Download NEONATAL ABSTINENCE SYNDROME

MATERNAL & NEONATAL
WITHDRAWAL SYNDROME
BY:
Dr. F.Goudarzi
Clinical Toxicologist
SUMS
TREATMENT OF THE PREGNANT
WOMAN MEANS THAT ONE IS
CARING FOR
TWO PATIENTS, NOT ONE
* IT IS SUGGESTED THAT PHYSICIANS ADDRESS THE ISSUE OF ALCOHOL AND DRUG USE DURING PREGNANCY
WITH ALL WOMEN OF CHILD BEARING AGE
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What is MNAS?
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Presence of withdrawal behaviors in
neonates exposed to dependency-producing
substances in utero.
These behaviors include central nervous
hypersensitivity, gastrointestinal dysfunction
and vague autonomic symptoms.
25-40 % of infants with known exposure are
asymptomatic or display only mild symptoms
Substances that can cause
MNAS
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Opiates- (55-94% of neonates exposed in
utero will have withdrawal symptoms)
Alcohol
Tobacco
Benzodiazepines
Barbiturates
SSRIs (neonatal behavioral syndrome)
?Amphetamines
?Cocaine
?Marijuana
TCA
SEDATIVE/HYPNOTICS
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BENZODIAZEPINE &PHENOBARBITAL WITHDRAWAL
• NO DIFFERENCE BETWEEN PREGNANT AND NON-PREGNANT
WOMAN, ALTHOUGH SEVERE WITHDRAWAL CAN PRODUCE
STATUS EPILEPTICUS AND FETAL RESPIRATORY ARREST
• CAN LAST 3 TO 5 WEEKS
• VERY MUCH LIKE ACUTE ALCOHOL WITHDRAWAL
• TIME COURSE AND SEVERITY DEPEND ON
• DOSE OF DRUG
• DURATION OF USE (DOES NOT WORSEN AFTER ONE YEAR OF
USE)
• DURATION OF DRUG ACTION
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FETAL EFFECTS FROM
BARBITURATES
CLEFT PALATE
 HYPOSPADIAS (PENILE ORIFICE IS
TOO LOW)
 MICROCEPHALY (SMALL HEAD SIZE)
 SHORT NOSE
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FETAL EFFECTS FROM
BENZODIAZEPINES
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????CLEFT LIP AND PALATE
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OPIOIDS
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OPIOIDS WITHDRAWAL IN THE
MOTHER –EARLY & MIDDLE
PHASE
RESTLESS SLEEP
 DILATED PUPILS
 ANOREXIA
 GOOSEFLESH
 IRRITABILITY
 TREMOR
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OPIOIDS WITHDRAWAL IN THE
MOTHER - LATE PHASE
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INCREASE IN ALL PREVIOUS SIGNS AND SYMPTOMS
INCREASE IN HEART RATE
INCREASE IN BLOOD PRESSURE
NAUSEA AND VOMITING
DIARRHEA
ABDOMINAL CRAMPS
LABILE MOOD
DEPRESSION
MUSCLE SPASM
WEAKNESS
BONE PAIN
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OPIOIDS WITHDRAWAL

IT IS NOT RECOMMENDED TO TAPER
PREGNANT WOMEN OFF OF
METHADONE, BUT THE SAFEST TIME IS
THE 2ND TRIMESTER (TIPS2)
• BEFORE 14 WEEKS AND AFTER 32
WEEKS THERE IS AN INCREASED
INCIDENCE OF SPONTANEOUS
ABORTION AND PREMATURE LABOR
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OTHER WITHDRAWAL AGENTS
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CLONIDINE
• NO TERATOGENIC EFFECTS
• LONG TERM USE NOT RECOMMENDED
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BUPRENORPHINE
• APPEARS SAFE WITH NO TERATOGENIC
EFFECTS, BUT NOT APPROVED FOR USE
YET ( JONES AND JOHNSON 2001)
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NEVER USE NARCAN UNLESS AS A
LAST RESORT
• SPONTANEOUS ABORTION
• PREMATURE LABOR
• STILLBIRTH
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FETAL EFFECTS OF OPIOIDS
LOW BIRTH WEIGHT
 FETAL DISTRESS
 PREMATURITY
 NEONATAL ABSTINENCE SYNDROME
 STILLBIRTH
 SUDDEN INFANT DEATH SYNDROME
 MECONIUM ASPIRATION
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NEONATAL ABSTINENCE
SYNDROME
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60-80% OF OPIOIDS EXPOSED INFANTS
• 72 HOURS AFTER BIRTH
• CNS EFFECTS
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IRRITABILITY
HYPERTONIA (INCREASED MUSCLE TONE)
HYPERREFLEXIA
ABNORMAL SUCK
POOR FEEDING
SEIZURES ( 1 TO 3%)
• GI EFFECTS
• DIARRHEA
• VOMITING
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METHADONE DOSING
STRATEGIES IN THE PREGNANT
WOMAN
INITIAL 10 TO 40 MG
 EXTRA 5 TO 10 MG IN 3 TO 4 HOURS IF
SIGNS AND SYMPTOMS OF
WITHDRAWAL
 REPEAT 5 TO 10 MG Q 3 TO 4 H PRN
 STABILIZE AT THIS DOSE FOR SEVERAL
DAYS
 DECREASE BY 2 .5 MG Q 7 TO 10 DAYS
AND MONITOR OB STATUS
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NEONATAL ABSTINENCE
SYNDROME
MEDICATION
DOSING
INDUCTION
TITRATION
STABILIZATION
TAPERING
TINCTURE OF OPIUM
0.1 ML/KG (2
DROPS/KG) Q 4 H
WITH FEEDINGS
INCREASE BY 0.1 ML/KG
Q4H AS NEEDED
Q 4 H WITH FEEDINGS FOR
3 TO 5 DAYS
TAPER GRADUALLY
BY REDUCING
DOSE NOT
FREQUENCY
PAREGORIC
MG/ML)
0.1 ML/KG ( 2
DROPS/KG) Q 4H
WITH FEEDINGS
INCREASE BY 0.1 ML/KG
Q 4H PRN
Q4H WITH FEEDINGS FOR
3 TO 5 DAYS
TAPER GRADUALLY
BY REDUCING
DOSE NOT
FREQUENCY
0.05 TO 0.1 MG/KG Q
6H
INCREASE BY 0.05
MG/KG Q 6 H PRN
WHEN STABLE, GIVE TOTAL
DAILY DOSE ONCE DAILY
OR ½ BID
TAPER GRADUALLY
TO 0.05 MG/KG,
THEN D/C MED
METHADONE
(0.4
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Diagnosis
Maternal history of drug use
 Positive identification of substance in
maternal or neonatal specimen
 Scoring
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
Once diagnosed- consult social
services
TIME TO ONSET OF MATERNAL
WITHDRAWAL SIGNS
DRUG
TIME
ALCOHOL
6 to 60 HOURS
BARBITUATE
4 to 10 DAYS
DIAZEPAM
1 to 12 DAYS
OPIOID
12 to 72 HOURS
*MATERNAL WITHDRAWAL DEPENDS ON THE DRUG, FREQUENCY OF USE, AND DURATION OF USE. TIMES CAN
VARY SIGNIFICANTLY.
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TIME TO ONSET OF NEONATAL
WITHDRAWAL SIGNS
DRUG
TIME
ALCOHOL
3 to 12 HOURS
BARBITUATE
4 to 7 DAYS
DIAZEPAM
1 to 12 DAYS
OPIOID
48 to 72 HOURS
USUALLY THE ONLY WITHDRAWAL SYNDROME THAT REQUIRES TREATMENT IS OPIOID WITHDRAWAL
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Clinical Presentation
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Onset of symptoms varies with
the substance being used by
the mother, the quantity,
frequency and duration of
intrauterine exposure, timing
and amount of the last maternal
use, as well as maternal and
infant metabolism and excretion
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CNS
•
Tremors, irritability, increased
wakefulness, high-pitched
crying, hypertonicity and
hyperactive reflexes, seizures,
yawning, sneezing and skin
excoriation
•

Gastrointestinal
Poor feeding, uncoordinated
and constant suck, vomiting or
regurgitation, diarrhea,
dehydration
Autonomic Signs
increased sweating. Nasal
stuffiness. Rhinorrhea, mottling,
temperature instability, fever,
tearing
W
I
T
H
- wakefulness
- irritability
-tremors, twitching, tachypnea
- hyperventilation, hypertonia,
hyperpyrexia,
hyperaccusis, hiccups
D - diarrhea, diaphoresis,
R - rub marks
A - alkalosis
W - weight loss
A - apnea
L - lacrimation,
S - seizures (myoclonic), sneezing, skin
mottling
Frequency of Clinical Signs
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Disturbed sleep – 53%
Mottling 53%
Excess sucking 45%
Tremors 43%
Tachypnea – 43%
Hypertonia 41%
Fever 40%
Seizures 2-11% (often later)
STIMULANTS
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STIMULANTS
WITHDRAWAL IN THE MOTHER
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DYSPHORIA
FATIGUE
UNPLEASANT DREAMS
INSOMNIA
HYPERSOMNIA (INCREASED SLEEP)
INCREASED APPETITE
PSYCHOMOTOR RETARDATION
AGITATION
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MATERNAL EFFECTS OF
STIMULANT AND COCAINE
ABRUPTIO PLACENTAE
 PREMATURE LABOR
 SPONTANEOUS ABORTION
 DECREASE DURATION OF DELIVERY
 GREATER NUMBER OF OBSTETRICAL
COMPLICATIONS
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NAS
video clip
ALCOHOL WITHDRAWAL
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MATERNAL WITHDRAWAL
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THE RATE OF ALCOHOL METABOLISM
MAY BE FASTER DURING PREGNANCY,
SO BE AWARE THAT WITHDRAWAL CAN
START SOONER THAN EXPECTED.
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MINOR WITHDRAWAL IN THE
MOTHER
TIME
• 6 to 60 HOURS
SYMPTOMS
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TREMORS
INSOMNIA
NAUSEA
ANOREXIA
ANXIETY
WEAKNESS
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MINOR WITHDRAWAL IN THE
MOTHER
SIGNS
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ACTION TREMOR
INATTENTION
EASY STARTLE
PLETHORA
CONJUNCTIVAL INJECTION
INCREASED REFLEXES
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EARLY WITHDRAWAL IN THE MOTHER
TREATMENT
• WATCH FOR DT’S
• EVALUATE FOR OTHER ILLNESSES AND
INJURIES
• LIGHT SEDATION WITH
BENZODIAZEPINES
• THIAMINE
• ELECTROLYTE BALANCE
• PATIENTS MUST UNDERSTAND THAT
THEY NEED FURTHER TREATMENT
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LATE WITHDRAWAL IN THE
MOTHER
DELIRIUM TREMENS
• HIGH RISK FOR DT’S IF BLOOD ALCOHOL LEVEL GREATER THAN
300 mg% OR WITHDRAWAL SEIZURES
• PROFOUND CONFUSION AND MISPERCEPTIONS
• DISORIENTATION
• HALLUCINATIONS
• PARANOID DELUSIONS
• MOTOR HYPERACTIVITY
• TREMOR, RESTLESS, AGITATED, INCREASED REFLEXES
• AUTONOMIC HYPERACTIVITY
• INCREASED HEART RATE, PROFUSE SWEATING,
DILATED PUPILS
• MORTALITY OF THE MOTHER IS 10 to 15% IF
UNTREATED, 1 to 2% IF TREATED
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FASD
BINGE DRINKING (5 OR MORE DRINKS
ON ONE OCCASION) IS ESPECIALLY
DETRIMENTAL TO THE FETUS
 THERE IS NO PROVEN “SAFE” AMOUNT
OF ALCOHOL TO USE DURING
PREGNANCY
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• ALCOHOL HAS BEEN FOUND IN BREAST
MILK
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NICOTINE AND
TOBACCO
NICOTINE AND TOBACCO
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IF THE PREGNANT WOMAN CANNOT
STOP SMOKING USING BEHAVIORAL
INTERVENTIONS, THEN NICOTINE
REPLACEMENT PRODUCTS CAN BE
USED
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NICOTINE WITHDRAWAL
SYMPTOMS IN THE MOTHER
90%
80%
Anxiety
Irritability
Poor conc.
Restless
Craving
GI prob.
Headache
Drowsy
70%
60%
50%
40%
30%
20%
10%
0%
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CANNABINOIDS
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CANNABINOIDS
WITHDRAWAL IN THE MOTHER
• 10 HOURS AFTER USE
• TREMOR OF THE TONGUE AND
EXTREMITIES
• INSOMNIA
• SWEATS
• LATERAL GAZE NYSTAGMUS
• EXAGGERATED DEEP TENDON REFLEXES
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MNASS
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Used to initiate, adjust and wean pharmacologic
treatment.
Scoring should begin within 4 hours after birth and
continue every 4 hours until the onset of
symptoms. At the onset of symptoms scoring
should be done every 3 hours for 24 hours and
then every 4 hours for the duration of treatment.
Observation should be made after feedings,
newborns must be awake and calm to asses
muscle tone, respirations and Moro reflex.
Newborns should be observed for 20 to 30 minutes
before scoring is determined.
Management
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Supportive
Swaddling ( decreases the
added stimulation of startled
movements)
Reduction of environmental
stimuli ( decreased light and
noise)
Frequent small feeding
Frequent diaper change are
necessary to reduce skin
excoriation
Monitor intake, output and
weigh daily to assess
hydration and caloric status
related to vomiting, diarrhea
and poor feeding status.
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Pharmacologic intervention is
indicated for evidence of acute
withdrawal such as seizures, poor
feeding (excess weight loss),
severe diarrhea, vomiting,
dehydration, inability to sleep and
fever not due to any infectious
etiology
3 consecutive NAS scores of 8 or
more or the average of 3
consecutive NAS scores is 8 or
more.
or 2 consecutive NAS scores of
12 or more or the average of 2
consecutive score is 12 or more.
Pediatric consult is recommended
when considering pharmacologic
treatment.
Cardio respiratory monitoring.
Pharmacologic Therapies in
Neonatal Abstinence Syndrome
Phenobarbital
Paregoric
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0.2-0.5 ml/dose q 3-4 p.o. or 4-6
drops q 4-6h; may increase by 2
drops until clinical improvement
Improves most of the withdrawal
symptoms especially diarrhea,
taper dose by 10-20% per day
over 2-4 week after symptoms
stable for 3-5 days.
Neonatal Opium Dilution 0.4%
solution (contains 0.4 mg
morphine equivalent per ml)
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guidelines:
0.8 ml/kg/day for NAS 8-10
1.2 ml/kg/day for NAS 11-13
1.6 ml/kg/day for NAS 14-16
2.0 ml/kg/day for NAS >16
Doses given orally every 3-4 h with
feeds ( not prn)
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15-20 mg/kg/day loading dose
to achieve level of 20-40 mg/ml.
Maintenance dose =2-8
mg/kg/day.
Taper dose by 10-20% per day
after symptoms stable for 3-5
days.
Diazepam
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0.3-0.5 mg/kg q 8 h; initial dose
i.m then p.o
Allows rapid suppression of
symptoms, decreased suck,
avoid in jaundice or premature
infants.
Pharmacologic Therapies in
Neonatal Abstinence Syndrome
Methadone
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0.1-0.5 mg/kg/day divided q
4 to 12 h
Increase by 0.05mg/kg/dose
until symptoms are well
controlled
Taper dose by 10-20% per
day over 1 mo
Treatment usually longer (5
days-4 mo)
Long half-life (26 h )
Chlorpromazine
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0.5-0.7 mg/kg/dose loading
then 2-2.8 mg/kg/day in
divided doses q 6 h
Decrease dose over 2-3 wk
Clonidine
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0.5-1 ug/kg single dose
then 3-5 ug/kg/day divided
dose q 4-6 h
Increase by 0.5 ug/kg over
1-2 days until maintenance
dose is achieved
Weaning Guidelines
Once NAS are consistently 6-8, maintain the
same therapeutic dose 48 hours before
weaning. Wean by 10% of maximum dose
every 1-2 days. If symptoms increase,
return to effective dose. Therapeutic agents
should be gradually decreased over a 2-6
Neonatal opium
solution should be weaned
first, then Phenobarbital.
week period.