Download Neonatal Abstinence Syndrome Objectives Objectives, continued

9/22/2015
Neonatal Abstinence Syndrome
Jennifer Manning, DO
Neonatologist, Akron Children’s Hospital Mahoning Valley
Clinical Associate Professor of Pediatrics, NEOMED
September 27, 2015
Adapted from a lecture by Linda Cooper, M.D.
Neonatologist, Akron Children’s Hospital Mahoning Valley
Clinical Assistant Professor of Pediatrics, NEOMED
Objectives
•
•
•
•
Define Neonatal Abstinence Syndrome (NAS)
Discuss the symptoms of NAS
List the drugs used by mothers
Review the Ohio Dept of Alcohol and Drug
Addiction Services (ODADAS ) data on drug
patterns
• Discuss testing of newborns- urine,
meconium, and cord tissue
• Describe Finnegan Scoring
Objectives, continued
• Discuss non-pharmacologic and
pharmacologic treatment of NAS
• Review our data 2012-2015
• Describe new approaches to
treatment for mothers and babies
1
9/22/2015
Why This Matters To You
• As family health care providers, you provide
care for parents and their children
• You have the ability to influence and educate
your patients resulting in healthier women
and children
• You have an established relationship with
your patients. They trust you and they will
listen to you
Neonatal Abstinence Syndrome
• A constellation of signs and symptoms of
withdrawal in infants who have been
exposed to maternal opiates during
pregnancy
• These symptoms are
manifested by CNS irritability,
gastrointestinal disturbances,
and autonomic instabilities
NAS Facts
• 55-94 % of term infants exposed to narcotics
develop NAS
• Severity of withdrawal may not correlate with the
dose or duration of exposure
• Infants < 34 weeks rarely develop typical
symptoms of withdrawal seen in term infants
• The early symptoms are mostly autonomic and
central nervous system irritability, followed by
gastrointestinal dysfunction
- American Academy of Pediatrics Committee on Drugs
Pediatrics. Jan 30, 2012
2
9/22/2015
More NAS Facts
• Seizures occur in 2-10% of infants
withdrawing from opioids
• Over 30% of infants will have abnormal
EEGs without overt seizure activity
• Multi-drug exposure may manifest
clinically with a biphasic pattern of
withdrawal which include an exacerbation
of symptoms 1-2 weeks after successful
treatment of initial symptom
Onset of Withdrawal Symptoms
Substance Used
Timing of Withdrawal
Heroin
24-72 hours
Methadone/buprenorphine
At birth up to 7 days
Benzodiazepines
1-2 weeks
CNS Signs/Symptoms
•
•
•
•
•
•
•
Hypertonia
Tremors at rest or when disturbed
High-pitched or prolonged crying
Extreme irritability and/or restlessness
Exaggerated Moro reflex
Sleep disturbances
Seizures
3
9/22/2015
GI Symptoms
• Frequent loose, watery stools
• Poor or ineffective feeding (chew or bite
the nipple)
• Emesis
• Poor weight gain
• Dehydration
• Failure to pass stool in first day or two
Autonomic Symptoms
•
•
•
•
Elevated temperature
Nasal stuffiness
Sneezing
Skin mottling
Miscellaneous Symptoms
• Tachypnea
• Skin excoriation, especially on the
buttocks due to loose and frequent stools
• Apnea- not commonly seen
4
9/22/2015
Differential Diagnosis
Sepsis
Hypocalcemia
Hypoglycemia
CNS hemorrhage
Meningitis
Perinatal asphyxia
Polycythemia
Drugs of Abuse
Opium Poppy
5
9/22/2015
Opium History
• 3400 B.C. in lower Mesopotamia, Sumerians
cultivated and used opium for its euphoric effects
(the joy plant). They passed it on to the Assyrians,
then to the Egyptians
• Over the centuries its reputation spread, and the
trade stretched to India and China via the Silk Road
• The British Empire secretly smuggled it to Chinaresulting in the first Opium War of 1839. Britain won;
Hong Kong was ceded to Britain
• Chinese immigrants brought opium to the US in the
mid 1800’s with the railroad and the Gold Rush
Opium Den San Francisco
Heroin History
• London, 1874: C.R. Alder Wright synthesized
first heroin from opium by adding 2 acetyl
groups to the molecule (diacetyl morphine)
• Germany, 1897: Felix Hoffman was working
for the pharmaceutical lab now known as
Bayer Labs in Elberfeld, Germany
• Hoffman re-synthesized heroin (diacetyl
morphine) in an attempt to make codeine, a
less potent form of morphine
• Bayer named this new compound Heroin,
from the Greek heros, or hero
6
9/22/2015
Bayer Heroin Bottle
Bayer Heroin
• Heroin was marketed from 1898 to 1910
as a non-addicting morphine substitute
and cough suppressant
• It later became an embarrassment for
Bayer when it was discovered that heroin
was quickly metabolized to morphine
• A federal law banned OTC sale in 1914
• Heroin was banned completely in 1924 by
the US Congress
Drugs of Abuse
Opiates:
Heroin
Methadone
Oxycodone(OxyContin),
Morphine
Codeine
Meperidine
Opium
Vicodin(hydrocodone/acetaminophen)
Buprenorphine(Subutex or Suboxone)
Benzodiazepines: diazepam(Valium),
alprazolam(Xanax), lorazepam(Ativan)
Barbiturates-rare in our infants
Alcohol
7
9/22/2015
Opana®
• Street names: “pandas”, “bears”, “panas”
• Oxymorphone: a semi-synthetic opioid with
high abuse potential
• Introduced in 1959 as an analgesic
• FDA approved immediate release(Opana®)
and extended-release (Opana® ER) in
2006
• More potent than oxycodone, hydrocodone,
or morphine
Substances not associated with
NAS
•
•
•
•
•
•
•
•
Tobacco
Marijuana
Cocaine
Antidepressants
Amphetamines
SSRIs- may have toxicity symptoms
Caffeine
Bath Salts-designer stimulants e.g.
Mephedrone and MDPV
Opium Poppy with Latex
8
9/22/2015
9
9/22/2015
Ohio Substance Monitoring
June 2013-January 2014
10
9/22/2015
Initial Screening and Subsequent
Action
• Mother: Ideally, urine toxicology during
pregnancy. This should include urine for
opiates
• Mothers with positive screens should be
counseled, and appropriate referrals should
be made, e.g. to a drug rehab facility and
also to neonatologists to discuss baby’s
chances of withdrawal and treatment options
• Subutex is preferable to methadone, but not
always possible
Indications to Screen for Substance
Abuse
Maternal Factors
• Known maternal substance use-either
prescribed medication or “street drugs”
• Late or no prenatal care
• History of depression, chronic pain
• Incarceration
• Severe mood swings or bizarre behavior
Indications to Screen, continued
Maternal Factors
• Previous infant with NAS
• History of physical and/or sexual abuse
• History of STIs
• Previous unexplained fetal demise
• Preterm labor
11
9/22/2015
Indications to Screen for Substance
Abuse
Neonates with high risk factors
• Prematurity
• Unexplained IUGR or low birthweight
• Abnormal CNS exam: tremors, irritability,
poor state control
• Emesis, diarrhea, or failure to pass stool in
first few days of life
Infant Screening
• Urine for toxicology
• Urine for opiates (above screen does not
test for oxycodone, buprenorphine, etc)
• Meconium toxicology- must collect all the
meconium, not just one sample; reflects
any exposure after 20 weeks gestation
• Infants with known exposure should
remain in hospital for 5 days to assess for
neonatal abstinence
CordStat
• A relatively new drug test that utilizes
umbilical cord tissue as the sample matrix
• Universal
• Noninvasive, simple to collect
• Allows for a higher level of sensitivity for
specific drugs
• Faster turnaround time than meconium
screen
– USDTL.com
12
9/22/2015
Cord Tissue Testing
• A study in Utah of 100 umbilical cord samples
demonstrated the ability to assay cord tissue
for drugs of abuse
• Enzyme-linked immunosorbent assay
(ELISA) was compared to gas or liquid
chromatography mass spectrometry
• Categories: opiates, cocaine,
amphetamines, cannabinoids and PCP
• Results: > 90% agreement between paired
specimens
– Montgomery, et.al. Journal Perinatology 2006
Cord Tissue Testing
• Follow-up study in Utah and New Jersey
• 498 umbilical cord samples
• Results: > 90% agreement between paired
specimens
– Montgomery, et al. Journal of Perinatology, July
2008
CordStat®
•
•
•
•
•
•
•
•
•
•
•
•
•
Amphetamines
Barbiturates
Buprenorphine
Benzodiazepines
Cannabinoids
Cocaine
Methadone
Meperidine
Opiates
Oxycodone
PCP(Phencyclidine), “angel dust”
Propoxyphene (Darvon, discontinued)
Tramadol
13
9/22/2015
Cordstat® Add-ons
• Ethyl glucuride
• Designer stimulants (bath salts)
• Cotinine
CordStat®
The opiate screen includes:
• Codeine
• Morphine
• Hydrocodone
• Hydromorphone
• 6-MAM (heroin metabolite)
14
9/22/2015
The Finnegan Score for Neonatal
Abstinence
• A tool developed by Loretta Finnegan, M.D.
in 1975
• It provides a quantitative measure of the
severity of withdrawal symptoms
• The most widely used form consists of 21
signs and symptoms grouped by system
• The scoring method allows for
standardization of assessment, and
consistency of management of infants with
NAS
Finnegan Scoring
• Nurses begin the scoring at birth, or
whenever symptoms develop
• Scores are obtained every 2-4 hours, and
reflect the entire time period since the
previous score
• A score above 8 denotes neonatal
abstinence syndrome requiring nonpharmacologic treatment and possibly
treatment with phenobarbital, opiates, or both
15
9/22/2015
Finnegan Scoring
• Once an infant is stable on treatment
protocol, the scores are used for weaning
• When scores are consistently <9 for 48
hours, the dose may be decreased by 1015 % every 1-2 days
Non-Pharmacologic Treatment
•
•
•
•
•
•
Quiet environment in private rooms
Swaddling
Frequent feeds on demand
Low lactose formula
Holding, rocking, swinging
Massage and calming techniques
Encourage parents to stay as much as
possible
Consults
• Infant Therapy
• Occupational Therapy
• Speech Therapy
• Infant Massage
• All patients are interviewed by the Staff
Social Worker
• CSB Referrals when indicated
• Lactation and Nutrition
16
9/22/2015
Breastfeeding and NAS
• Acceptable:
– When the mother is Hepatitis C positive
– Low dose Methadone treatment
• Morphine best analgesic for breastfeeding mothers
– Morphine concentrations in human milk is low and the
oral bioavailability is poor
• Codeine and hydrocodone are regarded as safe when
used in low-to-moderate doses
• Methadone concentrations in human milk are very low,
generally not exceeding more than 5% of the maternal
dose
• Not acceptable, if mother has HIV, has active HSV
lesions on the breast, untreated active TB, or is an active
drug abuser.
Pharmacologic Treatment
• Any infant who has serious symptoms of
withdrawal, or two Finnegan scores >8 is
given a loading dose of phenobarbital 16
mg/kg (We use the tablet form)
• This is followed by phenobarbital 2.5
mg/kg/dose BID
Pharmacologic Treatment,
continued.
• Infants who have serious NAS at the
outset or who are not controlled on Pb
alone are given morphine
• Starting dose for morphine is 0.03 - 0.05
mg/kg/dose every 3 hours. This may be
increased as needed to a maximum of 1.6
mg/kg/day (0.2 mg/kg/dose)
17
9/22/2015
Adjunct Therapy
• Clonidine: added to regimen if phenobarbital
and morphine do not control symptoms
• Dose: 0.1 mcg/kg q 4-6 hours
• Clonidine is well studied and used in adult
addicts, and has been shown to be effective
in newborns as well
- A. Agthe, Pediatrics. May 2009
Infants with NAS
ACH Mahoning Valley 2008-2015
•
•
•
•
•
•
•
2008: 5
2009: 28
2010: 28
2011: 60
2012: 48
2013: 76
2014: 66
Infants with NAS
ACH Mahoning Valley
80
70
60
50
40
NAS Infants
30
20
10
0
2008
2009
2010
2011
2012
2013
2014
18
9/22/2015
Maternal Race
N= 207
6%
Caucasian
African American
94%
Marital Status
N= 207
2%
11%
Single
Married
Separated
87%
Maternal Employment
N= 207
9%
Unemployed
Employed
91%
19
9/22/2015
Prenatal Care
N= 207
8%
13%
NPC
Late
Adequate
79%
Maternal Smoking
N= 207
22%
Tobacco
No Tobacco
78%
Size for Dates
N= 207
15%
AGA
SGA/IUGR
85%
20
9/22/2015
Treatment of Infants with NAS
N= 207
11%
14%
Pb Only
No Rx
Opiates
75%
Length of Treatment for NAS
Akron Children’s Mahoning Valley
2008-2013
• Shortest treatment time: 1 day
• Longest treatment time: 81 days
• Average length of treatment: 22.6 days
Treatment for NAS
First 10 months 2014
All GA
37 weeks +
< 37 weeks
Total exposed
64
51
13
NAS
54
45
9
Phenobarbital only
22
16
6
Length of Rx days
12
12.6
8.8
LOS days
13
13.5
11.6
21
9/22/2015
Promising New Therapies
Methadone vs. Buprenorphine
• Study in NEJM published in December 2010
• Compared NAS after maternal methadone or
buprenorphine
• 175 pregnant women were treated with either
methadone or buprenorphine in a blinded,
randomized trial
• Treatment was discontinued by 16 of 89 in
methadone group (18 %)
• Treatment was stopped by 28 of 86 women in
buprenorphine group (33%)

Jones,H. et al. NEJM December 9, 2010
Methadone vs. Buprenorphine,
cont.
• 131 newborns were studied (58 exposed to
buprenorphine and 73 to methadone)
• Results: Buprenorphine babies had
– Significantly less total morphine
– Significantly shorter treatment time
– Significantly shorter LOS
Jones,H. et al. NEJM December 9, 2010
22
9/22/2015
Methadone vs. Buprenorphine
Jones et al, NEJM Dec. 9, 2010
Methadone vs. Buprenorphine
Jones, et. al, NEJM Dec. 9, 2010
Sublingual Buprenorphine
• Study in 2008: compared morphine to sublingual
buprenorphine for NAS
• Buprenorphine group had shorter length of
treatment
• 22 days versus 32 days for morphine
• Starting dose of buprenorphine was 13.2
mcg/kg/day; increased to max of 39 mcg/kg/day
– Kraft WK et al. Pediatrics 2008
23
9/22/2015
Sublingual Buprenorphine,
continued.
• Follow-up study on treatment of NAS 3 years later
• A revised dose schema
• Buprenorphine: 15.9 mcg/kg/day in 3 doses
– Maximum dose of 60 mcg/kg/day
• Morphine: 0.4 mg/kg/day up to 1 mg/kg/day
• Phenobarbital was used only if symptoms were
not controlled with opiates
– Kraft WK et al. Addiction, March 2011
Buprenorphine Study, cont.
Buprenorphine and Breast Milk
• Recent study looked at 7 women on
buprenorphine treatment during lactation
• Maternal dose: 2.4 to 24 mg/day (Mean of 7)
• Levels of buprenorphine and norbuprenorphine
were < 1 % of maternal weight-adjusted dose
• Levels were not enough to cause any adverse
effects
• Levels were also not sufficient to prevent
withdrawal
– Ilett, et al. Breastfeeding Medicine, August 2012
24
9/22/2015
NAS In Summary
• Neonatal Abstinence Syndrome has become
a significant problem around the world
• Our own population has seen a huge
increase in the numbers of affected newborns
• Maternal substance patterns change with the
availability of drugs on the market or on the
street
• New and promising treatments for both
mother and infant are within reach
• Our goal: minimize maternal addiction when
possible
NAS in Summary, continued
The goal for our infants:
• Shorten their length of stay
• Maintain them in a comfortable, relatively
symptom- free environment while under
treatment
• Encourage maternal-infant bonding when
possible and appropriate
• Continue our search for novel ways to treat
infants with NAS (minimize their time on
opiates)
How You Can Help
• Routinely work to identify mothers with risk
factors for substance use
• Refer substance abusing mothers for
counseling and or treatment programs
• Screen all mothers with a urine drug
screen during pregnancy
• Recognize infants at high risk for Neonatal
Abstinence Syndrome and refer when
needed for treatment
25
9/22/2015
Questions?
26