New Neonatal Abstinence Syndrome in NICU

Dr. Darshan Shah Asst. Professor of Pediatrics Quillen College of Pediatrics

 Drug use in general population  How Common or Uncommon it is?

 Prescribed/Illicit/Not intended

New Neonatal Abstinence Syndrome in NICU

   2010 Data of National Drug Survey: High School Senior : 1 in 3 used medical prescription or OTC drug for Non-Medical reason #### 33%%% Pregnant women 18-25 years 23% Vs 13% Non pregnant

New Neonatal Abstinence Syndrome in NICU

 Why rise in narcotic prescription?

 What it takes to get prescription?

 What it makes easy or difficult in pregnancy?

New Neonatal Abstinence Syndrome in NICU

    MMT shifted from FDA to Center of Substance Abuse and Addiction in 2001 Standard for Methadone prescription not well defined and not uniformly followed More philosophy to “treat and better outcome” Rise in number of ‘Pain Clinics” last decade

New Neonatal Abstinence Syndrome in NICU

Pain Clinics

            DC Recovery Atenley Drug Center DRD Knoxville Medical Clinic DRD Knoxville Medical Clinic Central 0661 Memphis TN Greenville Jackson Professional Associates (901) 375-1050 TN Knoxville TN Knoxville TN Jackson TN (423) 639-5255 (865) 522-0161 (865) 522 (731) 660-0880 Memphis Treatment Center for Research and Addiction Treatment Memphis TN (901) 722-9420 Nashville TN (615) 321 Middle Tennessee Treatment Center 2575x104 Midsouth Treatment Center 6535 Raleigh Professional Associates Solutions of Savannah Savannah Dyersburg Memphis TN TN TN (731) 285 (901) 372-7878 (731) 925-2767x2760 The Mustard Seed Newport TN Volunteer Treatment Center Inc Chattanooga 3122 TN (423) 265-

Pain clinics in TN

                            Western Carolina Treatment Center ADS Alcohol and Drug Services Burlington Alcohol and Drug Abuse Treatment Ctr Ashville NC Butner McLeod Addictive Disease Center Charlotte NC Metro Treatment of North Carolina LP Charlotte Treatment Center Mountain Area Recovery Center West BAART Community Healthcare Durham Durham Treatment Center Durham Clyde NC NC Carolina Treatment Center (CTC) Fayetteville NC Metro Treatment of North Carolina LP Fayetteville Treatment Center McLeod Addictive Disease Center Gastonia Alcohol and Drug Services ADS East NC Greensboro Greensboro Metro Treatment Center PORT Human Services Methadone/IV Programs Greensboro Greenville Walter B Jones Alcohol and Drug Abuse Treatment Ctr Greenville McLeod Addictive Disease Center Hickory Alcohol and Drug Services ADS West Jacksonville Treatment Center Jacksonville McLeod Addictive Disease Center Marion McLeod Addictive Disease Center Monroe Carolina Treatment Center of Pinehurst Raleigh Methadone Treatment Center (RMTC) Rocky Mount Treatment Center Sanford Treatment Center LLC Rocky Mount Sanford McLeod Addictive Disease Center Statesville New Hanover Metro Treatment Center Wilmington Treatment Center Insight Human Services Wilmington Winston Salem Hickory High Point NC Marion NC Pinehurst Raleigh NC NC Statesville Wilmington NC NC NC (336) 532-0500 NC (704) 332-9001 Charlotte NC (925) 726-1063 (919) 286-1509 (910) 864-8739 Fayetteville (704) 865-1558 NC NC NC NC NC NC (910) 347-2205 NC (704) 332-9001 NC NC (252) 972-4357 (919) 776-0711 NC NC (800) 992-3671 (336) 725-8389 (828) 251-1478 (919) 575-7928 NC (828) 454-0560 NC (336) 333-6860 (336) 273-9611 (252) 353-5346 (252) 830-3426 (828) 464-1172 (336) 882-2125 (828) 659-3966 (910) 235-9090 (919) 781-5507 (704) 871-2992 (910) 251-6644 (704) 697-0044 (910) 483-0958

Pain clinics in NC

     What it takes to get prescription for pain?

History of Heroine/IV drug use/Morphine History of illicit Hydrocodone/Percocet/other drugs History of chronic pain(?) not relieved by other medicine History of anxiety/nervousness

Pain Clinic

 Methadone is used to relieve moderate to severe pain that has not been relieved by non-narcotic pain relievers. It also is used to prevent withdrawal symptoms in patients who were addicted to opiate drugs and are enrolled in treatment programs in order to stop taking or continue not taking the drugs. Methadone is in a class of medications called opiate (narcotic) analgesics. Methadone works to treat pain by changing the way the brain and nervous system respond to pain. It also works as a substitute for opiate drugs of abuse by producing similar effects and preventing withdrawal symptoms in people who have stopped using these drugs.

Reason to Use Methadone According to NID

 What all these medications use has done?

Pain Clinics

Effects of Illcit/prescribed/Abused medication

Effects on Mortality

Incidence Across States

 2000:  2003: 1.7/1000 2.2/1000  2006: 3.1/1000  2009: 5.7/1000

Data Regarding Maternal Drug Use

 2000: 1.5

 2003: 1.9

 2006: 2.3

 2009: 2.9

NAS rate

Maternal drug use and NAS

Newborn Vs NAS baby

 Which is better?

◦ Methadone ◦ Subutex (Bupronorphine) ◦ Suboxone (Bupronorphine and Naloxone)

Maternal Medication

      Methadone: Only recommended treatment for pregnant women till recently (2007-8) Longest experience in pregnancy Full mu-opioid agonist Dose: 40 mg to 120 mg Minimum possible dose

Maternal Medication

   Methadone: Earlier studies shown treatment with methadone better than “street drug; no treatment or detox” during pregnancy regarding preterm birth, infectious complication, neonatal death and maternal morbidity.

So it became “standard of care” for IVD and other illicit opioid drug

Maternal Medication

    Problems after Methadone: Higher incidence of NAS It depends on dose, duration and other concomitant drugs Umbilical cord level of EDDP (Ethylene Dimethyl Diphenylpyrolidine) correlates NAS better than Methadone concentration

Maternal Medication

  Subutex (Buprenorphine) Partial-mu-oipiod agonist and kappa opioid antagonist ◦ ◦ ◦ Less than maximal opioid effect Diminished risk of overdose Minimal risk from abrupt withdrawal ◦ Dose: 4 mg to 30 mg

Maternal Medication

   Trial of Methadone Vs Subutex Drugs and Alcohol: only 20 patients combined It showed Subutex not inferior to Methadone   NEJM 2010: 131 Neonates were part of study. Drugs 2012: Meta analysis  Results

Maternal Medication

    Buprenorphine exposed newborn required significantly less morphine Shorter duration of treatment Shorter hospital stay  So what’s problem?

Maternal Medication

 Dissatisfaction rate was 71% in Subutex group versus13% in Methadone group in NEJM trial.

 Main barrier for use of Subutex

Maternal medication

   Suboxone ( Buprenorphine and naloxone in 4:1 combination) Combination of partial mu Opioid receptor agonist with opioid antagonist When taken by sublingual route no effect of Naloxone only Buprenorphine like Subutex effect but when injected/Parental route it causes withdrawal in opioid dependent subjects

Maternal Medication

  Doses: 4/1 , 8/2 and 16/4 No direct comparison with Methadone but essential same as Subutex when taken as a sublingual tablet

Maternal Medication

Newborn

 When born to drug exposed mother what to expect and when to expect?

 How to diagnose Neonatal Abstinence Syndrome (NAS) or Maternal Medication Withdrawal Syndrome ?

Newborn

    NAS: CONSTELLATION OF SIGNS AND SYMPTOMS RESULTING FROM DYSFUNCTION OF Autonomic nervous system Gastrointestinal tract Respiratory system

NAS

 Finnergan Scoring System  Most widely used screening method What’s significant score?

NAS

  Treatment: Nonpharmacological  Noise/light/distraction free QUITE atmosphere  Bundle care  Hyper caloric feeding

NAS

NAS

Medication  Morphine: 0.1mg/kg q 4 hrs    Methadone: 1mgkg q 24 hrs Clonidine: 0.5 -1 by mouth every 6 hrs Phenobarb: 2-5 mg/kg every 12 hrs

NAS

     Future treatment Ondansetron (Zofran) Immunomodulator Vaccine Genetic

NAS

NAS

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NAS