Neonatal Drug Withdrawal

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1 History Neonatal Drug Withdrawal Katherine Wang, MD, FAAP Avera McKennan Children s Hospital NICU Morphine has been used for pain for many years Congenital morphinism was not recognized as an entity until ~1950 First reported case of successful treatment of seizures in an infant with congenital morphinism At that time it was renamed neonatal abstinence syndrome Methadone was introduced in 1964 Initial misconception that use was not associated with withdrawal in neonates Recent trends in Drug Use in Pregnancy The dramatic increase in rates of drug use in the last 10 years has brought neonatal drug withdrawal to its current prominence 2009 National Survey on Drug Use and Health Showed dramatic increases in illicit drug use as well as nonmedical use of prescription medications (including pain relievers, tranquilizers, stimulants, and sedatives) In pregnant women aged yrs : 4.5% reported recent use of illicit drugs 11.9% reported binge or heavy drinking in first trimester 15.3% report recent tobacco use In general, rates of drug use and smoking were lower among pregnant women compared with non-pregnant women EXCEPT for the age group years Rates were higher in pregnant women Illicit drug use in pregnant women = 15.8% vs 13% in nonpregnancy women Smoking in pregnant women = 20.6% vs 13.9% in non-pregnant women Cocaine and Stimulants Drugs of Abuse Primarily looking at the effects of intrauterine use of cocaine and amphetamines In moms there is an increased risk of preterm birth, placental abruption, fetal distress, and intrauterine growth restriction (IUGR) No well defined syndrome in the neonate Some studies suggest may see irritability, hyperactivity, tremors, high-pitched cry, excessive sucking Theses are typically seen 2 nd -3 rd postnatal day There are reports of long-term effects on behavior, cognitive skills, and physical dexterity 1

2 Methamphetamines Given the recent epidemic of methamphetamine use, there has been a push for increased research However, reliable results are often difficult to obtain due to poly-drug abuse The drug use can be at any time during the pregnancy so it is difficult to assess exposure at time of delivery Withdrawal symptoms, if present, usually clear in 3-10 days Rarely need pharmacologic intervention Again, this picture is clouded by high likelihood of poly-drug abuse So may need pharmacologic treatment but may not be for the cocaine/methamphetamine Depressants and Sedatives Alcohol one of the few substances that are known to have teratogenic effects in utero Can lead to Fetal Alcohol Syndrome Characteristic facies, growth retardation, mental retardation, hyperactivity, gross/fine motor delay, memory problems, learning problems, seizures Signs of withdrawal can being 3-12 hours after birth Concominant use with narcotics can sometimes exacerbate symptoms of NAS Selective Serotonin Reuptake Inhibitors (SSRIs) Class of antidepressant medications Fluoxetine/Prozac, paroxetine/paxil, sertraline/zoloft, citalopram/celexa, escitalopram/lexapro Most commonly used antidepressants 1.8% of pregnant mothers use antidepressants Some studies link third trimester use to neonatal signs of withdrawal Can be seen in up to 30% of exposed neonates Symptoms typically seen in first 48 hours of life Some studies have linked maternal use in the last half of the pregnancy with development of persistent pulmonary hypertension (PPHN) in the newborn Opiates and Narcotics This is the class of drugs which has been studied most Includes morphine, oxycodone, codeine, heroin, methadone, buprenorphine There has been significant increase in use of opiates over the last 20 years There has been large increase in prescriptions written by physicians Subsequently also an increase in the non-prescription use of narcotics JAMA. 2012;307(18): In utero opioid use is associated with 60-80% risk of NAS requiring pharmacologic treatment Thus far, there is no correlation between maternal dose and risk of NAS in the infant Symptoms can peak at 3-4days or may not appear until days of age Subacute withdrawal may persist for as long as 4-6 months From: Neonatal Abstinence Copyright Syndrome 2012 and American Associated Medical Health Care Expenditures: of download: 11/6/2012 United States, JAMA. Association. 2012;307(18): All rights reserved. 2

3 Epidemiology Neonatal Abstinence Syndrome The term NAS originally was coined to refer specifically to neonatal withdrawal from narcotics As research has expanded, it has also expanded Includes almost any substance of abuse which could result in withdrawal symptoms in a neonate Admissions for NAS have increased from 7 per 1000 NICU admission to 27 per 1000 admissions from 2004 to 2013 NAS Symptoms Can be varied based on type of opioid, and most recent use of drug before delivery Synthetic opiates cross the placenta more easily than semisynthetic opiates Presentation is also varied due to maternal metabolism, transfer of drug across the placenta, and placental metabolism Again, also influenced by other potential concomitant drug use If withdrawal is from heroin, typically will see symptoms within 24hrs of birth If methadone, there is a delay, typically 24-72hrs of birth Could be as late as 7 days Opioid receptors are concentrated in the CNS and GI systems, thus the symptoms follow Neurologic Excitability Symptoms Tremors Irritability Increased wakefulness High-pitched crying Increased muscle tone Hyperactive deep tendon relfexes Exaggerated Moro reflex Seizures Frequent yawning and sneezing Gastrointestinal Dysfunction Symptoms Poor feeding Uncoordinated and constant sucking Vomiting Diarrhea Dehydration Poor weight gain Metabolic/Vasomotor/Respiratory Symptoms Sweating Hyperthermia Nasal flaring Tachypnea Nasal stuffiness, excessive secretions Mottling Temperature instability 3

4 Assessment Drug screening Urine - helpful if maternal sample is obtained as well only few days for window of detection, typically better yield if infant sample obtained from first void Meconium can detect substances from 20wks gestational age may get false negative results for marijuana Combo of maternal urine and infant meconium usually yields best results Natural opioids are easily detected but semisynthetic and synthetics are not Can get false-positive results with amphetamines Can also get false positives if soap or alcohol has been used for cleaning before collection There are (4-5) commonly available clinical assessment tools Modified Finnegan Lipsitz Ostrea Neonatal Withdrawal Inventory Neonatal Narcotic Withdrawal Index Modified Finnegan tool is the most widely used The Neonatal Drug Withdrawal Scoring System (Lipsitz tool) This is a screening tool Shorter only 11 items 77% sensitivity when using a value of >4 as indication of significant signs of withdrawal Infant should be monitored for first 72 hours of life Use a new scoring sheet for each date make sure to include date and time of each score Infants are scored every 3 hours Do not wake a baby to score Modified Finnegan s Neonatal Abstinence Scoring Tool Screening, monitoring, and management tool More complex 31 items More resource intensive More potential for bias and subjectivity Initiate pharmacologic treatment if one score >12 or two scores 8 Begin scoring 2-3hrs after birth Score q4hr after a feed; do not wake if infant sleeping If score 8, then increase scoring to q2hr 4

5 Central Nervous System Disturbances Metabolic/ Vasomotor/ Respiratory Disturbances Gastrointestinal Disturbances 4/1/2016 Modified Finnegan Neonatal Abstinence Score Sheet 1 System Signs and Symptoms Score AM PM Comments Excessive high-pitched (or other) cry < 5 mins 2 Continuous high-pitched (or other) cry > 5 mins 3 Sleeps < 1 hour after feeding 3 Sleeps < 2 hours after feeding 2 Sleeps < 3 hours after feeding 1 Hyperactive Moro reflex 2 Markedly hyperactive Moro reflex 3 Mild tremors when disturbed 1 Moderate-severe tremors when disturbed 2 Mild tremors when undisturbed 3 Moderate-severe tremors when undisturbed 4 Increased muscle tone 1 Excoriation (chin, knees, elbow, toes, nose) 1 Myoclonic jerks (twitching/jerking of limbs) 3 Generalised convulsions 5 Sweating 1 Hyperthermia C 1 Hyperthermia > 38.4C 2 Special Population: Premature infants Neither has been validated in premature infants In general, premature infants do not typically manifest symptoms of NAS Overall less exposure to drug due to shorter gestation Possibly due to immaturity of brain receptors Frequent yawning (> 3-4 times/ scoring interval) 1 Mottling 1 Nasal stuffiness 1 Sneezing (> 3-4 times/scoring interval) 1 Nasal flaring 2 Respiratory rate > 60/min 1 Respiratory rate > 60/min with retractions 2 Excessive sucking 1 Poor feeding (infrequent/uncoordinated suck) 2 Regurgitation ( 2 times during/post feeding) 2 Projectile vomiting 3 Loose stools (curds/seedy appearance) 2 Watery stools (water ring on nappy around stool) 3 Total Score Date/Time Initials of Scorer Monitoring Treatment Infants at high risk of NAS should be observed for at least 3 days prior to discharge Modified Finnegan tool is used to monitor progress May still manifest symptoms later, depending on presence/amount of other illicit substances Picture can be confused by breastfeeding If mom abruptly stops breastfeeding, can result in withdrawal symptoms Non-pharmacologic therapy First line treatment is non-pharmacologic therapy this is the cornerstone of treatment Ad lib feeds make sure to monitor hydration and weight closely May need increased caloric feeds Breast milk if possible AAP removed restrictions on breastfeeding for moms on any dose of methadone While there is no research to support the association between abrupt cessation of breastfeeding Swaddling Low stimulation dim lights, quiet (ear muffs if needed) Clothed cuddling Rocking/swaying Rooming in Cluster care to minimize handling Soft blankets/sheepskin if needed for skin excoriations 5

6 Pharmacologic Therapies Medical intervention is needed in 27-91% of infants with NAS Used when non-pharmacologic interventions fail to control symptoms, serious signs (ie, seizure) are observed, association with severe dehydration Delays in treatment are associated with higher morbidity and longer hospital stays Remember that opioid antagonists (Narcan) are contraindicated because they may precipitate seizures Morphine most commonly used Short half life so must be dosed every 3-4 hrs Stable and easy to administer Typically favored for inpatient treatment because of its short half life Methadone Most common alternative to morphine Longer half life so sometimes titration can be a little more prolonged/difficult Phenobarbital drug of choice for non-opiate withdrawal Also used as adjunct therapy in difficult opiate withdrawal cases Clonidine also typically used as adjunct therapy Theoretical risk of hypotension and bradycardia Treatment pearls 2 Finnegan scores >8 or one score >12 INITIATE: Morphine at 0.05mg/kg/dose po q3hr Increase NAS trigger scores by 2 points if >21 days old Table 1 Morphine IV dosing: Initiation is 0.02mg/kg/dose IV q3hr; Escalation is increase by 0.01mg/kg/dose q3hr If you are going to treat NAS, it is better to have an algorithm or protocol Studies have demonstrated decreased length of hospital stay and fewer treatment failures The more involved family is, the better the outcome Moms who room in to help hold or cuddle provide soothing Also more emotionally attached to infants ESCALATE: Are there 2 Increase Are there consecutive morphine by indications for scores >8 or one 0.03mg/kg/dose adjunct therapy?* score>12? po Observe until scores </=8 for 48 hours Wean morphine every 24 WEAN: decrease Are scores </=8 for the hrs by 10% of stabilization dose by 10% 24hrs following wean? dose (Subtract the same number of mg of morphine each day) Call provider to BACKSLIDE: 2 examine patient consecutive and ensure all nonpharmacologic scores>8 during the weaning process measures taken Add Phenobarbital or Clonidine Stop morphine when dose is <0.02mg/kg/dose and observe minimum of 48hrs before discharge Back-up to prior dose and continue to adjust until scores are <8 again Rescue dosing: If single score >/= 12, double the previous dose and give x1, then escalate appropriately Methadone dosing: Initiation is 0.05mg/kg/dose po q6hr; Escalation is 0.01mg/kg/dose; wean is same as morphine but maintain q6hr dosing Adjunct Therapy: If 1) polysubstance exposure suspected/confirmed, AND 2) CNS findings (tremors, increased muscle tone, etc.), AND 3) Morphine dose >0.3mg/kg/dose with score remaining >8 OR unable to wean for 2 consecutive days Phenobarbital Loading dose = 10mg/kg/dose po q12hr x 2 doses OR 20mg/kg/dose IV x1; Maintenance dose = 5mg/kg/dose po daily (do not weight adjust); Discontinue when on second to last step of morphine wean to assess tolerance Clonidine Dose = 1mcg/kg/dose po q4hr; consult pharmace regarding need for taper (watch for hypotension and bradycardia; possible rebound hypertension) Follow-up Infant may or may not be discharged home on medication Depends on reliability of follow-up Community resources available The level of comfort of primary care physician with NAS management Social situation ie, mom receiving treatment or not Follow-up is especially important in these patients as they may continue to display subacute symptoms for months For mom s that are breastfeeding it is suggested that mom s wean gradually from breast milk 6