Post on 29-Dec-2015
transcript
Neonatal Abstinence Syndrome
Lauritz Meyer, MDSeptember 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 morphineo Called Congenital Morphinism
• 1947: Seizures in a baby with Congenital Morphinism were successfully treated with morphineo 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 2002o Sublingual tablets
• Also leads to NASo May cause less severe NAS symptoms than methadone
Illicit Drug Use in the U.S.
• 2013 National Survey on Drug Use and Healtho 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 Healtho 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 citieso Increased use of prescription pain medications in pregnant womeno Improved recognition of NAS
NAS Causing Drugs• Opioids
o Morphine, Methadone, Hydromorphone, Fentanyl, Heroin
• CNS Depressantso Benzodiazepines, Alcohol, Barbiturates
• CNS Stimulantso Amphetamines, Cocaine, Nicotine, Caffeine
• Hallucinogenso 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 systemo Leads to inhibition of noradrenaline release
• Effects include:o Sedationo Euphoriao Respiratory depressiono Decreased GI motility
• Long term use leads to physical dependence
Opioids• Withdrawal
o The initial condition that led to the diagnosis of NASo 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 longero Dependent on type of drug, metabolism, etc.
Clinical Symptoms of NAS due to Opioids
• Gastrointestinalo Vomiting/diarrheao Poor feedingo Uncoordinated sucko Constant suckingo Dehydrationo Poor weight gain/FTT
• Autonomico Excessive sweatingo Temperature instabilityo Nasal stuffinesso Mottlingo Yawning
• Neurologico Tremorso Irritabilityo Increased wakefulnesso High-pitched cryo Hypertonicity o Hyperactive reflexeso Exaggerated Moroo Seizureso Frequent sneezing/yawning
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 weighto 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 withdrawalo 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 metabolizedo Most common with stimulants such as cocaine or methamphetamine
Premature Infants• Lower risk of developing NAS <35 weeks• Central Nervous System developmentally
immatureo 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 positiveo Rapid turn around time (within 24 hours)
• Meconiumo High sensitivity and specificityo Slow turn around time (days to a week)o May miss meconium if stooled in-utero or at birth and not collected
• Umbilical Cordo Increasing useo Not dependent upon collection of urine or meconiumo 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. seizureso Establish a physiologic sleep patterno Establish consistent weight gaino Allow the infant to communicate needs with caregiverso 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 lighto 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 exposureo Increases length of stayo May impact maternal-infant bonding as a result
• Benefits:o Decreases the acute signs of NASo 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 neonateso 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 doseo 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
2nd 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 medicationo 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 importanto 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 No 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 buprenorphineo Low doses excreted in breastmilk
• Mothers who are in a treatment program prior to delivery or are enrolled into a program at birtho 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 volumeso Provide for 1-2 feeds on day 1, and gradually increase as supply
increases over the following days
• Discontinuation of breastfeedingo 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 exposureo With known history of short half life drugs such as morphine or
hydrocodone, may be discharged after 72 hourso 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 Courseo Observation for at least 3-7 days for signs and symptoms of NASo Non-pharmacologic therapy is the primary treatmento 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 symptomso Helpful to have a breastfeeding plan prior to delivery
• Social Concernso Vital to discuss the importance of caregiver involvement in treatment
of NASo 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/population-data-nsduh