Substance Abuse In Pregnancy. N.L. Meyer, MD University of Tennessee Health Science Center November 18, 2016

Transcription

1 Substance Abuse In Pregnancy N.L. Meyer, MD University of Tennessee Health Science Center November 18, 2016

2 Disclosures No Financial Relationships To Disclose

3 Substance Use Disorders DSM - IV Abuse at least one in the past 12 months Recurrent use resulting in failure to fulfill major role obligations Work Home School Recurrent use in physically hazardous situations Legal problems Continued use despite persistent or recurrent social or interpersonal problems

4 Substance Use Disorders DSM - IV Dependence at least 3 in the past 12 months Tolerance Increase in amount or decrease in effect Withdrawal symptoms Taken in larger amount over longer period Persistent desire or unsuccessful attempt to quit Significant time and activity spent to obtain, use and recover Ceased or reduced social, occupational or recreational activities Continues despite knowledge of adverse consequences

5 Scope Estimated 810,00 to 1,000,000 chronic opioid users 6.4 million abusers of prescription drugs year olds 12% prescription opioid abuse year olds 22% prescription opioid abuse 22.1 million met criteria for substance abuse/dependency in million women abuse alcohol 3.5 million women abuse prescription drugs 3 million women regularly use illicit drugs 30,000 to 160,0000 prenatal exposures to cocaine (3%)

6 Commonly Abused Prescription Drugs Opioids Usually prescribed to treat pain CNS depressants Anxiety Sleep disorders CNS stimulants Usually prescribed to treat attention-deficit hyperactivity disorder

7 Opioid Prescriptions

8 Opioid Prescriptions Increased prescriptions increased overdose Deaths from prescription overdose outnumbered deaths from heroine and cocaine combined (2007) National Institute on Drug Abuse NIH Publication Oct 2011.

9 Prescription Drugs Epidemic In Tennessee 2 nd leading state in US in pounds of opiate pain relievers sold Prescription opioids ranked #1 abused drug among individuals receiving state-funded treatment services 15% increase in convicted DUI offenders abusing opiates ( ) Cost of caring for children in state custody increased from 29 million (2008) to 52 million (2011)

10 Pills Per Tennessean

11 Prescription Drugs Epidemic in Tennessee Deaths increased from 422 (2001) 1063 (2011) More deaths due to drug overdose (2010) than MVA, homicides, suicides 40% of deaths in year old age group Urban and rural problem More prevalent in east Tennessee but moving west

12 Opioid Prescriptions Prescription painkiller overdose killed in US in 2008 >3 times the 4000 people killed in million Americans used prescription drugs for nonmedical reasons in 2010 Half million ER visits in 2009 for nonmedical prescription abuse $72.5 billion annual cost to health insurers for nonmedical prescription drug abuse

13 Prescription Drug Monitoring Programs (PDMP) Requires physicians and pharmacists to log each prescription into a state database Track prescriptions Identify doctor shoppers

14 Controlled Substance Monitoring Database (CSMD) and Prescription Safety Act Tennessee Prescription Safety Act of 2012 Tennessee Public Chapter 880

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16 Scope Persistent abuse in Pregnancy Substance % of women Tobacco 16.3% Alcohol 10.8% Illicit Drugs 4.4%

17 Financial Impact Substance Alcohol Tobacco Opiates (NAS) Estimated National Cost $5.4 billion $122 million $720 million

18 Screening Limitations of providers 41% screen for EtOH 20% screen for illicit drugs Physician discomfort Fear of losing patients Appropriate response to positive screen Lack of resources Instruments 4P s Plus CAGE-AID

19 Biochemical Screening Maternal Blood, urine, hair, saliva, sweat Limitations Neonatal Urine Meconium CordStat 5, 7, 9, 12, or 13 drug panels with add-ons for EtOH and designer stimulants

20 CordStat 13 Panel Amphetamines Cannabinoids Cocaine Opiates Phenclyclidine Methadone Barbituates Benzodiazepines propoxyphene Meperidine Tramadole Oxycodone Buprenorpherine EtOH Designer stimulants (Bath Salts) Methylone Ethylone Mephedrone Butylone MBDB mcpp TFMPP MDPV

21 Opioids Heroine Oxycodone (OxyContin, Percocet ) Hydrocodone (Vicodan ) Morphine Cocaine Methadone Complicates 4.4% of pregnancies 16% of pregnant women with addiction use heroine primarily

22 Opioids Maternal Risks Related to the predominance of IV injection as the route of administration Acute overdose Inherent infectious risk

23 Opioids Inherent Infectious Risk Hepatitis C Prevalence 48% Vertical transmission 2-8% Correlates with maternal HCV RNA titers >106/mL Hepatitis B Prevalence 3.5% Vertical transmission rate with HBIG/vaccines HIV Prevalence 5.8% Vertical transmission rate with HAART/C-section

24 Opioids Maternal Risks Unplanned pregnancies 70% vs 34.8% without dependence Tobacco 93% vs 22% without dependence Psychiatric illness 61% Unsafe practices Sex trading 60% Violence 81% commission of violent crime 93% victim of violent crime 35% victim involving a weapon

25 Opioids Fetal Risks Preterm delivery Growth restriction Low birth weight Stillbirth (?) Infant mortality methadone Rate of 24.4/1000 vs 4/1000 livebirths Sudden infant death syndrome (SIDS) Neonatal abstinence syndrome (NAS)

26 Opioids - Management Detoxification Limited data in pregnancy Opioid maintenance treatment Improved compliance and overall sobriety compared to detoxification Methadone Buprenorphine (Subutex ) Buprenorphine-naloxone (Suboxone )

27 Opioids - Detoxification High rate of recidivism Relapse rates exceed 50% Withdrawal has historically been associated with increased risk of stillbirth Rementeria and Nunag AJOG;116:1152

28 Detoxification - Withdrawal Zuspan et al. AJOG. 1975;122:43-46 Single case report Amniotic fluid levels of fetal epinephrine and norepinephrine were elevated during detoxification Interpreted as a significant stress to the intrauterine development of the fetus Dashe et al. Addiction. 2010;105: patients electing opioid detoxification 59% successful detoxification rate. Remaining patients relapsed to illicit drug use or opted for methadone maintenance. Fetal distress was not demonstrated in any of the patients during detoxification. Nodocumented intrauterine fetal demises, IUGR, or PTD <36 weeks gestation in the detoxification group

29 Opioid Maintenance Treatment Standard for opioid dependence in pregnancy Improved outcome compared with continued drug use Reduces illegal drug use Prevents fluctuations of maternal levels Enhances fetal growth Reduces obstetrical complications Decreases high-risk behavior

30 Maintenance Treatment vs Detoxification Remained in treatment longer Earlier and more compliant prenatal care Improved nutrition/weight gain Fewer children in foster care Improved enrollment in treatment and recovery programs Harm reduction

31 Maintenance Therapy - Methadone Federally funded maintenance programs Gold standard Higher doses in pregnancy Not associated with increased risk of neonatal withdrawal Is associated with maternal drug abuse Average dose mg daily Split dosing Physiologic adaptations of pregnancy Decrease fetal depression

32 Methadone Treatment Facilities Memphis Raleigh Professional Association 29 Austin Peay Highway Suite B Memphis Treatment Center 1270 Madison Ave American Drug Care 3041 Getwell Rd

33 Methadone Fetal Neurobehavioral Function FHR (slower) FHR variability FHR accelerations fetal motor activity Attenuated integration between motor activity and HR FBM

34 Maintenance Therapy - Buprenorphine Specifically certified physicians Patient autonomy and broader availability drug craving Equally effective as methadone Ceiling effect Additional dosing may not achieve additional benefits risk of respiratory depression

35 Buprenorphine Providers Shelby County

36 Buprenorphine Fetal Effects Less severe NAS Lower medication doses Shorter hospital stay

37 Buprenorphine-naloxone Limited data in pregnancy Naloxone may produce maternal or fetal hormonal changes Naloxone limits abuse potential Limited bioavailability orally Withdrawal when injected/inhaled No known significant adverse outcomes Buprenorphine remains preferred over the combination preparations

38 Methadone vs Buprenorphine Overall incidence of NAS similar Buprenorphine Less intense withdrawal symptoms (maternal) NAS Lower doses of morphine for treatment Shorter duration of treatment Decreased hospital stay Less severe NAS 50% less placental transfer/drug exposure Maternal Opiate Treatment: Human Experimental Research Project Jones et al. NEJM 2010;363:

39 Breastfeeding Risk related to no treatment vs treatment Opioid abuse without treatment Exposes infants to levels sufficient to cause tremors, restlessness, vomiting, poor feeding, and addiction Breast feeding is not recommended Treated with opioid agonist Concentration is low in breast milk Infant s ingestion is independent of maternal dose Protective effect on rate of NAS neonatal therapy Breastfeeding is recommended for agonist-maintained women

40 Cocaine 1.5 million current users Blocks catecholamine reuptake Intense sympathetic response - vasoconstriction Blocks dopamine reuptake Profound euphoria high abuse potential Augments norepinephrine release vasoconstriction Screening No validated screening tools Biochemical screening Benzoylecgoine metabolite present in urine 2-4 days after exposure

41 Cocaine Hypertensive emergencies Placental abruption Increased myocardial O 2 demand No increase in congenital malformations Breastfeeding contraindicated Tachycardia Hypertension Choking/vomiting Agitation/irritability

42 Cocaine Gouin et al. AGOJ 2011;204:340. e1-340.e12 Combined data from 31 well controlled studies OR CI Preterm birth Low birth weight SGA infant Earlier GA at delivery Reduced birth weight 1492 gm

43 Cocaine Treatment No pharmacologic treatment or replacement Psychosocial treatment Acute withdrawal No effective medication Hospitalization rarely indicated Fetal surveillance usually not warranted Obstetrical complications

44 Pain Management Common misconceptions may hinder adequate pain management Maintenance opioid agonists provide anesthesia Opioids for analgesia precipitate relapse Additive effects of opioid analgesia and maintenance therapy respiratory and CNS depression Complaints of pain signify drug seeking behavior

45 Pain Management Verify and continue usual daily maintenance dose Avoid mixed agonist/antagonist opioids Withdrawal Neuraxial anesthesia preferred Tolerance to parenteral analgesia Continous vs prn analgesia Multimodal anesthesia Nonsteroidal anti-inflammatory drugs (NSAIDs) Adjuvant enhancement of opioid effect TCA Clonidine

46 Pain Management Historical cohort control study of 68 patients on MMT vs matched controls 35 vaginal delivery vs 33 C/S Similar intrapartum pain interventions and responses Pain scores were elevated after VD in MMT but no difference in amount or frequency of opiate use Cesarean delivery MMT had higher pain scores and required 70% more oxycodone equivalents Higher than usual opiod analgesic doses may be required Opiod cross tolerance Increased pain sensitivity Meyer et al. Ob Gyn 2007;118: