DB 5

Identifying Neonatal Abstinence Syndrome (NAS) and Treatment Guidelines University of Iowa Children’s Hospital -11/2014

What is Neonatal Abstinence Syndrome?

• Neonatal withdrawal after intrauterine exposure to certain drugs (illicit or prescription) • Occurs with the abrupt cessation of the drug exposure at birth • Most commonly seen with opioid exposure, but also seen after exposure to sedatives, selective serotonin

reuptake inhibitors (SSRI), polysubstance abuse, and occasionally barbiturates and alcohol • Develops in 55-94% of opioid drug-exposed infants and 28-30% of SSRI-exposed infants

Screening

• Maternal history • Urine drug screen

• Meconium drug testing • Umbilical cord testing

Clinical Signs of Withdrawal Central Nervous System Metabolism/Vasomotor/Respiratory Gastrointestinal

• Irritability • Increased wakefulness • High-pitched cry • Tremor • Increased muscle tone • Hyperactive deep

tendon reflexes • Frequent yawning • Sneezing • Seizures

• Diaphoresis • Nasal stuffiness • Fever • Mottling • Temperature instability • Piloerection • Mild elevations in respiratory

rate and blood pressure

• Vomiting • Diarrhea • Dehydration • Poor weight gain • Poor feeding • Uncoordinated and constant

sucking

Onset of withdrawal symptoms

• Onset of withdrawal depends on the half-life of the drug, duration of the addiction, and time of last maternal dose prior to delivery. On average, observation period for symptoms to appear is 3 days.

Drug Approximate time to onset of withdrawal symptoms Barbiturates 4-7 days but can range from 1-14 days Cocaine Usually no withdrawal signs but sometimes neurobehavioral abnormalities (decreased

arousal and physiologic stress) occur at 48-60 hours Alcohol 3-12 hours Heroin Within 24 hours Marijuana Usually no clinical withdrawal signs Methadone 3 days but up to 5-7 days; rate of severity of withdraw cannot be correlated to dose of

maternal methadone Methamphetamines Usually no withdrawal signs but sometimes neurobehavioral abnormalities (decreased

arousal, increased physiologic stress, and poor quality of movement) occur at 48-60 hours Opioids 24-36 hours but can be up to 5-7 days Sedatives 1-3 days SSRIs Usually 2nd day of life—ranges from 5-48 hours Preterm Infants and NAS

• Due to immaturity, less total body fat, and differences in total drug exposure, preterm infants may exhibit fewer signs of withdrawal than near-term and term infants.

Revised: 11/2014; 06/2013; 2/2013 by Sarah Tierney, PharmD. Written: 09/2012 by Sarah Tierney, PharmD UICH Approved: 09/2012 J Klein MD

Treatment of Neonatal Abstinence Syndrome

Goal: stabilize clinical manifestations of withdrawal and restore normal newborn activity Scoring of NAS

• Finnegan scoring (tool to quantify severity of NAS) (See last page for Finnegan Scoring System) o Begin scoring within 3 hours of life o Continue scoring every 3-4 hours to coordinate with feedings and cares o Scoring should be done after feeding and nursing cares to eliminate irritability related to

normal baby activities o Do not wake a sleeping baby to score

• Used to determine initiation of pharmacologic therapy

Non-Pharmacologic Intervention

• Swaddling • Rocking • Minimal sensory or environmental stimulation • Maintain temperature stability • Feed (consider alternating bottle and pacifier during feed to compensate for excessive sucking and

possibly prevent emesis) • Breast milk feedings when appropriate can help reduce the need for pharmacological intervention

Pharmacologic Therapy

• Begin when 3 consecutive Finnegan scores are ≥ 8 or when the average of two scores OR two consecutive scores is ≥ 12.

• Morphine is the first-line agent and the mainstay of treatment. • Phenobarbital is the first line additional therapy for polysubstance exposure and may be used in

combination with opioid therapy for NAS secondary to opiate withdrawal. • Opioid-dependency is likely seen after exposure to buprenorphine (Subutex), codeine, heroin,

hydrocodone (Lortab, Vicodin), hydromorphone (Dilaudid), methadone, morphine, oxycodone (Percocet).

• Polysubstance-dependency is likely seen with the above drugs as well as barbiturates, sedatives, SSRIs. • See next page for Pharmacologic Management of NAS guidelines.

Revised: 11/2014; 06/2013; 2/2013 by Sarah Tierney, PharmD. Written: 09/2012 by Sarah Tierney, PharmD UICH Approved: 09/2012 J Klein MD

Pharmacologic Management of Neonatal Abstinence Syndrome in the NICU University of Iowa Children’s Hospital

•STARTING POINT•

*0.05 mg/kg PO is recommended starting dose for NAS

Increase dose to 0.08 mg/kg PO q4 hours if Finnegan scores remain > 8.

If scores still are not stabilized after 24 hours can increase to a maximum dose of 0.1 mg/kg PO q4

hours.

YES

NO

Sum of 3 Finnegan Scores > 24 First line of therapy:

Morphine 0.05 mg/kg PO q4 hrs*

If possible, observe off morphine for 48 hours

prior to discharge.

YES

YES

Hold morphine dose constant for 24-48

hours to help stabilize patient before weaning.

Taper morphine and continue on phenobarbital.

Finnegan Scores stabilized?

NO

Phenobarbital and continue on morphine.

Give phenobarbital

loading dose of 16 mg/kg PO divided

into 2 doses administered 12 hours apart to avoid emesis. Followed by

maintenance dose of 2.5 mg/kg PO

q12 hrs.

Finnegan Scores Stabilized on Morphine?

Patient can go home on

phenobarbital and be tapered off by weight gain OR the dose can be tapered by 20% every other day.

Observe off morphine for 48

hours prior to discharge.

Taper dose every 24- 48 hours as tolerated guided by Finnegan

Scores < 8. First decrease dose then

increase interval. See taper schedule on

next page.

NO

Polysubstance Abuse? ADD

Revised: 11/2014; 06/2013; 2/2013 by Sarah Tierney, PharmD. Written: 09/2012 by Sarah Tierney, PharmD UICH Approved: 09/2012 J Klein MD

Tapering Schedule (Start this AFTER the patient is stabilized on a dose) • Dosing on chart is in absolute mgs (NOT mg/kg) • Find the dose on the chart that is closest to the dose the patient has been stabilized on and start there

(this means you may not be starting at the top of the chart) • Taper dose every 24-48 hours as tolerated, guided by Finnegan Scores of < 8

Recommended Tapering Schedule AFTER the infant is stabilized on a dose and ready to wean Morphine TAPERING schedule (follow this side for infants > 3 kgs)

Morphine TAPERING schedule (follow this side for infants < 3 kgs)

0.4 mg PO q 4 hrs 0.4 mg PO q 4 hrs 0.3 mg PO q 4 hrs 0.3 mg PO q 4 hrs 0.2 mg PO q 4 hrs 0.2 mg PO q 4 hrs 0.2 mg PO q 6 hrs 0.1 mg PO q 4 hrs 0.2 mg PO q 8 hrs 0.1 mg PO q 6 hrs 0.2 mg PO q 12 hrs 0.1 mg PO q 8 hrs 0.2 mg PO q 24 hrs 0.1 mg PO q 12 hrs Discontinue 0.1 mg PO q 24 hrs Discontinue

Alternative pharmacological treatment (not first-line at UIHC NICU)

1) Methadone for opioid-dependency as an alternative to morphine. Dose 0.05 mg/kg PO every 12 hours. Increase by 0.05 mg/kg every 12 hours until NAS scores stabilize. Adverse effects include bradycardia and tachycardia and an ECG should be obtained to evaluate for QT-prolongation. Methadone has an extremely long half-life which can be up to 24 hours in a neonate. Methadone must be tapered by 10- 20% per week over 4-6 weeks.

2) Clonidine as an alternative to phenobarbital. Clonidine is given in addition to morphine for polysubstance-dependency in term neonates with moderate to severe NAS uncontrolled by morphine alone. Dose 1 mcg/kg PO every 4 hours. Adverse effects include hypotension, rebound hypertension if clonidine is not tapered off over more than a week, AV-block, and bradycardia. MUST taper clonidine off over 10-14 days.

Outcomes Alcohol Acute ingestion: Hyperactivity, tremors for 72 hours followed by lethargy

for 48 hours Chronic ingestion: abnormalities include CNS, growth deficiency, facial features, cardiac and musculoskeletal anomalies.

Amphetamines IUGR, cardiac anomalies Cocaine Neurological complications (infarct, IVH, cystic lesions)

Higher incidence of prematurity, low birth weight, placental abruption Associated with higher incidence of genitourinary tract and gastrointestinal anomalies Short and/or long term neurobehavioral abnormality

Heroin Low birth weight Marijuana Higher incidence of tremors and altered visual responses Methamphetamines IUGR, prematurity, placental abruption, fetal distress, adverse long-term

neurotoxic effects on behavior, cognitive skills, and physical dexterity. Opioids Active/passive detoxification results in fetal distress or fetal loss

No other adverse outcomes identified so far SSRIs No adverse neurodevelopmental outcomes identified so far

Revised: 11/2014; 06/2013; 2/2013 by Sarah Tierney, PharmD. Written: 09/2012 by Sarah Tierney, PharmD UICH Approved: 09/2012 J Klein MD

Modified Finnegan Scoring System7 System Symptoms Points Score

C en

tr al

N er

vo us

S ys

te m

Excessive cry Excessive cry (inconsolable)

2 3

Sleep < 1 hour after feeding Sleep 1-2 hours after feeding Sleep 2-3 hours after feeding

3 2 1

Hyperactive Moro reflex Marked hyperactive Moro reflex

1 2

Mild tremors: disturbed Moderate-severe tremor: disturbed

1 2

Mild tremors: undisturbed Moderate-severe tremors when undisturbed

1 2

Increased muscle tone 1-2 Excoriation: skin red, intact Excoriation: skin broken

1 2

Generalized seizures 8

M et

ab ol

is m

V

as om

ot or

R

es pi

ra to

ry Hyperthermia: axilla temperature ≥ 37.3°C 1

Frequent yawning (≥ 4/interval) 1 Sweating 1 Nasal stuffiness 1 Sneezing (≥ 4/interval) 1 Tachypnea (rate > 60/min) 2

G as

tr o-

in te

st in

al Poor feeding 2

Vomiting 2 Loose stools 2 Weight loss/Failure to thrive 2 Excessive irritability 1-3

Scoring TOTAL SCORE Initials of Scorer

References:

1. Agthe AG et al. Clonidine as an Adjunct Therapy to Opioids for Neonatal Abstinence Syndrome: A Randomized, Controlled Trial. Pediatrics 2009; 123:e849-e856.

2. American Academy of Pediatrics Committee on Drugs (2012). Neonatal Drug Withdrawal. Pediatrics 2012; 129; e540.

3. Bio LL, Siu A, and Poon CY. Update on the pharmacologic management of neonatal abstinence syndrome. Journal of Perinatology (2011) 31, 692-701.

4. Leibovitch L, Rymer-Haskel N, et al. Short-Term Neonatal Outcome among Term Infants after in utero Exposure to Serotonin Reuptake Inhibitors. Neonatology 2013; 104: 65-70.

5. Thomas Reuters. Neofax. 2011. 24th Edition. 6. Neurotoxicol Teratol. 2008; 30(1): 20–28. doi:10.1016/j.ntt.2007.09.005. 7. Modified Finnegan Scoring adopted from the Provincial Council for Maternal and Child Health NAS

Clinical Practice Guidelines. 2009.

Revised: 11/2014; 06/2013; 2/2013 by Sarah Tierney, PharmD. Written: 09/2012 by Sarah Tierney, PharmD UICH Approved: 09/2012 J Klein MD