JOGNN

PRINCIPLES & PRACTICE

Safe Management of Chronic Pain in Pregnancy in an Era of Opioid Misuse and Abuse Ursula A. Pritham and Laura McKay

Correspondence Ursula A. Pritham, PhD, WHNP-BC, FNP-BC Assistant Professor, School of Nursing Georgia Southern University 521 C.O.E. Drive Statesboro, GA 30458. [email protected]

ABSTRACT Safe and effective management of chronic pain in pregnancy is challenging. Use of over-the-counter analgesics, opioids, opioid substitution therapies, complementary and alternative therapies, antidepressants, and anxiolytics each have benefits and risks for the mother and neonate that must be considered. Because of their potency, opioids are often used despite associated risks for adverse effects, abuse, diversion, and addiction. Development of a pain management protocol for the counsel and care of pregnant women with pain is necessary.

JOGNN, 43, 554-567; 2014. DOI: 10.1111/1552-6909.12487 Accepted May 2014

Keywords Opioids opiates chronic pain pregnancy preconception care pain management

regnant women with chronic pain diagnoses present a unique challenge for obstetric care providers. Some present for prenatal care with pain related to prior injuries, surgeries, or other causes, and they are already taking opioid analgesics for episodic or continuous treatment. Others have pain issues that develop during pregnancy or are exacerbated by pregnancy and need to take opioid analgesics while pregnant to manage their conditions (Babb, Koren, & Einarson, 2010; Kellogg, Rose, Harms, & Watson, 2011; Kennedy, 2011). Failure to adequately treat pain can have a negative effect on maternal health, resulting in depression, anxiety, and physical manifestations such as hypertension (Babb et al., 2010; Bruehl, Chung, Jirjis, & Birdiepalli, 2005; Kennedy, 2011). As the use of analgesics and other medications for pain becomes more common and acceptable in pregnancy, it is necessary for obstetric care providers to be knowledgeable as to their safe use to manage maternal pain with the lowest risk for harmful effects on the mother, fetus, and neonate (Hadi, daSilva, Natale, Boyd, & Morley-Forster, 2006; Kellogg et al., 2011; Wunsch, Stanard, & Schnoll, 2003).

P

Ursula A. Pritham, PhD, WHNP-BC, FNP-BC, is an assistant professor in the School of Nursing, Georgia Southern University, Statesboro, GA 30458. Laura McKay, DNP, is an assistant professor in the Department of Graduate Nursing, South University, Savannah, GA.

The authors report no conflict of interest or relevant financial relationships.

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Background and Significance For women who require pain management during pregnancy, there is little research available regarding what modalities are safe for fetal development and produce the least occurrence of adverse pregnancy outcomes. Ethically, there are difficulties with developing well-designed studies of any type of medications or therapies in pregnancy due to the potential effects on the fetus. It is even more difficult to conduct research regarding analgesic medications, opioid substitution therapies, and opiate agonists due to the subjective nature of pain management (Winklbaur-Hausknost et al., 2012). Issues that arise concern how the treatments will affect the neonate at delivery, whether the clinician’s assessment of efficacy of treatment is congruent with that of the patient, and whether the treatment or lack of treatment could produce unfavorable outcomes in the mother, fetus, or neonate, or long term in the infant or child. The scarcity of information about safe use of pain medications is compounded by the lack of access to appropriate care for women with chronic

 C 2014 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses

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Pritham, U. A., and McKay, L.

pain in pregnancy. These women have legitimate pain syndromes but may not have access to physical therapy, appropriate pain management, or alternative therapies, due to lack of insurance or inadequate coverage for pain management services. Third-party payers often deny or limit adjunctive nonmedication options such as physical therapy, acupuncture, chiropractic care, and exercise programs (Atkinson, Schatman, & Fudin, 2014). Pain management specialists may not see women in pregnancy due to the lack of evidencebased standards for care in this population, or because they are not reimbursed for their services. Typically, nonobstetric pain in pregnancy is either undertreated or not treated at all (Babb et al., 2010). Obstetric care providers may shoulder the responsibility for pain management with little or no training, and no clear treatment guidelines. The purpose of this article is to present the evidence for continuation or revision of pain management therapies during pregnancy. Findings from a review of the literature of current trends in pain management in pregnancy is presented with an examination of perinatal outcomes for those infants exposed in utero to the commonly prescribed analgesics and other medications used to treat pain. Emphasis is placed on prescribed opioids due to the increasing prevalence of use. Although they have great potency as analgesics, they may pose substantial risks for adverse effects, abuse, diversion, and addiction (Atkinson et al., 2014). Strategies and resources for developing a pain management protocol are presented. Practitioners can utilize the information obtained to lead in formulation of evidence-based practices for management of chronic pain in pregnancy.

PRINCIPLES & PRACTICE

The scarcity of information about pain medications in pregnancy is compounded by the lack of access to care for the women who need it most.

case studies, reviews of selected literature, and retrospective reviews.

Use of Analgesics in Pregnancy Kennedy (2011) estimated that as many as 85% of pregnant women use some type of medication during pregnancy, and that analgesics are the most commonly ingested after vitamins and supplements. The exact prevalence of recommended or prescribed analgesics in pregnancy is difficult to determine, but from available reports their worldwide use appears to be steadily increasing even though many are classified as pregnancy category B or C by the U.S. Food and Drug Administration (FDA) (Andrade et al., 2004; Briggs, Freeman, & Yaffe, 2011). In the United States, 20% of pregnant women reported first-trimester opioid use in 2009. Among Tennessee Medicaidinsured pregnant women, use of opioid analgesics increased nearly 2 fold from 1995 to 2009 (Epstein et al., 2013). Furthermore, in a populationbased cohort study of 194,937 singleton pregnancies in Norway between March 2004 and January 2009, about 6% of the women were dispensed opioid analgesics before, during, or after pregnancy. Most of the women were prescribed a weak short-acting opioid such as codeine in combination with paracetamol (acetaminophen) and less was dispensed after pregnancy was diagnosed. A small group of women (N = 271) took codeine throughout their pregnancies (Handal, Engeland, Rønning, Skurtveit, & Furu, 2011).

Opioid Analgesics

Review of the Literature A review of the literature included searching multiple databases from medicine, nursing, and psychology. The searches were conducted for articles published from 2000 through the first quarter of 2014. Keywords included pregnancy and narcotics, opiates, opioid analgesics, methadone, buprenorphine, chronic pain, suboxone, and subutex. Databases used for this search were the following: Academic Search Complete, Alt Health Watch, CINAHL, Cochrane Databases, ERIC, Health Source: Consumer Edition, MEDLINE, PsycInfo, Psychology and Behavioral Sciences Collection, and PubMed. Reference lists from included articles were also searched for other sources. Publication types included were research studies, systematic reviews of literature, JOGNN 2014; Vol. 43, Issue 5

Opioid analgesics are becoming more commonly prescribed as awareness of chronic pain in pregnancy increases and as retrospective studies begin to demonstrate safety profiles (Hadi et al., 2006). One of the biggest risks of chronic opioid use during and outside of pregnancy is dependence, which often leads to misuse and abuse (Babb et al., 2010). As these medications are more widely available, abuse potential is higher. For example, Kelly et al. (2011) reported an increase in oxycodone consumption from 8.4% to 17.2% over an 18-month period during which their study of narcotic abuse in pregnancy was being conducted. For many years, the opiate class of drugs appeared to have a relatively low-risk profile for 555

PRINCIPLES & PRACTICE

Analgesics are the most commonly used medications in pregnancy other than vitamins and supplements, and the use of opioid analgesics in pregnancy is steadily increasing.

the neonate with little evidence for increased prevalence of major congenital anomalies and reassuring studies of neuro-developmental characteristics of exposed children after the initial newborn period (Babb et al., 2010; Malek & Mattinson, 2011). However, more recent researchers have found an association between opiate use prior to conception and in the first trimester and birth defects (Broussard et al., 2011; NezvalovaHenriksen, Spigset, & Nordeng, 2011); therefore, use in women at risk of becoming pregnant or in early pregnancy should be undertaken cautiously (Brennan & Rayburn, 2012). The prevalence of neural tube defects in offspring of mothers who used opioids was estimated to be six per 10,000 live births (Yazdy, Mitchell, Tinker, Parker, & Werler, 2013). Women who are considering pregnancy while taking opiates will need to be advised to take at least 1 mg of folic acid daily to reduce the risk of fetal neural tube defects and to continue with folic acid supplementation while pregnant (Yazdy et al., 2013). Another risk of maternal use of opioids for chronic pain during pregnancy is that the exposed fetus is likely to experience neonatal abstinence syndrome (NAS), with an estimated overall rate of 5.6% (Kellogg et al., 2011). To minimize the adverse risks of opioid use in pregnancy and provide adequate maternal pain control, many factors must be considered when initiating or adjusting dosing of opioid analgesics in pregnancy. Genetic factors can affect metabolism and either decrease efficacy or increase the rate of conversion to active metabolites (Kahan, Wilson, Mailis-Gagnon, & Srivistava, 2011; Koren, Cairns, Chitayat, Gaedigk, & Leader, 2006; Madadi, Avard, & Koren, 2012). Drug absorption may be affected by decreased gastrointestinal motility, emesis, and gastroesophageal reflux (Wunsch et al., 2003). Additionally, there is an increase in cutaneous blood flow, an alteration of distribution in the maternal compartment, and the possibility of effects on drug absorption due to placental and fetal factors (Kennedy, 2011; Wunsch et al., 2003). Opioid receptors also play a part in the dosing of opioid analgesics in pregnancy. Most agents are lipophilic and bind to mu receptors as agonists; therefore, they cross the placenta rapidly and are readily available. For this reason, extended-release agents may not be as effective in pregnancy and have the potential to 556

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Safe Management of Chronic Pain in Pregnancy

accumulate in the placental or fetal compartments (Malek & Mattison, 2011). The most commonly prescribed opiate analgesics in pregnancy are codeine, fentanyl, hydrocodone, morphine, oxycodone, oxycontin, and tramadol. Codeine is the most widely studied of these agents. Some researchers demonstrated associations between codeine use prior to conception and in the first trimester and congenital cardiac anomalies (Broussard et al., 2011), but researchers’ studies failed to produce the same results (Babb et al., 2010; Nezvalova-Henriksen et al., 2011). Practitioners may need to counsel patients that there is an overall risk of 3% for major congenital anomalies and 15% for spontaneous pregnancy loss in all women regardless of any medication exposure, and risks with any medication use should be reviewed taking the background risk into consideration (Kennedy, 2011). There is also a greater risk for NAS with codeine than with any other opioid analgesics (Babb et al., 2010; Handal et al., 2011; Nair, Soraisham, & Akierman, 2012; Reynolds, Riel-Romero, & Bada, 2007). Fentanyl use in pregnancy is not well reported in the literature. In one case report the authors described NAS in a pregnancy during which the mother used a 125 mcg/hour transdermal patch throughout gestation (Regan, Chambers, Gorman, & MacSullivan, 2000). The infant was treated conservatively and showed no signs of withdrawal by day 4 of life. Normal developmental milestones were observed in follow-up through at least 6 weeks of life. In a similar case report (Cohen, 2009) of a mother using a 100 mcg/hour transdermal patch throughout pregnancy and lactation, the author described an infant who showed no signs of NAS and had an undetectable serum fentanyl level on day 27 of life. Case reports of fentanyl use in labor demonstrated little fetal uptake of the drug in 10 infants born to mothers with fentanyl added to epidural anesthetic (de Barros Duarte et al., 2009), however this information cannot be translated for use outside of the labor setting. Although hydrocodone is widely prescribed, there is a paucity of literature on the use of hydrocodone in pregnancy (Babb et al., 2010; Kellogg et al., 2011). In one older, small study (N = 40) researchers found no correlation with congenital malformations and no association with adverse neonatal outcomes (Schick, Hom, Tolosa, Librizzi, & Donnefield, 1996). Data from a subset (n = 31) of 500 patients treated in a prenatal substance abuse recovery program between 2000 http://jognn.awhonn.org

Pritham, U. A., and McKay, L.

PRINCIPLES & PRACTICE

through 2010 indicated that opioid dependent chronic pain patients who used only opioids (40 to 80 mg per day of hydrocodone or oxycodone) had the lowest maternal and neonatal morbidity as compared to opioid-dependent pain patients with positive drug screens for multiple illicit and licit substances (Nocon, 2013). The incidence of preterm delivery and low birth weights were found to be similar to that of non-opioid-dependent pregnant women.

when methadone is used solely for pain and found 13 out of 19 neonates experienced NAS. Sublingual buprenorphine is also being used in pregnancy for the management of chronic pain with less potential for NAS. Administration of a lowered dosed transdermal buprenorphine patch (3/5 of a 35 microg/h patch corresponding to release of 21 microg/h buprenorphine) was reported in a single pregnant woman without adverse outcomes and good pain control (Ebner & Wiedmann, 2006).

Oxycodone was reported in a study of narcotic abuse in a region of Ontario, Canada, where it was heavily used as an illicit substance (Kelly et al., 2011). No adverse effects were reported and no incidence of NAS, but the authors cited episodic use due to erratic availability as a possible limitation of the study. Other researchers have shown a possible association between oxycodone and NAS (Kellogg et al., 2011; Schick et al., 1996.)

For some opioid-only-dependent chronic pain patients, switching them to methadone or buprenorphine may not be possible. Therefore, Nocon (2013) recommended that pregnant women maintain their current opioid regimens to avoid withdrawal. Hydrocodone 5/325 or 10/325 (up to two tabs q 6h) or oxycodone 5/325 or 10/325 (up to two tabs q 6h) are acceptable since a low rate of NAS has been noted with these doses. However, hepatotoxicity from repeated doses of such combination medications that contain acetaminophen (> 4 grams/24 hours) must be considered. Newer more concentrated formulations of opioids with 55% less acetaminophen (e.g., Lortab Elixir) are now available to prevent the potential for hepatotoxicity. Total daily opioid dose to achieve adequate pain control may increase as pregnancy progresses and, therefore, pain moderators may be helpful. Adjunctive therapy with amitriptyline 50mg to 100 mg at night, gabapentin 300 mg every 8 hours, and physical therapy to maintain and improve mobility are useful in individual cases (Nocon, 2013).

We found only one report regarding oxycontin use in pregnancy. This case study described an infant with NAS with an initial negative maternal urine drug screen and negative meconium drug screen. However, the neonatal urine drug screen was positive, and the neonate had signs of withdrawal. The finding of oxycontin in the neonatal urine screen after initially negative maternal urine and fetal meconium drug screens was thought by the authors to be due to the long-acting nature of oxycontin (Rao & Desai, 2002). Morphine has not been shown to have any teratogenic effect, but it does appear to be the most affected by pregnancy with an increased rate of clearance, decreased half-life, and rapid placental transport (Malek & Mattinson, 2011). Fetal metabolism and clearance have been reported to be constant in late gestation in animal studies, contributing to its acceptance for use in labor (Garland et al., 2006). In one case report of a continuous intrathecal infusion throughout pregnancy, the authors found mild NAS, which did not require pharmacologic treatment (Byrd, Jadoon, Lieberman, & Johnston, 2007).

Methadone and Buprenorphine for Pain and Opioid Replacement Methadone can be used for treatment of chronic pain as well as for opioid dependence; however, total daily doses for chronic pain management are less than doses used for opioid-replacement therapy (Nocon, 2013). In one small study (N = 19), Kellogg et al. (2011) examined incidence of NAS

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A growing number of women of reproductive age have substance use and substance use disorders, namely opioid dependence (World Health Organization [WHO], 2014). Pregnant women who have a dependence on opioids in the absence of an active chronic pain syndrome may be encouraged to wean or undergo medically supervised detoxification (Stewart et al., 2013) during the second trimester of pregnancy or initiate opioid-replacement therapy with methadone or buprenorphine (American College of Obstetricians and Gynecologists [ACOG], 2012; Jones et al., 2008; Kellogg et al., 2011). There are many studies about the use of methadone and buprenorphine as opioid substitution therapies to reduce the maternal and fetal risks of withdrawal during pregnancy in the setting of illicit opioid addiction. Most studies demonstrate a higher risk of NAS with methadone than with buprenorphine (Jones et al., 2008; Pritham et al., 2012; Unger et al., 2011; Winklbaur-Hausknost et al., 2012),

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yet methadone has been the standard of care for opioid-dependent pregnant women since the early 1970s due to the large number of wellconducted studies. Knoppert (2011) estimated the incidence of NAS to be as high as 70% when methadone is used for the treatment of opioid dependence in pregnancy and is not dose dependent. The widely publicized multinational Maternal Opioid Treatment: Human Experimental Research (MOTHER) project (Jones et al., 2012), along with other studies in the United States and internationally, have contributed to the body of knowledge regarding the safety of opioid analgesics and opiate substitution therapies in pregnancy (WHO, 2014). Continued inclusion of pregnant women in clinical trials on opioid-replacement therapies will provide additional evidence for the safety of these medications over illicit drugs (WinklbaurHausknost et al., 2012). Although the incidence of NAS has increased due to the use of methadone as opioid-replacement therapy (National Institute on Drug Abuse, 2012; Patrick et al., 2012), perinatal outcomes from episodic illicit opioid use and withdrawal are worse (Malek & Mattinson, 2011). Poor outcomes may be exacerbated by concurrent use of tobacco, alcohol, and other harmful substances, and by an unhealthy maternal lifestyle that often accompanies substance abuse. Studies show an increase in the amount of epinephrine in the amniotic fluid and signs of withdrawal occurring as early as 6 hours following the most recent exposure to any type of opioid (Malek & Mattinson, 2011; Sinha et al., 2001). These findings underscore the need for careful monitoring of all chronic opiate use in pregnancy.

tential risks, taking into consideration the overall risks for adverse outcomes in any pregnancy, and closely managed and monitored for compliance (Babb et al., 2010; Brennan & Rayburn, 2012; Hadi et al., 2006; Kellogg et al., 2011). Ideally, women would be advised to wean to the lowest effective dose in the final weeks of pregnancy that will likely reduce the occurrence of NAS. Women who require opioid analgesics in pregnancy for chronic pain benefit from a multidisciplinary team approach to include board certified pain management professionals, maternal-fetal specialists, and neonatologists. Whenever possible, use of overthe-counter analgesics and complimentary or alternative methods for pain management should be considered to limit or reduce the use of opioids.

Atypical Narcotic-Like Analgesics Tramadol is reported in several individual case studies and one small prospective study (N = 146). There appeared to be an increase in the incidence of spontaneous abortion with the use of tramadol, but no increase in congenital anomalies (Bloor, Paech, & Kaye, 2012). All of the case studies demonstrated an association with NAS in tramadol users (Bloor et al., 2012; Hartenstein, Proquitte, Bauer, Bamberg, & Roehr, 2010; Willaschek, Wolter, & Buchhorn, 2009).

Over-the-Counter Analgesics

Clinicians must consider the benefits and risks of opioid analgesics in pregnancy when a patient with chronic pain has not achieved adequate pain control with other pain therapies. If pharmacological therapy with opioids is selected, patients must be adequately counseled of the po-

Over-the-counter analgesics can be safely used in most pregnancies. Acetaminophen is the most widely used medication in pregnancy for pain and fever (Babb et al., 2010; Kennedy, 2011) and up until recently has not been associated with the occurrence of congenital anomalies or adverse neonatal outcomes (Rebordosa et al., 2008). However, Kallen, Finnstrom, Nygren, and Olausson (2013) reported an increase in asthma risk among children whose mothers used acetaminophen during pregnancy and Brandlistuen and colleagues (2013) found that children exposed to acetaminophen in utero tend to start walking later, have poorer communication and language skills, and more behavior problems than those with less or no exposure. According to Liew, Ritz, Rebordosa, Lee, and Olson (2014), acetaminophen is a hormone disruptor and thus has the potential to influence fetal brain development. In a Danish study (N = 64,322) maternal acetaminophen use during pregnancy was associated with a higher risk for hyperkinetic disorders, attention-deficit and hyperactivity disorder-like behaviors in children. Subsequently, the use of acetaminophen alone or as part of a multimodal pain

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Researchers studying long-term neurodevelopmental outcomes of infants exposed to opioids in utero have shown an increase in the incidence of learning problems, behavioral problems, and lagging language development (Hunt, Tzioumi, Collins, & Jeffrey, 2008; Knoppert, 2011; Pulsifer, Butz, O’Reilly, Foran, & Belcher, 2008). However, these studies do not account for other factors known to contribute to these problems, such as prematurity and other in-utero exposures (e.g., alcohol, tobacco, and other drugs).

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management approach for women with chronic pain during pregnancy has been questioned. Aspirin has been found in some studies to increase the risk of gastroschisis when taken in the first trimester (Kozer et al., 2002) but is not associated with other congenital anomalies. Aspirin may also interfere with platelet function and increase bleeding risk in some women and should therefore be used with caution at dosages typically recommended for analgesia (Babb et al., 2010; Bloor & Paech, 2013; Kennedy, 2011). However, use of low dose aspirin (81 mg/day) in women with antiphospholipid syndrome, recurrent pregnancy loss, and preeclampsia risk is associated with overall positive outcomes (Bloor & Paech, 2013; Bujold et al., 2010; James, Brancazio, & Price, 2007; Henderson et al., 2014). Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen may increase the risk of first-trimester spontaneous abortion by as much as 80% but are not associated with major congenital anomalies when taken in the second trimester of pregnancy (Bloor & Paech, 2013; Li, Liu, & Odouli, 2003; Ofori, Oraichi, Blais, Rey, & Berard, 2006). NSAIDs have been shown to inhibit cyclo-ogenase that helps to maintain the patency of the fetal ductus arteriosis and pulmonary resistance vessels. Use after 30-weeks gestation is contraindicated due to the increased fetal risks of premature closure of the ductus arteriosus, persistent pulmonary hypertension, renal compromise, oligohydramnios, necrotizing enterocolitis, and intracranial hemorrhage (Bloor & Paech, 2013; Kennedy, 2011; Ofori et al., 2006). Thus, NSAIDs are not typically used outside of the second trimester for management of chronic pain in pregnancy. Table 1 lists commonly prescribed opioid and nonopioid analgesics in pregnancy in alphabetical order by generic ingredient and also provides brand names, combination preparations, and delivery systems. Table 2 outlines management of chronic pain in women of reproductive age, and Table 3 outlines the safety of analgesics in pregnancy by trimester.

PRINCIPLES & PRACTICE

antidepressants and some selective serotonin reuptake inhibitors (SSRIs) (specifically fluoxetine) have been shown to help control chronic pain and reduce opioid exposure with no documented increase in the incidence of congenital anomalies or neurobehavioral effects in the neonate (Kennedy, 2011). There have been other studies showing a potential for increase in congenital cardiac defects when fluoxetine is used in the first trimester; therefore, it is probably safer to delay initiation until the second trimester when possible (DiavCitrin et al., 2008). Use of SSRIs in pregnancy, particularly in the third trimester, has been linked to neonatal withdrawal and persistent pulmonary hypertension (PPH) of the newborn, which is a lifethreatening condition that occurs in up to two per 1,000 live born infants and most often in those born at term or postterm (Keiler et al., 2012; Tuccori et al., 2009). Fifteen percent of newborns with PPH will die. Use of SSRIs after gestational week 20 is associated with a doubled risk of PPH, and specific SSRIs have the same increased risks, which suggest a class effect (Keiler et al., 2012). Benzodiazepines are rarely used as a sole agent but have been prescribed with opioid analgesics for pain. Handal et al. (2011) observed a large sample of pregnant women in Norway on a short course of codeine and found that as the number of opioid prescriptions increased there was also increased benzodiazepine use. Benzodiazepines have been associated with cleft lip and palate in animal studies, but the association in humans is controversial and a single dose has not been linked with teratogenicity (Safra & Oakley, 1975). Long-term use of benzodiazepines should be avoided due to the association with NAS (Armstrong & Fernando, 2013) and when used with opioids has the potential to significantly worsen NAS (Metz, Comer, & Fischer, 2013; Pritham, Paul, & Hayes, 2012). Furthermore, concomitant use of opioids with benzodiazepines increases maternal risk for respiratory depression and death (Nocon, 2013).

Complementary and Alternative Therapies

Adjuncts to Analgesics for Chronic Pain Therapy Antidepressants and Anxiolytics Antidepressants and anxiolytics have been used for the treatment of chronic pain in pregnancy with certain comorbidities but with caution, particularly when used with opiates (Nocon, 2013). Tricyclic

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There are a number of alternative and complementary therapies for management of acute and chronic pain in pregnancy that should be considered as primary or adjunctive measures. Among the most commonly recommended are the use of positioning aids, application of heat or cold, massage and vibration, acupuncture, relaxation, Hatha yoga, music, and chiropractic

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Opana, Opana ER

Talwin

ConZip, Rybix ODT, Ryzolt, Ultram, Ultram ER

Pentazocine lactate

tramadol

Avinza, Kadian, MS Contin, Oromorph SR, Roxanol

Morphine sulfate

oxymorphone

Dolophine, Methadose

methadone

Oxycontin, Oxyfast, Roxicodone, Oxecta

Demerol

meperidine

oxycodone

Dilaudid, Exalgo

hydromorphone

hydrocodone

fentanyl

dihydrocodeine

codeine sulfate

Sublimaze

Buprenex, Subutex

buprenorphine

Codeine phosphate,

Brand Names

Generic Ingredient

Tramadol/acetominophen

Pentazocine/naloxone (Talwin NX), pentaxocine/acetaminophen (Talacen)

oxycodone/ibuprofen (Combunox)

Roxicet, Tylox, Xolox) Oxycodone/aspirin (Percodan),

oxycodone/acetaminophen (Endocet, Magnacet, Percocet, Primalev,

hydrocodone/ibuprofen (Ibudone, Reprexain, Vicoprofen)

Norco, Vicodin, Vicodin ES, Vicodin HP, Zamicet, Zydone,

Hydrocodone/acetaminophen (Hycet, Lorcet, Lorcet Plus, Lortab, Maxidone,

Zerlor) dihydrocodeine/aspirin/caffeine (Synalogos-DC)

dihydrocodeine/acetaminophen/caffeine (Panlor DC, Panlor SS, Trezix,

promethazine for cough, and carisoprodol/aspirin as Soma compound

Codeine is also found in other combinations such as with guiafenesin or

Butalbital/acetaminophen/caffeine/codeine (Fiorinal)

Butalbital/aspirin/caffeine/codeine (Fioricet)

Codeine/acetaminophen (Tylenol #3 & #4)

Buprenorphine/naloxone (Suboxone)

Combination Preparations

Table 1: Commonly Prescribed Opioid and Nonopioid Analgesics in Pregnancy

DepoDur (liposomal)

Lazanda (nasal)

Subsys (transmucosal)

Abstral, Actiq, Fentora, Onsolis,

Duragesic (transdermal)

Fentanyl transdermal, transmucosal,

Alternative Delivery Systems

PRINCIPLES & PRACTICE Safe Management of Chronic Pain in Pregnancy

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PRINCIPLES & PRACTICE

Pritham, U. A., and McKay, L.

Table 2: Management of Chronic Pain with Opioids in Women of Reproductive Age Not Currently Pregnant, Not Considering Pregnancy Counsel on consistent use of effective contraception

Not Currently Pregnant, Planning Pregnancy Counsel patient on risks of untreated

pain versus risks to fetus and risks of

neonatal withdrawal following in utero

neonatal withdrawal following in utero exposure

Continue or initiate use of effective,

folic acid in the event of an

reversible contraception while

unintended pregnancy

weaning from opioid analgesics

Discuss weaning from opioid analgesics Begin taking prenatal vitamins with at well in advance of planning for

Counsel patient on risks of untreated

pain versus risks to fetus and risks of

exposure Encourage taking multivitamins with

Currently Pregnant

least 1 mg of folic acid

Counsel patient on risks of reducing or stopping medication once pregnant

Ensure that patient is taking vitamins with at least 1 mg of folic acid throughout the pregnancy, but

pregnancy

especially in the first 16 weeks Refer to pain management provider for

Transition to equianalgesic immediate

management of weaning from opioid

release preparation if patient is using

analgesics

extended release

If pain management provider is not

Offer routine prenatal screening tests,

available to the patient, make a long

explain to patient that her genetic

term weaning plan with the patient,

risks are separate from risks for

allowing for at least 3–6 months off all

anomalies associated with opiate use

analgesics prior to conception Refer to maternal-fetal specialist for detailed anatomy scan at 18–20 weeks Schedule neonatology consult and anticipate delivery at a tertiary care center Adjust dosing as necessary to maintain at the lowest effective dose. The need for increased dosage as pregnancy progresses is likely with musculoskeletal conditions or other conditions worsened by pregnancy

(Kvorning, Holmberg, Grennert, Aberg, & Akeson, 2004; Wang et al., 2005). Methods to provide distraction from pain include reciting poetry, meditating with a calm phrase, watching movies or television, visiting with friends, playing cards, participating in crafts, and art and music therapy. Listening to music has been found to decrease the intensity of pain and reduce the amount of opioids needed, but the magnitude of the benefit was small (Cepeda, Carr, Lau, & Alvarez, 2006). Among 87 hospitalized patients presenting with lumbar pain, fibromyalgia, inflammatory disease, or neurological disease, the use of a music intervention method during hospitalization and while home was helpful in managing chronic pain be-

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cause it significantly reduced the need for analgesics (Guetin ´ et al., 2012). Physical therapy may have some utility (Stuge, Hilde, & Vollestad, 2003) but has not been demonstrated in high quality studies to be as effective as other nonmedical modalities. Hypnosis may also be effective for reducing chronic pain, although outcomes vary between individuals (Jensen & Patterson, 2014).

Recommendations for Clinical Practice There are no pain management protocols or practice guidelines for the care of pregnant women with chronic pain. Therefore, clinicians must

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Codeine∗

other NSAIDS

Ibuprofen and

the third trimester (Kallen et al., 2013).

defects (Broussard et al., 2011)

Possible increased risk for cardiac

miscarriage by 80%

Generally considered safe

Generally considered safe

2014).

was limited (Henderson et al.,

identified, but long-term evidence

Generally considered safe

Kennedy, 2011; Ofori et al., 2006).

hemorrhage (Bloor & Paech, 2013;

enterocolitis, and intracranial

oligohydramnios, necrotizing

hypertension, renal compromise,

arteriosus, persistent pulmonary

premature closure of the ductus

due to the increased fetal risks of

30 weeks gestation contraindicated

pulmonary hypertension. Use after

ductus arteriosus and persistent

Increased risk of premature closure of

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2007). (Continued)

et al., 2011; Nair et al., 2012; Reynolds et al.,

opioid analgesics (Babb et al., 2010; Handal

use showed increased risk of NAS over other

increased risk for cardiac defects. Continuous

pregnancy and in first trimester due to

Use with caution in women at risk for unintended

Use in second trimester only.

morbidity and mortality from

Kennedy, 2011).

Increased risk of first trimester

(Henderson et al., 2014).

second trimester to prevent

et al., 2010; Bloor & Paech, 2013;

preeclampsia. No harms were

morbidity and mortality from preeclampsia

aspirin beginning as early as the

considered safe and being used to prevent

Prophylactic low dose aspirin is generally

analgesic doses. Daily low-dose

analgesic doses

Increased risk of bleeding at

Increased risk of bleeding at

pregnancy, and may be higher when used in

increases with the total amount of use in

maternal acetaminophen use. The risk

beginning to link childhood asthma with

Use only when benefit outweighs risk. Studies are

Recommendation

bleeding at analgesic doses (Babb

Increased risk of gastroschisis (Kozer

Aspirin

Generally considered safe

Third Trimester

Generally considered safe

Second Trimester

et al., 2002), increased risk of

Generally considered safe

First Trimester

Acetaminophen

Analgesic

Table 3: Safety of Analgesics in Pregnancy by Trimester

PRINCIPLES & PRACTICE Safe Management of Chronic Pain in Pregnancy

JOGNN 2014; Vol. 43, Issue 5 et al., 2007).

Continuous use can result in mild NAS (Byrd

placental transport (Malek & Mattinson, 2011).

rate of clearance, decreased half-life, and rapid

Most affected by pregnancy with an increased

although widely used in pregnancy.

No significant safety information available,

Recommendation

miscarriage (Bloor et al., 2012)

nature of the drug (Rao & Desai, 2002).

(Pritham et al., 2012; WHO, 2014).

designed studies, possibly as high as 70%

Demonstrated increased risk of NAS in many well

et al., 2012).

studied as methadone in pregnancy (Pritham

but less than that of methadone. Not as well

Risk of NAS higher than with opioid analgesics

Hartenstein et al., 2010; Willaschek et al., 2009).

Increased risk of NAS (Bloor et al., 2012;

Note. ∗ Opioid analgesic as a class of drugs have been associated in some studies with an increased risk of cardiac and neural tube defects, neonatal abstinence syndrome (NAS), and behavior and learning problems in exposed children. ∗∗ Opioid substitution therapies carry a high risk of NAS; however, neonatal outcomes with these therapies are dramatically better than for those exposed to illicit drugs, making treatment with buprenorphine or methadone the standard of care for opioid dependent women in pregnancy with chronic pain.

Methadone∗∗

Buprenorphine∗∗

Tramadol∗

Probable increased risk of NAS due to long acting

Third Trimester

Oxycontin∗

Second Trimester

No significant safety information available.

Increased risk of first trimester

available

No significant safety information

First Trimester

Oxycodone∗

Morphine∗

Hydrocodone∗

Fentanyl

∗

Analgesic

Table 3: Continued

Pritham, U. A., and McKay, L.

PRINCIPLES & PRACTICE

563

PRINCIPLES & PRACTICE

Women who require opioid analgesics in pregnancy should be monitored by a multidisciplinary team, including pain management professionals when possible, maternal-fetal specialists, and neonatologists.

refer to treatment strategies for the general population and adapt them for use with pregnant woman. If an analgesic treatment modality is selected, it needs to match the likely underlying pain pathophysiology (Institute of Medicine [IOM], 2011). Typically, a multimodal treatment approach is best and should incorporate pharmacologic, psychological, physical rehabilitation, and interventions that address the sensory, emotional, cognitive, interpersonal, and social contributions to causation and maintenance of pain (IOM, 2011). A common source of frustration for patients with chronic pain and their providers is the lack of ability to predict which treatment or combination of treatments will work best in an individual case. Different treatment approaches may need to be tried and modified over the course of pregnancy to achieve optimum pain control with minimal adverse effects on pregnancy outcome. Fishman (2007) identified seven principles set by the Federation of State Medical Boards guiding the safe management of opioid therapy in the nonpregnant patient with chronic pain. These principles are performing a comprehensive evaluation of the patient, developing a detailed treatment plan, securing informed consent and agreement for treatment, conducting periodic review of efficacy and compliance, consultation when needed, maintenance of thorough medical records, and compliance with laws and regulations for controlled substances. Table 3 presents pathways for management of women of childbearing age who are taking opioid analgesics, based on Fishman’s principles and the research available for safe use in pregnancy.

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sibilities, and provide patient education. They recommend a periodic review of the management plan, though there is no specific suggested interval. The pain treatment modality selected needs to be communicated to everyone involved in the care of the pregnant woman, and in particular the patient’s primary care provider (PCP), to prevent overprescribing and misuse of controlled substances (ACOG, 2012; Masterson & Wilson, 2012). The U.S. Department of Veterans Affairs (VA) (2010) provides criteria for appropriate patients to consider for chronic opioid therapy. The criteria state that patients must have moderate to severe chronic pain that is refractory to nonopioid alternatives and use of nonmedicinal therapies (such as physical therapy and chiropractic care), there must be no absolute contraindications, patients must be fully informed and consent to the treatment, and there must be clear and measurable goals for therapy. In the pregnant patient with chronic pain, nonmedicinal therapies should be considered as an adjunct to opioid analgesics in an attempt to maintain efficacy at the lowest effective dosing (Kvorning et al., 2004; Wang et al., 2005). Multiple modalities may be required to adequately manage pain and to prevent women from seeking illicit substances for improved pain control that could compound the problem of safe medication use in pregnancy.

There are differing opinions in the literature about whether patients should be required to sign agreements or contracts when initiating opioid therapy or assuming responsibility for care of a patient on chronic opioid therapy. Limited studies on their use have failed to demonstrate that contracts or agreement improve compliance or reduce misuse (Arnold, Han, & Seltzer, 2006; Collen, 2009; Payne et al., 2010). Recommendations by Chou et al. (2009) are for obtaining a detailed informed consent to include goals, expectations, risks, and alternative therapies as well as a written management plan to include patient and clinician respon-

Clinicians treating pregnant women on long-acting or extended release opiates are obligated to inform them of the risk of NAS (U.S. FDA, 2013) and should consider transitioning these women to an immediate release preparation during pregnancy. Extended release formulations may be less effective in pregnancy (Malek & Mattison, 2011) and have a higher risk of accumulation in the placenta or fetus (Kennedy, 2011; Wunsch et al., 2003). The U.S. Department of Veterans Affairs (2010) recommends that when initiating therapy with a new agent, the dose be 50% to 67% of the calculated equivalent dose due to the potential for incomplete cross-tolerance that may yield more adverse effects and higher relative analgesic effect. Regardless of the specific opioid analgesic agent and dosage ordered, women and their families require counseling about how the medications can affect the developing fetus and the neonate, the signs of NAS, the treatment if NAS is diagnosed, and the potential long-term consequences of chronic exposure. A consultation with a neonatologist is beneficial, and delivery should take place at a tertiary care center with adequate neonatal facilities for evaluation and management, if NAS should occur.

JOGNN, 43, 554-567; 2014. DOI: 10.1111/1552-6909.12487

http://jognn.awhonn.org

PRINCIPLES & PRACTICE

Pritham, U. A., and McKay, L.

Conclusion Clinicians involved in the care of pregnant women with chronic pain require up-to-date evidence on the safety of various analgesics. For women requiring chronic use of opioids and other analgesics, clinicians must consider the implications for mother and fetus when determining individualized care. The challenges associated with making the best clinical decisions regarding management of chronic pain in pregnancy include lack of a specific guide for the assessment and management of pain in pregnancy, lack of availability of pain specialists to consult with or refer pregnant women to, and the need for more research evidence in the treatment of chronic pain in pregnancy. Development of a chronic pain management protocol for the counsel and care of pregnant women with pain is necessary. The prevalence of chronic pain syndromes among pregnant women in the United States is expected to increase with rising rates of diabetes, obesity, and a growing number of older pregnant women. Greater public awareness of pain as a condition warranting medical management with long-acting opioids requires that clinicians educate women on the risks and benefits of opioid use prior to pregnancy and during pregnancy and offer alternative therapies whenever possible. Clinicians who treat women for chronic pain have a responsibility to remain current as scientific knowledge of pain pathophysiology evolves and more information becomes available about the safety and effectiveness of various analgesics prior to and throughout pregnancy.

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