From 1997–2002, oxycodone use in the US rose over 400%.² While less than 5% of the world’s population, Americans utilize 80% of the world’s opioid supply and 99% of the world’s hydrocodone supply.² For many patients with opioid use disorder (OUD), their use began with an opioid prescription following an injury.^4,5 In a CDC report in 2011, Medicaid enrollees are more than twice as likely as non-Medicaid populations to be prescribed an opioid analgesic and are six times more likely to die from an opioid overdose [https://www.medicaid.gov/federal-policy-guidance/downloads/cib-02-02-16.pdf].

For women’s health providers, the data emerging on gender differences in OUD is alarming. Between 1999 and 2010, the increase in opioid-related mortality in women rose nearly 150% higher than in men.⁶ Mehta et al (2016) highlighted the dangers of substance use disorder among pregnant and postpartum women, citing drug overdose and substance-related injuries as the leading causes of maternal mortality.⁷

OUD is a chronic, relapsing neurobiological disease characterized by repetitive, nonmedical use of opioids despite physical and social consequences.¹ Treatment of OUD with pharmacotherapy and recovery counseling dramatically reduces the risk of opioid-related overdose deaths.⁸ The American Congress of Obstetricians and Gynecologists (ACOG) recommends pharmacotherapy (methadone, buprenorphine) for treatment of OUD in pregnancy for the health of both mother and fetus.^9,10 (Fig. 48-1)

INTRODUCTION

Patients may present with a variety of symptoms when they are in an acute state of opioid withdrawal. This may include muscle aches, increased tearing, runny nose, dilated pupils, piloerection, agitation, anxiety, insomnia, sweating, yawning, abdominal cramping, nausea, and vomiting.

DIAGNOSIS

Unfortunately, many opioid withdrawal symptoms are vague and nonspecific, so they can be attributed to other common illnesses in pregnancy. However, given the current prevalence of opioid use in the United States, acute opioid withdrawal should remain as a possible diagnosis for obstetrical (OB) providers. Other disease processes that should be included in the list of differential diagnoses are the following:

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  Preeclampsia

  
  
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  Infectious etiologies:

  
  
  
  
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    Urinary tract infection (UTI) or pyelonephritis

    
    
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    Viral gastroenteritis (e.g. rotavirus, norovirus)

    
    
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    Bacterial gastroenteritis (e.g. Campylobacter, Escherichia coli, Salmonella, Staphylococcus)

    
    
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    Viral respiratory infection (e.g. influenza)

  
  

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  Hyperemesis gravidarum (HG)

  
  
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  Acute opioid withdrawal

Ultimately, the final diagnosis is one of exclusion, which includes the patient’s recent history of opioid use and discontinuation.

EVALUATION

The severity of opioid withdrawal symptoms will vary by the dose, duration of substance use, timing from last dose, and the route of use. By using the Staging and Grading Systems of the Opioid Withdrawal Fig. 48-2 , the OB provider can monitor the patient’s progress because symptoms will often worsen. The initial evaluation should include a thorough history, physical exam, and laboratory findings, as follows:

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  The history should pay special attention to mental illnesses, psychiatric disorders, possible polysubstance abuse, intimate partner violence, trauma, and high-risk sexual behavior.

  
  
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  Vitals, including tachycardia, hypertension, and hypotension.

  
  
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  Physical exam: Pupil dilation, piloerection, perspiration, chills, and possible skin infections.

  
  
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  Labs: Complete blood count (CBC) with differential, liver function tests (LFTs), urine protein:creatinine ratio, urine culture, urine drug screen (with consent), urinalysis (specific gravity and protein), and stool culture. Also consider testing based on risk factors for tuberculosis, human immunodeficiency virus (HIV), hepatitis B and C, and other sexually transmitted infections.

  
  
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  Fetal heart rate assessment.

TREATMENT

After discussing her symptoms and suspected OUD with the patient, the treatment options should be introduced. Options for OUD pharmacotherapy in pregnancy include methadone and buprenorphine. Prior to beginning this complex discussion of OUD, it is crucial that the provider is familiar with the availability of local resources for methadone (clinic availability, proximity and capacity) and buprenorphine (local providers/programs, referral options). Collaboration with community addiction medicine providers, counseling services, intensive outpatient programs (IOPs), and residential treatment programs can enable OB providers to deliver comprehensive care for these women. Pharmacotherapy should not be initiated without a community infrastructure in place to support continued treatment upon hospital discharge. If no community or outpatient program exists, OB/GYN hospitalists can offer an opioid taper for symptom relief, supportive care, and comfort medications.¹¹

OB providers can play a critical role in encouraging the patient to participate in treatment. Pregnant patients are often more motivated to improve their lifestyle choices to achieve a healthy pregnancy outcome, which presents a unique opportunity to intervene in this population. The following are helpful practice points when initiating a conversation to patients about their OUD:

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  Remain nonjudgmental: Ask about any current pain medication use or recent stopping of any pain medications. She may not be aware of withdrawal symptoms. A sample statement might be: “I know you are very uncomfortable, and we are doing everything we can to help you. I need to know if you have recently started or stopped any pain medications (prescribed or not)?”

  
  
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  Let her know that opioid withdrawal in pregnancy is not uncommon and help is available: Many women seek help during pregnancy, so perhaps say to them, “Be aware of your local treatment resources.”

  
  
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  Do not use accusatory language: Effective language might include:“What drugs have you been abusing?” or “Are you high at the moment?”

  
  
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  Avoid stigmatizing terms: Do not refer to the patient as a “drug addict” or a “junkie.”

  
  
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  Do not make judgments regarding motherhood: Avoid making statements such as, “How could you [use] while pregnant?” or “Think about the baby.”

Acute opioid withdrawal in adults may not be fatal, but it can be extremely uncomfortable. Abrupt opioid withdrawal in pregnancy has been associated with stillbirth in some studies.¹² Medications for management of symptoms are listed in Figure 48-3.

Detoxification

Monitored, medication-assisted withdrawal can be done safely in the second trimester; however, this option is inferior to stabilization on opioid pharmacotherapy and may increase the risk of opioid overdose mortality.^8,13–15 In May 2015, the American Society of Addiction Medicine (ASAM) published national practice guidelines for treating pregnant women stating that “pregnant women who are physically dependent on opioids should receive treatment using agonist medications rather than withdrawal management or abstinence[,] as these approaches may pose a risk to the fetus. Furthermore, withdrawal management has been found to be inferior in effectiveness over pharmacotherapy with opioid agonists and increases the risk of relapse without fetal or maternal benefit.”

Pharmacotherapy

Methadone is a full mu-receptor agonist that has a peak serum concentration approximately 4 hours after the dose is given and an elimination half-life range of 10 to 30 hours. Currently, it is a Category C medication in pregnancy. Prior to the initiation of methadone, a full evaluation of the patient and fetus should be taken. Full disclosure of the available treatment options should be presented to the patient in a low-stimulation, private setting. In addition, caution should be taken with patients who may be using medications that increase or decrease the metabolism of methadone, as this will alter the effective dose (listed in Figs. 48-4 and 48-5). These patients should also be counseled on the possible impact of discontinuing these medications while they are on methadone treatment.

If methadone is determined by both the provider and the patient to be the best treatment choice, these steps should be taken prior to the initial dose:

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  Take the patient’s full history and do a physical exam.

  
  
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  Assess withdrawal symptoms on the Clinical Opiate Withdrawal Scale (COWS).

  
  
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  Obtain a urine drug screen (with patient consent).

  
  
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  Obtain an electrocardiogram (ECG) to rule out prolonged QT syndrome.

  
  
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  Obtain a fetal assessment (based on gestational age recommendations).

  
  
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  Review the methadone clinic requirements, including daily dosing; counseling; method and frequency of drug testing; side effects; need for potential dose increases throughout pregnancy; risks of overdose with illicit use of opioids, benzodiazepines, and other sedating medications; and the expectation of neonatal abstinence syndrome (NAS) (Figs. 48-6 and 48-7).

More recently, buprenorphine has emerged as an alternative to methadone. It is a pregnancy Category C medication that acts as a partial mu-opioid agonist and a kappa-opioid receptor antagonist. It has a peak serum concentration that is dose dependent, and the mean elimination half-life is 37 hours. It also has low oral bioavailability, so it is given sublingually. The US Food and Drug Administration (FDA) requires that qualified providers be trained, and the secretary of the US Health and Human Services Department must be notified of the provider’s intent to treat patients with buprenorphine prior to prescribing the drug. Two formulations of buprenorphine are available: monotherapy (buprenorphine alone) and dual therapy (buprenorphine and naloxone). At this time, buprenorphine monotherapy is recommended over dual therapy during pregnancy due to the limited number of controlled studies and in order to avoid prenatal naloxone exposure.

If buprenorphine is determined to be the best choice, these steps should be taken prior to initial dose:

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  Take the patient’s full history and do a physical exam.

  
  
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  Assess withdrawal symptoms on COWS.

  
  
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  Obtain a urine drug screen (with patient consent).

  
  
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  Obtain an ECG to rule out prolonged QT syndrome.

  
  
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  Obtain a fetal assessment (based on gestational age recommendations).

  
  

  (Fig. 48-8)