Effective pain management should be a key priority in women undergoing cesarean delivery. Suboptimal perioperative pain management is associated with chronic pain, greater opioid use, delayed functional recovery, impaired maternal–fetal bonding, and increased postpartum depression. Severe acute postoperative pain is also strongly associated with persistent pain after cesarean delivery. Multimodal analgesia is the core principle for cesarean delivery pain management. The use of neuraxial morphine and opioid-sparing adjuncts such as scheduled nonsteroidal anti-inflammatory medications and acetaminophen is recommended for all women undergoing cesarean delivery with neuraxial anesthesia unless contraindicated. Additional analgesic and opioid-sparing options such as wound instillation of local anesthetics, transversus abdominis plane blocks, dexamethasone, gabapentin, and ketamine may be used as appropriate in women at risk of severe postoperative pain or in women whose postoperative pain is not well controlled despite standard analgesic regimes.
Cesarean delivery is the most common major surgical procedure . In the United States in 2014, 1.28 million women underwent cesarean delivery, accounting for 32% of all births . For obstetric anesthesia providers caring for women undergoing cesarean delivery, the delivery of effective postoperative analgesia is of primary importance for several reasons. First, women rank avoidance of pain during and after cesarean delivery as their highest priority . Second, acute pain after cesarean delivery may develop into persistent pain, which may result in greater opioid use, delayed functional recovery, and increased risk of postpartum depression . Third, ensuring effective analgesia can optimize maternal–neonatal bonding and breastfeeding after delivery .
Chronic pain after cesarean delivery
Chronic incisional pain and pelvic pain are well described after cesarean delivery. The reported incidence of persistent incisional pain or the need for analgesia beyond 6 months after cesarean delivery varies significantly , with reported rates ranging between 1% and 18% . Compared to vaginal delivery, the risk of chronic pain and impaired health-related quality of life is higher following cesarean delivery . The incidence and intensity of persistent pain appear to be lower after cesarean delivery than after other nonobstetric surgeries. It has been hypothesized that pregnancy and/or oxytocin may protect against the development of chronic postsurgical neuropathic pain ; however, this observation requires further evaluation.
Clinical interventions to decrease the incidence and severity of chronic postcesarean pain have not been consistently effective. This may be due to the analgesic drugs having a modest effect, or studies being underpowered because of the low incidence of chronic pain . To reduce the likelihood of chronic postoperative pain, several approaches have been recommended. Neuraxial and/or regional anesthesia may be associated with a lower incidence of persistent pain after cesarean delivery and hysterectomy than general anesthesia . Multimodal perioperative analgesia consisting of intravenous ketamine and neuraxial clonidine may reduce central sensitization and decrease the incidence and severity of chronic pain . In one study, the incidence of chronic pain after cesarean delivery decreased with higher doses than lower doses of spinal local anesthetics and the use of anti-inflammatory drugs . There are several psychosocial and pathophysiological factors, e.g., anxiety, pain catastrophizing, and depression, that are associated with an increase in the likelihood of chronic postoperative pain . Severe acute postoperative pain is one of the most prominent factors associated with persistent pain after cesarean delivery . Therefore, severe acute postcesarean pain may help identify women at risk of persistent pain, and effective treatment of acute postoperative pain may help reduce the risk of chronic pain after cesarean delivery.
Neuraxial opioids and adjuvants
Neuraxial anesthesia is recommended as the preferred anesthetic modality for cesarean delivery by the American Society of Anesthesiologists and the American Pain Society . Most cesarean deliveries in the United States are performed with neuraxial anesthesia (spinal, epidural, or combined spinal epidural techniques); spinal anesthesia is the most common technique for elective cesarean deliveries .
Neuraxial opioids provide high-quality postcesarean delivery analgesia . Lipophilic opioids such as fentanyl can optimize the quality of intraoperative anesthesia; however, these drugs have a relatively short duration of action (median effect of neuraxial fentanyl is 4 h) . In comparison, hydrophilic opioids such as morphine provide a longer duration of action. Intrathecal morphine has a duration of action between 14 and 36 h . The optimal dose of intrathecal morphine remains uncertain. The intrathecal morphine dose is related to the duration of effect but not to analgesic efficacy. Doses greater than 100 mcg (up to 250 mcg) prolong the time to first request for additional analgesia by a mean difference of 4.5 h compared to doses between 50 and 100 mcg (time to first analgesic request was 9.7–26.6 h for 50–100 mcg dose and 13.8–39.5 h for doses greater than 100 mcg) . The incidence of opioid-related side effects, including nausea, vomiting, and pruritus, may increase with escalating doses of intrathecal morphine. In a 2016 meta-analysis, the odds of nausea or vomiting [OR 0.44 (95% CI, 0.27, 0.73)] and pruritus [OR 0.34 (95% CI, 0.20, 0.59)] were lower with smaller doses of intrathecal morphine (50–100 mcg) than with higher doses (>100 mcg) . Importantly, respiratory depression did not occur in any study in this meta-analysis. Although women with obstructive sleep apnea and morbid obesity are potentially at increased risk of respiratory depression , neuraxial opioids are recommended because the risk of respiratory depression is higher if patients are exposed to intravenous opioids .
For women with pre-existing labor epidural catheters who require intrapartum cesarean delivery, epidural top-up is advocated to provide cesarean anesthesia . In this setting, epidural morphine is recommended to optimize postoperative analgesia. Prior studies have shown that the analgesic efficacy of epidural morphine (2–3 mg) is similar to intrathecal morphine (75–200 mcg) . The recommended optimal dose of epidural morphine is between 2 and 4 mg; doses greater than 4 mg have limited additional analgesic benefit but are associated with a higher incidence of dose-related adverse effects .
On occasion, when preservative-free morphine is unavailable, clinicians may consider using intrathecal hydromorphone. High patient satisfaction rates and similar adverse-effect profiles have been reported with hydromorphone compared with morphine . However, because morphine is more hydrophilic, the duration of analgesia after single-dose administration is longer than that after hydromorphone administration. The estimated dose ratio of intrathecal morphine to intrathecal hydromorphone is 2:1 .
Neuraxial clonidine has been studied as an adjunct to local anesthetics and opioids. Clonidine is associated with hypotension and sedation, and its US Food and Drug Administration package insert has a black box warning against its use in obstetrics because of the risk of hemodynamic instability . Therefore, clonidine should be reserved for patients at risk of severe pain after cesarean delivery, such as those with a known history of chronic pain. Neostigmine has historically not been recommended for neuraxial administration because of its high incidence of nausea . The American Pain Society does not advise administering neostigmine as a neuraxial adjuvant, citing a lack of clear benefit and insufficient evidence of safety .
Continuous and patient-controlled epidural infusions
Continuous epidural infusions and patient-controlled epidural analgesia may be considered for maintaining neuraxial analgesia beyond the perioperative period. However, postoperative epidural analgesia has several disadvantages: (i) maternal mobility may be reduced because of the need to transport an infusion pump, (ii) postoperative pharmacothromboprophylaxis becomes complicated, (iii) nursing workload is increased, and (iv) hospitals’ and patients’ costs are increased . For most healthy women with uncomplicated cesarean delivery, intrathecal or epidural opioids delivered by a “single-shot” spinal, epidural, or combined spinal epidural technique, in combination with systemic nonsteroidal anti-inflammatory drugs (NSAIDs), provides adequate postcesarean analgesia. Epidural catheter-based techniques may be considered in special circumstances (e.g., women with a history of chronic pain).
Neuraxial opioids and adjuvants
Neuraxial anesthesia is recommended as the preferred anesthetic modality for cesarean delivery by the American Society of Anesthesiologists and the American Pain Society . Most cesarean deliveries in the United States are performed with neuraxial anesthesia (spinal, epidural, or combined spinal epidural techniques); spinal anesthesia is the most common technique for elective cesarean deliveries .
Neuraxial opioids provide high-quality postcesarean delivery analgesia . Lipophilic opioids such as fentanyl can optimize the quality of intraoperative anesthesia; however, these drugs have a relatively short duration of action (median effect of neuraxial fentanyl is 4 h) . In comparison, hydrophilic opioids such as morphine provide a longer duration of action. Intrathecal morphine has a duration of action between 14 and 36 h . The optimal dose of intrathecal morphine remains uncertain. The intrathecal morphine dose is related to the duration of effect but not to analgesic efficacy. Doses greater than 100 mcg (up to 250 mcg) prolong the time to first request for additional analgesia by a mean difference of 4.5 h compared to doses between 50 and 100 mcg (time to first analgesic request was 9.7–26.6 h for 50–100 mcg dose and 13.8–39.5 h for doses greater than 100 mcg) . The incidence of opioid-related side effects, including nausea, vomiting, and pruritus, may increase with escalating doses of intrathecal morphine. In a 2016 meta-analysis, the odds of nausea or vomiting [OR 0.44 (95% CI, 0.27, 0.73)] and pruritus [OR 0.34 (95% CI, 0.20, 0.59)] were lower with smaller doses of intrathecal morphine (50–100 mcg) than with higher doses (>100 mcg) . Importantly, respiratory depression did not occur in any study in this meta-analysis. Although women with obstructive sleep apnea and morbid obesity are potentially at increased risk of respiratory depression , neuraxial opioids are recommended because the risk of respiratory depression is higher if patients are exposed to intravenous opioids .
For women with pre-existing labor epidural catheters who require intrapartum cesarean delivery, epidural top-up is advocated to provide cesarean anesthesia . In this setting, epidural morphine is recommended to optimize postoperative analgesia. Prior studies have shown that the analgesic efficacy of epidural morphine (2–3 mg) is similar to intrathecal morphine (75–200 mcg) . The recommended optimal dose of epidural morphine is between 2 and 4 mg; doses greater than 4 mg have limited additional analgesic benefit but are associated with a higher incidence of dose-related adverse effects .
On occasion, when preservative-free morphine is unavailable, clinicians may consider using intrathecal hydromorphone. High patient satisfaction rates and similar adverse-effect profiles have been reported with hydromorphone compared with morphine . However, because morphine is more hydrophilic, the duration of analgesia after single-dose administration is longer than that after hydromorphone administration. The estimated dose ratio of intrathecal morphine to intrathecal hydromorphone is 2:1 .
Neuraxial clonidine has been studied as an adjunct to local anesthetics and opioids. Clonidine is associated with hypotension and sedation, and its US Food and Drug Administration package insert has a black box warning against its use in obstetrics because of the risk of hemodynamic instability . Therefore, clonidine should be reserved for patients at risk of severe pain after cesarean delivery, such as those with a known history of chronic pain. Neostigmine has historically not been recommended for neuraxial administration because of its high incidence of nausea . The American Pain Society does not advise administering neostigmine as a neuraxial adjuvant, citing a lack of clear benefit and insufficient evidence of safety .
Continuous and patient-controlled epidural infusions
Continuous epidural infusions and patient-controlled epidural analgesia may be considered for maintaining neuraxial analgesia beyond the perioperative period. However, postoperative epidural analgesia has several disadvantages: (i) maternal mobility may be reduced because of the need to transport an infusion pump, (ii) postoperative pharmacothromboprophylaxis becomes complicated, (iii) nursing workload is increased, and (iv) hospitals’ and patients’ costs are increased . For most healthy women with uncomplicated cesarean delivery, intrathecal or epidural opioids delivered by a “single-shot” spinal, epidural, or combined spinal epidural technique, in combination with systemic nonsteroidal anti-inflammatory drugs (NSAIDs), provides adequate postcesarean analgesia. Epidural catheter-based techniques may be considered in special circumstances (e.g., women with a history of chronic pain).
Opioid-sparing analgesic options
Supplemental nonopioid medications are important for optimizing the quality of postoperative analgesia and lowering the requirement for oral or intravenous opioids in the postpartum period. This is particularly important because up to 1 in 300 opioid-naïve women become persistent users of opioids after cesarean delivery . In a opioid-naïve population, the odds of chronic opioid use was significantly greater among women one year after cesarean delivery than those in a randomly selected 1-year period in nonsurgical patients (odds ratio 1.28 [95% CI, 1.12, 1.46]) . The use of multimodal analgesia (e.g., NSAIDs and acetaminophen) provides superior pain relief and decreases the need for supplemental opioid use compared to a unimodal analgesic approach.
Nonsteroidal anti-inflammatory drugs
NSAIDs are a key component of multimodal postoperative pain management. NSAIDs have a 30%–50% opioid-sparing effect , which may reduce the incidence of opioid-related adverse effects after surgery . For healthy women undergoing uncomplicated cesarean delivery, scheduled NSAIDs should be given routinely in the postpartum period. No studies have compared the analgesic efficacy of different NSAID formulations, and NSAID use should be based on hospital drug availability, breastfeeding transfer, and drug safety data ( Table 1 ). There are limited studies examining the efficacy of cyclooxygenase-2 (COX2) inhibitors for postcesarean delivery analgesia. Evidence suggests that COX2 inhibitors have limited postcesarean analgesic efficacy ; therefore, their use should be reserved for patients who are intolerant of nonselective NSAIDs.
| Analgesic | Relative infant dose (%) |
|---|---|
| Opioids | |
| Morphine | 5.8–10.7 |
| Fentanyl | 0.9–3 |
| Oxycodone | 1.5–8 |
| Hydrocodone | 1.6–3.7 |
| Tramadol | 2.4–2.9 |
| Nonopioid analgesics | |
| Ibuprofen | 0.1–0.7 |
| Ketorolac | 0.2–0.4 |
| Celecoxib | 0.3 |
| Acetaminophen | 1.3–6.4 |
| Dexamethasone | No data |
| Gabapentin | 1.3–6.5 |
Acetaminophen
In the perioperative setting, acetaminophen has an opioid-sparing effect of approximately 20% . By providing effective analgesia with minimal adverse effects and breastmilk transfer , acetaminophen is an important component of postcesarean multimodal analgesia. Although as-needed acetaminophen–opioid combination drugs are often prescribed for breakthrough pain, scheduled acetaminophen with as-needed oral opioids is recommended. In a retrospective study comparing opioid use with two different multimodal regimens, cumulative opioid use was significantly lower among patients receiving scheduled acetaminophen regimens ( Fig. 1 ) . This approach also limits the likelihood of inadvertently prescribing acetaminophen doses that are higher than the daily recommended maximum dose .
Combining acetaminophen and NSAIDs has an additive analgesic effect , and both drugs should be administered after cesarean delivery. Given the higher cost and lack of clear evidence, routine administration of intravenous NSAIDs or intravenous acetaminophen is not recommended; oral administration is suggested . However, intravenous drug delivery may be worthwhile for patients who cannot tolerate oral formulations or for those who develop postoperative nausea or vomiting.
Dexamethasone
Glucocorticoids have analgesic, antiemetic properties and anti-inflammatory effects. A single preoperative dose of dexamethasone can reduce postoperative pain compared to placebo among patients undergoing surgery with general anesthesia . However, dexamethasone use was associated with marginally higher blood glucose levels 24 h postoperatively and thus should be avoided in patients with insulin resistance . In meta-analyses that included studies of patients undergoing a variety of surgical procedures, a single-dose perioperative dexamethasone did not impair wound healing or increase the risk of infection . The addition of a single preoperative dose of dexamethasone improved postcesarean analgesia and decreased the incidence of nausea and vomiting . Doses between 1.25 and 20 mg were described, and the optimal dose was not determined .
Gabapentin
There has been growing interest in the use of gabapentin as either preemptive analgesia or to supplement postoperative analgesia. Gabapentin has been shown to decrease opioid-associated vomiting and pruritus . However, gabapentin has notable side effects, including sedation [number needed to harm (NNH) = 8–35] and dizziness (NNH = 12) . In the setting of cesarean delivery, initial studies suggested that a single preoperative dose of gabapentin 600 mg decreased postcesarean delivery pain and increased maternal satisfaction . Subsequent studies have not validated these findings . Gabapentin is a neurotropic drug with a high umbilical vein-to-maternal vein ratio that limits preemptive use, and breastmilk transfer is a potential concern ( Table 1 ) . Because strong evidence is lacking regarding a significant maternal analgesic effect and because of concerns for maternal and neonatal side effects, gabapentin is not recommended as a routine postcesarean analgesic. However, the benefit–risk ratio of administering gabapentin may be favorable in patients with a history of chronic pain or postoperative pain unrelieved by standard treatment protocols.
Ketamine
The efficacy of ketamine as a postcesarean analgesic adjunct is uncertain. For patients undergoing cesarean delivery with spinal anesthesia with intrathecal morphine and scheduled ketorolac, compared to saline, a single dose of 10 mg ketamine, administered after delivery, did not offer any acute postoperative pain or opioid-sparing benefits . However, ketamine may improve perioperative analgesia if intrathecal morphine is not provided . Side effects of ketamine include hallucinations, visual effects, disturbing dreams, dizziness, and lightheadedness . A single intraoperative dose of 10 mg ketamine has been associated with lower pain scores 2 weeks postpartum , and the drug may have a role in patients with chronic pain or women at risk of developing persistent incisional pain after cesarean delivery.
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