or prescribed drugs
• Also called Neonatal Drug Withdrawal
• Short term syndrome but may have long lasting
effects
• Can be caused by in-utero exposure or iatrogenic
exposure in hospitalized neonates
Opiate History
• Opium derived from the poppy
• First records of opium addiction are from the late
18th century
• Increase in opioid addiction among women noted
in the 19th century
Opiate History
• Morphine isolated in 1804
o Use among women was associated with sterility
• Heroin synthesized in 1874
• Initially thought addiction among women did not
affect infants
Opiate History
• 1875: first reported case of neonatal abstinence
o More over years, most died, no specific treatment
• 1903: First report of neonate surviving abstinence
after Tx with morphine
o Called Congenital Morphinism
• 1947: Seizures in a baby with Congenital Morphinism
were successfully treated with morphine
o Led to increased awareness and name changed to Abstinence
Syndrome in Neonates
Opiate History
• Methadone:
• Introduced in 1964 as a replacement treatment for
opioid addiction
• Methadone clinics became very common for
treating recovering heroin addicts
• Initially thought to not cause withdrawal in
neonates, likely secondary to increased half life but
since has become a common cause of NAS
Opiate History
• Buprenorphine:
• Approved as an alternative to methadone for
opioid addiction in U.S. in 2002
o Sublingual tablets
• Also leads to NAS
o May cause less severe NAS symptoms than methadone
Illicit Drug Use in the U.S.
• 2013 National Survey on Drug Use and Health
o 9.4% of population age 12 and older used illicit drugs within the past
month (24.6 million individuals)
o 5.4% of pregnant women aged 15-44 were current illicit drug users
• 14.6% in age 15-17 year olds
• 9% in the first trimester
• 4.8% in the second trimester
• 2.4% in the third trimester
o 22.9% of population age 12 and older were binge alcohol users in the past
month (60.1 million individuals)
• 6.3% were defined as heavy drinkers
o 9.4% of pregnant women were current alcohol users, 2.3% were binge
drinkers, and 0.4% were heavy drinkers
Illicit Drug Use in the
Upper Midwest
• 2013 National Survey on Drug Use and Health
o South Dakota
• 6.17% of 12 years and older have used illicit drugs in the past month
(42 thousand individuals)
o Minnesota
• 7.63% of 12 years and older have used illicit drugs in the past month
(343 thousand individuals)
o Iowa
• 7.34% of 12 years and older have used illicit drugs in the past month
(188 thousand individuals)
Incidence of NAS
• Rising
• Incidence has nearly doubled in the past 15 years
based on national ICD-9 coding
• Becoming more widespread
o No longer just inner cities
o Increased use of prescription pain medications in pregnant women
o Improved recognition of NAS
NAS Causing Drugs
• Opioids
o Morphine, Methadone, Hydromorphone, Fentanyl, Heroin
• CNS Depressants
o Benzodiazepines, Alcohol, Barbiturates
• CNS Stimulants
o Amphetamines, Cocaine, Nicotine, Caffeine
• Hallucinogens
o LSD, inhalants, mescaline
• Polysubstance use
• SSRIs
Opioids
• Among the world’s oldest known drugs
o Use of opium poppy goes back milennia
• Three types: natural, endogenous, and synthetic
• Produces analgesia by binding to mu-opioid
receptors in the CNS, PNS, and GI system
o Leads to inhibition of noradrenaline release
• Effects include:
o
o
o
o
Sedation
Euphoria
Respiratory depression
Decreased GI motility
• Long term use leads to physical dependence
Opioids
• Withdrawal
o The initial condition that led to the diagnosis of NAS
o Abrupt discontinuation leads to:
• Massive release of noradrenaline
• Leads to autonomic, behavioral, and GI symptoms/signs
o Timing, presentation, and severity of symptoms dependent upon maternal
and neonatal factors
• Drug, dosage, time since last use, placental transfer, metabolism
• Mu-opioid receptor (OPRM1) and catechol-o-methyltransferase
(COMT) gene genetic variations affect the need for and the length of
treatment
Opioids
• Neonates exposed in-utero have signs/symptoms of
opioid withdrawal 55-94% of the time
• Addition of other maternal or neonatal
medications, neonatal diet, and environmental
stimuli can affect the severity and incidence of NAS
• Symptoms can present within the first 24 hours of life,
or be delayed for 7 days or longer
o Dependent on type of drug, metabolism, etc.
Clinical Symptoms of
NAS due to Opioids
• Neurologic
o
o
o
o
o
o
o
o
o
Tremors
Irritability
Increased wakefulness
High-pitched cry
Hypertonicity
Hyperactive reflexes
Exaggerated Moro
Seizures
Frequent sneezing/yawning
• Gastrointestinal
o
o
o
o
o
o
Vomiting/diarrhea
Poor feeding
Uncoordinated suck
Constant sucking
Dehydration
Poor weight gain/FTT
• Autonomic
o
o
o
o
o
Excessive sweating
Temperature instability
Nasal stuffiness
Mottling
Yawning
Video
• https://www.youtube.com/watch?v=2eP5EnFSG0c
Clinical Symptoms (cont.)
• Seizures occur in 2-11 percent of NAS cases
• EEG abnormalities have been seen in up to 30% of
NAS cases attributed to opioids
• Increased incidence of Small for Gestational Age
(SGA) births
• Increased incidence of respiratory difficulties
Timing of Withdrawal
• Wide variation dependent upon the half-life of the
drug and the recent history of drug use
• Symptoms can present within the first 24 hours for
short half life drugs (Heroin), but may not present for
72 hours up to 7 days or longer for long half life
drugs (Methadone, Buprenorphine)
• Neonates born to mothers who have gone >7 days
from last use are at much lower risk for NAS, but still
require close monitoring
Methadone
• Common prescription drug used for recovering
Heroin addicts
• Long half life leads to delayed presentation of NAS
symptoms for several days
• Higher daily doses are more likely to lead to NAS
o >95% of infants will develop symptoms with doses >20mg/day
• Difficult to wean mothers during pregnancy due to
high risk of fetal complications with abrupt dose
changes
Buprenorphine
• Increasing use for opiate withdrawal including
during pregnancy
• Lower transplacental transfer due to higher
molecular weight
o Thought to lower the incidence and severity of NAS
• Decreased length of stay for infants with NAS
• Subutex – buprenorphine only
• Suboxone – buprenorphine plus naloxone to guard
against misuse
Fentanyl
• Use of transdermal patch increasing for treatment
of chronic pain
• Short half life leads to rapid symptoms of NAS in the
first 24 hours
• Risk of rapid withdrawal for mother if lose access to
supply of patches
• Breastfeeding a concern due to risk of rapid
withdrawal
Depressants
• Alcohol withdrawal can present 3-12 hours after
birth
• May show symptoms of NAS similar to opioid
withdrawal although usually more mild
• Benzodiazepine withdrawal can have a variable
onset dependent upon half life and dosage
Stimulants
• Methamphetamine and cocaine have low rates of
NAS requiring therapy
• Symptoms at birth more likely the result of drug
effects vs withdrawal
o Similar symptoms to opioid NAS – tremors, irritability, poor sleep pattern,
excessive sucking, etc
• High rates of prematurity and IUGR status
• Increased risk of placental abruption
• Common to see polysubstance use
SSRIs
• Used in 7-13% of pregnancies
• 10-30% risk of Poor Neonatal Adaptation Syndrome
• Tremors, increased tone, high pitched cry, poor
sleep patterns are common symptoms
• Increased rate of respiratory distress
• Increased risk of PPHN
• Generally presents in the first 48 hours of life and
resolve within another 48 hours
• Paroxetine (Paxil) carries the highest risk
Withdrawal vs Toxicity
• Withdrawal:
o Symptoms develop as the amount of drug decreases, indicative of
dependence on the drug
o Most common with opioids, but also with depressants and SSRIs
• Toxicity:
o Symptoms present early and decrease as the drug is metabolized
o Most common with stimulants such as cocaine or methamphetamine
Premature Infants
• Lower risk of developing NAS <35 weeks
• Central Nervous System developmentally immature
o Motor dysfunction less able to be expressed
• Lower total drug exposure in-utero
• Lower fat stores limits build up in the body
• Lack of accurate assessment tools to identify
symptoms in premature infants – all assessment tools
created for term infants
• Risk decreases with decreasing GA
Iatrogenic NAS
• Many NICU patients are exposed to opioids and
benzodiazepines during their stay (surgical, sedation
for PPHN, ect.)
• May develop after 5-7 days of exposure to
fentanyl/morphine or benzodiazepines
• Important to recognize the risk and treat these
infants similar to in-utero exposure to avoid adverse
outcomes
What To Do?
• Neonate is at risk for NAS based on known exposure
history or has other risk factors that are concerning
for possible NAS
• Drug Screen
• Initiate abstinence scoring system
• Close observation
Drug Screening
• Urine
o Low sensitivity due to need for a recent exposure to show positive
o Rapid turn around time (within 24 hours)
• Meconium
o High sensitivity and specificity
o Slow turn around time (days to a week)
o May miss meconium if stooled in-utero or at birth and not collected
• Umbilical Cord
o Increasing use
o Not dependent upon collection of urine or meconium
o Eliminates possibility of false positive secondary to exposure after birth
Abstinence Scoring
• Several scoring systems are available with no clear
standard
• Not drug specific – primarily for opiates
• Most hospitals choose one and adapt to their
needs
• Two most common: Finnegan Neonatal Abstinence
Scoring System, Neonatal Withdrawal Scoring
System (Lipsitz)
• Others available: Ostrea criteria, Neonatal
Withdrawal Inventory, Riley Infant Pain Scale
Finnegan
Finnegan
• Most widely used scoring system
• Comprised of 20 most common signs and grouped
into CNS, metabolic/respiratory, and GI categories
• Each symptom assigned a score based on
significance and potential for harm
• Cumulative score of 7 or less considered mild NAS
without need for pharmacologic treatment
• Scores >8 suggest careful monitoring and likely
need for pharmacotherapy
Lipsitz
• Assigns a score of 0 to 3 for tremors, irritability,
reflexes, stools, muscle tone, skin abrasions, and
tachypnea
• Assigns a score of 0 to 1 for frequent sneezing,
frequent yawning, and vomiting or fever
• A score of 5 or greater suggests opiate exposure
• A score of 8 or greater indicates need for
pharmacotherapy
Treatment
• Goals of treatment:
o Allow the infant to withdraw without excessive excitation that can lead to
withdrawal symptoms
o Especially important to avoid the most severe, i.e. seizures
o Establish a physiologic sleep pattern
o Establish consistent weight gain
o Allow the infant to communicate needs with caregivers
o Help the infant manage new stimuli in its new environment
Non-pharmacologic
Treatment
• First line therapy is ALWAYS non-pharmacologic
• Required for all infants with suspected NAS
• Keep environmental stimulation to a minimum
o Low light
o Quiet environment
•
•
•
•
•
Swaddling
Gentle handling with cares/cluster cares
Quick response to symptoms
Demand feeding
***Cuddlers***
Non-pharmacologic
treatment
• Many large centers with a high population of NAS
cases have a specific section or completely
separate NICU dedicated to the care of NAS
babies
• Nursing care with experience in caring for NAS
babies is crucial to help ensure a safe and swift
recovery
Pharmacotherapy
• Decision to initiate pharmacotherapy based on
abstinence scoring and the known or suspected
drug exposure
• Indicated when non-pharmacologic treatment is
insufficient
• Indicated for moderate/severe symptoms
• Required to prevent severe complications, i.e.
seizures
Pharmacotherapy
• Drawbacks:
o Increases length of drug exposure
o Increases length of stay
o May impact maternal-infant bonding as a result
• Benefits:
o Decreases the acute signs of NAS
o Decreases the risk of severe complications like seizures or failure to thrive
Pharmacotherapy
• Ideally treat with the same class of drug as that
causing NAS
• Choice can be a challenge when drug of exposure
is unknown or in setting of polysubstance use
Pharmacotherapy
• Mainstay of therapy has been opioids
• Opioids are first line treatment based on available
evidence
• Historic use of tincture of opium and paregoric have
fallen out of favor due to safety concerns
• Morphine and Methadone are the two most
common opioids used to treat NAS
• Buprenorphine is a potential option but limited
safety and efficacy data in neonates
o Sublingual dosing appeal
Pharmacotherapy Morphine
• Variety of dosing regimens available for Morphine
• High dose
o 0.08-0.1 mg/kg every 4 hours PO
• Low dose
o 0.03-0.04 mg/kg every 4 hours PO
• With either regimen, the dose may be increased by
20% every 8 hours until symptoms are well controlled
• Typical maximum dose is 0.2 mg/kg/dose
• Other regimens include escalation by changing to
every 3 hour dosing
Pharmacotherapy Morphine
• Weaning is individualized to each patient
• Typical approach is to maintain current dose when
adequate symptom control is achieved
• After 48-72 hours of stability may begin weaning
• Wean by decreasing dose by 20% every other day
• May require delayed taper or escalation if
symptoms worsen
Pharmacotherapy Methadone
• Typical starting dose of 0.05-0.1 mg/kg every 6 hours
PO
• Adjust doses up and down by ~20% as needed
similar to Morphine
• May require less frequent adjustments since half life
is longer and effects of dose changes may be
slower to manifest than with Morphine
nd
2
Line Treatment
• Used for severe NAS that is not controlled with a first
line agent
• Phenobarbital
o Most commonly used second line drug
• Diazepam
o First line if the known cause of NAS is a benzodiazepine
• Clonidine
o Used to avoid the sedative effects of phenobarbital
Phenobarbital
Preferred medication for non-opiate NAS
GABA agonist
Does not prevent seizures at typical NAS doses
Minimal benefit for GI symptoms
Usual dose: 16 mg/kg loading dose, then 2-8
mg/kg/day divided BID for maintenance
• Route: Oral, IV, or IM
• Continue treatment until Morphine or Methadone
are weaned off before weaning phenobarbital
• Taper phenobarbital by 10-20% per day
•
•
•
•
•
Diazepam
• Requires caution due to limited capacity of infants
to metabolize
• Contains sodium benzoate
o Requires monitoring for jaundice as it may displace bilirubin for
conjugation and excretion
• Initial dose 1-2 mg every 8-12 hours
• May also consider lorazepam or midazolam
dependent on preference and experience
Clonidine
• Effective adjunctive medication with opioids in
shortening the duration of treatment
• Centrally acting alpha adrenergic agonist
• Requires monitoring for hypotension and
bradycardia
• Initial dose 0.5-1 mcg/kg followed by 3-5
mcg/kg/day divided every 4-6 hours
• Requires taper due to risk of hypertension and
tachycardia with abrupt discontinuation
Naloxone
• Contraindicated in the treatment of NAS due to the
risk for rapid and severe NAS symptoms
• May precipitate seizures in some neonates
Iatrogenic NAS
• Treat with same drug class that was used for pain
control/sedation
• Calculate total daily cumulative dose and divide
into a schedule of equivalent medication
o Do not forget PRN doses!!
Nutrition and NAS
• May have increased metabolic demands
o May require significant increase in kcal/kg/day to offset losses from NAS
o Fortified feeds
• Ad lib demand schedule
o Prompt response to hunger cues important
o May be frequent, small volume feeders
• Requires close monitoring of weight gain/loss and
fluid status
o Vomiting and loose stools may lead to increased fluid requirements
• PO intake may be poor N
o NG supplementation or IV hydration
Breastfeeding
• Low rates of breastfeeding among NAS affected
neonates
• AAP supports breastfeeding in appropriate
situations
• May help with withdrawal symptoms
• Requires strict adherence and review of risks and
benefits with the mother before initiation
Breastfeeding Allowed
• Ok to breastfeed when mothers are on a stable
dose of methadone or buprenorphine
o Low doses excreted in breastmilk
• Mothers who are in a treatment program prior to
delivery or are enrolled into a program at birth
o Requires strict adherence to the program with continued close follow up
• No other contraindications to breastfeeding
Breastfeeding
Contraindications
• Polysubstance abuse or history of non-adherence
to treatment programs
• HIV or other infectious risk
• Mothers taking hydrocodone or oxycodone
o Require closer monitoring as these drugs are highly excreted in breastmilk
• Any illicit drug use during the 30 day period prior to
delivery
Breastfeeding
• Best to follow strict feeding protocols to ensure a
similar amount of breastmilk is provided each day
• Have mothers pump and provided pumped
breastmilk early on to ensure consistent volumes
o Provide for 1-2 feeds on day 1, and gradually increase as supply increases
over the following days
• Discontinuation of breastfeeding
o Important to stress weaning off of breastmilk as abrupt discontinuation
may precipitate NAS symptoms at that time
Discharge and Follow Up
• Infants at risk for NAS require in-hospital monitoring
until past the window for severe withdrawal
• Dependent upon the drug exposure
o With known history of short half life drugs such as morphine or
hydrocodone, may be discharged after 72 hours
o With known history of long half life drugs such as methadone, may be
discharged after 5-7 days
• Follow up visit should be scheduled within 2 days of
discharge to ensure continued close monitoring
Discharge after Treatment
• Infants requiring pharmacotherapy:
o Discharge frequently delayed until fully weaned off of medications with
an adequate observation period off pharmacotherapy to ensure no
rebound NAS
o Discharge while still on therapy is an option if parents are reliable, taper is
easily followed, and adequate follow up is assured
o Extensive education about non-pharmacologic measures for treatment of
symptoms and strict criteria for seeking evaluation are vital at discharge
Prenatal Counseling
• Important to be empathetic and nonjudgemental
• Teratogenicity
o Opioids and stimulants can cause SGA status, prematurity, abruption, SAB
o Cocaine and methamphetamine may lead to long term
neurodevelopmental issues
• Expected Clinical Course
o Observation for at least 3-7 days for signs and symptoms of NAS
o Non-pharmacologic therapy is the primary treatment
o Pharmacotherapy will require treatment that may last weeks to months
Prenatal Counseling
• Breastfeeding
o Breastfeeding may be suitable in certain situations dependent upon the
drugs used
o Breastfeeding may help decrease NAS symptoms
o Helpful to have a breastfeeding plan prior to delivery
• Social Concerns
o Vital to discuss the importance of caregiver involvement in treatment of
NAS
o Adherence to follow up schedule and treatment recommendations will
be vital to outcomes
Take Home Points
• NAS is a common condition in newborns and the
incidence is rising
• Close monitoring is vital for infants at risk of NAS
• Infants who demonstrate symptoms without known
risk factors require evaluation for NAS
• Non-pharmacologic measures are the first line
therapy for NAS
• Breastfeeding is not contraindicated in NAS in some
situations and can be beneficial in NAS treatment
References
•
•
•
•
•
•
•
Avery’s Diseases of the Newborn, 9th Ed. 2012
Burgos A, Burke B. Neonatal Abstinence Syndrome. NeoReviews. 2009;10(5)e222-229.
Kocheriakota P. Neonatal Abstinence Syndrome. Pediatrics. 2014;134(2):e547-561.
Tolia V, Patrick S, Bennett M, et al. Increasing Incidence of the Neonatal Abstinence
Sydrome in the U.S. Neonatal ICUs. NEJM. 2015;372(22)2118-2126.
Jansson L. Neonatal abstinence syndrome. UpToDate. 2015.
Patrick S, Davis M, Lehman C, Cooper W. Increasing incidence and geographic
distribution of neonatal abstinence syndrome: United States 2009-2012. J Perinatology.
2015. 1-6.
2013 National Survey on Drug Use and Health. http://www.samhsa.gov/data/populationdata-nsduh