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Review Articles

Optimal pain management for cesarean delivery

Holland, Erica MDa; Sudhof, Leanna S. MDb; Zera, Chloe MD, MPHb

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International Anesthesiology Clinics: Spring 2020 - Volume 58 - Issue 2 - p 42-49
doi: 10.1097/AIA.0000000000000272
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Cesarean delivery is the most common inpatient surgical procedure among women in the United States, affecting 1.4 million women annually.1,2 Opioids are routinely used for postcesarean pain management. However, the prevalence of opioid use disorder (OUD) is increasing,3 and as in other surgical fields, the obstetric community is reassessing its approach to postoperative pain management to reduce the risk for opioid misuse. One study using claims data found that 1 in 300 women will persistently use opioids at 1 year after delivery.4 In addition, many patients receive excess opioids at the time of discharge after cesarean delivery, leaving multiple tablets available for diversion.5,6 Health care providers must balance the risks of misuse and diversion against those of untreated pain. Several groups have aimed to decrease postcesarean opioid use through interventions including shared decision-making and postoperative order set changes.7,8 The optimal approach to pain management at the time of delivery remains a topic of active debate.

The prevalence of OUD among pregnant women in the United States has also risen dramatically over the last 20 years,9 presenting challenges to perioperative pain management at the time of cesarean delivery. Women with OUD often have higher opioid tolerance than opioid-naive women, requiring greater quantities of opioid medication to achieve similar pain control. Similarly, opioid-induced hyperalgesia often results in higher levels of postoperative pain for women with OUD, and those treated with buprenorphine may experience decreased effectiveness of adjuvant opioids due to buprenorphine’s high affinity for the mu opioid receptor.10

Postcesarean pain is multifactorial and includes incisional pain, contractions from uterine involution, bloating from bowel dysfunction that is common both postoperatively and postpartum, perineal discomfort with or without hemorrhoids if the cesarean was performed in the second stage of labor, breast engorgement, and nipple trauma. Furthermore, evidence suggests that the experience of postcesarean pain may be associated with preoperative sleep quality and anxiety,11,12 both of which are usually worse postpartum than before delivery. Adequate treatment of pain is particularly important postpartum due to the need to provide infant care, which requires patient mobility, and the potential for uncontrolled pain to increase the risk for postpartum depression. A prospective observational study of a cohort of 213 nulliparous women in Northern California without a history of chronic pain or opioid use demonstrated significant variability in the postpartum pain experience, with a wide range of days to opioid cessation (0 to 39 d)13 and disproportionately higher pain scores for patients in the top quintile of opioid use compared with the rest of the cohort.11 An optimal approach to pain management should therefore be multimodal and stepwise to achieve adequate individualized pain control, allow for mother-infant bonding and breastfeeding, and minimize unnecessary opioid exposure.

Current recommendations from national obstetric professional organizations including the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal Fetal Medicine (SMFM) include neuraxial analgesia and nonopioid adjunctive medication as first-line agents, with oral and parenteral opioids reserved for those whose pain is inadequately controlled; the guidelines also recognize that women with OUD will likely require higher quantities of opioids postpartum to achieve adequate analgesia. We will review options for pain management after cesarean delivery for both opioid-naive women and those with opioid dependence. We will then review system-wide approaches to help prevent OUD and improve quality of care for women with OUD.

Opioid-naive women

Standard approach

The vast majority of cesarean deliveries in the United States are performed under regional anesthesia.14 Intrathecal or epidural morphine provides 12 to 36 hours of analgesic effect and is the standard of care for immediate postoperative pain control, reflected by national obstetric and anesthesia societies’ guidelines.10,15,16 Multiple randomized controlled trials (RCTs) have shown the superiority of intrathecal or epidural opioids compared with intravenous (IV) or intramuscular (IM) opioids for postcesarean analgesia.17–19 Congruent with other examples in the literature, the rates of nausea and vomiting are similar irrespective of the route of opioid administration; however, pruritis is much more common among women who received neuraxial opioids (40% to 50%). Sedation or respiratory depression is more common with the IV or IM routes.17,18 Optimal dosing of intrathecal morphine is not known, and the tradeoff of increased duration of analgesia with the increased rate of side effects with higher morphine doses20–22 likely varies for each patient. Patient-controlled epidural infusion for postcesarean pain is not standard due to the duration of action of intrathecal morphine and the extra costs associated with the use of patient-controlled epidural23; however, it may be an option for patients who are expected to have prolonged postoperative pain. Neuraxial clonidine as an addition to intrathecal opioids may improve analgesic effect, but increases the risk of intraoperative hypotension (odds ratio, 2.8) and intraoperative sedation (odds ratio, 2.4).24

Standing acetaminophen and ibuprofen, administered orally or intravenously, should be initiated perioperatively and continued for the following 2 to 3 days.10,16 An RCT (n=214) of scheduled versus as-needed dosing of oral tramadol, diclofenac, and paracetamol in the first 48 hours after cesarean showed improved analgesia and patient satisfaction with scheduled dosing, without adverse maternal or neonatal effects.25 There has been interest in the perioperative use of IV acetaminophen for improved analgesia. A retrospective claims-based study of cesarean sections and hysterectomies showed less opioid use and shorter length of stay associated with patients who received IV acetaminophen as opposed to oral acetaminophen.26 A randomized, double-blinded, placebo-controlled trial of 60 patients in Turkey showed that IV acetaminophen administered 15 minutes before induction of general anesthesia decreased opioid requirements in the first 24 hours after cesarean.27 However, an RCT of 141 women undergoing elective cesarean delivery showed no difference in opioid consumption between women receiving 24 hours of IV versus oral acetaminophen; notably, women who received acetaminophen, IV or oral, had reduced opioid consumption compared with those who received no acetaminophen.28 The patients in this study all received intrathecal opioids and scheduled postoperative ketorolac. These studies together suggest that scheduled oral acetaminophen should be used in the first 2 days, with IV administration reserved for patients who have nausea and vomiting, as there has been no clearly demonstrated benefit of the IV route and the cost is significantly higher for the IV formulations. With respect to oral nonsteroidal anti-inflammatory drugs (NSAIDs), naproxen, diclofenac, and celecoxib have been shown to be effective compared with placebo, but there are no published studies comparing nonselective and selective COX2 inhibitors for postcesarean analgesia.29 NSAIDs should be avoided in patients with coagulopathy, severe thrombocytopenia, renal failure, and a history of gastric ulcers or gastric bypass surgery.

Oral oxycodone or hydrocodone should be administered as needed, targeting a maximum daily dose of 30 mg.10 Tramadol and codeine should be avoided in women who are breastfeeding due to concern for unpredictable metabolism and high levels of morphine in breastmilk resulting in neonatal sedation and respiratory depression.30,31 If insufficient, parenteral opioids may be used, although this would be expected to occur rarely in patients who are opioid-naive and tolerating liquids by mouth.

Women not requiring opioids before discharge should be discharged without an opioid prescription.10 Women requiring opioids at discharge may be engaged in a shared decision-making process to decide on the amount to be prescribed, understanding the anticipated improvement in pain, risks of ongoing opioid use, and the previously published median number of 20 tablets of 5-mg oxycodone needed by patients postdischarge.5–7,10 As mentioned above, the median number of postpartum days to cessation of opioids is 9 days, less than a week after discharge.13

Additional pharmacological considerations

Adjunct pharmacologic options for postcesarean analgesia have been studied, but not been found to have sufficient or consistent benefit to recommend for routine use. However, several of these options are useful for select patients, such as those with chronic pain, those who did not receive intrathecal morphine, or those who have failure of neuraxial anesthesia.

Nonopioid adjuncts

Perioperative dexamethasone has been shown to improve pain relief in patients undergoing cesarean under general anesthesia32 and improve pain and nausea in patients who have spinal anesthesia.33 However, a more recent placebo-controlled RCT in patients undergoing cesarean with intrathecal morphine found no difference in analgesic effect when administered dexamethasone.34 Currently, dexamethasone is frequently used immediately postoperatively to improve postoperative nausea and vomiting.29

Perioperative gabapentin has been shown to improve postcesarean analgesia at 24 hours postop in patients who received neuraxial anesthesia.35,36 However, due to a clinically small benefit and increased sedation associated with its use, gabapentin is not recommended for routine postcesarean analgesia. For patients with OUD or chronic pain, it may help prevent significant pain.

Ketamine is another medication administered perioperatively that can modulate the analgesic experience postcesarean by multiple mechanisms. One mechanism is its interaction with the mu opioid receptor; ketamine seems to delay desensitization and improve resensitization of the opioid signaling pathway and thus increase the duration of opioid analgesia.37 Two systematic reviews of ketamine for postcesarean analgesia showed improved analgesia in the first 24 hours postoperatively for patients who received regional anesthesia and improvement in nausea and vomiting.38,39 A randomized double-blinded placebo-controlled trial of low-dose ketamine after cord clamp in women undergoing elective cesarean under regional anesthesia showed no difference in analgesia in the first 24 hours; there was, however, improvement in the pain score at 2 weeks postpartum in women who received ketamine.40 Drowsiness and restlessness were more common in patients who received ketamine, but there were no reported hallucinations. In a minority of trials, dysphoria, sedation, and diplopia have also been reported as side effects.39 On the basis of this evidence, ketamine may be helpful in certain situations where the delivery is traumatic or where immediate postoperative pain is expected to be difficult to control.

Local anesthetic injection and various nerve blocks have also been described; the transversus abdominis plane (TAP) block seems to be the most well-studied and most commonly used procedure.41 TAP blocks are not superior to neuraxial analgesia as they only provide somatic relief, and they do not appear to provide additional analgesia in patients who have received intrathecal morphine.42,43 They may be effective for incisional pain in patients who have not received intrathecal morphine or have breakthrough pain after neuraxial opioids. The mean duration of effect is 9 hours.44 Local anesthetic toxicity is a reported complication due to the high volumes injected.45 An RCT comparing TAP block to continuous wound infusion46 and another comparing TAP block to postoperative bupivacaine wound infiltration47 in women who received neuraxial anesthesia, but no intrathecal morphine, showed no difference in postoperative analgesia between these methods. Local wound infiltration with anesthetics has also been shown to be effective in the absence of intrathecal morphine.48

A randomized double-blinded controlled trial of continuous wound infusion in patients who received intrathecal morphine showed improved postoperative analgesia with infra-fascial versus supra-fascial placement of the catheter, but there was no placebo, and no clear benefit of continuous wound infusion was demonstrated.49 A recent randomized placebo-controlled trial of liposomal bupivacaine injected in the incision at the time of fascial closure in patients who received intrathecal morphine showed no difference in postoperative pain scores or opioid requirements.50

Additional nonpharmacological considerations

Several nonpharmacologic tools with minimal patient safety concerns have been trialed for postcesarean pain relief: use of an abdominal binder, music, and aromatherapy. An RCT in which women were randomized to an abdominal binder placed in the operating room after cesarean versus no binder showed no difference in postoperative pain; however, 17 of the 88 patients assigned to the control arm dropped out due to requesting the binder for pain control.51 It is possible that the abdominal binder is helpful for patients once they are more than 24 to 48 hours postpartum. Limited studies suggest that lavender aromatherapy can reduce postcesarean pain.52,53 The data on periprocedural music are more mixed. An RCT in China showed that playing classical Chinese music before elective cesarean delivery reduced anxiety and pain in study participants,54 and an RCT in India showed that playing meditative music during emergent cesarean under spinal anesthesia improved postoperative pain and anxiety.55 However, an RCT in the United States showed that playing a patient-selected Pandora station before epidural placement in labor did not affect postprocedure pain and increased patient anxiety.56 Perhaps the choice of music matters. A systematic review and meta-analysis showed that preoperative, intraoperative, and postoperative music improves postoperative pain, especially when patients are conscious during surgery and when used preoperatively.57 Managing patient anxiety, with music or reassurance, is very likely to impact postoperative pain; anxiety as measured by State Trait Anxiety Inventory was a predictor for total cesarean analgesic requirements in patients undergoing elective cesarean at term under neuraxial anesthesia.58

Postcesarean pain control for women with OUD

The few studies addressing postcesarean pain control among women with OUD all describe multimodal approaches to postoperative analgesia.59–61 The SMFM advocates a combination of acetaminophen and NSAIDs in addition to opioids needed for pain control.10 Specifically, they recommend (1) neuraxial morphine, (2) acetaminophen 975 mg PO every 8 hours standing, (3) ketorolac 30 mg IV every 6 hours standing for 24 hours, followed by ibuprofen 600 mg PO every 6 hours, and (4) a short course of oxycodone (maximum daily dose 30 mg) as needed. Multiple adjuncts have been proposed and are discussed individually below.

Women with OUD, including those receiving medication-assisted treatment, have more pain and require more opioids postcesarean than women without OUD. A retrospective cohort control study of 33 women treated with methadone for OUD undergoing cesarean delivery demonstrated a significant increase in postoperative oxycodone use compared with matched controls (111.8±89.2 vs. 67.5±31.2 mg oxycodone equivalents during the 24 hours after delivery, P=0.02, and 80.1±48.4 vs. 47.2±19.1 mg per 24 hours from 25 to 72 hours after delivery).59 Oxycodone use was greatest during the first 24 hours postoperatively amongt cases and controls. Postoperative pain scores were also higher among women with OUD versus controls [5.3 (4.1-6.0) vs. 3.0 (2.2-3.9), P=0.001] despite treatment with greater quantities of opioids. Of interest, only 9 of the 33 women received long-acting intrathecal morphine, and quantities of acetaminophen and ibuprofen were not statistically different between cases and controls, highlighting opportunities for nonsystemic opioid approaches to pain.

A subsequent retrospective cohort control study of 19 women treated with buprenorphine for OUD found similar results. Women with OUD maintained on buprenorphine used significantly more oxycodone equivalents after cesarean delivery than controls during the first 24 hours postoperatively (113.9±52.7 vs. 79.5±19.6 mg P=0.036) and from 25 to 72 hours postoperatively (82.1±40.6 vs. 50.0±12.5 mg per 24 hours P=0.001).60 Only 6/19 received long-acting intrathecal opioids. Post-operative pain scores were similarly higher among women with OUD than controls [5.3 (4.1-6.0) vs. 3.0 (2.2-3.9)], although these patients received greater quantities of opioids and equivalent quantities of ibuprofen and acetaminophen to controls.

It is unclear whether there are differences in postoperative pain experience for women managed with methadone compared with those taking buprenorphine. Both retrospective studies above were carried out at the same institution and found similar post-cesarean opioid requirements for both women treated with methadone and those treated with buprenorphine for OUD at both time intervals.59,60 A retrospective cohort study of 185 women treated with methadone and 88 women treated with buprenorphine at a single institution over a 9-year period found no significant differences in opioid use between these groups postcesarean [97.7±65.6 vs. 85.1±73.0 mg morphine equivalent dose; mean difference, −12.6; 95% confidence interval (CI), −31.1 to 5.8].61

Although several studies address the quantities of opioids required in-hospital after cesarean delivery for women treated with methadone or buprenorphine for OUD, there is a gap in the literature on opioid requirements after discharge from the hospital. Experts recommend that decisions about opioid prescriptions at discharge incorporate a shared decision-making approach, balancing the risks of untreated pain, including relapse, with the potential for misuse and diversion of leftover tablets.10

Perioperative management of medication-assisted therapy (MAT) for OUD

Buprenorphine

Buprenorphine acts with high affinity at opioid receptor sites as a partial mu agonist and a kappa antagonist. This poses a unique challenge to perioperative pain management as high receptor affinity may decrease the effectiveness of opioid analgesia. In the nonobstetric literature, authors have debated the optimal approach to perioperative pain management and specifically the question of preoperative buprenorphine discontinuation.62–64 One commentary proposes an algorithm that recommends preoperative discontinuation of buprenorphine for women with expected moderate to severe pain after surgery and continuation of buprenorphine for women with expected minimal pain after surgery or for those at high risk for relapse.62

Because of the concern for relapse and the risks associated with reinduction during the stressful and potentially destabilizing postpartum period, SMFM, ACOG, and the American Society of Addiction Medicine all recommend that pregnant women continue buprenorphine before and after cesarean delivery.10,65 Several studies of pregnant women undergoing cesarean delivery without cessation of buprenorphine demonstrated that postoperative pain can be effectively managed with a multimodal analgesic regimen combining opioids with acetaminophen and NSAIDs.60,66 Moreover, collective data from 2 retrospective cohort control studies of women with OUD undergoing cesarean delivery found that women treated with methadone do not have superior pain control to women treated with, and continued on, buprenorphine perioperatively.60 The authors concluded that their data further support the use of buprenorphine throughout the delivery process with multimodal analgesia including opioids as needed for pain control.

Methadone

Methadone presents fewer perioperative challenges as it is a full opioid agonist. Several studies demonstrate effective pain control when opioid analgesia is used in conjunction with methadone for postoperative pain control.66,59,63 Historically, concern has existed that women will use surgery as an opportunity to seek additional opioids for the purpose of misuse.63,59 However, a retrospective cohort study demonstrated that women treated with methadone for OUD required the same percentage increase in opioid medication postoperatively as did controls.59

Postpartum dose adjustments of methadone and buprenorphine

Little data exist to guide dose adjustments of methadone and buprenorphine in the immediate postpartum period. A secondary analysis of 10 patients treated with methadone and 8 patients treated with buprenorphine demonstrated dose stability in the month postpartum; only 3 of 18 participants needed any variation in dose during the 7-week study period.67 Participants received mean buprenorphine doses of 18.8 mg (SD=3.8, range=14 to 24 mg) 3 weeks before delivery versus 19 mg (SD=3.7, range=14 to 24 mg) 4 weeks postpartum. Methadone doses were 79 mg (SD=35.7, range=25 to 100 mg) before delivery versus 78.5 mg (SD=35.4, range=25 to 100 mg) 4 weeks postpartum. ACOG recommends against routine dose reductions in postpartum methadone and buprenorphine in the absence of oversedation.

Adjunctive analgesia for women with OUD

Patient-controlled epidural analgesia (PCEA)

PCEA after cesarean section may be a useful approach for women with OUD; however, data are limited. In a retrospective cohort control study of 33 women with OUD maintained on methadone undergoing cesarean delivery, 3 received PCEA. Of these, 2 did not require any opioids and 1 required only 20 mg oxycodone during the 24 hours of PCEA infusion. One patient maintained on methadone who required 140 mg oxycodone equivalents in the first 4 hours postoperatively did not require any further opioids for the next 32 hours after PCEA placement.59 A case series of 19 women treated with buprenorphine for OUD in which 2/19 received PCEA for intractable pain similarly demonstrated that it was effective.60 A retrospective cohort study comparing postcesarean opioid use among women with OUD treated with methadone versus buprenorphine found that women treated with buprenorphine were 1.6 times more likely to receive an epidural for intraoperative anesthesia (95% CI, 1.0-2.5) and 2.7 times more likely to receive a combined spinal-epidural than women treated with methadone (95% CI, 1.2-6.0).61 Larger studies are needed to assess the comparative efficacy of PCEA versus other adjuvants among women with OUD.

Long-acting intrathecal opioids

Data are similarly limited for the use of long-acting intrathecal opioids. In 2 retrospective cohort-control studies assessing opioid use among women with OUD after cesarean delivery, a minority received long-acting intrathecal opioids. Long-acting intrathecal morphine or meperidine was administered at the discretion of the anesthesia team for 7 of 19 women treated with buprenorphine and 1 of 19 controls (P=0.09). These women subsequently required oxycodone quantities that were not statistically different from their respective groups60; however, patients who received long-acting intrathecal opioids likely differed from those who did not, limiting the conclusions that can be drawn from this study. Similarly, the 9 of 33 women treated with methadone who received long-acting intrathecal opioids at cesarean delivery required more oxycodone postoperatively than the 7 of 33 controls who received long-acting intrathecal opioids. However, a comparison of opioid use between the women treated with methadone who received intrathecal opioids and those who did not was not performed.59 Additional research is needed to assess the benefit of long-acting intrathecal opioids as adjuvant analgesia for women with OUD.

Neuraxial clonidine

A case series of 7 patients undergoing scheduled cesarean section reported the substitution of clonidine/bupivacaine for a standard fentanyl/bupivacaine solution.68 All patients received a combined spinal-epidural with 12 mg bupivacaine infused in the spinal. Postoperatively, a 0.1% bupivacaine/1.2 μg/mL clonidine epidural infusion was initiated in the recovery room and maintained at 10 mL/h for 24 hours. One patient requested epidural removal. No patient required any adjunctive oral or IV opioid analgesia, and pain scores after catheter removal ranged from 0 to 5 on a scale from 0 to 10. Other reviews have suggested adding clonidine to the fentanyl/bupivacaine solution instead of as a fentanyl replacement.69 The possibility of hypotension, a potential side effect of clonidine, and need for monitoring, are other important considerations. Overall, this approach appears promising for women with OUD and requires further study.

Thoracic epidural analgesia

One case in a series of 4 women treated with buprenorphine for OUD at the time of cesarean delivery involved preoperative placement of a thoracic epidural catheter at T10-11, followed by a spinal at L2-3 with 25 mg bupivacaine.70 Postoperatively, the epidural was infused with bupivacaine 0.0625% at 4 mL/h. The patient’s maximum pain score was 1/10 during the first 24 hours after delivery and 0/10 during the second 24 hours after delivery, during which she was able to ambulate without assistance. Two hours after her epidural catheter was removed, her pain score remained 0/10. No pain scores are reported after this time point. The combination of analgesia with mobility offered by this technique is appealing, although pain control after catheter removal remains unclear. Further investigation is warranted.

Regional blocks

No studies have specifically looked at the efficacy of TAP blocks among women with OUD after cesarean delivery. A multi-center trial of TAP blocks versus PCEA was initiated in 2014 and discontinued due to lack of enrollment.71 This approach has led to decreased postoperative opioid use among opioid-naive women, and warrants further study in the population of women with OUD.72

Dexmedetomidine

A case report of a pregnant woman treated with 80 mg/d methadone for OUD describes that poorly controlled pain after cesarean delivery improved with dexmedetomidine, an alpha-2-adrenoreceptor agonist.73 Intraoperatively, the patient received a spinal infused with 12 mg bupivacaine, 10 μg fentanyl, and 0.2 mg morphine. Thirty minutes after surgery, she reported 8/10 pain and received 10 mg IV morphine, 30 mg ketorolac, and 2 mg hydromorphone over 2.5 hours, with no improvement in pain. A dexmedetomidine infusion was initiated and titrated from 0.2 to 0.7 μg/kg/h, with a subsequent pain score of 0/10. Methadone was held during the dexmedetomidine infusion. The infusion was stopped after 20 hours and her pain score was 4/10, at which point she was transitioned to oxycodone and acetaminophen. Continuous respiratory monitoring may be required, particularly if used in conjunction with opioids or other sedative agents.69 Further study is needed to evaluate whether this approach is useful for women with OUD and intractable postcesarean pain.

Ketamine

Low-dose ketamine has been proposed to potentiate the effects of opioids without causing the psychoactive side effects seen at higher doses.10 Intraoperative ketamine has been shown in opioid-naive women to decrease pain scores at 2 weeks after cesarean delivery, although it did not alter acute pain after cesarean.40 One case in a series of 8 women treated with buprenorphine for OUD describes a patient who presented with intrauterine fetal demise and underwent cesarean section with general anesthesia. A ketamine infusion was initiated intraoperatively at 8 mg/h and was continued postoperatively for 24 hours in conjunction with a fentanyl PCA, acetaminophen, and ibuprofen. Her buprenorphine dose of 8 mg TID was continued throughout her hospital stay. The authors report that the patient was satisfied with her pain control. No postdischarge data were available. Additional data are needed to further characterize the role for ketamine in postoperative analgesia for women with OUD.

Gabapentin

Gabapentin has been used as an adjunctive analgesic in multimodal pain management pathways across disciplines and has been proposed for use among postpartum women with OUD.69 An RCT was registered with clinicaltrials.gov in 2017 to evaluate the effects of oral gabapentin on postcesarean opioid use and pain scores; however, it was withdrawn due to lack of enrollment.74 The ACOG does not recommend gabapentin for routine postcesarean pain control due to lack of evidence, but suggests that it can be considered as part of a multimodal pain management strategy for women with chronic pain or those with intractable pain. Further research is needed to evaluate the possible impact of this medication on postcesarean analgesia among women with OUD.

Special considerations

Naltrexone

There is a paucity of data to guide the management of antenatal or postpartum care of women treated during pregnancy with naltrexone, a nonselective opioid receptor antagonist that Food and Drug Administration approved for the use of OUD. Naltrexone carries potential advantages over opioid agonists in the pregnant population; however, use in pregnancy is not well studied. Specifically, use of naltrexone avoids the fetal exposure to opioids accompanying agonists and the associated potential for neonatal opioid withdrawal syndrome. However, this treatment presents unique challenges in the perioperative setting, as its mechanism of action can significantly decrease the effectiveness of other opioids.75 Although robust data are lacking, experts recommend optimizing nonopioid and nonpharmacologic analgesia for women treated with naltrexone who require cesarean delivery. High doses of opioids may overcome the naltrexone receptor occupancy, but close monitoring is required in this context due to the risk of respiratory depression.10

Cesarean at the time of active withdrawal

Patients presenting in active withdrawal and requiring cesarean delivery should theoretically have intraoperative and postoperative pain that is more easily managed than those already maintained on an opioid antagonist. Patients in active withdrawal can be initiated on maintenance therapy with methadone or buprenorphine after surgery and managed with a multimodal approach to pain control in the same manner as those women previously stabilized on medication-assisted treatment.10 Additional respiratory monitoring and analgesia tailoring may be required if the patient is using other drugs that influence mental status such as benzodiazepines.

Trauma informed care

Acute pain in the 24 hours after childbirth is associated with postpartum depression and the development of chronic pain independent of delivery mode.76 Many women with OUD have co-existing psychiatric comorbidities including posttraumatic stress disorder secondary to sexual trauma, increasing the risk of postpartum depression.65 Moreover, surgery is associated with postoperative exacerbation of posttraumatic stress disorder.77 A trauma-informed approach to postcesarean pain management, acknowledging the association between preexisting psychiatric comorbidities, and postoperative sequelae, may play a role in mitigating morbidity.

Breastfeeding

Infant exposure to both methadone and buprenorphine through breast milk is minimal. Methadone and buprenorphine levels in human milk are both <3% of the maternal weight-adjusted dose.78 In addition to well-established benefits in a general population, breastfeeding is associated with lower neonatal opioid withdrawal syndrome scores, less pharmacologic treatment requirements for neonates, and shorter length of hospital stay among neonates of women treated with methadone or buprenorphine for OUD. The American Academy of Pediatrics, ACOG, and SMFM encourage breast feeding for women who are stable on medication-assisted therapy.10,65,78

System-level approaches to optimizing pain control at cesarean delivery

Adapting an enhanced recovery after surgery (ERAS) paradigm to cesarean delivery is one way to incorporate preoperative counseling, shared decision-making, and a stepwise multimodal approach to make postcesarean pain control both standardized and multidisciplinary. Preoperative and postoperative steps to optimize return of bowel function, early mobilization, measures to reduce surgical-site infection, venous thromboembolism prophylaxis, and minimization of opioid analgesia are key tenets of all ERAS pathways. Currently, ACOG has not yet endorsed an ERAS pathway for cesarean delivery; however, there is an ERAS Society Guideline for cesarean delivery,79–81 and the Society of Obstetric Anesthesia and Perinatology (SOAP) recently published a consensus statement on Enhanced Recovery After Cesarean.82 The implementation of an ERAS pathway after cesarean delivery reduced inpatient and outpatient opioid exposure in the Kaiser Permanente system.83 Another study found that implementation of an ERAS pathway for cesarean was associated with a 4.9 hour decrease in hospital stay, translating into lower costs (−$642.85 per patient, P<0.001).84 Adoption of ERAS for cesarean therefore has the potential to increase the value of maternity care by improving quality and reducing costs in addition to reducing the contribution of cesarean deliveries to the opioid epidemic.

The Alliance for Innovation in Maternal Care (AIM) is a national quality improvement organization representing a wide range of stakeholders, including the American Society of Anesthesiologists, the SOAP, and the American Association of Nurse Anesthetists. Among the maternal safety bundles that have been developed, the OUD bundle is uniquely focused both on mitigation of the underlying epidemic through opioid stewardship and on optimal multidisciplinary management of opioids at the time of delivery. Specifically, AIM calls for the development of care pathways and standardized pain management protocols for women with OUD, multidisciplinary case review teams for evaluation of adverse outcomes, and continuing education for all providers caring for women with OUD during pregnancy. Anesthesiology providers are critical team members to engage and lead quality improvement efforts to optimize pain management for cesarean delivery.

Conclusions

Optimal pain control after cesarean delivery includes a multimodal strategy utilizing intrathecal or epidural opioids, acetaminophen, and nonsteroidal anti-inflammatory agents as a first line, with oral or parenteral opioids reserved for breakthrough pain (Table 1). Additional options are relatively understudied and should be individualized to patient needs. Women with stable OUD should continue medication-assisted therapy perioperatively; however, data are limited to guide pain control beyond standard approaches. System-wide strategies should include implementation of ERAS protocols and maternal safety bundles to achieve optimal pain management, minimize excess opioid prescribing, and provide standardized multidisciplinary care for women with OUD.

Table 1
Table 1:
Strategies for pain control by population

Conflict of interest disclosure

The authors declare that they have nothing to disclose.

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