Opioid Dependence in Pregnancy James J. Nocon, M.D., J.D.

Opioid Dependence in
Pregnancy
James J. Nocon, M.D., J.D.
Indiana University School of Medicine
Chairman, Indiana Prenatal Substance Abuse Commission
Director, Prenatal Recovery Clinic
Wishard Memorial Hospital
1001 West 10th Street, F5102
Indianapolis, Indiana 46202
[email protected]
October 7, 2011
Objectives
• Review Opioid Pharmacology
• Types of Opioid Dependence
• Managing Opioid Dependence
– Prenatal
– Intrapartum
– Breast Feeding
• Effects on the fetus and newborn
– Withdrawal
– Breast Feeding
Pregnancy Enhances Recovery
• Pregnancy makes a difference in longterm recovery.
• After one year of treatment:
– 65.7% of women who entered treatment while
pregnant used no drugs, while
– Only 27.7% of non-pregnant women remained
drug free. (p<0.0005)
•
Peles E, Adelson M. Gender Differences and Pregnant Women in a Methadone
Maintenance Treatment (MMT) Clinic. J Addictive Diseases 2006; 25: 39-45.
3
America Has Never Been Drug-free
Most commonly used drugs in order of frequency:
1800 to 2000
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Cocaine – the 7% solution
Cannabis (THC) (2737 B.C China)
Laudanum – tincture of opium;
Morphine – from the Civil War
Methadone – developed in Nazi
Germany prior to WWII
Alcohol –how the West was won
Amphetamine -1887; used
extensively in WWII to keep soldiers
alert; the US military uses with
airmen today in Iraq
Methamphetamine -1893
Methylenedioxymethamphetamine (MDMA)
Developed by Merck in 1912 as an
appetite suppressant; today it’s
called ecstasy
21st Century: 2002-2007
Cocaine
Cocaine and THC
THC
Methadone
Other Opiates
Alcohol
Other Combinations
(opiates/amphetamines)
52
59
49
42
27
10
48
Based on 287 pregnant patients
treated from 2002 to 2007.
What’s the Difference Between
Opioids and Opiates?
• Opiates
– Alkaloids derived from the opium poppy
– Morphine, Codeine, Thebaine
• Opioids
– All Opiates, plus:
– Semi Synthetics – derived from the alkaloids
(thebaine): hydrocodone; oxycodone; heroin
– Synthetics: methadone; fentanyl; nubain;
buprenorphine
Changes In Opioid Use
• Percent of pregnant patients dependent on opioids
referred to an Indiana Substance Use Program:
• 2002-2007: 69/287 patients: 24%
• 2008: 69.3%
• 2009: 79.1%
• 2010: 75.5%
• Includes heroin, opioid dependent chronic pain patients,
opioid poly-substance users, methadone and
buprenorphine maintenance.
Opioid Abuse Skyrockets
• Opioid prescription abuse is the fastest
rising addiction and public health problem
in the United States.
• Over 2,000 deaths per week have been
attributed to opioid abuse.
• Most of the fatalities are due to Oxycontin
• http://www.foodconsumer.org/newsite/Politics/32/opioid_abuse_skyr
ockets_061820100141.html
What’s Oxycontin?
• Oxycodone
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Made by Perdue Pharma
Special coating allows for extended release
Marketed as safe – low addictive risk
Perdue Pharm sued for misbranding, among other issues.
East to remove the coating – rapid onset
• Most abused Rx drug:
– Especially in Kentucky and Tennessee: “Hillbilly Heroin”
– OxyContin's warning label said to not crush the controlledrelease tablets because of the potential for rapid release of
oxycodone, which led many people to crushing the tablets and
injecting or snorting the drug.
Typical Doses of “Oxy”
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10 mg - white
15 mg - grey
20 mg - pink
30 mg – brown – most often prescribed
40 mg – yellow
60 mg - red
80 mg – greenish blue
Addicts typically use 250 mg/day to feel normal.
And 500-550 mg to get high.
It sells for about $1 per milligram
PMP Restricts “Oxy” Abuse
• 47 states have a Prescription Monitoring
Program (PMP)
• Inspect: http://www.in.gov/pla/inspect.htm
• Florida’s program in jeopardy due to lack of
state funding.
• Lack of effective PMP allows “pill mills” to
flourish as “Pain Clinics.”
– 41 million prescriptions for Oxy in Florida (July to Dec
2010)
– Only 4 million Rx for entire US.
Political Ideology Enables “OXY” Abuse;
Intent vs. Impact
• Intent of Florida Governor
– To reduce federal government and spending.
– Rejects 15 million in Federal funds for the PMP.
– Rejects the PMP because of opposition to supporting a
“government database.”
– Attempts to repeal Florida Law creating PMP
• Impact:
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Allows pill mills to flourish.
More “pain clinics” in Florida than McDonalds.
Kills 10 people per day in Florida
#1 drug of abuse among 12-17 year olds
Others Enable “Oxy” Abuse
• Organized Crime
• Pharmacies
• Doctors
– Over $5,000 a day to write prescriptions in
“pill mills” in Florida.
– Can easily make over a million dollars/year
– No nights, no call, just writer’s cramp.
• And, America has never been drug free!
What is Addiction?
• Great question. Like obscenity, hard to
define but, I know it when I see it.
• Dependence
– Psychological: withdrawal
– Physical; tolerance and withdrawal
• Addiction: continuing the behavior in spite
of the adverse and illegal consequences of
the behavior.
Relationship View of Addiction
• If the behavior keeps me from being
physically and emotionally present for
those I love and those who love me.
• Then I have a problem with the behavior.
• May be alcohol, tobacco or other drugs
(ATOD)
• May be eating, sex, gambling, etc.
• Hoarding?
Addiction in Women
• Late 19th Century: Women accounted for 2/3 of
America’s opiate addicts and a large percentage of
marijuana, sedative, cocaine and amphetamine addiction.
• Only 1 in 5 illegal drug addicts during 1914-1954 were
women
• Approximate 15% of all pregnant women today are using
alcohol, illegal and illicit drugs during pregnancy.
• Note: Americans constitute 4% of the world’s
population and consume 2/3 of the entire drug
supply.
Psychiatric Gender Issues
in Maternal Addiction
• If sexually abused as a child:
– 6 times more likely to become drug addict (opiates)
– 4 times more likely to become an alcoholic
– Kendler KS, et al. Childhood sexual abuse and adult psychiatric and substance
use disorders; an epidemiological and co-twin control analysis. Arch Gen
Psychiatry. 2000;57:953-959.
• Major depression more frequent in women
substance users.
– Prescott et al. Sex specific genetic influences on the co-morbidity of alcoholism
and major depression in a population-based sample of U.S. twins. Arch Gen
Psychiatry. 2000;57:803-811.
Other Women’s Issues in
Addiction
• Alcoholic women usually have alcoholic spouses
and less spousal support. (Holds true for
opiates, as well)
– Redgrave, et al, Alcohol misuse by women. Int. Rev. Psychiatry
2003;15:256-268
• Women more likely to abuse prescription drugs
– “My mother gave me her Xanax.”
– Vicodin, Lortab, Xanax and Klonopin.
– Bardel, et al. Reported current use of prescription drugs and some
of its determinants among 35-65 year old women in mid-Sweden; a
population based study. J Clin Epidemiol. 200 53;637-643
The Pathophysiology of Addiction
• Just as alcohol, tobacco, and drugs activate the pleasure circuit in
the brain, so do many behaviors such as sexual activity, winning a
contest, gambling, and being praised.
• What drugs and behaviors have in common is the release of various
neurotransmitters in nucleus accumbens in the brain:
– Dopamine – creates the “buzz.”
– Serotonin – sense of well being.
– Endorphins – euphoria.
– GABA (gamma amino butyric acid) – satiety and somnolence
(sleepy after a big meal or sex)
• As repeated use of the drug or behavior depletes the dopamine,
more activity is required to get the same effect. “Tolerance.”
• There comes a point when the affected person becomes an addict,
as if a switch in the brain is flipped, and the person no longer has
the ability to make free choices about the continued use of the drug.
•
Leshner AI. Addiction is a brain disease, and it matters. Science 1997;278:45-47
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Pleasure in the Brain
http://thebrain.mcgill.ca/flash/index_i.html
• Ventral Tegmental Area
– Nucleus Accumbens –
dopamine rich center in the
limbic area
– Prefrontal Cortex – short
term memory
– Amygdala – moderates
emotional influences on
memory – fear response
– MFB: medial forebrain
bundle
• These are the primary
centers involved in
pleasurable sensations.
• Often referred to as “the
Pleasure Circuit”
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Continuous Use of Drugs
Changes Brain Cells
• Dopamine System
– Cocaine inhibits transporters
– Amphetamine affects receptor and neurotransmitter
release
• Serotonin
– Hallucinogens inhibit receptors
• GABA/NMDA
– Etoh inhibits and facilitates receptor function
– Opiates have negative effect (Morphine; Heroin)
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Pathophysiology:
Addiction Changes Brain Cells
Addiction is a “double whammy.”
1.
2.
Tolerance - The brain needs
more and more of the drug in
order to get the same effect.
And in this process, the brain
cells are actually altered.
Drugs reduce fear response in
Amygdala and Prefrontal cortex
– person uses more drug with
less fear of consequences.
McCann UD, Szabo Z, Scheffel U, Dannals RF, Ricaurte
GA. Positron emission tomographic evidence of
toxic effect of MDMA ("Ecstasy") on brain
serotonin neurons in human beings. Lancet 1998
Oct 31;352(9138):1433-7.
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You Know You Are Addicted
• When you will do anything including
breaking the law to obtain the drug,
• Just to feel normal.
An Important Digression:
• Alcohol and tobacco cause more fetal
damage than all the other drugs combined
including all the known teratogens.
Strong Link Between Alcohol/Nicotine
Use and Use of Illicit Drugs
• Among Women using BOTH Alcohol and
Nicotine in the pregnancy
• 20.4% used Marijuana
• 9.5% used Cocaine
• Women NOT using Alcohol or Nicotine
• 0.2% used Marijuana
• 0.1% used Cocaine
Alcohol and Nicotine use is also a
marker for other drug use.
Opiate Use In Pregnancy
Derived from Poppy, Papaver Somniferum, 4000 BC
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Morphine 1806
Codeine 1832
Heroin 1898 (Bayer) – was the drug of choice for obstetrical
analgesia immediately post WWII
Methadone 1930 (Bayer) – synthetic opioid
Other Commonly Used drugs
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Marijuana noted in China 2737 BC – Major Cash crop in Jamestown
1611
Cocaine - Spanish taxed it use 1569
Amphetamine marketed by Smith Kline in 1887.
Most Common Opiates Used
by Pregnant Patients
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Hydrocodone: Vicodin; Lortab
Oxycodone: Oxycontin: Percocet
Methadone
Heroin
Opiates were mostly Category B Drugs
– Animal studies appear to pose no risk, but
– Definite risk established in humans
– Visual defects confirmed in human studies with
methadone.
Maternal Treatment with Opioid
Analgesics and Risk of Birth Defects
• National Birth Defects Prevention Study, case-control study for
infants born October 1, 1997, through December 31, 2005, in 10
states
• Therapeutic opioid use was reported by 2.6% of 17,449 case
mothers and 2.0% of 6701 control mothers.
• Treatment was statistically significantly associated with:
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conoventricular septal defects (OR, 2.7; 95% CI, 1.1–6.3
atrioventricular septal defects (OR, 2.0; 95% CI, 1.2–3.6),
hypoplastic left heart syndrome (OR, 2.4; 95% CI, 1.4–4.1),
spina bifida (OR, 2.0; 95% CI, 1.3–3.2), or
gastroschisis (OR, 1.8; 95% CI, 1.1–2.9) in infants
http://www.ajog.org/article/S0002-9378(10)02524-X/abstract
Methadone: Visual Problems
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Reduced acuity (95%),
Nystagmus (70%),
Delayed visual maturation (50%),
Strabismus (30%),
Refractive errors (30%), and
Cerebral visual impairment (25%).
•
Hamilton; Ophthalmic, clinical and visual electrophysiological findings
in children born to mothers prescribed substitute methadone in
pregnancy. Br J Ophthalmol doi:10.1136/bjo.2009.169284
Opiate Pharmacology
• Bind to receptors
– Mu: analgesia; euphoria, respiratory depression,
constipation, sedation, miosis
– Kappa: dysphoria, sedation, psychotomimetic
– Delta: unknown
• Rate of Excretion faster than withdrawal
– Morphine excreted within 72 hours
– Methadone takes 4-5 days.
– Clinical relevance is patient in withdrawal may have negative
UDS.
• Withdrawal in Adult: 6-24 hours from last dose
– Morphine: 3-7 days duration
– Methadone: 10-20 days or more
Opiate Agonists
• Morphine/Codeine/Dilaudid and
Derivatives
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Specificity for Mu receptor
Metabolized by liver
½ life 2-4 hours
90% excreted in urine/24 hrs
• Methadone
– 90% bound to protein
– ½ life 20-40 hours
– Slow release into blood
Opiate Antagonists
• Naloxone - Narcan
– Very strong affinity for Mu receptor
– Rapid competitive antagonist – 2-4 minutes
– Lasts about 45 minutes
– “Jump starts” withdrawal
• Naltrexone - Vivitrol
– Binds more slowly
– ½ life 4 hours
– Used in alcohol and opiate treatment.
Opiate Agonist/Antagonists
• Nalbuphine (Nubain)
– 10 mg. IV or IM q. 3 hours ; onset 2-3 min IV
– Neonatal half life: 4.1 hours
– A favorite of OB nurses – less nausea
• Butorphanol (Stadol)
– 1-2 mg. IV or IM every 4 h; onset 1-2 min IV
– Neonatal half life unknown
• Buprenorphine (Subutex/Suboxone)
– Long acting; long half life
– Used for maintenance like methadone
Pregnancy Increases
Metabolism of Specific Opiates
• Certain enzyme systems increases the
metabolism of specific opiates, especially:
– Methadone
– Hydrocodone
– Oxycodone
• This is especially true of Methadone
•
Jarvis, M. A., S. Wu-Pong, et al. (1999). "Alterations in methadone
metabolism during late pregnancy." J Addict Dis 18(4): 51-61.
Increased Opioid Metabolism
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Increases with each trimester, especially third
30-40 percent of patients
Doses may increase by 50%.
May require more drug to treat pain
Methadone patient may be in chronic withdrawal
by third trimester.
• Higher does methadone actually has better
outcome.
•
McCarthy, J. J., M. H. Leamon, et al. (2005). "High-dose methadone maintenance in
pregnancy: maternal and neonatal outcomes." Am J Obstet Gynecol 193(3 Pt 1):
606-610.
Clinical Management of Opioid
Dependence in Pregnancy
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What is the Evidence?
Standard of Care
Opiate Overdose
Opiate Withdrawal
Opiate Maintenance
– Chronic pain patients
– Methadone maintenance
– Buprenorphine maintenance
• Opiate analgesia: labor; delivery; Cesarean
• Neonatal Abstinence Syndrome (NAS)
• Breastfeeding
Opioid Use in Pregnancy
This is the Evidence
• 2002-2010
• Four Groups: 213 Patients
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Pain patients using only opioids – 31
Opiate dependent poly-substance patients – 45
Methadone Maintenance - 90
Buprenorphine Maintenance – 46
• Subutex – 12
• Suboxone - 34
Opioid Dependent Chronic Pain
Patients Using Opioids Only
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Includes opioid/acetamenophen preparations.
N = 31
Preterm Labor: 4 (12.9%)
Positive Meconium (other than opiates): none
Mean newborn weight: 3085.9 grams
LOS (newborn): 3.3 days; range 2-21 days
NAS treated: 1
Intrapartum complications: 7
– No overdoses.
• Nicotine use (> 0.5ppd): 21 (67.7%)
Opioid Dependent Poly-substance
Patients
• Opioids plus cocaine, or THC or benzodiazepines or all three or
more
• N = 45
• Preterm Delivery: 8 (17.7%)
• Positive Meconium (other than opiates): 12 (26.6%)
• Mean newborn weight: 2879 grams
• LOS (newborn): 7.8 days; range 2-89 days
• NAS treated: 5
• Intrapartum complications: 7
– One antenatal overdose – mother and fetus survived
– One fatal postpartum overdose
• Nicotine Use (> 0.5ppd): 30 (66.6%)
Opioid Only Patients
Postpartum Visit
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Routinely at 4 weeks postpartum
N=31
Did not return: 3
Returned with positive UDS for drugs
other than prescribed opioids: 5
• Returned “negative:” 23 (74.2%)
Opioid Poly-substance Patients
Post Partum Visit
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Routinely at 4 weeks postpartum
N=45
Did not return: 13 (28.8%)
Returned with positive UDS for drugs
other than prescribed opioids: 7
• Returned “negative:” 25 (55.5%)
Comparison of Opioid and Opioid Plus
Use in Pregnancy
Preterm Delivery
Low Birth Weight (<2500g)
Mean Birth Weight
Positive Meconium
NAS Treated
Mean Length of Stay
Failed to return PP
Returned PP “negative”
Opioid (31)
Opioid + (45)
p
4 (12.9 %)
3
3085 g
0
1
3.3
3
23 (74.2%)
8 (17.7%)
8
2879g
12 (26.6%)
5
7.8
13
25 (55.5%)
NS
NS
NS
0.001
NS
0.01
0.01
NS
Methadone Maintenance
Patients
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N = 90 (92 babies)
Preterm Delivery:
28 (30%)
Mean newborn weight: 2718g
LBW (< 2500g):
31/92 (33.7%)
Positive meconium:
9 (10.8%)
Mean LOS
30.3 days
NAS treated:
80 (86.9%)
Intrapartum Complications: 15
Nicotine:
51/90 (56.6%)
Methadone Maintenance
Post Partum
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Routinely at 4 weeks postpartum
N=90 (92 babies)
Did not return: 28 (31.1.%)
Returned with positive UDS for drugs
other than prescribed opioids: 3
• Returned “negative:” 59 (65.5%)
Buprenorphine Patients
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Subutex N = 12; Suboxone N = 34; Total N= 46
Preterm Delivery: 5 (10.9%)
Mean newborn weight: 3079.5 g
LBW (< 2500g): 5 (10.8%)
Positive meconium: 3 (6.9%)
Mean LOS: 6.78 days; range 2-49 days
NAS: 8
NAS treated: 6
Intrapartum Complications 8
Nicotine: 29 (63%)
Buprenorphine Postpartum
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Routinely at 4 weeks postpartum
N=46
Did not return: 13 (28.2%)
Returned with positive UDS for drugs
other than prescribed opioids: 4 (8.6%)
• Returned “negative:” 29 (63%)
Methadone vs. Buprenorphine
Major Pregnancy Outcomes
Preterm Delivery
Low Birth Weight (<2500g)
Mean Birth Weight
Neonatal Abstinence (NAS)
NAS Treated
Mean Length of Stay
Failed to return PP
Returned PP “negative”
Bup. (46)
Meth (90)
p
5 (10.9 %)
4
3079 g
8
6
6.78
13 (28.8%)
29 (65.1%)
27 (30%)
26
2718g
89
80
30.3
28 (31.1%)
59 (65.5%)
0.001
0.01
0.005
0.001
0.001
0.001
NS
NS
See also, Kakko J, Heilig M, Sarman I. Buprenorphine and methadone
treatment of opiate dependence during pregnancy: comparison of fetal
growth and neonatal outcomes in two consecutive case series. Drug
Alcohol Depend 2008 Jul 1;96(1-2):69-78.
The Evidence Suggests New
Treatment Strategies
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Prevention of Withdrawal
Opioid Overdose
Withdrawal
Detoxification
Maintenance
– Methadone
– Buprenorphine
– Opioid dependent chronic pain patient
• Polysubstance Use in Chronic Pain Patient
Standard of Care:
Prevention of Withdrawal
• Evidence based literature clearly indicates that it is
imperative to prevent opiate withdrawal in pregnancy:
– Increased rate of preterm labor – 41%
– Increased incidence of abruption 12%
• Efforts to wean off or “detox” opiates in pregnancy carry
an increased risk of harm to the fetus.
• This represents a shift in the standard of care from
“lowest possible dose” to “appropriate” doses to
prevent withdrawal.
Opiate Overdose
• Characterized by pinpoint pupils, respiratory depression, coma, and
pulmonary edema.
• Establish airway.
• Inject Naloxone – repeat if long acting opiate present, e.g.,
methadone.
• Naloxone will not harm fetus.
• Treatment will precipitate a severe withdrawal.
• Will need to restart and modify an opioid dose
• For maintenance, use methadone or buprenorphine
• Methadone: start at 20 mg BID and increase 5-10 mg per day until
stable.
• Buprenorphine/naloxone: start at 2 – 4 mg BID; increase by 2-4 mg
every 6 hours until withdrawal is abated
Opiate Overdose Recovery
• Will need to restart and modify opiate dose
to prevent withdrawal.
• Methadone maintenance – only by a
federally certified clinic.
• But a licensed physician may legally
prescribe methadone to treat withdrawal in
pregnancy for an inpatient.
• Buprenorphine – only by a federally
certified clinician.
Opiate Withdrawal
Affects Major Systems
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CNS – tremors, seizures
Metabolic – sweating; yawning
Vascular – hot flashes and chills
Respiratory – increased rate; respiratory
alkalosis
• GI – cramps, nausea, vomiting, diarrhea
• Drug specific effects – methadone has a
prolonged withdrawal: 10 – 20 days.
Onset of Opiate Withdrawal
• Short Acting (heroin; morphine; vicodin):
– begins 6-24 hours;
– peak 1-3 days;
– lasts 5-7 days
• Methadone:
– Begins 1-3 days;
– peaks 3-6 days;
– Lasts 2 weeks or more
Opiate Withdrawal
Clinical Picture
• Patient presents with abdominal pain, cramps and
diarrhea and may complain of contractions
• Also has yawning, lacrimation, restlessness; may have
tachycardia.
• UDS may be negative for opiates!
• Typical history reveals Rx for hydrocodone/acet. 5/500
for injuries in auto accident years ago
– Admits taking more than prescription allows – commonly up to
15 - 20 pills a day
– UDS positive for opiates; often find THC, Benzodiazepines,
cocaine.
Opiate Withdrawal in Pregnancy
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High rate of preterm labor - 41%
Increased abruption - 13%
Low Birth weight – 27%
Increased incidence HIV; Hep B; Hep C
Current recommendation is to avoid withdrawal during
pregnancy
• This includes “detoxification” during pregnancy.
• The risk of adverse events from withdrawal is far greater
than from the treatment of neonatal abstinence.
•
Lam SK, To WK, Duthie SJ, Ma HK. Narcotic addiction in pregnancy with adverse maternal and
perinatal outcome. Aust N Z J Obstet Gynaecol 1992 Aug;32(3):216-21.
Opiate Withdrawal Treatment
• Initiate methadone or buprenorphine to stabilize
withdrawal: may use oxycodone 10 mg q 4-6h for up to
72 hours to stabilize patient and then switch to
methadone or buprenorphine.
• Phenergan 25 mg q 4-6 H for withdrawal symptoms –
best for nausea, vomiting and GI symptoms
• Or, Phenobarbital, 30 mg TID for neurological withdrawal
symptoms.
• Clonidine 0.1 mg TID – vascular withdrawal symptoms.
• Check acetaminophen levels in patients using
opiate/acetaminophen compounds.
Opioid Detoxification
• Must be closely controlled. Benefits rarely outweigh
risks.
• Gradual reduction to minimize withdrawal
• Symptomatic treatment.
• Phenergan 25 mg q 4-6 H for withdrawal symptoms –
best for nausea, vomiting and gastrointestinal symptoms
• Phenobarbital, 30 mg TID for neurological withdrawal
symptoms.
• Clonidine 0.1 mg TID – vascular withdrawal symptoms.
Opioid Maintenance
Methadone
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Encourage patient to remain on methadone during pregnancy.
Expect dose to increase up to 50% during pregnancy in about 35% of
patients.
Doses range from 50-150 mg. per day.
Higher doses not associated with severity of NAS but improve maternal
compliance with prenatal care.
Patient should be encouraged to breast feed.
Note: Methadone is NOT FDA approved for treatment for opiate
dependence in pregnancy.
McCarthy JJ, Leamon MH, Parr MS, Anania B. High-dose methadone
maintenance in pregnancy: maternal and neonatal outcomes. Am J Obstet
Gynecol 2005;193:606-10.
Philipp BL, Merewood A, O'Brien S. Methadone and breastfeeding: new
horizons. Pediatrics 2003;111:1429-30.
Opioid Maintenance: Buprenorphine
• Patient must be in opioid withdrawal to start
buprenorphine treatment.
• Inpatient: some recommend initiating treatment with
buprenorphine, 2-4 mg sublingual by either tablet of film.
• Increase dose by 2-4 mg every 6 hours to stop
withdrawal symptoms.
• Convert to buprenorphine/naloxone for outpatient use.
• Target doses rage from 4 to 24 mg per day
• Most pregnant patients are stable at 8-16 mg per day in
divided doses.
Opiate Dependent
Chronic Pain Patient
• Maintain current opiate regimen – avoid
withdrawal (both legal to do and meets
standard of care)
– Hydrocodone 5/325 or 10/325 (up to 2 tabs q 6h)
– Oxycodone 5/325 or 10/325 (up to 2 tabs q 6h)
– Low rate of NAS noted with these doses
• Requirement of opiate may increase
• Pain moderators may be helpful
– Amytryptilene 50-100 mg h.s.
– Gabapentin 300 mg TID
• Physical Therapy – maintain mobility
Polysubstance Use
– Concomitant use of two or more psychoactive
substances, in quantities and frequencies that cause
individually significant distress or impairment.
– In one study, 107/287 or 37.2% of pregnant women
presented for prenatal care with polysubstance use.
– Opiates are a common a component.
– As are Alcohol and Tobacco
– Common conditions with polysubstance use:
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Chronic pain conditions
Fibromyalgia
Bipolar
Anxiety disorders
Chronic Pain
Polysubstance Treatment
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Maintain opioid component
Prevent withdrawal
Reduce or eliminate benzodiazepine.
Eliminate illegal substances – cocaine;
THC
• Smoking Reduction
• Most require more intensive addiction
counselling
Co-morbid Psychiatric Illness in
Chronic Pain Patients
• Depression most common – 45%
• Substance Abuse - 19%
– Many chronic pain patients have been treated with a
benzodiazepine and easily become dependent:
especially Xanax; Klonopin
• Anxiety disorders – 16% (Xanax very common)
• PTSD (grossly under diagnosed)
• Bipolar – often unrecognized; be aware of
aripiprazole – may cause significant HTN and
Diabetes.
Reconditioning Physical Therapy in
Chronic Pain Management
•
•
•
•
The sine qua non of good pain management.
Components: Strengthening, aerobics, etc
Painful activities become comfortable
Rehabilitates physically and psychologically
– Reduces depression and anxiety
– Enhances self efficacy
– Empowers patient to become functional
Red Flags for Abuse
•
•
•
•
Lost/stolen Rx
Early refills
Calling unfamiliar physicians
Use for psychoactive effect
Benzodiazepines
• Used in patients for musculoskeletal spasm and
pain.
• Most often used for anxiety/panic disorder.
• Alprazolam and Clonazepam are Category D
• However, abrupt cessation will cause
withdrawal, often severe.
• More prudent to prevent withdrawal.
• Neonatal withdrawal will often occur.
• Best to avoid starting benzodiazepine in
pregnancy.
Analgesia and Anesthesia for
Methadone Patients
•
•
•
•
Epidural – labor/delivery/cesarean
Spinal
Can use intrathecal opiates/caines
Post op pain management
– Use standard opiates – morphine, dilaudid
– Use 70-100% more or double the dose for a
morphine or dilaudid pump
– Ibuprofen; 800 mg q 8 h as soon as tolerated
– Lots of stool softener
Buprenorphine Maintenance
• Note: Methadone is NOT FDA approved for
treatment for opiate dependence in pregnancy.
• Buprenorphine has been found safe and
effective in world-wide studies and recent
studies indicate it is also safe for use in neonatal
withdrawal.
• Easy to treat opiate withdrawals
• Has become standard of opiate dependency
management in Scandinavia, Europe and the
United Kingdom.
Buprenorphine History
• France 1996: buprenorphine registered to
treat opiate dependence
• Physicians allowed to dispense by
prescription
• 2002: Drug Addiction Treatment Act
amended to allow qualified physicians to
dispense buprenorphine by prescription
Buprenorphine
Initial Observations
• Thousands treated with increasing
numbers of pregnant patients
• Neonatal withdrawal noticed to be absent
or mild
• Less preterm birth
• Normal birth weights
• Fischer G, Etzersdorfer P, Eder H, Jagsch R, Langer M, Weninger
M. Buprenorphine maintenance in pregnant opiate addicts. Eur
Addict Res 1998;4 Suppl 1:32-6.
Buprenorphine
Subutex and Suboxone
• Subutex:
– Buprenorphine – used for INPATIENT
initiation
– High abuse potential for IV use
• Suboxone
– Buprenorphine/naloxone – created to
eliminate IV abuse
– Majority of outpatients currently treated with
suboxone
Buprenorphine
Issues for Pregnant Patients
• Initial recommendation to use Subutex only –
fear of effects of naloxone on fetus, specifically
“intrauterine withdrawal.”
• Subsequent pharmological evidence reveals
naloxone absorbed in extremely low dose with
no evidence of harm
• Almost all current outpatients are treated with
Suboxone.
• Majority of those pregnant conceived under
Suboxone treatment.
Buprenorphine and NAS
• Recent evidence indicates buprenorphine
safe and effective in weaning newborn
from methadone with reduced length of
stay when compared to morphine.
• Kraft WK, Gibson E, Dysart K, et al. Sublingual Buprenorphine for
Treatment of Neonatal Abstinence Syndrome: A Randomized Trial.
Pediatrics 2008;122:e601-607
Using Opiates In L&D
• Use of agonist/antagonist opiates popular
because of reduced nausea and vomiting.
• However, Nalbuphine (Nubain) noted for excess
sedation.
• Butorphanol (Stadol) may increase blood
pressure – avoid in hypertension.
• Morphine best tolerated by largest group of
patients.
Opioid Effects in Obstetrics
•
•
•
•
Analgesic effect in labor is limited.
Sedative effect is excellent.
Major factor in prolonging latent phase labor.
Ironically, morphine is the drug of choice for treating
prolong latent phase – heavy sedation effect.
• Best analgesic effect is at beginning of active phase –
use longer acting opiate MORPHINE
• Change drugs when ineffective (incomplete cross
tolerance).
• Use adequate amounts; whatever it takes.
Dose of Opiates: Whatever It Takes.
• Morphine
– 2-5 mg. I.V. every 4 hours; onset 5 min.
– 10-15 mg. I.M. every 4 hours; onset 30-40 min
– Neonatal half life: 7.1 hours but less sedating than
Nalbuphine
• Nalbuphine (Nubain)
– 10 mg. IV or IM q. 3 hours ; onset 2-3 min IV
– Neonatal half life: 4.1 hours
• Butorphanol (Stadol)
– 1-2 mg. IV or IM every 4 h; onset 1-2 min IV
– Neonatal half life unknown
Analgesia and Anesthesia for Methadone
and Buprenorphine Patients
•
•
•
•
Epidural – labor/delivery/cesarean
Spinal
Can use intrathecal opiates/caines
Post op pain management
– Use standard opiates – morphine, dilaudid
– Use 70-100% more or double the dose for a
morphine or dilaudid pump
– Ibuprofen; 800 mg q 8 h as soon as tolerated
– Lots of stool softener
Opiate Effects on Newborn
• All Opiates cause some depression but significant
depression is rare.
• Meperidine (normeperidine): dose dependent
neurobehavioral depression up to 63 hours.
• Nalbuphine - reduces neonatal perception to sound
and tone for more than 24 hours.
• Morphine has the least toxic effect on fetus.
• Naloxone (Narcan) is the drug of choice for neonatal
depression secondary to opiate sedation.
Neonatal Abstinence Syndrome (NAS)
• Hydrocodone babies rarely have NAS
• Morphine: Heroin – acute, severe but rapid
– over in 72 hours
• Methadone – prolonged – 14-28 days with
6-8 weeks not uncommon
• Buprenorphine – mild and often not
requiring treatment
• Breastfeeding assists NAS recovery
Assessment of Newborn with NAS
Four Key Neurobehavioral Signs
• CNS signs:
– Irritability, excessive crying; voracious appetite
– Seizures
•
•
•
•
GI signs: vomiting; diarrhea
Respiratory signs: tachypnia; hyperpnea
ANS signs: sneezing, yawning, tearing
Finnegan Scale
• Finnegan and Kaltenbach (1992) in Hoekelman (ed) Primary
Pediatric Care. St. Louis; CV Mosby 1367-1378.
Current Treatment NAS
• Combination therapy
– Oral clonidine; phenobarbital
– Dilute morphine drops
• Increase morphine dose until signs of
withdrawal controlled
• Maintain controlling dose for 2 days
• Then wean morphine dose every 1-2 days.
• AAP Committee on Drugs. Neonatal Drug Withdrawal. Pediatrics
1998; 101: 1079-1088.
Drug Concentration in Breast Milk
• Milk to plasma ratio.
• Varies over time.
• When the amount of drug ingested from
the milk, per unit of time, is less than the
therapeutic dose (clinical effect),
• Then the level of exposure is low.
• Regardless of the milk to plasma ratio.
Methadone
• Long half life
• BUT, transfer to milk is minimal.
• Maternal dose of 80 mg. per day (typical) yields
infant dose about 2.8% of maternal.
• Some studies indicate concentrations in breast
milk unrelated to maternal methadone dose.
• Appears to have mitigating effect on NAS –
shorter LOS of breast-fed infants.
• Phillip BL, Merewood A, O’Brien S. Methadone and breastfeeding;
new horizons. Pediatrics 2003;111:1429-1430.
Buprenorphine
Suboxone and Subutex
•
•
•
•
•
Suboxone: buprenorphine and naloxone.
Oral Rx for opiate dependent maintenance.
Substantially reduced NAS.
Minimal to no effect on breastfeeding.
Most recent literature indicates using
buprenorphine to treat NAS in newborn:
improved efficacy and shortened LOS
– Kraft WK, et al. Sublingual buprenorphine for treatment of neonatal
abstinence syndrome: a randomized trial. Pediatrics; published online
August 11, 2008.
Opiate Dependent Chronic Pain
Patients and Breastfeeding
• Hydrocodone, oxycodone and fentanyl.
• Usual doses for pain relief appear to have
minimal to no effect on infant.
• However, many of these patients also use pain
moderators which may depress infant:
–
–
–
–
Benzodiazapines: Xanax; Klonopin
Gabapentin: Neurontin
Amytryptilene: Elavil (generally safe)
Cyclobenzaprine: Flexoril
• High rate of tobacco use in these patients.
Methamphetamine
• Documented High dose in Breast Milk
• Resulted in infant death.
• Breast feeding contraindicated.
Recovery, Relapse and
Breastfeeding
• Does breastfeeding enhance or detract from
ongoing recovery in the postpartum patient?
• The most common cause of relapse is stress,
and it doesn’t take much.
• If breastfeeding is not going well and the patient
is experiencing significant stress, she is ripe for
relapse.
– Plays into low self esteem - “I’m a failure”
– Baby always crying – “I need some peace and quiet.”
– Despair – using drugs to “numb out.”
Treating Addiction in Pregnancy
• What works - just about anything:
– Identifying the problem - 50% will abstain
– Motivating the patient - 85% will abstain
• What doesn’t - ignoring the problem.