Labor and delivery is a stressful place for patients and staff. As a combination emergency department, intensive care unit, operating room, and birthing center, both patients and staff bring a heterogeneous mix of expectations and clinical skills to the bedside. For women with substance use disorders, the additional stresses of guilt and concerns of judgment by caregivers, as well as the effects of past trauma, heighten the anxiety. In this chapter, we will review the labor and delivery management of women with substance use disorders, with an emphasis on opioid-dependent patients.
Admission in the Setting of Acute Intoxication/Withdrawal
Those caring for women with substance use disorders have a few special considerations when they are admitted to labor and delivery. Those include treating acute intoxication or withdrawal, managing pain appropriately, providing trauma-informed care, and addressing infectious disease concerns. Infectious disease screens and liver and renal function evaluation should be repeated if ongoing illicit use is suspected (especially HIV, hepatitis B, and syphilis since intrapartum and immediate newborn management may be altered). Given that most women with opioid use disorders use multiple substances, special considerations must be given to those substances whose use and withdrawal pose an immediate risk of harm to the pregnant woman and fetus.
Alcohol: Women who have been misusing alcohol during pregnancy have specific risks when admitted to labor and delivery. Women presenting with acute intoxication may be agitated and combative. Serum glucose should be assessed at admission as hypoglycemia may exacerbate behavior issues. Women with AUD are frequently dehydrated and benefit from IV hydration. Thiamine (100 mg) should be added to IV fluids to prevent Wernicke’s encephalopathy [1]. For control of agitation that interferes with patient care, short acting benzodiazepines (midazolam) may be indicated to allow initial evaluation and fetal assessment. Women presenting with chronic alcohol use during pregnancy are at risk for withdrawal during the course of hospitalization even in the absence of obvious intoxication. Serial evaluation for alcohol withdrawal can be performed with the CIWA-Ar scale (Figure 12.1), with intermittent doses of a long acting benzodiazepine (chlordiazepoxide (Librium®) 25–50 mg, diazepam (Valium®) 5–10 mg, or lorazepam (Ativan®) 1–2 mg) for scores greater than 8 [2, 3]. Mild withdrawal can occur by 6 hours of abstinence; hallucinosis after 12–24 hours of abstinence; withdrawal seizures after 12–48 hours of abstinence; and delirium tremens (hallucinations, disorientation, tachycardia, hypertension, hyperthermia, agitation, diaphoresis) after 48–96 hours of abstinence. Delirium tremens is most common in older individuals (age 40–50) with long-standing chronic alcohol use. Common obstetric complications such as preeclampsia or hyperthyroidism that can mimic alcohol withdrawal should be carefully considered in the differential diagnosis. Obstetric providers should work closely with other medical providers (emergency room colleagues would be helpful if no addiction specialist is available) to diagnose and treat alcohol withdrawal and titrate medications. Benzodiazepines are the mainstay for the prevention and treatment of alcohol withdrawal and should be administered as indicated. Pediatricians should be made aware of both alcohol exposure and benzodiazepine treatment if required, with availability for respiratory support of the neonate if high doses of benzodiazepines are needed.
Figure 12.1 The Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar)
Benzodiazepine misuse: Benzodiazepines are commonly misused with other illicit substances, complicating specific identification and treatment. Oral benzodiazepine misuse alone does not usually cause severe respiratory depression; patients present with depressed mental status but no other findings, the “coma with normal vital signs.” Standard supportive care is indicated. Many benzodiazepines will not be identified by routine urine drug screen (clonazepam, lorazepam), thus the diagnosis requires a high level of suspicion, and specific drug screens ordered. Reversal of benzodiazepine effect with flumazenil should be avoided: flumazenil does not reverse respiratory depression and acute reversal can precipitate seizures in chronic benzodiazepine users. The risk/benefit does NOT favor reversal with flumazenil [4]. Benzodiazepine withdrawal can occur after chronic, long-term use; symptoms include seizures, tremors, perceptual disturbance, and psychosis.
There are three options for treatment of chronic benzodiazepine use.
1. Treatment with long-acting benzodiazepines (chlordiazepoxide 25–50 mg or lorazepam 5–10 mg) during the hospitalization with referral to outpatient treatment for taper postpartum.
2. Taper with long-acting benzodiazepines (chlordiazepoxide 25–50 mg or lorazepam 5–10 mg) during the hospital course based on symptoms and CIWA-B scores.
3. Taper with phenobarbital during the hospital course. This taper was first reported by Kawasaki et al. [5] and has been used often in our center with good results. This taper has the advantage of not requiring use of specialized scoring systems (such as CIWA-B), which require nursing training.
The latter two options are useful for women who will be entering residential treatment centers without capability for benzodiazepine taper upon release.
Cocaine/methamphetamine use: Both cocaine and methamphetamine intoxication are characterized by profound sympathetic overload: hypertension, cardiovascular derangements including tachycardia and ischemia, and cardiovascular collapse [6]. Acute intoxication is treated with supportive measures but other diseases such as preeclampsia and hyperthyroidism should be excluded. It is critical to differentiate stimulant intoxication from other etiologies of hypertension (i.e., preeclampsia, hyperthyroidism); neither beta blockers nor labetalol should be used for the treatment of hypertension related to cocaine or amphetamine intoxication. Beta blockade in the setting of cocaine intoxication can cause unopposed alpha adrenergic stimulation, coronary vasoconstriction, or end organ ischemia. In the absence of acute hypertensive crisis, first line therapy should be benzodiazepines (diazepam 10 mg then 5–10 mg q 3–5 minutes); this approach reduces the central catecholamine release rather than blocking peripheral action. If additional medication for hypertension is required, the alpha antagonist phentolamine is the treatment of choice, with nitroglycerine added for cocaine-associated chest pain. Any antihypertensive therapy should be carefully titrated, as the effects of amphetamines or cocaine can be short lived and self-limiting, and overtreatment and hypotension may occur suddenly. Anesthetic management in the setting of cocaine intoxication is complicated: succinylcholine and cocaine are both metabolized by plasma cholinesterase, so the effects of both medications may be prolonged; anesthesia induction in the setting of acute hypertension can be dangerous; effects of inhaled anesthetic agents can be modified by amphetamines. Given the high rate of pregnancy complications (abruption, nonreassuring fetal assessment) that might lead to emergent cesarean delivery, early consultation with anesthesiology should be requested. It is always important to note that correction of maternal cardiovascular derangements can often improve fetal status and allow prolongation of pregnancy.
Opioid intoxication/withdrawal: Treatment for opioid intoxication is supportive, including respiratory support as needed. It is of note that pulse oximetry can be used to assess oxygenation but not ventilation. End tidal CO2 or arterial blood gas measurements should be used to monitor ventilation if respiratory depression is observed. Reversal with naloxone should be used only to reverse respiratory depression, not to normalize mental status. If withdrawal is inadvertently precipitated by naloxone, treatment should be supportive as naloxone has a short half-life. Women presenting with acute opioid withdrawal can be stabilized with a short acting full opioid agonist (such as fentanyl 50–100 mcg) until a definitive treatment plan can be developed or with methadone 10 mg. It is of note that if buprenorphine is likely to be the long-term medication of choice, short-term stabilization with short acting opioids rather than the longer acting methadone may be preferable due to ease of transition to buprenorphine.
Other substances: There are few data regarding various synthetic agents, bath salts, inhalation agents, etc. Most of these substances require supportive care and are often used with other more commonly misused medications. Pregnancy specific data are limited.
Approach to the patient with unknown intoxicants: Unfortunately, most illicit drugs do not travel alone, so the guidelines outlined above may require modification. Talking with addiction medicine or emergency room colleagues can give a sense of which drugs are present in a given community. Clinicians can also get a sense of the most predominant drug at presentation based on physical exam. Patients presenting with agitation, paranoia, and hallucinations with tachycardia, hypertension, and tachypnea are under the predominant effect of sympathomimetics (methamphetamines, cocaine), anticholinergics (belladonna alkyloids), or hallucinogens (PCP, LSD, MDMA). The presence of nystagmus is more suggestive of hallucinogens; urinary retention is more common with anticholinergics, and tremors, seizures, and hyperreflexia more characteristic of sympathomimetics. Patients presenting with depressed mental status often have bradycardia, hypotension, and bradypnea. Serotonin syndrome more often has mydriasis, as opposed to opioids or sedative/hypnotics which may have miosis. Rapid lab evaluation can help identify alcohol levels and urine drug screen may identify opioids, which can assist with the differential. Supportive care will be similar for all.
Substance use (and cigarette smoking) is associated with fetal growth restriction; assessment of fetal weight clinically or with ultrasound will facilitate planning for monitoring, delivery, and newborn care. Admission urine drug screen may be of assistance for all patients with substance use disorder to assist the pediatric management. All urine drug testing must be done with the patient’s consent and explanation as to what the results will be used for.
Fetal Assessment in the Setting of Intoxication/Withdrawal
Fetal monitoring is influenced by both uteroplacental perfusion and the direct effect of the intoxicant. As with many other maternal illnesses, correction of maternal physiology can improve fetal status. When feasible, optimization of maternal status should be performed before delivery for nonreassuring fetal status due to substance intoxication.
Uterine perfusion can be compromised by acute maternal hypertension or vasospasm, which can occur with stimulant use or acute opioid withdrawal. Treatment should be directed as noted above, with benzodiazepines to decrease sympathetic output with stimulant use or opioid agonists to reverse opioid withdrawal. Unfortunately, both benzodiazepines and opioids can then lead to decreased fetal heart rate variability and decreased fetal movement; careful titration can minimize these effects. Similarly, fetal activity on ultrasound may be reduced so additional testing such as biophysical profile assessment should be interpreted with caution [7]. Both alcohol and opioid intoxication have been associated with reduced fetal heart rate variability and late decelerations which improve with resolution of intoxication. There are no data to guide the difficult decision of conservative management versus delivery in the setting of non-reassuring fetal assessment. This decision will be a complicated assessment of gestational age, fetal status and ability to improve maternal physiology to achieve fetal recovery. Assessment of fetal acid base status by umbilical cord blood gas analysis at the time of delivery will assist the pediatricians in the evaluation of the infant.
Admission (Routine) and Intrapartum Management
Most women with substance use disorder will not present with acute intoxication or withdrawal, but rather in labor or for planned delivery. Infectious disease screens and liver and renal function evaluation should be repeated if ongoing illicit use or misuse is suspected. Women that admit to chronic alcohol or untreated chronic opioid use should be followed for withdrawal symptoms and treated accordingly. Urine drug screen at admission should be performed to assist the pediatricians in the evaluation of the neonate with permission of the mother and disclosure as to how the results will be used. If the woman refuses testing, careful explanation should be given as to its importance in a nonjudgmental manner. Women have valid fears of drug screening: positive tests have been used for prosecution and loss of custody. Clinicians should advocate for treatment as opposed to punishment in their communities. Urine drug screens are limited in the detection of illicit drug use: the assays have limited detection of commonly misused opioids (fentanyl, oxycodone) and some substances have very short excretion windows (i.e. cocaine). These limitations can be overcome with a careful history and explanation regarding the importance of disclosure for optimal neonatal care. For the rest of intrapartum and postpartum care, women with alcohol, cocaine, or other substance use is unchanged from the standard of care.
Women with opioid use disorder (OUD), however, have specific considerations which are discussed in detail below. Women receiving medication assisted therapy (MAT) should continue medication as scheduled throughout hospitalization. It should be emphasized to the care team that MAT is for prevention of opioid withdrawal only and does NOT provide analgesia. Fetal monitoring may be altered by MAT, particularly methadone; decreased fetal movement and variability may occur for a few hours following a dose [7]. Because MAT medications have a long half-life, a short delay in medication administration can be appropriate if delivery will occur close to the time of usual administration. The partial opioid agonists nalbuphine (Nubain®) and butorphanol (Stadol®) are contraindicated in women with OUD, as they may precipitate withdrawal in the opioid-dependent patient [8, 9]. Pediatricians should be aware of opioid-exposed newborns to ensure assessment for neonatal withdrawal symptoms.
Intrapartum Care for the Parturient with Opioid Use Disorder (OUD)
Below are recommendations for three common presentations of the parturient with OUD: excellent prenatal care and stable in MAT treatment; limited or no prenatal care but stable in MAT treatment; or no MAT treatment and currently using illicit opioids.
Scenario 1: Patient has been Receiving Regular Prenatal Care and is in a Program with Medication Assisted Therapy (MAT) with Either Methadone or Buprenorphine
On admission, medications should be reviewed and the current MAT medication and dose verified and ordered. Ideally, this information would be current in the patient’s prenatal record. While verification from the prescribing physician is optimal, it is not always feasible and patient report can be used. Daily MAT medication should be prescribed on schedule to avoid opioid withdrawal. If the patient has been providing regular urine drug screens that are readily available to the pediatric providers, this could be omitted.
Scenario 2: Patient has been Noncompliant with Prenatal Care but is Well Established in an MAT Program
When pregnancy care and MAT care are not co-located, some obstetric patients are compliant with MAT but not obstetric care. It is important for MAT providers to incorporate compliance with obstetric care into the MAT treatment plan and respond accordingly. Nonetheless, women will arrive in labor and delivery stating they have OUD-treated with MAT without other documentation. In this setting, management is similar to the approach to any patient lacking prenatal care, including rapid tests for infection. Medication and dose should be verified. If the patient arrives off hours, if they have been compliant with MAT the center could be called in the AM (if daily dosing) or pharmacy or prescription monitoring system used to verify dose and prescriber (buprenorphine). Medication assisted therapy should be prescribed on schedule to avoid opioid withdrawal. Urine drug screening at admission is indicated.
Scenario 3: Patient Admits to Opioid Use Disorder at the Time of Arrival to Labor and Delivery; No Active Treatment
This scenario can be the most challenging. There are few studies in the literature to guide the optimal approach. A detailed history of opioid intake, frequency, and symptoms of withdrawal that the patient has experienced in the past can be helpful in predicting when the patient might experience withdrawal. Urine drug screen is required. Liver enzymes, renal function, and infectious disease screening should be performed at the time of admission (in addition to prenatal labs) due to the potential of exposure with illicit drug use. Assessment for opioid withdrawal should be performed throughout the entire hospitalization, using a tool familiar to the nursing staff such as COWS (see Chapter 11). Fetal monitoring should be initiated with evidence of withdrawal. Medication assisted therapy can be initiated with the medication that best fits the needs of the patient for longer term follow-up. Women taking illicit methadone may tolerate methadone better than buprenorphine due to precipitated withdrawal symptoms observed with methadone to buprenorphine transitions [10]. Methadone can be started at a dose of 10 mg, not to exceed 30 mg daily for the first 3–4 days due to the long half-life and risk of overdose with rapid escalation. Buprenorphine/naloxone may be the optimal medication in some settings when it is known that will be the available medication for post-delivery care. Buprenorphine initiation should follow the usual buprenorphine induction policies as detailed in Chapter 11; if patients are experiencing mild withdrawal symptoms, buprenorphine is not likely to precipitate opioid withdrawal symptoms. Buprenorphine can be started at dose of 2–4 mg and titrated as needed for symptoms. Regardless of medication choice, the goal of therapy is to prevent overt withdrawal during hospitalization; dose optimization can occur over the next days or as an outpatient.
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