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Perinatal Progress Recognizing and Managing Opioid Use Disorder in Pregnancy Meredith K

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Perinatal Progress Recognizing and Managing Opioid Use Disorder in Pregnancy Meredith K Perinatal Progress Recognizing and Managing Opioid Use Disorder in Pregnancy Meredith K. Williams, MD Opioids are a class of drugs that include the illicit drug the process and the SBIRT technique (screening, brief heroin, as well as prescription medications, including intervention and referral to treatment) has been used oxycodone, hydrocodone, codeine, morphine, fentanyl successfully to screen patients (www.integration.sahmsa. and tramadol, among others. They act on the mu recep- gov). Recently, the Oregon Health Authority convened a tors in the brain to relieve pain and produce sensations of workgroup to formulate recommendations for manage- pleasure. Of the 20.5 million Americans age 12 or older ment of opioids in pregnancy. This was a multidisciplinary that had a substance use disorder (SUD) in 2015, 2 million approach to women who are pregnant or planning on had a substance use disorder involving prescription pain becoming pregnant to establish best practices in regards relievers and 591,000 had a substance use disorder to opioid prescribing, opioid use disorder and medication involving heroin.1 It is estimated that of those who misuse assisted therapy (MAT).6 These are divided into primary opioids, approximately 1.2 million are women.2 and secondary prevention and treatment. A review of these guidelines is beyond the scope of this publication, There has been a steady increase in deaths from opioids but the full text of the document, Oregon Pregnancy and with drug overdose being the leading cause of accidental Opioids Recommendations, can be found at oregon.gov. death in the US. Opioid addiction is driving this epidemic, with 20,101 overdose deaths related to prescription pain Urine drug screens are a mainstay in the evaluation and relievers and 12,990 overdose deaths related to heroin treatment protocols for women with suspected or con- in 2015.3 There has been a concomitant increase among firmed OUD. The standard UDS screens for multiple illicit pregnant women and the solutions being developed are in substances, such as amphetamines, benzodiazepines, large part not being directed towards pregnant women.4 cocaine, marijuana, ecstasy and a variety of opioids. It This edition of Perinatal Progress outlines the risks of opi- does not screen for buprenorphine, fentanyl or tramadol. oid use in pregnancy, general principles of management in These drugs stay in the circulation for varying amounts pregnancy and local resources in our community. of time related to timing of last use, frequency of use and other maternal characteristics, such as BMI. The frequency Impact in Pregnancy of UDS monitoring may depend on many factors including maternal compliance with care, positive UDS results in the Chronic opioid exposure has both maternal and fetal past or protocols set up by individual clinics/providers. effects regardless of whether the opioid is licit or illicit; There are also limitations with the UDS with false posi- however, there are special concerns among populations tives caused by common medications used in pregnancy, that are illegally obtaining opioids. Use has been linked to such as Labetalol, Zantac, Zoloft, NSAIDs, Amoxicillin, an increased risk of adverse pregnancy outcomes, includ- Benadryl and Wellbutrin. Positive screens go on to be ing miscarriage, preterm birth, stillbirth, intrauterine fetal confirmed with gas chromatography-mass spectrometry growth restriction, neonatal withdrawal and SIDS. Mater- or high-performance liquid chromatography.7 nal effects include opioid dependence, poor pain control, escalating dose needs and risk of overdose. Polysubstance Fig. 1: Length of time drugs are detectable in urine abuse is common among patients with an opioid use dis- DRUG TIME AFTER INGESTION order (OUD); tobacco is the most common, but marijuana, Codeine 48 hours Heroin 48 hours alcohol, cocaine, benzos are also common.5 Hydromorphone (Dilaudid) 2-4 days Methadone 3 days Screening and Guiding to Treatment Morphine 48-72 hours Oxycodone 2-4 days Identifying patients who have an OUD is the first step in Volume 12, Number 2: October 2019 northwestperinatal.com Perinatal Progress DRUG TIME AFTER INGESTION this long half-life, achieving drug steady state requires 4 Marijuana Single use 3 days to 5 days on average, but can take much longer in some Moderate use (4x/wk) 5-7 days individuals. Daily use 10-15 days Long term heavy use > 30days During pregnancy, doses are usually between 60–100 mg Amphetamines 2-3 days daily with third trimester dose increases being typical, and Alcohol 2-3 days Benzodiazepines Short acting 3 days a higher concentration of methadone is transferred across Long acting 30 days the placental barrier.9 Methadone has been the traditional medication used for MAT; however, there are some limita- Other recommended screening includes testing for STIs tions with this drug. It is metabolized by the cytochrome at the first prenatal visit as well as again in the third tri- P450 enzyme and many other medications also interact mester. Ultrasounds to include first trimester to have the with this which can alter methadone concentrations (an- most accurate dating, detailed ultrasound at 20 weeks to tidepressants such as Effexor, Zoloft, Prozac, Zofran, HIV screen for structural anomalies and a growth ultrasound medications, antiepileptics, among many others). Meth- at 32 weeks. Consider weekly antepartum testing start- adone can also prolong the QT interval, particularly with ing at 32 weeks to evaluate fetal wellbeing due to the risk rapid dose increases, which can lead to sudden cardiac of stillbirth in patients who are using illicit substances. death.10 Additional providers that should be involved in the care Fig. 3: The Buprenorphine effect and management of these patients include neonatolo- gists, social work, behavioral therapy and substance use counselors. FULL AGONIST (Methadone) Medication Assisted Therapy (MAT) For pregnant patients who have or are suspected to have T OUD, the mainstays of treatment are methadone and FFEC buprenorphine (Subutex). There are published studies that ID E PARTIAL AGONIST focus on tapering opioids or doing a supervised with- OPIO (Buprenorphine) drawal during pregnancy; however, this is not the current standard of care.8 Methadone is a full mu agonist with a slow onset and half-life of around 24 hours. Because of ANTAGONIST (Naloxone) Fig. 2: Steady state simulation - methadone maintenance Steady state attained after 4-5 half-lives -1 dose every half-life LOG DOSE 800 Buprenorphine is the other medication used for the treat- 700 ment of OUD. It comes in two formulations, buprenor- 600 phine alone (Subutex) and buprenorphine combined with 500 naloxone (Suboxone). Both are used for treatment of OUD, 400 but currently only Subutex is recommended for pregnancy 300 due to lack of data on the effects of naloxone on the de- 200 veloping fetus. Buprenorphine is only a partial mu agonist 100 and reaches a plateau in the dose effect response curve at 0 0 1 2 3 4 5 6 7 about 24mg daily. Preparing for Delivery and Postpartum Consultation with anesthesiology prior to delivery may be Volume 12, Number 2: October 2019 2 Opioid Use Disorder in Pregnancy, continued... warranted in some cases to discuss pain management can help to mitigate some of the effects of withdrawal for during labor and the postpartum period. Because of the the neonate and can decrease length of hospital stays.8 alteration in the mu receptors with chronic opioid expo- sure, this can be challenging. Many women with OUD will Postpartum, it is important to limit the quantity of opioids have significantly higher opioid needs to achieve ade- prescribed. Most vaginal delivery patients will not need quate analgesia. Recommendations include: to go home with opioids and those having a c-section are increasingly going home with no opioids or significantly • Setting realistic expectations about goals for pain prior decreased quantities. This is a mainstay in preventing the to hospital admission; development of OUD. For those patients with OUD, it is • Continuation of MAT during the intrapartum period, important to help these women establish with a long term in addition to the use of epidural, spinal or combined MAT provider who will manage their ongoing needs. In spinal-epidural (CSE); addition, establishment with a primary care provider to • Continuation of the epidural for a period postpartum; manage their overall health is key. • Avoidance of opioid agonist-antagonist drugs, such as Nubain and Stadol, which can precipitate withdrawal; SUMMARY OF RECOMMENDATIONS • Limiting narcotics after vaginal delivery; 1. Early universal screening and brief intervention • Use of scheduled NSAIDs with additional opioids for for SUD. pain relief on top of that, as needed for postoperative 2. Medication assisted treatment with methadone patients; and or buprenorphine for OUD. • Divided doses (BID or TID) for either methadone or 3. Coordinated care with obstetrics, anesthesiology, buprenorphine can help with pain control postpartum neonatology, social work, behaviorists and while still preventing withdrawal.8 substance use counselors during pregnancy. 4. Ultrasounds in the first trimester for dating, second Maternal withdrawal is assessed using a COWS score. This trimester for anatomy and third trimester for evaluates multiple symptoms, including heart rate, pupil growth. size, GI distress, restlessness and anxiety, among others, 5. Limit discharge prescriptions of opioids. with the score used to determine severity of withdrawal. 6. Set up patients with a long term provider to manage It is used to guide treatment with scores in the moderate their SUD. or severe range indicating the need for higher medication dosing.11 There are limited options for pregnant women to receive treatment in the Portland Metro area. Some clinics, such Neonatal withdrawal effects can be seen with both as Coda, Allied, and other non-obstetric MAT physicians, Methadone and Buprenorphine. Effects typically occur are focused only on the provision of MAT, but do not within 24-72 hours after birth and are evaluated using the provide prenatal care.
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