A 25-year-old patient, gravida 3 para 2, at 38 weeks’ gestation, with a body mass index of 36 kg/m2, presented for elective repeat cesarean delivery (CD). She developed severe pruritus after her 2 previous CDs performed under spinal anesthesia with bupivacaine (10 mg), preservative-free morphine (200 mcg), and fentanyl (20 mcg). Given her history, spinal anesthesia was performed with bupivacaine (12 mg) and preservative-free morphine (100 mcg). Ondansetron (4 m g) was administered 30 minutes before the spinal, and ketorolac (30 mg intravenously) was given at the end of the surgical procedure and 15 mg every 6 hours, for a total of 24 hours. The patient did not experience pruritus, and the visual analog pain score after 24 hours was 2, on a scale of 0 to 10.
Adequate postoperative analgesia is a crucial consideration for women undergoing CD. Post-CD pain is the primary concern for expectant mothers.1 Uncontrolled pain during this period prolongs recovery and interferes with the mother–neonate interaction. Conversely, appropriate analgesia decreases thromboembolic complications by allowing for early ambulation, thereby reducing a leading cause of maternal morbidity and mortality.
Incidence of Acute and Chronic Post-CD Pain
Eisenach et al found that 1 in 5 women experience severe acute pain after CD.2 Severe post-CD pain was associated with 2.5 times higher risk for postpartum depression and 3 times higher risk for developing chronic pain, compared with women who experience mild post-CD pain.2Identifying patients at risk for severe postoperative pain allows for the provision of individualized anesthetic care. Pan et al used a simple 3-item questionnaire to predict, with reasonable accuracy, pain at 24 hours post-CD.3 The nocebo effect of such questionnaires on postoperative pain also must be considered. Patients questioned about “comfort” rather than “pain” levels were less likely to request additional postoperative analgesia.4
Landau et al defined chronic pain after CD as “abdominal wound scar pain persisting for more than three months after delivery, and unrelated to menstrual pain.”5 Severe acute pain after CD may become chronic in up to 18% of cases. Thus far, clinical interventions have not been consistently effective at reducing its incidence and severity.5,6 Preoperative risk factors associated with acute and chronic post-CD pain are a history of chronic pain (usually back pain), substance abuse, migraines, scar hyperalgesia from a previous CD, and regular use of analgesics before CD.5 General anesthesia also increases the risk for postoperative pain.6 Surgical factors contributing to increased incidence of post-CD pain are uterine exteriorization for uterine closure and closure of the parietal peritoneum.7
Although the incidence of chronic pain after CD is far from negligible, it may occur less frequently than expected given the degree and location of physical trauma. This suggests that protective mechanisms may exist during the puerperium that reduce the risk for developing chronic pain after tissue injury.8
Intrathecal Preservative-Free Morphine
Intrathecal preservative-free morphine is the gold standard for postoperative pain control in CD parturients undergoing spinal anesthesia. Intrathecal morphine acts on mu receptors in the dorsal horn of the spinal cord to reduce the release of excitatory neuropeptides from group C nerve fibers.
The lowest effective dose is controversial. Ideally, adequate pain control should be balanced with minimal medication side effects. In a landmark dose–response relationship study, Palmer et al showed that 100 mcg or less of intrathecal morphine provided analgesic effects comparable to doses as high as 500 mcg. However, the incidence of pruritus increased proportionally to the dose.9
Aiono-Le Tagaloa et al surveyed members of the Society for Obstetric Anesthesia and Perinatology to determine their anesthetic preferences for CD patients. Eighty-five percent of respondents preferred spinal anesthesia to epidural or combined spinal–epidural techniques, and the median dose of morphine used was 200 mcg.10 A meta-analysis that included 480 patients across 11 publications compared the effects of high-dose (>100-250 mcg) with low-dose (50-100 mcg) intrathecal morphine. The mean reported time to first request for supplemental analgesia was significantly longer in the high-dose group; however, the incidence of nausea, vomiting, and pruritus also was higher.11
In an effort to minimize the dose of intrathecal morphine and its opioid-related side effects, multimodal analgesic approaches have been studied, with encouraging results. Berger et al reported similar analgesia regardless of the amount of intrathecal morphine administered (50, 100, or 150 mcg) when combined with IV ketorolac (30 mg before leaving the OR, and an additional 15 mg every 6 hours, for a total of 24 hours).12 Administration of ketamine was found, in a meta-analysis, to prolong the time to the first post-CD analgesic request by 50 minutes.13
The most frequent side effect after intrathecal morphine administration is pruritus, with a reported incidence of 60% to 80%. The mechanism of intrathecal opioid–induced pruritus has not been fully elucidated. Pruritus is dose-dependent and more frequent in parturients than the general population, most likely due to the interaction of estrogens with opioid receptors.14Administration of opioid antagonists, opioid agonist-antagonist analgesics, propofol, gabapentin, and nonsteroidal anti-inflammatory drugs, in treating intrathecal morphine–induced pruritus, resulted in conflicting results regarding efficacy. Recently, Koju et al showed that prophylactic administration of 4 mg of ondansetron, 30 minutes before intrathecal administration of morphine, significantly reduced the incidence of nausea, vomiting, and pruritus. The authors postulated that the antipruritic effect of ondansetron was due to antagonizing 5-HT3 receptors located in the dorsal horn of the spinal cord, which were activated by intrathecal administration of morphine.14Additionally, desaturation episodes after intrathecal morphine are more frequent in patients with obesity and sleep apnea.15
Transversus Abdominis Plane Block
Ultrasound-guided transversus abdominis plane (TAP) block is an effective method for postoperative analgesia, as part of a multimodal approach, when intrathecal morphine is not used. Single-shot TAP blocks require large amounts of local anesthetics, and cases of symptomatic toxic plasma concentrations of bupivacaine have been reported.16 Recently, the ultrasound-guided quadratus lumborum block with ropivacaine was shown to be effective as part of a multimodal approach, excluding parturients receiving intrathecal morphine.17
Post–Hospital Discharge Opioid Consumption After CD
In a prospective observational study of 246 patients, Osmundson et al found the median time of post-discharge opioid use to be 8 days. Seventy-five percent of women who filled the prescription had unused opioids remaining, with 63% of those respondents storing them unlocked. The authors concluded, “Most women … are prescribed opioids in excess of the amount needed.”18
Bateman et al reported that 1 in 300 opioid-naive women become “persistent opioid users” in the first year after CD. Predictors of “persistent use” include history of illicit substance abuse, tobacco use, use of psychotropic medications, and chronic pain.19
- Preoperative identification of risk factors for severe acute or chronic post-CD pain can greatly influence the development of an individualized approach for analgesic treatment.
- Intrathecal morphine alone, although capable of providing adequate analgesia, is not the ideal analgesic for treating post-CD pain.
- A multimodal analgesic approach is preferred in the treatment of post-CD pain.
- Opioids are frequently overprescribed during discharge after CD.
- Carvalho B, Cohen SE, Lipman ss, et al. Patient preferences for anesthesia outcomes associated with cesarean delivery. Anesth Analg. 2005;101(4):1182-1187.
- Eisenach JC, Pan PH, Smiley R, et al. Severity of acute pain after childbirth, but not type of delivery, predicts persistent pain and postpartum depression. Pain. 2008;140(1):87-94.
- Pan PH, Tonidandel AM, Aschenbrenner CA, et al. Predicting acute pain after cesarean delivery using three simple questions. Anesthesiology. 2013;118(5):1170-1179.
- Chooi CS, White AM, Tan SG, et al. Pain vs comfort scores after caesarean section: a randomized trial. Br J Anaesth. 2013;110(5):780-787.
- Landau R, Bollag L, Ortner C. Chronic pain after childbirth. Int J Obstet Anesth. 2013;22(2):133-145.
- Nikolajsen L, SØrensen HC, Jensen TS, et al. Chronic pain following caesarean section. Acta Anaesthesiol Scand. 2004;48(1):111-116.
- Lavand’homme P. Chronic pain after vaginal and cesarean delivery: a reality questioning our daily practice of obstetric anesthesia. Int J Obstet Anesth. 2010;19(1):1-2.
- Eisenach JC, Pan P, Smiley RM, et al. Resolution of pain after childbirth. Anesthesiology. 2013;118(1):143-151.
- Palmer CM, Emerson S, Volgoropolous D, et al. Dose-response relationship of intrathecal morphine for postcesarean analgesia. Anesthesiology. 1999;90(2):437-444.
- Aiono-Le Tagaloa L, Butwick AJ, Carvalho B. A survey of perioperative and postoperative anesthetic practices for cesarean delivery. Anesthesiol Res Pract. 2009;2009:510642.
- Sultan P, Halpern SH, Pushpanathan E, et al. The effect of intrathecal morphine dose on outcomes after elective cesarean delivery: a meta-analysis. Anesth Analg. 2016;123(1):154-164.
- Berger JS, Gonzalez A, Hopkins A, et al. Dose-response of intrathecal morphine when administered with intravenous ketorolac for post-cesarean analgesia: a two-center, prospective, randomized, blinded trial. Int J Obstet Anesth. 2016;28:3-11.
- Heesen M, BÖhmer J, Brinck EC, et al. Intravenous ketamine during spinal and general anaesthesia for caesarean section: systematic review and meta-analysis. Acta Anaesthesiol Scand. 2015;59(4):414-426.
- Koju RB, Gurung BS, Dongol Y. Prophylactic administration of ondansetron in prevention of intrathecal morphine-induced pruritus and post-operative nausea and vomiting in patients undergoing caesarean section. BMC Anesthesiol. 2015;15:18.
- Ladha KS, Kato R, Tsen LC, et al. A prospective study of post-cesarean delivery hypoxia after spinal anesthesia with intrathecal morphine 150μg. Int J Obstet Anesth. 2017;32:48-53.
- Trabelsi B, Charfi R, Bennasr L, et al. Pharmacokinetics of bupivacaine after bilateral ultrasound-guided transversus abdominis plane block following cesarean delivery under spinal anesthesia. Int J Obstet Anesth. 2017;32:17-20.
- Krohg A, Ullensvang K, Rosseland LA, et al. The analgesic effect of ultrasound-guided quadratus lumborum block after cesarean delivery: a randomized clinical trial. Anesth Analg. 2018;126(2):559-565.
- Osmundson ss, Schornack LA, Grasch JL, et al. Postdischarge opioid use after cesarean delivery. Obstet Gynecol. 2017;130(1):36-41.
- Bateman BT, Franklin JM, Bykov K, et al. Persistent opioid use following cesarean delivery: patterns and predictors among opioid-naÏve women. Am J Obstet Gynecol. 2016;215(3):353.e1-353.e18.