Opioid Use Disorder- Pregnancy Principles and Myths Brian Iriye MD - - PowerPoint PPT Presentation

Opioid Use Disorder- Pregnancy Principles and Myths

Brian Iriye MD and Farzad Kamyar MD High Risk Pregnancy Center

History of NAS / NOWS

• Prior t o 1875 infant s not t hought t o be affect ed
• Congenit al Morphinism
• Normal at birth
• Crying inconsolably day 3 of life
• S
• metimes developed seizures
• Frequently fatal
• 1901
• Result of withdrawal
• Give babies small quantities of morphine to ease the symptom
• S

ympt oms occur in 60-80%

• f neonat es
• Neonat al Opioid Wit hdrawal S

yndrome (NOWS )

Again, this is data up to 2012

Cost of NAS

• 2009
• $732 million hospital cost
• 3.4/ 1000 births
• 2012
• $1.5 billion
• 5.8 / 1000 births
• 81%
• f costs - Medicaid

Patrick Am J Perinatol 2015

Increase in Opioid Rxs

Opioid Rx Map

Overdose Death Rates as a S ign of S UD

Maternal Mortality Rates- US A vs Developed Nations

Maternal Mortality Texas: 2012-2015

Total Maternal Deaths 382 Deaths from Drug OD 64 (16.7% ) Deaths from Opioid OD 37 Opioid 23 Heroin 18 Fentanyl 1

Pregnancy Associated Deaths and Drugs

5 10 15 20 25 Texas Maryland Alaska Georgia Virginia

%

• f total deaths

%

• f t ot al deat hs

Methadone Vs Buprenorphine in Pregnancy

Jones NEJM 2010

Methadone Vs Buprenorphine in Pregnancy

Jones NEJM 2010

Pros of Buprenorphine vs Methadone

• Lower risk of overdose
• Fewer drug interactions
• Ability to be treated in a private office setting without the need for daily visits to a licensed treatment program
• Dosing of buprenorphine is similar to that in nonpregnant women
• Insurance in the United States may cover buprenorphine prescribed by a private physician in an office

setting, while not covering methadone dispensed in a licensed opioid treatment program

• Fewer side effects
• Low risk of adverse cardiovascular side effects (in contrast, methadone is associated with small increase in

risk of arrhythmia)

• For the newborn, in utero exposure to buprenorphine rather than methadone may result in a lower risk of

preterm birth, higher birth weight, larger head circumference, and, potentially, a lower rate and severity of neonatal withdrawal

Cons of Buprenorphine Vs Methadone

• Only limited data are available on pregnancy outcomes after first trimester exposure
• Lack of long-term neurodevelopmental outcome data
• Clinically important patient dropout rate due to dissatisfaction with the drug
• More difficult induction protocol with the potential risk of precipitated withdrawal
• Increased risk of diversion -especially the buprenorphine monotherapy formulation
• Less stringent structure of some office-based treatment programs
• Reports of maternal hepatic dysfunction and elevated transaminases
• Effects of buprenorphine are only partially reversible by naloxone
• The maximum daily dose of buprenorphine is 32 mg, due to a ceiling effect, which may not be sufficient in all

women (usually those requiring more than 140 mg per day of methadone)

• More expensive than methadone
• Treatment with methadone may result in greater reduction in illicit opioid use

Buprenorphine in Pregnancy

• Drug dosing similar to non-pregnancy women with standard induction protocols
• Initiation after obj ective observable signs of moderate opioid withdrawal
• Greater than 6 hours after short acting opioid
• 24-48 hours after longer acting opioids
• Dose adj ustments may be needed with increasing gestational age
• Blood volume increases from 5 to 8 L in pregnancy
• Maximum blood volume and cardiac output at 28 weeks
• Maintain dosing intrapartum and postpartum
• Women should be encouraged to breastfeed
• Less than 1%
• f maternal dose in breast milk

Buprenorphine Administration

• Very important to discuss and educate patient on sublingual

administration

• Ingested buprenorphine gets extensively first pass metabolized with

extremely poor bioavailability. What they swallow will not work.

• Conservative recommendation to place under tongue and
• Do not eat , drink, t alk or smoke for 30 minut es
• Let complet ely dissolve

Buprenorphine Induction

• S

etting can vary [Inpatient  Office  Home]

• Patient should be abstinent
• From short acting opioid for > 6 hours (have them stop the day before)
• From long acting opioids from 1-3 days (ie. Methadone)
• Key here is to monitor for signs and symptoms of “ mild to moderate”

withdrawal, not j ust time since last use

• S

core signs and symptoms using the Clinical Opiate Withdrawal S cale (aka COWS ).

• Looking for COWS

score of ~10-12

• This will lessen the likelihood of precipitated withdrawal

Buprenorphine Induction Cont.

Day 1

• Administer test dose to patient of 2-4 mg sublingually
• Monitor for ~2 hours
• If still experiencing withdrawal symptoms can administer another 2-4

mg dose

• This can be repeated later in the day when the patient is at home

depending on previous dosing

• Max on day one 8 mg

Buprenorphine Induction Cont.

Day 2

• Administer total dose from day 1 sublingually
• Monitor for ~2 hours
• If still experiencing withdrawal symptoms can administer another 2-4

mg dose

• This can be repeated later in the day when the patient is at home

depending on previous dosing

• Max on day two 12 mg

Buprenorphine Induction Cont.

Day 3

• Administer total dose from day 2 sublingually
• Monitor for ~2 hours
• If still experiencing withdrawal symptoms can administer another 2-4 mg

dose

• This can be repeated later in the day when the patient is at home

depending on previous dosing

• Max on day three 16 mg
• This will likely be the stabilization dose
• Continue this dose for next several days to let it reach steady state

Buprenorphine S tabilization and Maintenance

• Early on recommend more frequent visits (ie. Weekly) and can advance as

patient becomes more stable with their sobriety (ie. Monthly)

• Perform Urine Drug S

creen testing – make sure to test for buprenorphine

• If patient experiences cravings, withdrawal symptoms, return to substance

use, etcetera. Assess needs, reasons, social situation, other stressors

• Consider increasing frequency of visits
• Consider increased intensity of treatment (including behavioral interventions)
• Consider increasing dose or split dosing
• Most will stabilize and maintain on 8-16 mg daily.
• Consider capping maximum dose at 24 mg daily (per guideline

recommendations)

S ubutex vs S uboxone

• No reason for preferential starting of one over the other in pregnancy
• Past concerns of naloxone in suboxone probably unwarranted
• Do to risks of diversion, suboxone use will probably expand
• No need to preferentially switch a patient already on either

medication

Methadone Risks--Reprotox

• Neonatal effects that were related to the gestational use of this agent included

prematurity, low birth weight, microcephaly, j aundice, thrombocytosis, arrhythmias, abnormal flash visual evoked potentials, the neonatal abstinence syndrome, lower language and cognition scores, and poorer neurological development, particularly with respect to executive function, up to 57 months

• f age
• Quick Take: Experimental animal studies show congenital anomalies to be

increased in the offspring of some species after pregnancy exposure to high dose levels of methadone. The main concern in humans has been neonatal withdrawal after antepartum exposure to methadone.

S ubutex Risks (buprenorphine)

• Placental transfer of buprenorphine might be limited in comparison with other
• pioids including methadone, thereby limiting fetal exposure and the

development of dependency.

• However, there are reports of neonatal abstinence syndrome of variable intensity

that might occur less often or subside sooner than in methadone-exposed infants. S tudies indicated better outcome as evaluated by Apgar score, birth length, respiratory distress, or preterm labor with buprenorphine compared with methadone.

• Quick t ake: Based on experiment al animal st udies, buprenorphine exposure during

pregnancy is not expect ed t o increase t he risk of adverse out comes at birt h but might produce lat er behavioral changes. As wit h ot her opioids, a neonat al abst inence syndrome can occur.

S uboxone Risks- Buprenorphine/ naloxone

• S

ame as buprenorphine

• For Naloxone Component: Quick take: Based on experimental animal studies,

use of naloxone during pregnancy is not expected to increase the risk of congenital anomalies.

• It is not known whether naloxone administration to pregnant women might

increase the risk of preterm labor by blocking the endogenous opioid suppression

• f oxytocin release from the posterior pituitary, a phenomenon observed in rats-

BUT THIS IS NOT S EEN IN LIMITED S TUDIES WITH S UBUXONE IN PREGNANCY IN HUMANS

• There is a decrease in prolactin after naloxone administration (not oral dose)-

Old Category C

• Oral bioavailability of naloxone is 0.5-2.0%

NAS and Newborn HC

Visconti, Towers 2015 AJP

These pregnancies require special ultrasound follow up during pregnancy- usually only available in MFM centers

Drug Withdrawal During Pregnancy- Old S chool

• Not recommended from the 1970s until recently due to risk
• Fetal Demise
• Fetal Distress
• 1973 Rementeria AJOG
• Case report of stillbirth in a patient with withdrawal sxs shortly before 39

wks

• Reviewed literature from preceding 10 years on stillbirth and meconium

stained fluid in opioid addicted women

• Conclusion- methadone maintenance----Don’ t withdrawal during

pregnancy

Drug Withdrawal During Pregnancy- Old S chool

• Zuspan 1975 AJOG
• S

erial amnios to assess epi and norepi levels over 9-10 weeks in pregnancy being detoxed from methadone

• Epinephrine levels increased suggesting fetal stress so the

process was discontinued

• Delivered at 39 weeks on methadone maintenance
• Conclusion- Detox causes stress----don’ t do it!!

Drug Withdrawal During Pregnancy

• 57 mothers over 7 years in methadone detox program
• 30%

(n=17) successful- 2 cases of NAS (12% )

• 70%

(n=40) unsuccessful- 30 cases of NAS (75% )

• NO FETAL DEATHS OR ADVERSE OUTCOMES REPORTED

Mass 1990 (J Perinatal Med)

• 34 mothers over 10 years with inpatient 10-20 day methadone detox
• 20 (59%

) successful- 3 cases of NAS (15% )

• NO FETAL DEATHS OR FETAL DISTRESS

Dashe 1998 (Obstet Gynecol)

• 101 mothers over 12 years with inpt methadone detox (21 days)
• 1 S

AB in the 5 pts detoxed in the first trimester

• No fetal deaths in 2nd or 3rd tri detox
• No data on relapse or NAS

Luty 2003 (J S ub Abuse Treat)

Drug Withdrawal During Pregnancy

• 175 pts over 7 years in a comprehensive care center
• 95 with methadone withdrawal over 3-7 days
• 51/ 95 relapsed (54%

)- NAS rate of 28%

• 80 maintained on methadone- NAS

rate of 24%

• No fetal loss or PTD in detox group
• More prenatal visits in Methadone maintenance (MM) group
• Conclusion – Methadone maintenance is better due to relapse rates

Jones 2008 (A J Addict)

• 95 pts over 6 years with 15-25 day methadone detox program
• 53/ 95 successful- NAS

rate 10%

• 42/ 95- unsuccessful- NAS

rate of 80%

• No fetal deaths or distress during detox

S tewart 2013 (AJOG)

Conclusions of Withdrawal S tudies

• 5 papers spanning 24 years
• 382 patients who went thru detox
• NO FETAL DEATHS
• 1 S

AB with first trimester detox- not significantly different from baseline miscarriage rate but limited data

Possibilities of Opioid Withdrawal

• Haabrekke 2014 (J Addictive Dis)
• 21 pts in residential living detox program over 5 years

compared to 78 pregnancies of opioid addicted pregnant women

• 22%

NAS vs 77% NAS

• No fetal deaths or preterm deliveries in the detox group
• 26%

preterm deliveries in the opiate group

Detox in Pregnancy- Bell &Towers AJOG 2016

• Evaluate the safety of opiate detoxification in pregnancy
• S

econdary outcome- to assess the manner of detox and the rate of NAS

• Prospective observational data collection during ongoing

prenatal care of opiate addicted pregnant women during a 5 ½ year period from 2010 to 2015 with the complete data assessed retrospectively at the end

Detox in Pregnancy- Bell &Towers AJOG 2016

• Four Groups of patients were studied
• Group 1 – acute detox of incarcerated patients
• Group 2 – inpatient detox with intense outpatient behavioral health

follow-up

• Group 3 – inpatient detox without intense outpatient behavioral

health follow-up

• Group 4 – slow outpatient buprenorphine detox with ongoing

behavioral health

Detox in Pregnancy- Bell &Towers AJOG 2016

• 301 total patients in the study
• 28 patients (9%

) detoxed in the first trimester (5-13 weeks gestation)

• 2 IUFD’s
• First was fully detoxed at 10 weeks but had an IUFD at 18 weeks from

a placental abruption (she was still incarcerated and her drug screen was negative)

• S

econd was fully detoxed at 12 weeks but had an IUFD at 34 weeks – fetus was hydropic – autopsy declined – all testing was negative on the fetus and her drug screen was negative

Detox in Pregnancy- Bell &Towers AJOG 2016

• 148 patients (49%

) detoxed in the second trimester (14 to 26 weeks) – no fetal losses

• 125 patients (42%

) detoxed in the third trimester (27 weeks and greater) – no fetal losses

• No cases of preterm labor/ delivery or PPROM during the

process of detox

Detoxification with appropriate behavioral health follow up should be considered an appropriate option for well selected patients

incarcerated IP det ox +BH OP det ox - BH S low OP det ox + BH

Detox in Pregnancy- Bell &Towers AJOG 2016

• Excluding Group 1 patients that were acutely detoxed after being

incarcerated

• Combining Groups 2 & 4 (those fully detoxed and maintained in

intense long-term behavioral health follow-up)

• The rate of NAS

was 20 in 116 patients (17.2% )

• Compared with Group 3 (not maintained in FU)
• The rate of NAS

was 54 in 77 patients (70.1% )

• Highly significant difference p < .0001
• YOU NEED TO HAVE BEHAVIORAL THERAPY F/ U for

DETOXED MOMS

Detox Fears Appear Overstated

• With this study data and a review of the current literature, there are

more than 700 cases of reported opiate detoxificat ion during pregnancy without a fetal demise related to the process

• Risk of stillbirth in the low risk population of pregnant women in U.S

. is 3-4 per 1000

What to Do Now With This Data

• Offer patients continued treatment vs detox
• No coercion…

… j ust options

• Put patients into MAT program to stabilize and then wean down
• r enter an inpatient detox program.
• Do this only in motivated patients with access to behavioral

health and adequate follow up

Detoxing in Pregnancy--Method

• For outpatient slow detoxification, each patient is different, but
• verall, the dose is decreased systematically in a stair step pattern per

week

• Methadone 10 mg increments
• Buprenorphine 2 mg increments
• When fully discontinued, use ancillary treatments of symptoms
• Clonidine / antiemetics / antidiarrheals / others
• Naltrexone
• Antenatal testing in 3rd trimester
• Need behavioral health thru delivery and 6 months PP
• Relapse Rate in Towers Group in 13%

up to 6 months PP

Prenatal Care Issues

• Discuss the role of DCS

involvement

• How participation will help
• Birth control
• 80%
• f patients are multiparous
• LARC/ BTL
• Antenatal testing at 32 weeks
• Growth sonography monthly after 28 weeks
• Routine 39 week delivery unless o/ w indicated

Post Partum Issues

• Vaginal Delivery
• 95%
• f time does not need opiates
• Cesarean delivery
• Bupivicane inj ection incisionally- recent data not great
• NS

AIDs/ acetaminophen

• Naltrexone if completely off opioids
• Maintain patient’s current total daily dose of buprenorphine
• Can spilt into TID dosing for better pain control regimen, supplement as above.
• If above not providing adequate coverage for breakthrough consider fentanyl or dilaudid

Post partum

• Pregnancy only coverage

stops 60 days after delivery + remaining month

• Increased stressors after

delivery with new baby, increased housing and financial needs

• OD deaths peak 7-12

months after delivery

• New paperwork and new

doctors after delivery