A System of Care Surrounding the Drug Exposed Neonate. Disclosures. Objectives 11/17/2015. I have no financial disclosures

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1 A System of Care Surrounding the Drug Exposed Neonate Sean Loudin MD Disclosures I have no financial disclosures Objectives Discuss the epidemiology of Neonatal Abstinence Syndrome (NAS) both nationally and regionally Understand the mechanism of withdrawal Discuss the management of infants with NAS Describe our system of care surrounding NAS 1

2 NAS per 1000 deliveries NAS per 1000 deliveries 11/17/2015 How big is the problem? Rate of NAS per 1000 births US Department of Health and Human Services, Agency for Healthcare Research and Quality How big is the problem? AHRQ CHH How big is the problem? Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to 2012 Patrick et al. J Perinatology April 2015 Incidence increased from 3.4 to 5.8 per 1000 live births Geographical variation East South Central Division (Kentucky, Tennessee, Mississippi and Alabama) showed 16.2 per 1000 live births West South Central Division (Oklahoma, Texas, Arkansas and Louisiana) showed 2.6 per 1000 live births 2

3 NAS per 1000 deliveries 11/17/2015 How big is the problem? AHRQ CHH Drugs Causing Withdrawal Classic NAS due to opiates Nicotine withdrawal from maternal tobacco exposure Alcohol withdrawal and birth defects Delayed withdrawal secondary to maternal benzodiazepine or psychotropic medications Substance Abuse at CHH CHH 2014 Cords Negative Single Positive CHH (30.67%) WV (48.83%) National (60.81%) 262 (47.55%) 563 (34.71%) 9308 (29.07%) Multiple Substances 120 (21.78%) 267 (16.46%) 3241 (10.12%) 3

4 Neonatal Abstinence Syndrome Neonatal Abstinence Syndrome Passive exposure of the newborn occurs when a mother uses a neuroactive drug during her pregnancy When the infant is deprived of these substances through the birthing process, a withdrawal syndrome may develop Neonatal Abstinence Syndrome Classic NAS consists of a wide variety of CNS signs of irritability, GI problems, autonomic signs of dysfunction, and respiratory symptoms The hallmark of neonatal withdrawal is a striking disorder of movement, most aptly termed jitteriness ~Volpe

5 Neonatal Abstinence Syndrome Autonomic over-reactivity is typically exhibited by yawning, sneezing, mottling and fever Cerebral irritation results in an irritable and hypertonic infant ~Oei and Lui 2007 Pathogenesis of NAS Pathogenesis of NAS Endogenous opiates (endorphins, enkephalins and dynorphins) Complex interactions between endogenous opiates and their receptors are important in the developing brain Locus ceruleus is a nucleus in the brain stem involved with physiological response to stress and panic 5

6 Pathogenesis of NAS Pathogenesis of NAS When the opiate is withdrawn, the inhibiting effect gone This results in a supranormal increase in norepinephrine levels, which are the likely cause of the signs and symptoms of NAS Pathogenesis of NAS Disuse Hypersensitivity A drug may depress certain neural systems Render the targets hypersensitive to their usual stimuli Removal of the depressing drug results in a rebound hypersensitivity of the affected targets May be caused in part by an increase in synthesis of certain receptors ~Volpe

7 Pathogenesis of NAS Alternate Pathways Drug may depress a primary neural pathway An alternate pathway, usually of minor activity, may become more prominent in attempt to compensate When the drug is removed, both pathways may operate in an additive fashion ~Volpe 2008 Pathogenesis of NAS Alternative Pathway Disuse Hypersensitivity Identifying Withdrawal 7

8 Identifying Withdrawal 2012 AAP Clinical Report: Neonatal Drug Withdrawal Screening for maternal substance abuse is best accomplished by using multiple methods, including maternal history, maternal urine testing, and testing of newborn urine and/or meconium specimens that are in compliance with local laws. The duration of urinary excretion of most drugs is relatively short, and maternal or neonatal urinary screening only addresses drug exposure in the hours immediately before urine collection. Thus, false-negative urine results may occur in the presence of significant intrauterine drug exposure. Identifying Withdrawal 2012 AAP Clinical Report: Neonatal Drug Withdrawal Although newborn meconium screening also may yield falsenegative results, the likelihood is lower than with urinary screening. The more recent availability of testing of umbilical cord samples may be considered a viable screening tool, because it appears to reflect in utero exposures comparable to meconium screening. Identifying Withdrawal 13 Panel USDTL Umbilical Cord Testing Amphetamines (amphetamine, MDA, MDEA, MDMA, methamphetamine) Cannabinoids (carboxy-thc) Cocaine (benzoylecgonine) Opiates (6-MAM, meconin, codeine, hydrocodone, hydromorphone, morphine) Phencyclidine (phencyclindine) (PCP) Methadone (EDDP, methadone) Barbiturates (amobarbital, butalbital, pentobarbital, phenobarbital, secobarbital) Benzodiazepines (alprazolam, diazepam, midazolam, nordiazepam, oxazepam, temazepam) Propoxyphene (propoxyphene, norpropoxyphene) Oxycodone (oxycodone, oxymorphone) Meperidine (meperidine, normeperidine) Tramadol (tramadol) Buprenorphine 8

9 Identifying Withdrawal 2012 AAP Clinical Report: Neonatal Drug Withdrawal Signs of drug withdrawal can be scored by using a published abstinence assessment tool. Together with individualized clinical assessment, the serial and accurate use of a withdrawal assessment tool may facilitate a decision about the institution of pharmacologic therapy and thereafter can provide a quantitative measurement that can be used to adjust drug dosing. Modified Finnegan Scoring System Treatment of NAS 9

10 Treatment of NAS No established optimal treatment 2005 Cochrane reviews suggest lack of high-quality evidence for any specific treatment Expert opinion suggest opioids as the class of agents with the greatest efficacy Treatment of NAS Opioid agents used Morphine sulfate Neonatal opium solution Methadone Buprenorphine Adjunct agents Phenobarbital Clonidine Treatment of NAS Cabell Huntington Hospital Methadone inpatient weaning protocol Clonidine is used for adjunct agent Weight based-symptom driven 9 step wean Average length of stay days Utilize the NICU and the Neonatal Therapeutic Unit Dedicated nursing staff 10

11 Break for Questions Transition to Home Transition to Home Caregivers educated throughout hospitalization Acute phase of withdrawal managed with medication Subacute signs of opiate withdrawal may last up to 6 months Infants are not symptom free at time of discharge 11

12 Transition to Home Withdrawing into Society: Characteristics of Neonatal Abstinence Syndrome on Final Day of Admission Laura G Wilson 1, Rachel G Clarke 1, James Denvir, PhD 2 and Sean Loudin, MD 1. 1 Pediatrics, Marshall University Joan C Edwards School of Medicine, Huntington, WV, United States and 2 Biochemistry and Microbiology, Marshall University Joan C Edwards School of Medicine, Huntington, WV, United States. Objective: To characterize the most common symptoms of NAS on the final day of hospital admission and identify any differences between symptoms based on the prenatal exposure. Transition to Home % of Patients discharged with symptoms Symptom Overall Occurrence Buprenorphine Methadone Opiates Mottling Increased muscle tone Mild tremors when disturbed Nasal stuffiness Sneezing (>3-5 times/interval) Sleeps < 3 hours after feeding Respiratory rate > 60/minute Excessive sucking Fever < 101 F ( F/ C) Transition to Home Range of all total scores during the last 24 hours and range of the average of all total scores from the last 24 hours broken down into prenatal opiate exposure. 12

13 Long Term Impact Long Term Impact Growth Alcohol- associated with poor growth Marijuana- Smaller head circumference at birth and the disparity increased as adolescents Opiates- no effect Cocaine, Amphetamines- Not conclusive Long Term Impact Behavior Nicotine- Impulsivity, attention problems, hyperactivity, negative and externalizing behaviors Alcohol- Attention and adaptive behavior Marijuana- Inattention and impulsivity at 10yrs of age, increased risk of childhood depressive symptoms by 10 years of age, increased risk of delinquency by 14 years of age, early initiation of drug abuse: male and simultaneously exposed to violence Opiates- hyperactivity and short attention span (toddlers) memory and perceptual problems in older children Amphetamines- possible association of peer problems 13

14 Long Term Impact Cognition/Executive Functioning Nicotine- learning and memory, slightly lower IQ Alcohol- IQ, poorer memory and executive functioning Marijuana- problem solving skills Opiates- No conclusive effects at this time Cocaine- visual-motor ability, attention, working memory Amphetamine- no data Long Term Impact Language Nicotine- poor language development in early childhood, with poor language and reading abilities in 9-12 yr olds Alcohol- interferes with the development and use of language (may lead to problems with social interactions) Cocaine- Subtle language delays Marijuana- Heavy use in 1st trimester: lower verbal reasoning Opiates, amphetamines- no data Long Term Impact Achievement Nicotine- poorer arithmetic and spelling tasks Alcohol- math skills, reading Marijuana- underachievement in reading and spelling Cocaine- increased odds of having an IEP and 2.8 times more likely to have a learning disability Amphetamines- lower math scores at yrs old, and higher rate of grade retention Opiates- No data 14

15 System of Care System of Care Increasing incidence of the neonatal abstinence syndrome in U.S. neonatal ICUs Tolia et al. NEJM May 2015 NICU admissions from across the Pediatrix hospital database 7 cases per 1000 admissions to 27 cases per 1000 admissions length of stay increased from 13 days to 19 days total percentage of NICU days attributed to NAS increased from 0.6% to 4.0% Infants increasingly received pharmacotherapy (74% in vs. 87% in ) System of Care Different environments for different roles NICU Neonatal Therapeutic Unit Lily s Place 15

16 Places For Treatment Places For Treatment Places For Treatment 16

17 Places For Treatment Places For Treatment Neonatal Therapeutic Unit Locked unit Unit clerk controls visitors Places For Treatment 5 rooms 3-4 beds per room Visiting hours 10 am-4 pm 17

18 Places For Treatment Keep room lights dimmed Natural light from window Places For Treatment Lily s Place Established as 501c3 Community support from day 1 Building donated and renovated Nurseries were sponsored Building brought up to code 18

19 Lily s Place WV DHHR DEA City of Huntington Licensed West Virginia HB 2999 Lily s Place Lily s Place 19

20 Lily s Place Future Directions Future Directions Increase access to substance abuse resources for adults Educate various populations about the consequences of substance abuse Continue to develop innovative ways to treat patients of all ages Expand research in the field of neonatal abstinence syndrome 20

21 Thank You 21