Barbara J. Francis DNP, CNM 2018

Substance Use, Pregnancy and Post Operative Pain Management

! 1. Identify the epidemiology of substance use in women.

! 2. Examine the physiologic needs in opiate use.

! 3. Differentiate the use of Methadone, Subutex and

Vivitrol.

! 4. Describe the use of maintenance of therapy.

! 5. Discuss post-operative pain management.

Objectives

! Opioid addiction first emerged as a serious problem in this country during and after the Civil War. At this time opioids were widely prescribed to alleviate acute and chronic pain as well as other types of discomfort and stress.

! Civil War veterans were treated both medically and surgically. ! White middle and upper class women were treated for menstrual

and menopausal discomforts and female problems SAMHSA 2005

Epidemiology/History

!During the 19th and early 20th century society generally viewed this as an unfortunate medical condition. !They were treated with empathy and tolerance as

neither group presented major social problems !Treatment consisted of continuing the medication

!Sanitariums !Realization of relapses

White, 2014

History

! In 1894, a prominent pediatrician, Dr. Louis Fischer warned that the use of soothing syrups and teething cordials were creating life threatening addictions in infants

! Dr. JB Mattison, a foremost authority (19th century) on narcotic addiction voiced his conviction that babies and children's’ dependence was more widespread than people believed and it played a hidden role in infant mortality

White, 2000

Past theories become present day reality:

! By the end of the 19th century doctors became more cautious when prescribing opioids and the addiction decreased.

! In the early 20th century the size and composition of the opioid population began to change resulting in increasing illegal means to obtain these “medications” ! Immigration ! Crowded tenements ! Ghettos ! Non-medical uses ! Desired euphoric effects

! This caused society to change its tolerance and empathy to negative attitudes, discrimination and promote law enforcement

SAMHSA, 2005

History cont’d

! This change in society lead to the creation of the Harrison Tax Act in 1914. ! Placed opiates and cocaine under federal control ! Placed physicians as gatekeepers for access to theses drugs

! Replaced the old way of continued prescribing with “not in good faith medical practice” to a indictable offense

! In the 1920s numerous municipal treatment programs were started

White, W. (2000)

History cont’d

! Here in lies the debate of 2 different views

!Opioid addiction stems from weak will, lack of morals, other psychodynamic factors, or an environmentally determined predilection that is rectified by criminalization of uncontrolled use and distribution and measures promoting abstinence

!Opioid addiction is an incurable disease which requires long-term maintenance with medication

Volkow et al, 2012; Wang et al, 2012

Epidemiology/History

! Research has shown that addiction is a psychiatric disease attributable to biological and environmental factors

! There are interactions of genetic and environmental factors in the development of substance dependence. The initiation is largely influenced by environmental factors and the use is largely affected by genetic factors

Volkow et al, 2012; Wang et al, 2012

What we know today…….

! Drug addiction is a chronic psychiatric disorder characterized by the persistent, compulsive, and uncontrolled use of a drug despite harmful consequences

! Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), now refers to substance abuse and/or substance dependence as substance use disorders (SUD), which are categorized on a mild, moderate and severe basis.

Volkow et al, 2012; Wang et al, 2012

Cont’d

! The development of addiction involves several steps ! The initiation of substance use ! The transition from experimental use to regular use ! Actual development of addiction

! Environmental factors play a major role in the initial decision to drink, smoke or take illicit drugs ! Peer pressure ! Parental monitoring ! Accessibility of a substance

! Beyond the initial step, the transition from regular substance use to dependence differs from person to person and is largely under genetic control

Wang et al, 2012

Development of Addiction

Approximately 10% of people who use illicit substances will develop a substance use disorder Worley, 2016

Wang et al, 2012

Development of Addiction

! Without medication assisted treatment (MAT), there is a relapse rate of 80-95%

! Adding behavioral therapy in combination with MAT results in long term recovery at least 50% of the time (similar to other chronic relapsing diseases i.e. diabetes and hypertension)

! The Center for Substance Abuse Treatment has found that the best treatment combines pharmacological and behavioral interventions. Ohio Executive Summary , 2011

! The National Institute on Drug Abuse (NIDA) has found stabilization on adequate sustained doses of methadone or buprenorphine can hold jobs, avoid crime and violence and reduce their exposure to HIV Ohio Department of Alcohol & Drug Addiction Services, 2011

Today we know from research that….

! According to Substance Abuse and Mental Health Services Administration (SAMHSA), 2010

! Not ready to stop (36.1%) ! No insurance and cost is a barrier (34.4%) ! Social Stigma is a barrier to seeking treatment (28.9%) ! Can’t handle the treatment (15.5%) ! Unaware of treatment center or abuse resources (13.2%) ! No time to start treatment (4.7%) ! Don’t believe treatment would help (2.7%)

Reasons for NOT seeking treatment

! Many women come from multigenerational substance abusing families

! Many women do not disclose all of the medications they are taking (nondisclosure rates) ! Antidepressants (25% – 50%) ! Opioids (50%)

! Women are more likely to abuse prescription drugs then men ! Women addicts are polydrug users while men typically only use

one drug ! Women are more likely to abuse tranquilizers but are just as likely to

abuse opioids as men Chasnoff, 2010; McKeever et al, 2014; PeriFacts, 2015

What we know about women……

!Many pregnant women with substance abuse have !Concomitant psychiatric illnesses (56% - 73%) !Experienced high rates of trauma and sexual abuse in their

past (39%) !History of intimate partner violence (25%- 88%)

McKeever et al, 2014

Challenges with Pregnant Women

! Additional challenges for the health team occur because they present late or lack prenatal care because ! Shame ! Fear of stigmatization ! Fear of pressure to enroll in a treatment program !Come from multigenerational drug abusing families !Never had a positive parenting role model ! Fear of jail ! Fear of children being removed from family

McKeever et al, 2014

Challenges cont’d

! Other Challenges include !Restrictive governmental regulations !Stigma of opiate addiction !Lack of healthcare providers and clinics sanctioned by

Food and Drug Administration that are capable of providing therapy to all patients who may benefits

Anderson, 2000

Challenges

!There is a difference between opioids and opiates !They both attach to the opioid receptors in the

nerve cells in the brain, so they alter the way pain is perceived

Use of Long Term Opioids/Opiates

!Opioids are synthetic or partially synthetic drugs that are manufactured to work in similar ways to opiates. They act like opiates because they have similar molecules !Methadone !Percocet, Percodan, OxyContin (oxycodone) !Vicodin, Lorcet, Lortab (hydrocodone) !Demerol (pethidine) !Dilaudid (hydromorphone) !Duragesic (fentanyl)

Opioids

!Opiates are derived from the opium poppy. Opium is a strong pain relieving medication !Morphine

!Codeine

!Heroin

!Opium

Opiates

! Methadone is a synthetic opiate primarily used in the detoxification and maintenance of patients who are dependent on opiates.

! Methadone has a long history of use in treatment and prevention of opioid withdrawal and reducing cravings by activating mu opioid receptors in the brain.

! Its long term administration allows a person to reintegrate as a functional member of society.

Anderson, 2000

Methadone

! In the United States, methadone may be prescribed by physicians and dispensed by community pharmacies for analgesia as a Schedule II drug under the regulations of the Controlled Substances Act. However, when used for the treatment of opiate dependence, methadone's accessibility is restricted to practitioners, clinics, and pharmacies licensed by the Food and Drug Administration for this purpose.

Anderson, 2000

Prescribing of Methadone/Harrison Act

! 5 mg of parenteral heroin is equivalent to 20 mg of oral methadone.

! The dosage of methadone in maintenance therapy remains controversial.

! It is usually started at 10 to 20 mg and increased in 10-mg increments until the withdrawal symptoms are controlled.

! Most patients can be maintained at 40 mg a day to control withdrawal symptoms but not eliminate drug craving.

! Doses of 80 to 100 mg a day versus 40 to 50 mg a day had a much lower incidence of illicit heroin use during maintenance therapy.

Anderson, 2000

Methadone

! In a retrospective study, Caplehorn and associates determined that patients receiving 40 mg of methadone a day were 2.2 times more likely to use heroin than patients receiving 80 mg a day when enrolled in a methadone maintenance treatment program.

! For detoxification, treatment doses are usually started at 10 to 20 mg and increased in 10-mg increments until the withdrawal symptoms are controlled.

Anderson, 2000

Methadone

! Methadone crosses the placenta and can cause fetal dependence.

! Pregnant women who are dependent on opiates and their fetuses do better on a regimen of methadone rather than being untreated. The advantages of methadone maintenance treatment during pregnancy include longer gestational periods and higher birth weights than in mothers who are heroin users and are not treated, as well as a lower risk of fetal exposure to infectious diseases contracted through needle sharing.

! Lower concentrations of methadone in the plasma and increased methadone clearances have been reported during pregnancy, likely due to increased metabolism. Higher doses may be required, especially in the third trimester. Dosage should be tailored to the individual during pregnancy to minimize the chance to relapse to heroin use and prevent withdrawal symptoms.

Anderson, 2000

Methadone in Pregnancy

! Has three indications ! opioid detoxification ! opioid maintenance ! pain management

! Absorbed through GI and mucosal membranes.

! Poor oral (only 10% of IV route)

! Sublingual (30-50% of iv route) Naabt, 2004

Buprenorphine (Subutex)/ Subxone

! It is a partial agonist that acts at mu opioid receptors !It attaches to same receptors but does not turn on or activate the

receptors as much as other opioids do !Binds tightly, preventing others from attaching !Releases slowly allowing clinical effects to last longer

!Appears to act as an antagonist at the kappa opioid (?spinal analgesia and anti dysphoric effects

!Agonist at delta receptor !Partial agonist at opioid –receptor – like 1

Naabt, 2004

Buprenorphine/ Suboxone

! The Drug Addiction Treatment Act of 2000 (DATA) has made it possible for physicians to manage opioid-dependent patients with opioid maintenance in an outpatient setting.

! This act states that a physician can prescribe and a pharmacist can dispense Schedule III, IV, or V “narcotic” medications approved by the Food and Drug Administration (FDA) for the treatment of narcotic-use disorders.

! In October, 2002, the FDA approved buprenorphine (Subutex®) and a combined formulation of buprenorphine plus naloxone (Suboxone®) for use in the treatment of opioid dependence.

Welsh & Meltzer, 2005

Buprenorphine

! The goal of maintenance is to prevent the emergence of opioid withdrawal symptoms, suppress the patient’s craving for opioids and greatly diminish the effect of self administered opioids episodically used

! The goal of induction is to safely suppress opioid withdrawal as rapidly as possible with adequate doses of Suboxone or Subutex

Naabt, 2004

Dosing

! Short acting opioids( morphine, oxycodone, hydrocodone & heroin)

! Instruct patient on how to take a sublingual tablet and provide patient information

! Administer patients first dose (4 mg) after moderate opioid withdrawal symptoms have developed. Use COWS. Symptoms are usually alleviated in 20 to 40 minutes following first dose.

! Observe for 1 to 2 hours give a second dose of 4 mg if no withdrawal is observed.

! Usual first day dose in 8 mg ! Sometimes give third dose 2 to 4 mg for later in evening for

withdrawal symptoms Naabt, 2004

Induction from Short acting opioids

! Assess patients response to first day dose

! If withdrawal symptoms are fully suppress and patient is feeling no withdrawal between doses keep the first days total dose

! Otherwise increase 2 to 4 mg on day 2

! Day 3 is the same/ assess and evaluate dose

! After 3 days, once the patient is stable or after a target dose of 16 mg or greater is achieved, continue that dose for 3 to 7 days until steady state levels are achieved before increasing the dose further

! Doses should be decreased by 2 mg at a time for experiencing intoxication/ not withdrawal

Naabt, 2004

Induction cont’d

! It is not recommended to transfer from methadone to Subutex or Suboxone but there are reasons

! They may experience discomfort for several days to 2 weeks ! Transfer is best achieved if pts equivalent methadone dose is first reduced to ≤ 30

(normal transfer) ! In doses greater >60 a day; reduce to ≤ 60 mg per day ! Normal transfer: at least 24 hours should lapse after last dose of long acting opioid

dose & initial COW should show moderate withdrawal ! High dose transfer (30 to 60 mg): Initial dose should be given when experiencing

maximum withdrawal discomfort (48 to 96 hours after methadone); if given early may precipitate withdrawal

! Be prepared to administer limited amounts of withdrawal medication (clonidine, loperamide, sleep aid, NSAIDS etc.) for symptomatic relief

Naabt, 2004

Induction of Long term opioid use

! Is a combination of buprenorphine and naloxone or narcan

! The naloxone is a full opioid antagonist that can precipitate withdrawal from opioids

! It is used in the long term management of opiate abuse ! Usually start with Subutex and then transition to Suboxone ! Is not used as a pain medication

! Lower potential for abuse ! High rate in treatment of opiate dependence

! If opioids are taken they will be blocked from the brains receptors preventing the normal high

Naabt, 2004

Suboxone

! Should not be used with barbiturates causes depression

! If used with SSRIs watch for serotonin syndrome: agitation, fever, sweating, shivering, tachycardia muscle stiffness or twitching if used with medications for depression, prevention of nausea and vomiting, migraines

Naabt, 2004

Subutex/ Suboxone

! Opioid antagonist

! Binds to and blocks mu opioid receptors

! Originally use in alcohol abuse reduced the craving

! Comes in pills but injection form promotes better compliance

! signs of liver problems - nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes).

FDA, 2017

Naltrexone/ Vivitrol

! Dose 50 mg multiple dosing programs: start with 25 mg 0 mg daily if no withdrawal then 50 mg daily. Also week days 50 daily and 100 mg on Saturday or 100 mg qod or 150 q 3 days. Which ever works for better compliance

! 380 mg IM every 4 weeks alternating buttocks ! Needs to free for 7 to 10 days and not having withdrawal signs

! Naloxone test ! Causes pupillary constriction

! Be a part of comprehensive management program that provides psychosocial support

! Opiate withdrawal test naloxone iv or sub q FDA, 2017

Vivitrol

!Initiate 3 to 5 days after last dose of Suboxone or Subutex

!Prior to administer the initial dose patients should receive a naloxone challenge test a period greater than 7 days.

FDA, 2017 ! ∗

Induction of Vivitrol

!anxiety, sleeplessness, yawning, fever, sweating, teary eyes, runny nose, goose bumps, shakiness, hot or cold flushes, muscle aches, muscle twitches, restlessness, nausea and vomiting, diarrhea, or stomach cramps.

Withdrawal from Opioids

COWNaabt, 2004

! Once the dose required is established to eliminate withdrawal symptoms, the patient is stabilized on this dose for 2 to 3 days. Then the dose is reduced daily or every other day. A 10% to 20% dose reduction is usually tolerated, but this must be tailored for each patient.

! If patients are experiencing abstinence symptoms or have a high risk of relapsing into heroin misuse, the practitioner should consider increasing the dose and slowing the tapering schedule. Individual tapering schedules may vary from weeks to months. Patients should be monitored for withdrawal symptoms after the discontinuation of methadone, bearing in mind that withdrawal symptoms may not be evident for 48 to 72 hours following their previous dose.

Anderson, 2000

Withdrawal from long term opiate medications

! Mothers Design: used international design

! Coordinating Center University of Maryland ! Johns Hopkins University; Baltimore, MD !University of Vienna; Austria !University of Toronto; Canada !Wayne State University; Detroit, MI !University of Vermont; Burlington, VT ! Thomas Jefferson University; Philadelphia, PA !Vanderbilt University; Nashville, TN ! Brown University; Providence, RI

Jones et al, 2010

! Eligibility Design !18 to 40 yrs old !Gestational age 6 to 30 weeks !Opioid- dependent (DSM-IV, SCID I) !Opioid-positive urine !Single-fetus pregnancy !Plan to deliver at site hospital

Jones et al, 2010

MOTHER Design

! Jones et al, 2010

- MOTHER Experimental Design

! Buprenorphine is a partial rather than full opioid. Therefore it may cause less severe fetal opioid dependence than methadone therapy.

! As the MOTHER researchers had hypothesized, the infants whose mothers were treated with buprenorphine experienced milder NAS than those infants exposed to methadone. Whereas most infants in both groups required morphine to control NAS, the buprenorphine group, on average, needed only 11 percent as much, finished its taper in less than half the time, and remained in the hospital roughly half as long as the infants exposed to methadone.

Whitten, 2012

Hypothesis & Conclusion

! The MOTHER study indicates that buprenorphine and methadone are both effective in the treatment of opioid dependence during pregnancy

! Given buprenorphine’s benefits for the neonate it should be considered as a front line treatment option.

! Must recognize that buprenorphine is not appropriate for all patients and that a subgroup of pregnant women will require methadone

! The primary consideration must always be hat is best for the mother and child

Jones et al, 2010

MOTHER Trial Conclusion:

! What is the best induction procedure for pregnant women onto buprenorphine?

! What is maternal and infant safety and efficacy of Suboxone during pregnancy?

! The safety and efficacy of methadone and buprenorphine in the presence of co morbid alcohol and/ or benzodiazepine exposure?

Jones et al, 2010

More questions to be answered?

! 2016 A retrospective study by Dooley et al, found Buprenorphine-naloxone appears to be safe for use in pregnancy for opioid-dependence substitution therapy.

! Transferring a pregnant patient to another opioid agonist that has greater abuse potential might not be necessary.

Dooley et al., 2016

Suboxone Retrospective Study from MOTHER

! How dependence is managed medically is critical determinant of the level of stress on both the fetus and mother/ a determinant of neonatal health

! There have been efforts to criminalize maternal opioid dependence and to coerce/ encourage withdrawal

! This poses both acute risks of fetal hypoxia and long term risks of adverse epigenetic programing related to catecholamine an corticosteroid surges from withdrawal

! Need of maternal comforting in NAS management McCarthy et al, 2017

Maintenance in Pregnancy, Further thoughts

! Pain management for opioid tolerant patients requires careful consideration in the peri operative period ! Early identification ! Need a detailed prehospital use ! Goal: to determine the specific daily dose

!Prevent opioid withdrawal ! daily dose should be continued as the baseline ! with any required analgesia provided in addition to prevent withdrawal

!Provide effective analgesia !Ensure continuity of care after discharge !Patients satisfaction

!Patients expectations ! as it establishes a partnership !contract

Grant et al, 2007; Simpson & Jackson, 2017

Peri Operative Pain Management

! Development of a management plan (create & adhere to) !Multidisciplinary team

!Pain management !Anesthesia !Pharmacy !Patient’s medication provider/provider !Nursing !Social service !Patient as a partner

Grant et al, 2007; Simpson & Jackson, 2017

Development of a Plan

! Create systems issues as their care requirements move pass safe guards ! pharmacy higher doses of medications and use of basal rates on PCAs; ! nursing to accommodate their care transferring to units such as ICU to

obtain higher doses

! Have increased length of stays

! Frequent readmits

! Increased outpatient and ER visits

! 72% comorbidity exists between substance use and psychiatric disorders Grant et al, 2007; Simpson & Jackson, 2017

Challenges with Substance Users

! They express higher rest and dynamic pain scores (hyperalgesia (requiring higher dosing due to increasing pain sensitivity) ! 2 to 3 times great opioid use via pca pump ! It is recommended that the patients baseline medication is continued ! Acute post surgical pain be managed with the addition of appropriate doses of IR

opioids

! Providers and nursing tend to undertreat pain due to biases, misconception and system problems

! Providers and nursing tend to use medication sparingly in patients with a history of substance use Grant et al, 2007; Simpson & Jackson, 2017

Challenges cont’d

! Create a peri operative team and plan ! Start dosing aggressively

! Schedule doses OTC not prn ! IV medication may be more effective than oral doses

! Provide faster relief ! Allow for titration

! May need to rotate to another opioid as cross tolerance is not universal

! PCA ! Continuous or basal rate ! Demand or bolus doses

! should be 20 – 50% of hourly basal rate ! Short lock out period such as 6 minutes

Grant et al, 2007; Simpson & Jackson, 2017

Active Management

! Traditionally prn doses are calculate on cumulative dose in preceding 24 hours and give 1/6 every 4 hours

! May start with standard dosing; regular assessment; titrate per patient response

! Use of opioid sparing techniques ! Nonsteroidal anti inflammatory drugs ! Use of local anesthetic techniques (wound infiltration, regional, or

neuroaxil blocks, maintain in post op period ! TENS units, acupuncture

! Ketamine use in acute pain management has shown to reduce post operative opioid use and pain scores

! Use of gabapentinoids Simpson & Jackson, 2017

Additional Management thoughts:

! Withdrawal is a consequence of physical dependence ! Research has shown that addiction is a psychiatric disease

attributable to biological and environmental factors

! 72% comorbidity exists between substance use and psychiatric disorders

! Discuss comfort vs ability to participate in therapeutic activity

! These patients generate a greater work load for ! Providers ! Pharmacy ! nursing

! Have more frequent consultations and rx alterations

Conclusions

! Need to develop a list of social resources and collaborative care with other providers

! Create a plan and stick to it

Conclusion

! Alto, W., & O’ Connor, A. (2011). Management of women treated with buprenorphine during pregnancy. Journal of Obstetrics and Gynecology, October 2011, 302 – 308. Doi: 10.1016/j.ajog.2011.04.001

! American Society of Anesthesiologists. (2016). Practice guidelines for obstetric anesthesia. Anesthesiology, 124(2), 1-30. Doi: 10.1097//ALN.0000000000000935

! Anderson, I. B., & Kearney, T. E. (2000). Use of methadone. Western Journal of Medicine, 172(1), 43–46.

! Ayumi,M., Bateman, B., Clancy, C., Creanga, A., Leffert, L. (2014). Opioid abuse and dependence during pregnancy. Anesthesiology 121(6). 1158-65. Retreived from https:// pubs.asahq.org/on 10/12/2017

! Center for Substance Abuse Treatment. Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2005. (Treatment Improvement Protocol (TIP) Series, No. 43.) Chapter 2. History of Medication-Assisted Treatment for Opioid Addiction. Available from: https://www.ncbi.nlm.nih.gov/books/NBK64157

! Compton, P., Kehoe, P., Sinha, K., Torrington, M. A., & Ling, W. (2010). Gabapentin improves Cold-pressor Pain Responses in Methadone-maintained Patients. Drug and Alcohol Dependence, 109(1-3), 213–219. http://doi.org/10.1016/j.drugalcdep.2010.01.006

! Dooley, J., Gerber-Finn, L., Antone, I., Guilfoyle, J., Blakelock, B., Balfour-Boehm, J., … Kelly, L. (2016). Buprenorphine-naloxone use in pregnancy for treatment of opioid dependence: Retrospective cohort study of 30 patients. Canadian Family Physician, 62(4), e194–e200.

References

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21, 2017

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