Neonatal Abstinence Syndrome: Forget the Finnegans

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Neonatal Abstinence SyndromeForget the
Finnegans Treat One Baby at a Time!

• Margaret McLaren, MD

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Neonatal Abstinence Syndrome

• A constellation of signs and symptoms which
  result from the abrupt cessation of a drug to
  which the fetus/neonate has become
  physiologically dependent

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History of NAS

• Illicit drugs (Heroin) / Methadone
• Iatrogenic withdrawal
• ECMO - Fentanyl infusions
• Around 50 of neonates older children
  requiring ICU support experience WD

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Drugs Causing NAS

• Opiates
• Heroin
• Methadone
• Morphine
• Other
• Oxycodone

• Non-opiates
• Alcohol
• Barbiturates
• Benzodiazepines
• SSRIs
• Other (caffeine, tricyclics, valproate,
  antihistamines)

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Other ?????

• Cocaine/ Amphetamines
• PCP
• Nicotine

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SSRIs Neonatal Withdrawal

• 3rd trimester exposure
• Case reports in 1990s (paroxetine, fluoxetine,
  citalopram, sertraline)
• Onset - within few days (long half life)
• Duration - 1 month

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Mechanism?

• SSRI withdrawal (due to rebound cholinergic
  effect) ?, or
• Serotonin syndrome?
• Isbister GK, Dawson A, Whyte IM, Prior FH, Clancy
  C, Smith AJ. Neonatal paroxetine withdrawal
  syndrome or actually serotonin syndrome? Arch Dis
  Childhood Fetal Neonatal Ed 200185F147-148

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Opiate Addiction

• Heroin addiction on the rise
• 0.1 pregnant women
• Less expensive, purer, more potent, even via
  oral route
• Prescription drugs
• Available via the internet

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Methadone Not simply another drug

• Eases symptoms of physical dependency
• Blocks euphoria
• Longer duration than heroin (T/224-36 hrs)
• Increases fetal safety
• Enables mother to attend to her health
  nutrition
• Stabilizes maternal metabolic processes/ ANS
• Prevents fetal withdrawal
• Optimal fetal growth

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Methadone Maintenance in Pregnancy

• Accelerated clearance from maternal circulation
  in late pregnancy due to
• Larger blood volume
• Increased metabolism (progestins)
• Higher fetal tissue concentration
• Pregnant women may need an increased/ split dose.

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Alternatives to Methadone

• Detoxification in a safe setting.
• Buprenorphine (partial mu-opioid agonist
• promising as preliminary reports show less
  severe less frequent NAS.

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Mechanism of NAS ?

• Neurochemical reaction due to depletion of drug
  from receptors in the brain.
• The neonate is NOT addicted / psychologically
  dependent.

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The Locus Ceruleus

• Opiates activate receptors in the locus ceruleus
  
• Inhibits adenyl cyclase activity
  cAMP
• Decrease in noradrenaline
  dopamine
• Over time the locus ceruleus adjusts upward to
  maintain homeostasis.
• Depletion of opiates removes the inhibition
• gtgtgtnoradrenergic overchargeltltlt

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Onset and Frequency of NAS Factors

• Drug properties
• Placental factors
• Infant factors
• Other Polydrugs?

• Timing, dose, T/2, maternal metabolism (genetics)
• Lipid solubility, molecular wt., Protein binding,
  ionization
• Placental blood flow, metabolism,
• And type of transfer
• Metabolism excretion of the drug - later in
  preterms
• CNS maturity

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Onset Frequency of NAS

• Onset
• Heroin 24-48 hr (1-6 days)
• Methadone 48 72 hr (2-28 days)
• Phenobarbitol 10 14 days

• Frequency
• 50-80
• 60-90

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Maternal Methadone NAS

• Dose
• No consistent correlation with incidence and
  severity of NAS
• No evidence to jeopardize adequate maternal
  treatment
• Onset (T/2 24 hrs)
• 48-52 hrs after the last maternal dose
• Serum methadone lt 0.06 ug/ml

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Clinical Features
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Clinical features of NAS

• CNS majority of signs especially
• Irritability sleep
  disturbance
• ANS
• GI
• In preterms less frequent milder
• Non specific
• R/O other conditions sepsis, hypoglycemia,
  hyperthyroidism, hypocalcemia, hypomagnesemia,
  asphyxia

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• W - wakefulness
• I - irritability
• T -tremors, twitching, tachypnea
• H - 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

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Frequency of Clinical Signs

• Disturbed sleep 53
• Mottling 53
• Excess sucking 45
• Tremors 43
• Tachypnea 43
• Hypertonia 41
• Fever 40
• Seizures 2-11 (often later)

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Sleep Disturbances- Related to NAS severity

• Regulation of quiet sleep is specifically
  affected
• Increased wakefulness
• Increased indeterminate sleep
• Decreased quiet sleep
• Sleep fragmentation (gt 59 arousals leading to
  wakefulness) in those requiring Tx
• Lower threshold for arousal
• Obrien Jeffery, 2002

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Sleep Disturbances in NAS Mechanism

• Hypotheses.
• CNS changes due to opiate dependency in utero -
  persist after withdrawal BUT less at 5 weeks.
  Also increased RR
• CNS hyperactivity due to withdrawal decrease
  when stabilized on treatment.
• Negative effect on maternal-infant
  interaction
• Prepare caregivers for sleep disturbance.

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Hyperphagia

• Prevalence 26 at day 8, 56 at day 16
• Maximum intake 290 kcal/kg/day
• More significant wt loss in week 1
• In 1st month - no significant increase in wt,
  vomiting/ diarrhea
• Represents higher metabolic needs/ inadequate
  control of withdrawal
• Martinez A, Kastner B, Taeusch HW. Arch Dis Child
  Fetal Neonatal Ed 199980178-182

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Assessment of NAS

• Potential for withdrawal
• Detection history, urine, meconium, hair
• Timing of last dose, gestational age?
• Polydrug exposure?
• Assess severity of withdrawal symptoms/signs -
  TOOLS

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Monitoring Tools for NAS (None developed on
preterms)

• Neonatal Narcotic Withdrawal Index
• 7 items, 1-2 point scale
• Inter-observer reliability - 77
• Physician-based
• Lipsitz scale
• 11 indicators, 1-3 point scale

• Neonatal abstinence scoring system (Finnegan)
• Validated in 1975
• 21 items, 1-5 point scale
• Inter-observer reliability - 82

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Do not throw away the Finnegans but use and
interpret them correctly !

• Assess infant post feeding.
• Do not hold off feeds until assessment time.
• Tremors and hypertonia may persist.
• Wakefulness increases with age.
• Ensure staff is adequately trained.

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The Finnegans are just an adjunct

• Additional monitoring is needed
• Daily weight and ability to feed
• Ability to achieve a quiet alert state for social
  interaction

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Management of NAS- A dyadic approachThe nurse
has a major role in care of the infant and
engaging the caregiver.
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Goals

• Alleviate signs/ symptoms of withdrawal
• Maintain optimal nutrition and development
• Facilitate positive caregiver-infant interaction
  bonding
• Ongoing parental education and support until
  symptoms are resolved.

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Supportive Care for NAS Principles

• ANTICIPATE
• Assess strengths and needs of each infant
• Sensitivity to different sensory stimuli
• Soothing responses
• Develop an individual care plan
• Assess the strengths and needs of the caregiver.

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Supportive Care - Mainstay of therapy

• Optimal nutrition
• Modify environment
• Containment/Soothing
• Skin care
• Safe, undisturbed sleep
• Support to the caregiver

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Promote Optimal Nutrition

• Problems
• Disorganized suck
• Prolonged sucking bursts (29x20secs)
• State instability
• Increased calorie needs
• Hypermetabolic
• Increased losses

• Interventions
• Low stimulation
• Swaddling
• Anticipate augment calories frequency of feeds

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Breastfeeding ?

• Encourage if HIV negative and no active drug use.
• What about methadone maintained mothers?
• 1994, AAP safe lt 20mg dose
• AAP Revised Recommendations NO dose limit
• An effective treatment strategy !

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Methadone and Breastfeeding

• Advantages
• Less hospital days
• (8 days)
• Reduced risk of SIDS
• Brain development
• Motivation for recovery

• Disadvantages
• Potential withdrawal if abrupt cessation (high
  maternal dose)
• HIV risk
• Exposure to other drugs

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Supportive Care Modify the Environment

• Rationale
• Promote sleep
• Enhance capacity to interact
• Decrease calorie expenditure

• Interventions
• Low-light/noise
• Minimal stimulation
• Gentle handling and holding
• Music (HR rhythm)
• Avoiding strong perfumes

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Supportive Care-Soothing

• Rationale
• Decrease energy expenditure
• Prevent escalation
• Promote positive interaction

• Interventions
• Early response to cry
• Swaddling
• Containment
• Vertical rocking, swing
• Carrying
• Non-nutritive sucking
• Warm bath
• Deferring circumcision

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Supportive CareSkin Care

• Prevention
• Swaddle
• Soothe
• Massage
• Protect buttocks frequent diaper changes,
  barrier
• Treat diaper rash aggressively triple cream,
  consider yeast.

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Supportive Care Safe Undisturbed Sleep

• Rationale
• Increased risk of SIDS if opiate/ methadone
  exposed.
• Sleep fragmentation

• Interventions
• Back position
• Quiet environment
• Allow to complete sleep cycles
• Containment

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Engage the Caregiver

• Key to her babys recovery
• Barriers
• Guilt
• Lack of trust
• Fear
• Poor self esteem
• Anxiety/ depression
• Arousal
• Goldfish bowl

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Attitudes of Staff

• Self report questionaire of 50 nurses/ midwives
• Generally negative, stereotypical, judgmental
• Inadequate knowledge base
• Experienced nurses - more judgmental
• Need for specialist education inservices on
  substance use and effects on mother and infant.
• Raeside, 2003

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Support to Caregiver

• Staff to Caregiver
• Non judgmental
• Show empathy
• Realistic expectations
• fatigue is a major trigger to relapse
• visitation
• Acknowledge as a parent first
• Include in care plan
• Keep informed

• Caregiver to Infant
• Help read infant cues
• Educate on soothing techniques feeding
• Signs of engagement overstimulation e.g. gaze
  aversion
• Affirm positive interaction
• Maintain connection photograph etc

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• Ideally preparation of the mother should begin
  PRIOR to the birth
• How her infant will be monitored
• Her role in her infants care
• Supportive care and treatment
• Breastfeeding if appropriate
• Length of stay
• Home nursing visit

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PharmacotherapyIndications

• Inadequate feeding/ wt loss
• Severity of signs/ symptoms
• FS gt8 3 scores/24 hrs or mean of 3 consecutive
  scores
• FS gt12 2 scores or mean of 2 consecutive scores
• Severe diarrhea / buttock escoriation
• Inability to sleep/ interact

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Pharmacologic Options
Paregoric (0.4mg/ml morphine equivalent) Tincture of Opium 10mg/ml Dil 25x Methadone Morphine PO/IV/SQ 4mg/ml
Phenobarb. Chlorpromazine extrapyramidal effects Clonidine Limited use CVS effects Diazepam
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Current Recommendations

• Drug of first choice
• Opioid dependency - Opioid
• Mixed opioid dependency Opioid
• Non-opioid dependency Phenobarbitol
• If not controlled at maximum dose of first line
  drug, add a second drug.

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Tincture of Opium Vs Paregoric

• Tincture of Opium
• Preferred drug (AAP)
• 18 alcohol
• No toxic additives
• Must be diluted 25-fold
• (0.4mg morphine equivalent per ml)

• Paregoric
• One of first drugs used
• 44-46 alcohol
• Potentially toxic additives
• Camphor (CNS stimulant)
• Anise oil (habituation)
• Benzoic acid (gasping baby syndrome, jaundice)
• Glycerin (diarrhea)

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Oral Morphine

• No randomized/comparative studies of
  effectiveness
• Available as 2 4 mg/ml
• Less alcohol (10)
• Should be diluted to the same ME as Paregoric

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Titration of Dose

• Initial dose 0.8cc/kg/day (0.1cc/kg/dose every 3
  hours)
• Increase by 0.05 cc/kg/dose every 12 hours until
  FS lt 8.
• If control not achieved, consider adding
  phenobarbitol, if supportive care is optimal and
  no other cause for symptoms.

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Opiate WeaningGoal Prior to discharge

• Allow 3 good days
• Criteria Wt stabilized/ increased FS lt 8
• Method
• Decrease by 10 of dose/ day
• If tolerated for 3 consecutive days, decrease by
  20
• D/C at 0.05cc/kg/dose or 0.02mg me/kg/day

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Methadone

• Advantages
• Effective orally and parenterally
• Duration of action is 8-10 hrs - infrequent
  dosing more physiologic care
• Enteral/ parenteral

• Disadvantages
• Pharmacokinetics data in neonates is lacking
• Difficult to titrate dose
• Stigma

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Phenobarbitol

• Drug of choice for non-opiate withdrawal
• NOT recommended as first line in opiate
  withdrawal
• Depression of suck reflex
• Tolerance induction of drug metabolism
• Seizures
• Hyperalgesic effect
• No effect on GI symptoms
• May discharge prior to weaning???????

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Combination Therapy

• In 1 partially randomised study (n20)
• Opiate dependent infants treated with DTO
  phenobarbitol
• Decrease in hospital stay (77d to 32d) and
• Average cost savings of 35,856 per patient.
• Rationale Phenobarb increases opiate depletion
  offset by DTO
• Infants weaned off opiate prior to discharge and
  continued on phenobarbitol.
• Coyle MG et al, J Pediatr, 2002140561-564.

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Methadone Weaning at Breast

• Gradual tapering
• Mother tapers dose slowly 2 to 2.5 mg/ 10 days.
  
• Minimal risk of WD if abrupt weaning at dose lt
  20 mg
• Wean slowly from breastmilk by intro of 1 oz
  formula per day/ 1 bottle formula/week

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In-Hospital Stay

• Minimum
• Heroin/ prescription drugs 4 days
• Methadone 7 days
• Most infants show some signs of NAS, requiring
  supportive care.
• If require pharmacotherapy average LOS 21 days.

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Factors Leading to Shorter Hospital Stays

• Dosing interval
• Peak dose
• Breastfeeding
• A caregiver available to provide support to the
  infant during the stay

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Discharge Readiness

• Able to feed and grow
• Abstinence score lt 8
• Weaned off opiate medication
• Safe home environment
• Caregiver able to calm and feed infant
  bio/foster
• Anticipatory guidance
• supportive care, prevention of SIDS
• Early and frequent follow-up
• Home-care

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The light at the end of the tunnel!

• Exaggerated crying curve in first 2 to 3 months
• By 4 months most infants have no s/ s of
  withdrawal
• Severity of NAS does not affect prognosis.