The Obstetric Patient Receiving Opioid Addiction Therapy

Educational Objectives

The goal of this program is to improve the care of obstetric patients undergoing therapy for opioid addiction. After hearing and assimilating this program, the clinician will be better able to:

1. Describe the pharmacology of methadone and buprenorphine.

2. Summarize current theories on the physiologic mechanisms of addiction and dependence.

3. Select appropriate analgesic regimens for obstetric patients on maintenance therapy for addiction and dependence.

Summary

Pregnant women addicted to opioids: detoxification programs do not work; pregnant women cannot maintain compliance with such programs; cannot tolerate symptoms of withdrawal; fetus also exposed; goal of addiction maintenance programs is to avoid symptoms of withdrawal and to maintain functional status throughout pregnancy

Methadone: first drug used for addiction programs, beginning in 1960s; long-acting pure agonist and N-methyl D-aspartate (NMDA) antagonist; slow-release preparation available with half-life of 15 to 60 hr; slow release tends to avoid euphoria otherwise associated with methadone, but difficult to titrate

Regulations: methadone — regulation of methadone clinics in 1973 required patients to visit clinic daily to receive dose; regulations made licensing of providers of addiction management very difficult; buprenorphine — in 2000, Drug Addiction and Treatment Act facilitated introduction of buprenorphine as alternative to methadone; pharmacokinetics of buprenorphine allowed transfer of management away from daily dosing in clinics and toward office management; new regulations facilitated significant increase in licensed addiction management providers, particularly for buprenorphine

Buprenorphine: semisynthetic; high affinity for receptors; 1000 times more avidly attached to mu receptor than morphine; fentanyl has more affinity than morphine but less than buprenorphine; necessary to allow buprenorphine to degrade; very difficult to displace; partial agonist with small effect on pain; antagonist of kappa site; longer half-life, so daily dosing not required; allows women to have more normal lifestyle than would otherwise be possible; buprenorphine only drug approved for office management; typically provided as sublingual preparation; once-monthly injection now available; combinations of buprenorphine and naloxone available; preparations of buprenorphine alone generally preferred during pregnancy; combination composed of 4:1 ratio of buprenorphine to naloxone; naloxone included to avoid potential for abuse; naloxone has negligible bioavailability when taken sublingually; crushing preparation or taking in any manner other than sublingually allows naloxone to take effect and potentially lead to withdrawal symptoms

Therapy during pregnancy: combination of buprenorphine and naloxone preferred outside of pregnancy; some concern about administration of naloxone during pregnancy; only animal studies available to show effects of administration of naloxone alone during pregnancy; changes in maternal hormones translate to fetus; corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) elevated; preterm labor — processes that may lead to preterm labor include exaggerated inflammatory response, abruption, pathologic uterine distention, and premature activation of hypothalamic-pituitary-adrenal (HPA) axis; elevation of CRH and ACTH increase activation on HPA axis, potentially leading to preterm labor and delivery; one human study found combination of buprenorphine and naloxone associated with lower 5-min Apgar score and shorter body length but not with preterm issues

Methadone vs buprenorphine: Jones et al (2010) showed that neonates of pregnant women taking methadone had higher neonatal abstinence scores than neonates of those taking buprenorphine (withdrawal is treated with small doses of morphine; higher score indicates worse withdrawal); neonates in methadone group had longer hospital stay and required more treatment; no difference in maternal outcomes; speaker states buprenorphine becoming preferred drug for addiction management during pregnancy

Anesthetic considerations: do not discontinue methadone; it has no effect on neuraxial analgesia; do not discontinue buprenorphine; buprenorphine provides small amount of analgesia; fine to use neuraxial analgesia; opioids ineffective for patients taking buprenorphine; patients on methadone may require lower doses of opioids, so exercise caution; avoid benzodiazepines in patients on methadone, as benzodiazepines shown to cause sedation and fatalities when given in conjunction with methadone maintenance; consider epidural infusion for postoperative analgesia after cesarean delivery for women on methadone; buprenorphine completely blocks mu receptor; speaker does not recommend administration of very large doses of opioids in attempt to displace buprenorphine from receptor and provide analgesia

Theory of addiction: stimulation of mu receptor leads to stimulation of cells in mesolimbic system, leading to release of dopamine; dopamine in turn causes sensations of pleasure and euphoria; addicted patients continue to use opioids to achieve pleasurable sensations, but sensations become progressively harder to achieve, potentially leading to overdoses; desire to reproduce effects of first experiences leads to cravings

Theory of dependence: stimulation of mu receptor in locus coeruleus leads to inhibition of release of norepinephrine; continued exposure leads to continued inhibition; cells produce more norepinephrine to compensate; discontinuation of opioids leads to symptoms related to excessive norepinephrine (eg, jitters, sweating); patients continue to use opioids to remain functional (as opposed to satisfaction of craving); raises concern about negative effects of exposing patient recovering or in maintenance to opioids

Clonidine: shown effective for relief of pain in labor epidurals; widely used in Europe; speaker’s group replaced opioids with clonidine (neuraxial α-2 agonist); clonidine currently under black box warning from Food and Drug Administration for use perioperatively and for obstetric patients; many institutions pushing back and substituting clonidine for opioid; concerns include hypotension, sedation, maternal bradycardia, and fetal bradycardia; speaker notes that routine epidural itself can cause same signs (except, perhaps, maternal bradycardia)

Appropriate dose: Hoyt et al (2018) published observational study on use of clonidine as substitute for opioids; found dose of 1.2 µg/mL clonidine effective and associated with fewer side effects than 2.0 µg/mL (total of 14 patients); hypotension main observed side effect; 2 out of 2 patients receiving 2.0 µg/mL and 3 out of 12 receiving 1.2 µg/mL experienced hypotension; dose-response studies still required; during labor, speaker’s patients received infusion of clonidine and 25% of daily maintenance dose of buprenorphine administered every 6 hr; patients given scheduled acetaminophen and intravenous ketorolac (Toradol) for first 24 hr postpartum, then switched to oral medications; dose of buprenorphine increased to ≤36 mg/day if needed; 5 of 7 patients who underwent vaginal delivery in study required no supplemental opioids; patients undergoing cesarean delivery received combined spinal/epidural technique; 3 of 7 required no supplemental opioids

Transversus abdominis plane block: option for patients in facilities without access to clonidine; found effective for patients undergoing cesarean delivery when neuraxial morphine (Duramorph) not used; quadratus lumborum blocks offer another option to consider

Fentanyl: higher affinity than morphine; use may require admission to intensive care unit because of high doses required; low-affinity opioids not effective for patients taking buprenorphine

Readings

Hoyt MR et al: Use of epidural clonidine for the management of analgesia in the opioid addicted parturient on buprenorphine maintenance therapy: an observational study. Int J Obstet Anesth 2018 May;34:67-72; Jones HE et al: Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med 2010 Dec 9;363(24):2320-31; Leighton BL et al: Case series of successful postoperative pain management in buprenorphine maintenance therapy patients. Anesth Analg 2017 Nov;125(5):1779-83; Lund IO et al: A comparison of buprenorphine + naloxone to buprenorphine and methadone in the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes. Subst Abuse 2013;7:61-74; Pan A et al: Peripartum anesthetic management of the opioid-tolerant or buprenorphine/suboxone-dependent patient. Clin Obstet Gynecol 2017 Jun;60(2):447-58.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose. In her lecture, Dr. Hoyt presents information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Hoyt was recorded at the Survey of Current Issues in Surgical Anesthesia, held November 26-30, 2018, in Naples, FL, and presented by the Cleveland Clinic Foundation Center for Continuing Education. For information about upcoming CME opportunities from the Cleveland Clinic Foundation Center for Continuing Education, please visit www.ccfcme.org. The Audio Digest Foundation thanks the speakers and the Cleveland Clinic Foundation for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

AN613402

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.