A Systematic Scoping Review of Peridelivery Pain Management for Pregnant People With Opioid Use Disorder: From the Society for Obstetric Anesthesia and Perinatology and Society for Maternal Fetal Medicine

During the past decade, opioid use disorder (OUD) has increased 4-fold among pregnant people.1 OUD increases risk for death from overdose, which is a rising leading cause of maternal deaths in the United States (Centers for Disease Control and Prevention [CDC]: http://www.cdc.gov/reproductivehealth/opioid-use-disorder-pregnancy/index.html). Peridelivery pain management for pregnant patients with OUD is suboptimal because of lack of evidence-based recommendations. Research suggests that suboptimal relief of acute postoperative pain has long-term sequelae, including chronic pain and depression.2,3 This problem of pain management is further complicated in patients with OUD because of concerns about return to use, triggered by pain itself or triggered by exposure to opioids if opioids must be used for pain control.

Medications for opioid use disorder (MOUD) is the mainstay for effective treatment of OUD in pregnancy because MOUD is associated with better prenatal care adherence and birth outcomes.4 MOUD in pregnancy typically includes opioid agonist or mixed agonist-antagonist medications (eg, methadone and buprenorphine). Chronic use of these medications can have implications on pain management during and after labor and delivery. These medications have a strong affinity for μ-opioid receptors, which, in theory, may increase the likelihood of higher doses of opioids needed or consumed to control pain during labor and after delivery. However, in contrast, both opioid exposure and untreated or poorly controlled pain can lead to return to use or OUD recurrence.5 How clinicians should optimally manage both acute pain and coexisting OUD is a source of frequent debate.

It is unclear what type of information is available in literature about pain management in patients with coexisting OUD. Systematically mapping the current research done and knowledge gaps, as well as existing limitations in study methodologies, will assist with planning specific directions for future research. The purpose of this scoping review is to identify and summarize the available literature on peripartum pain management in pregnant people with OUD, both treated with MOUD and untreated. The focus of this review is on 3 primary peripartum periods: predelivery pain management optimization; pain management in labor and delivery; and postcesarean delivery pain management. The scoping review aimed to characterize available evidence on how OUD affects pain management during the 3 peripartum periods mentioned above and to identify knowledge gaps to make recommendations for future research.

METHODS

The reporting of this scoping review was guided by the Preferred Reporting Items for Systemic Reviews and Meta-Analysis extension for Scoping Review standards (PRISMA-ScR).6 A working group from the Society for Obstetric Anesthesia and Perinatology (SOAP) defined, by consensus, specific key questions that would be important for peripartum pain management in pregnant people with OUD, both treated with MOUD or untreated (Supplemental Digital Content 1, Appendix 1, https://links.lww.com/AA/E11). Questions were developed to comprehensively capture all relevant clinical decision-making points before, during, and after labor and delivery. Two investigators (G.L. and M.S.) used these questions to identify and saturate on themes of topics that are of interest to pain management in pregnant people with OUD. These questions were considered for each of the following populations: (1) pregnant people receiving MOUD for whom OUD was due to an acute or chronic pain condition; (2) pregnant people receiving MOUD for whom OUD was not due to pain condition; (3) pregnant people with untreated OUD; and (4) pregnant people with OUD who are stable in recovery and not receiving MOUD.

Methodology and Sources

The databases PubMed and Embase were systematically searched from inception until March 31, 2020, for published journal articles. PubMed covers the health care literature where most peer-reviewed publications are indexed. Embase covers European, North American, and other non-North American literature. An experienced health sciences librarian (C.B.W.) designed the PubMed search, which was then translated for use in Embase.com by a second health sciences librarian (M.L.K.). For both databases, a search string was developed using both controlled vocabulary terms (eg, Medical Subject Headings [MeSH] terms) and natural language informed by a subject matter expert (G.L.) to represent the concepts of OUD, peripartum pain, and pain management (Supplemental Digital Content 2, Appendix 2, https://links.lww.com/AA/E12).

The results of the database searches were downloaded to an EndNote library, and duplicate records were removed by a health sciences librarian (M.L.K.) using a process developed by Bramer et al.7 Covidence systematic review software (Veritas Health Innovation) was used to manage citations and track ratings.

Inclusion/Exclusion Criteria

Articles included labor and delivery pain management for vaginal delivery, postpartum pain management for vaginal delivery, and postpartum pain management for cesarean delivery. Articles were included if they were original research, case studies, case series, or cohort studies, letters to the editor, commentaries, white papers, published abstracts, or review articles. All languages were included, with non-English articles translated by certified medical translator services to English, the authors’ primary language.

Study Selection

Article titles and abstracts were screened and included if they contained the following terms: pain, analgesia, or pain management; pregnancy, parturient, or perinatal; labor and delivery, intrapartum, or cesarean delivery or postpartum; OUD with MOUD, OUD without MOUD, or substance use disorder with OUD specified in the title or abstract. Articles were excluded if they pertained to acute or chronic pain not in the peripartum period, or if they were nonhuman or animal studies. Two reviewers independently screened titles and available abstracts using the above predetermined inclusion/exclusion criteria and key questions from Supplemental Digital Content 1, Appendix 1, https://links.lww.com/AA/E11 (A.C. and A.W.). Duplicate abstracts were removed from consideration. Discrepancies between the 2 abstract reviewers were resolved through discussion; for persistent discrepancies requiring a tiebreaker, a third party (G.L.) was consulted. Cohen’s kappa statistic was calculated to evaluate interrater reliability between the 2 initial raters for this level of review. Full text for these studies was then located and reviewed; if duplicates were detected by full text, they were removed, as were studies that were deemed to be irrelevant and studies in which full text could not be located. Two reviewers independently screened full text (A.C. and A.W.), with discrepancies resolved through discussion and persistent discrepancies resolved through a third-party tie breaker (G.L.).

Extraction/Charting the Results

For abstracts that met the inclusion/exclusion criteria, full-text articles were then reviewed. Each article was then individually reviewed by G.L. using the prespecified relevance criteria established by the key questions in Supplemental Digital Content 1, Appendix 1, https://links.lww.com/AA/E11. Each article was associated with one or more codes corresponding to the relevant key questions in the 3 primary peripartum phases: immediate predelivery optimization, management of labor pain, and postcesarean delivery pain management. Study characteristics, including first author, language of original publication, year, journal, journal type (eg, anesthesiology, pain management, addiction medicine, obstetrics/gynecology, etc), methodology, sample size, study objective, and salient findings, were summarized (Supplemental Digital Content 3, Appendix 3, https://links.lww.com/AA/E13).

RESULTS

The database searches yielded 994 publications for review (PubMed = 473 and Embase = 521). A PRISMA flow diagram for study screening and eligibility assessment is shown in Figure 1. Nineteen duplicate abstracts were removed, and 975 titles and abstracts were screened, with 884 screened as irrelevant with 6 resolved discrepancies (moderate interrater reliability κ = 0.57). There were then 91 full-text studies reviewed and assessed for eligibility, with 7 removed (duplicates, irrelevant, or unable to locate full text). There were 2 publications originally written in non-English (German and French). The final list included 84 full-text publications for complete review.

F1Figure 1.:

PRISMA flow diagram. PRISMA indicates Preferred Reporting Items for Systematic Reviews.

Table 1. - Clinical Questions and Corresponding Evidence Question Guideline Systematic review Narrative review Randomized trial Cohort study Case control/case series/case reports Opinion Predelivery pain management optimization 1. What comorbidities are associated with OUD that can affect peripartum pain management (anxiety, depression, and chronic pain)? Jones et al8 Korket al9 Ordeanet al13 Cengiz et al16 Jones et al18 Martin et al10 Gomar et al17 Smith et al14 Park et al11 Towers et al15 Eyler12 2. What comorbidsubstance use/abuse disorders are associated with OUD that can affect peripartum pain management (smoking and benzodiazepines)? Martin et al10 Hoflich et al19 Birnbach et al20 Tabi et al24 Eyler12 McCalla et al21 Robertson et al22 Schulman et al23 Ordean et al13 3. Should all patients with OUD have a predeliveryanesthesia consult? Wong et al25 Soens et al26 Cassidy and Cyna28 Eckeret al30 Wilder and Winhusen27 Reddi et al31 Wiegand et al29 4. Predelivery medication management: methadone Jones et al8 Brown32 Jones et al49 Ko et al51 Harter54 Jones and Terplan56 Faitot et al33 McNicholas et al50a Meyer et al52 Kliman55 a. For planned vaginal delivery, should the dose be continued, increased, reduced, or stopped in anticipation of the delivery admission? Wendling et al53 Fultz34 Wong et al25 Goff and O’Connor35 Ecker et al30 Wiegand et al29 Gopman36 Ordean et al13 b. For planned cesarean delivery, should the dose be continued, increased, reduced, or stopped in anticipation of the delivery admission? Jones 201237 Klaman et al38 Ludlow et al39 Lugo et al40 Mahoney et al41 Mozurkewichand Rayburn42 Pan and Zakowski43 Prithamand McKay44 Raymond et al45 Sen et al46 Tran et al47 Young et al48 Park et al11 Soens et al26 Wilder and Winhusen27 Martin et al10 5. Predelivery medication management: buprenorphine Jones et al8 Jones et al57 Jones et al49 Krans et al62 Leighton and Crock64 ACOG committee opinion1 Safleyand Swietlikowski58 McNicholas et al50a Tith et al63 Meyer et al65 Wendling et al53 Mittaland Suzuki66 a. For planned vaginal delivery, should the dose be continued, increased, reduced, or stopped in anticipation of the delivery admission? Stanhope et al59 Wiegandet al29 Harter54 Ecker et al30 Brown32 Faitot et al33 Gopman36 Jones et al4 Landau60 b. For planned cesarean delivery, should the dose be continued, increased, reduced, or stopped in anticipation of the delivery admission? Ludlow et al61 Mahoney et al41 Mozurkewich and Rayburn42 c. If continued, should the dose of buprenorphine be split? Pan and Zakowski43 Prithamand McKay44 Raymond et al45 Sen et al46 Tran et al47 Young et al48 Park et al11 Soens et al26 Wilder and Winhusen27 Martin et al10 6. Predelivery medication management: naltrexone Stanhope 201359 ACOG Committee opinion1 Tran 201747 a. For planned vaginal delivery, should the medication be continued or stopped in anticipation of the delivery admission? b. For planned cesarean delivery, should the medication be continued or stopped in anticipation of the delivery admission? c. If stopped, at what stage of pregnancy? Pain management in labor and delivery 1. Is there evidence for increased pain, analgesia dose requirement or increased use of analgesia during labor for patients on OUD treatment, including methadone, buprenorphine, and naltrexone? Souzdalnitski and Snegovskikh5 Kuczkowski67 Ludlow et al39 Thakrar et al71 Jones and Terplan56 Wolman et al68 Sander and Hays69 Fultz and Senay34 Ellis et al70 Wiegand et al29 2. Is there any evidence that the response to neuraxial opioids may be altered (less effective) in patients on buprenorphine? Kuczkowski67 Gupta et al72 3. Neuraxial Pan and Zakowski43 Martin et al73 Hoyt et al74 Ecker et al30 a. Should early epidural analgesia be recommended for patients with OUD? Silver et al75 Soens et al26 b. Should opioids in the epidural solution be increased, decreased, or omitted? c. Should the concentration of the local anesthetic be increased? d. Should nonopioid adjuvants be added to the epidural solution, including clonidine, epinephrine, dexmedetomidine, and/or neostigmine? 4. If the patient with OUD is not a candidate for neuraxial analgesia, is there a role for the following: Faitot et al33 Migliaccio et al76 Ecker et al30 a. Nitrous oxide? b. IV opioid PCA? (If PCA is used, is there a particular opioid that is optimal?) c. Ketamine? d. Dexmedetomidine? e. Other adjuvants? f. How do narcotic analgesic alternatives interact with MOUD management goals? Soens et al26 5. Treatment of postvaginal delivery pain a. If the patient has a high-order vaginal laceration, should long-actingopioids be administered through an indwelling epidural catheter? If so, what doses are recommended? b. Should NSAIDs be used? c. Should acetaminophen be used? d. Is there a role for the routine use of oral opioidsinhospital or at discharge? e. What is the role for other adjuvants for the treatment of postvaginal delivery pain? 6. Withdrawal Wolman et al68 a. If a patient with OUD experiences withdrawal during labor, how should it be treated? b. What are the potential interactions between MOUD and partial antagonists (eg, nalbuphine and butorphanol)?How should opioid-inducedintrapartum itching be managed in a patient on buprenorphine? 7. Monitoring a. Do patients with OUD require additional monitoring during or after labor? Postcesarean delivery pain management 1. Should history of OUD impact the planned mode of delivery (cesarean versus vaginal delivery)? Eyler12 2. Is there evidence for increased pain and analgesia intake after cesareandelivery for patients on OUD treatment, including methadone, buprenorphine, and naltrexone? Eyler12 Ellis et al70 Jones et al80 Jones et al8 Shainker et al77 Parad et al78 Vilkins et al79 Meyer et al65 Meyer et al52 Wendling et al53 3. Neuraxialanesthesia a. Should the usual dose of neuraxial opioids be increased, decreased, or should they be omitted? b. Should nonopioid adjuvants be added to the neuraxialanesthetic, including clonidine, epinephrine, dexmedetomidine, and/or neostigmine? c. Is there any evidence to suggest superiority of any specific nonopioid neuraxial adjuvant? 4. Postcesareandelivery pain management Brown32 Duzyj et al81 Kunycky82 Stanislaus et al84 Wasiluk et al85 Jones et al80 Leighton and Crock64 Vilkins et al83 a. What is the role for continuing neuraxial analgesia into the postpartum period? b. Should NSAIDs be used? c. Should acetaminophen be used? d. Is there a role for the routine use of oral opioidsin hospital? e. Are there special considerations regarding the type, dose, and quantity? f. Is there a role for the routine use of oral opioids at discharge? g. Are there special considerations regarding the type, dose, and quantity? h. What type of follow-up should be provided? i. What is the role for other adjuvants for the treatment of postcesarean pain? j. What is the role for regional anesthesia options, such as TAP, ESP, and QLB blocks, or continuous wound infiltration? Is any option more effective? k. What is the role for psychotherapeutic or behavioral interventions (eg, cognitive behavioral therapy) to address postcesarean pain? 5. Management of neuraxial opioid-induced side effects and complications in the patient on buprenorphine a. How should itching be managed (Nalbuphine? Dose?) b. How should respiratory depression be managed (Naloxone? Dose?) c. Is morphine-induced hypothermia more common in patients on buprenorphine? How should it be managed? 6. Monitoring a. Do patients with OUD require additional monitoring during or after cesarean delivery?

aSecond.

Abbreviations: ACOG, American College of Obstetricians and Gynecologists; ESP, erector spinae plane; IV, intravenous; MOUD, medications for opioid use disorder; NSAID, nonsteroidal anti-inflammatory drug; OUD, opioid use disorder; PCA, patient-controlled analgesia; QLB, quadratus lumborum block; TAP, transversus abdominis plane.


F2Figure 2.:

Publication type and counts according to journal type since 1975 indicating an increase in peer-reviewed publications on peripartum pain management in people with opioid use disorder over time. OBGYN indicates obstetrics and gynecology.

F3Figure 3.:

Study methodologies and counts within the study period 1975 to 2020. A disproportionate number of narrative review articles have been published, followed by retrospective studies and case reports. Only one systematic review and 5 randomized trials were published in the study period. RCT indicates randomized controlled trial.

Studies corresponding to the primary questions are shown in the Table, and study characteristics and details are shown in Supplemental Digital Content 3, Appendix 3, https://links.lww.com/AA/E13. One article was translated from German, and another was translated from French. Only 5 randomized trials (5.9%) and one systematic review (1.2%) were published in the study period. Most articles (n = 32; 38.1%) were published in obstetrics, gynecology, or perinatology journals, followed by anesthesiology (n = 22; 26.2%) and addiction medicine journals (n = 16; 19%; Figure 2). Peer-reviewed publications on peripartum pain management in pregnant people with OUD have steadily increased in volume over time (Figure 2), with most publications encompassing narrative review articles, retrospective cohort studies, and case reports or series (Figure 3).

Publications on Predelivery Pain Management Optimization

Most of the publications on predelivery pain management optimization for pregnant people with OUD consist of review articles, followed by retrospective chart reviews.1,8–15,19–31 Highlights include 6 case reports and series, 3 prospective observational studies, 2 guidelines, 1 randomized trial, and 1 committee opinion. Available evidence to guide medical care as it relates to pain management is notably limited.

The one randomized trial of 18 participants comparing pregnant people receiving methadone to those receiving buprenorphine found that after vaginal delivery, those treated with either buprenorphine or methadone reported adequate pain control (based on pain score ratings) with opioids and ibuprofen (main effect for medication group F[1, 19.3] = 0.01; P > .9).49 The methadone group used more ibuprofen postpartum (buprenorphine group decreased average ibuprofen use from 1725 to 1575 mg on average over postpartum days 1–5, during which the methadone group increased ibuprofen use from 1740 to 2040 mg on average). Another study investigated differences in pain management and analgesic medication use in 40 people receiving methadone or buprenorphine during pregnancy, matched to 80 nonopioid exposed pregnant people.19 After cesarean delivery, people with MOUD received fewer opioid analgesics (day of delivery, P = .03; day 1, P = .02), and nonsteroidal anti-inflammatory drugs (NSAIDs) were administered more frequently during surgery (MOUD group: 8/19 [42.1%]; comparison group: 4/38 [10.5%]; P = .006) and on postpartum day 3 (MOUD group: 10/19 [52.6%], comparison group: 9/38 [23.7%]; P = .029). Smoking status was an independent predictor of altered pain experience and had a strong influence on results in the MOUD group. Many currently available publications recommend continuing methadone and buprenorphine therapy throughout pregnancy and labor and delivery, rather than reducing or stopping the medication. These recommendations are primarily based on expert opinion that focused on chronic disease management throughout pregnancy86 rather than management of anticipated pain in labor and delivery. Most publications conclude that a multidisciplinary approach to patient management is necessary, with some recommending prenatal anesthesia consultation as part of that management.

Publications on Pain Management in Labor and Delivery

Articles on pain management in labor and delivery for people with OUD primarily included reviews, clinical opinions, case vignettes, retrospective studies, and a systematic review.5,29,34,39,56,67–71,87 The largest study on labor pain and labor analgesia in pregnant people with OUD was a retrospective chart review of 141 cases, published in 2004, that aimed to identify obstetric and perinatal outcomes in people using opioids (n = 91) or amphetamines (n = 50) during pregnancy; the epidural labor analgesia rate was 77%,39 and pharmacologic analgesia was used more often for labor and delivery (opioids, P = .007; amphetamines, P = .042). The possibility for return to use if opioids were used for labor analgesia was postulated by the authors of a 2014 systematic review, who emphasized the need for “good” labor analgesia because inadequate analgesia can instigate postpartum addiction recurrence and return to use.5 The authors suggested that to achieve good labor analgesia, neuraxial (not systemic) opioid doses need to be doubled or tripled in pregnant people with OUD,5 although these authors acknowledge the lack of available scientific data to guide appropriate dosing. Most published papers describe higher doses of opioids, if used, during labor and postpartum, due to the distinct phenomena of opioid tolerance and opioid-induced hyperalgesia. However, published opinions are conflicting on whether to use or to avoid systemic opioids. Opinions conflict due to concerns about risk for return to substance use that can be associated with exposure to systemic opioids (used for analgesia), as well as with poor pain control (which may result from avoidance of opioids).

Most publications, including the American College of Obstetricians and Gynecologists (ACOG) committee opinion,1 do not recommend medically supervised withdrawal during pregnancy, labor, and delivery. Comprehensive, multidisciplinary, individualized care planning—including chaplains, psychosocial services, and addiction medicine specialists—should be undertaken to optimize outcomes.5,71 Medically supervised withdrawal in pregnancy, labor, and delivery is not recommended over MOUD due to high return to opioid use rates (59%–90%), low detoxification completion rates, and limited data on maternal and neonatal outcomes beyond delivery.1 However, the lack of long-term outcomes and safe methods for medically supervised withdrawal in pregnancy or delivery urges more research to identify appropriate cases for which medically supervised withdrawal could be a noninferior and safe option in patients wishing to avoid medication during pregnancy.

Publications on Postcesarean Delivery Pain Management

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